Biofilm models of polymicrobial infection.

PubMed

Gabrilska, Rebecca A; Rumbaugh, Kendra P

2015-01-01

Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

PubMed

Press, A T; Butans, M J; Haider, T P; Weber, C; Neugebauer, S; Kiehntopf, M; Schubert, U S; Clemens, M G; Bauer, M; Kortgen, A

2017-11-13

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Escherichia coli Peritonitis in Peritoneal Dialysis: The Prevalence, Antibiotic Resistance and Clinical Outcomes in a South China Dialysis Center

PubMed Central

Feng, Xiaoran; Yang, Xiao; Yi, Chunyan; Guo, Qunying; Mao, Haiping; Jiang, Zongpei; Li, Zhibin; Chen, Dongmei; Cui, Yingpeng; Yu, Xueqing

2014-01-01

♦ Introduction: Escherichia coli (E. coli) peritonitis is a frequent, serious complication of peritoneal dialysis (PD). The extended-spectrum β-lactamase (ESBL)-producing E. coli peritonitis is associated with poorer prognosis and its incidence has been on continuous increase during the last decades. However, the clinical course and outcomes of E. coli peritonitis remain largely unclear. ♦ Methods: All of the E. coli peritonitis episodes that occurred in our dialysis unit from 2006 to 2011 were reviewed. The polymicrobial episodes were excluded. ♦ Results: In total, ninety episodes of monomicrobial E. coli peritonitis occurred in 68 individuals, corresponding to a rate of 0.027 episodes per patient-year. E. coli was the leading cause (59.2%) of monomicrobial gram-negative peritonitis. ESBL-producing strains accounted for 35.5% of E. coli peritonitis. The complete cure rate and treatment failure rate of E. coli peritonitis were 77.8% and 10.0% respectively. Patients with preceding peritonitis had a higher risk of ESBL production as compared to those without peritonitis history [odds ratio (OR): 5.286; 95% confidence interval (CI): 2.018 - 13.843; p = 0.001]. The risk of treatment failure was significantly increased when the patient had a baseline score of Charlson Comorbidity Index (CCI) above 3 (OR: 6.155; 95% CI: 1.198 - 31.612; p = 0.03), or had diabetes mellitus (OR: 8.457; 95% CI: 1.838 - 38.91; p = 0.006), or hypoalbuminemia (≤ 30g/l) on admission (OR: 13.714; 95% CI: 1.602 - 117.428; p = 0.01). Prolonging the treatment course from 2 to 3 weeks or more reduced the risk of relapse and repeat significantly (p < 0.05). ♦ Conclusions: E. coli peritonitis remains a common complication of PD. The clinical outcomes of E. coli peritonitis are relatively favorable despite the high ESBL rate. A history of peritonitis is associated with increased risk for ESBL development. The severity of baseline comorbidities, the presence of diabetes mellitus and hypoalbuminemia at admission are associated with poor outcomes. PMID:24497589

Biofilm models of polymicrobial infection

PubMed Central

Gabrilska, Rebecca A; Rumbaugh, Kendra P

2015-01-01

Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed. PMID:26592098

The Effects of Biocompatible Compared with Standard Peritoneal Dialysis Solutions on Peritonitis Microbiology, Treatment, and Outcomes: the balANZ Trial

PubMed Central

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

♦ Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products (“biocompatible”) compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. ♦ Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. ♦ Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. ♦ Conclusions: Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups. PMID:22991015

Morphogenesis Is Not Required for Candida albicans-Staphylococcus aureus Intra-Abdominal Infection-Mediated Dissemination and Lethal Sepsis

PubMed Central

Nash, Evelyn E.; Peters, Brian M.; Palmer, Glen E.; Fidel, Paul L.

2014-01-01

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of Staphylococcus aureus-Candida albicans intra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role of C. albicans morphogenesis in lethality, a trait involved in virulence and physical interaction with S. aureus. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 107 C. albicans (5× increase), coinfection with C. albicans yeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-locked C. albicans mutant given intravenously (i.v.) and S. aureus given intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host and C. albicans-S. aureus that results in strong inflammatory responses, dissemination, and lethal sepsis, independent of C. albicans morphogenesis. PMID:24891104

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

PubMed Central

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Cyclooxygenase-2 Deficiency Leads to Intestinal Barrier Dysfunction and Increased Mortality During Polymicrobial Sepsis 1

PubMed Central

Fredenburgh, Laura E.; Velandia, Margarita M. Suarez; Ma, Jun; Olszak, Torsten; Cernadas, Manuela; Englert, Joshua A.; Chung, Su Wol; Liu, Xiaoli; Begay, Cynthia; Padera, Robert F.; Blumberg, Richard S.; Walsh, Stephen R.; Baron, Rebecca M.; Perrella, Mark A.

2011-01-01

Sepsis remains the leading cause of death in critically ill patients despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase-2 (COX-2) is highly upregulated in the intestine during sepsis and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2−/− and COX-2+/+ BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD2, or vehicle and stimulated with cytokines. COX-2−/− mice developed exaggerated bacteremia and increased mortality compared with COX-2+/+ mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD2 attenuated cytokine-induced hyperpermeability and ZO-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis. PMID:21967897

Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree.

PubMed

Schmoeckel, Katrin; Mrochen, Daniel M; Hühn, Jochen; Pötschke, Christian; Bröker, Barbara M

2018-01-01

Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen "overload" by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness.

Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree

PubMed Central

Hühn, Jochen; Pötschke, Christian

2018-01-01

Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen “overload” by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness. PMID:29415028

Genome-wide transposon mutagenesis of Proteus mirabilis: Essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements.

PubMed

Armbruster, Chelsie E; Forsyth-DeOrnellas, Valerie; Johnson, Alexandra O; Smith, Sara N; Zhao, Lili; Wu, Weisheng; Mobley, Harry L T

2017-06-01

The Gram-negative bacterium Proteus mirabilis is a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Numerous prior studies have uncovered virulence factors for P. mirabilis pathogenicity in a murine model of ascending UTI, but little is known concerning pathogenesis during CAUTI or polymicrobial infection. In this study, we utilized five pools of 10,000 transposon mutants each and transposon insertion-site sequencing (Tn-Seq) to identify the full arsenal of P. mirabilis HI4320 fitness factors for single-species versus polymicrobial CAUTI with Providencia stuartii BE2467. 436 genes in the input pools lacked transposon insertions and were therefore concluded to be essential for P. mirabilis growth in rich medium. 629 genes were identified as P. mirabilis fitness factors during single-species CAUTI. Tn-Seq from coinfection with P. stuartii revealed 217/629 (35%) of the same genes as identified by single-species Tn-Seq, and 1353 additional factors that specifically contribute to colonization during coinfection. Mutants were constructed in eight genes of interest to validate the initial screen: 7/8 (88%) mutants exhibited the expected phenotypes for single-species CAUTI, and 3/3 (100%) validated the expected phenotypes for polymicrobial CAUTI. This approach provided validation of numerous previously described P. mirabilis fitness determinants from an ascending model of UTI, the discovery of novel fitness determinants specifically for CAUTI, and a stringent assessment of how polymicrobial infection influences fitness requirements. For instance, we describe a requirement for branched-chain amino acid biosynthesis by P. mirabilis during coinfection due to high-affinity import of leucine by P. stuartii. Further investigation of genes and pathways that provide a competitive advantage during both single-species and polymicrobial CAUTI will likely provide robust targets for therapeutic intervention to reduce P. mirabilis CAUTI incidence and severity.

Genome-wide transposon mutagenesis of Proteus mirabilis: Essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements

PubMed Central

Smith, Sara N.; Zhao, Lili; Wu, Weisheng

2017-01-01

The Gram-negative bacterium Proteus mirabilis is a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Numerous prior studies have uncovered virulence factors for P. mirabilis pathogenicity in a murine model of ascending UTI, but little is known concerning pathogenesis during CAUTI or polymicrobial infection. In this study, we utilized five pools of 10,000 transposon mutants each and transposon insertion-site sequencing (Tn-Seq) to identify the full arsenal of P. mirabilis HI4320 fitness factors for single-species versus polymicrobial CAUTI with Providencia stuartii BE2467. 436 genes in the input pools lacked transposon insertions and were therefore concluded to be essential for P. mirabilis growth in rich medium. 629 genes were identified as P. mirabilis fitness factors during single-species CAUTI. Tn-Seq from coinfection with P. stuartii revealed 217/629 (35%) of the same genes as identified by single-species Tn-Seq, and 1353 additional factors that specifically contribute to colonization during coinfection. Mutants were constructed in eight genes of interest to validate the initial screen: 7/8 (88%) mutants exhibited the expected phenotypes for single-species CAUTI, and 3/3 (100%) validated the expected phenotypes for polymicrobial CAUTI. This approach provided validation of numerous previously described P. mirabilis fitness determinants from an ascending model of UTI, the discovery of novel fitness determinants specifically for CAUTI, and a stringent assessment of how polymicrobial infection influences fitness requirements. For instance, we describe a requirement for branched-chain amino acid biosynthesis by P. mirabilis during coinfection due to high-affinity import of leucine by P. stuartii. Further investigation of genes and pathways that provide a competitive advantage during both single-species and polymicrobial CAUTI will likely provide robust targets for therapeutic intervention to reduce P. mirabilis CAUTI incidence and severity. PMID:28614382

Efficacy of Ethanol against Candida albicans and Staphylococcus aureus Polymicrobial Biofilms

PubMed Central

Peters, Brian M.; Ward, Raven M.; Rane, Hallie S.; Lee, Samuel A.

2013-01-01

Candida albicans, an opportunistic fungus, and Staphylococcus aureus, a bacterial pathogen, are two clinically relevant biofilm-forming microbes responsible for a majority of catheter-related infections, with such infections often resulting in catheter loss and removal. Not only do these pathogens cause a substantial number of nosocomial infections independently, but also they are frequently found coexisting as polymicrobial biofilms on host and environmental surfaces. Antimicrobial lock therapy is a current strategy to sterilize infected catheters. However, the robustness of this technique against polymicrobial biofilms has remained largely untested. Due to its antimicrobial activity, safety, stability, and affordability, we tested the hypothesis that ethanol (EtOH) could serve as a potentially efficacious catheter lock solution against C. albicans and S. aureus biofilms. Therefore, we optimized the dose and time necessary to achieve killing of both monomicrobial and polymicrobial biofilms formed on polystyrene and silicone surfaces in a static microplate lock therapy model. Treatment with 30% EtOH for a minimum of 4 h was inhibitory for monomicrobial and polymicrobial biofilms, as evidenced by XTT {sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide inner salt} metabolic activity assays and confocal microscopy. Experiments to determine the regrowth of microorganisms on silicone after EtOH treatment were also performed. Importantly, incubation with 30% EtOH for 4 h was sufficient to kill and inhibit the growth of C. albicans, while 50% EtOH was needed to completely inhibit the regrowth of S. aureus. In summary, we have systematically defined the dose and duration of EtOH treatment that are effective against and prevent regrowth of C. albicans and S. aureus monomicrobial and polymicrobial biofilms in an in vitro lock therapy model. PMID:23070170

Isolation of non-sporing anaerobic rods from infections in children.

PubMed

Brook, I

1996-07-01

From 1974 to 1994, 2033 microbiological specimens from children were submitted for cultures for anaerobic bacteria. Fifty-seven isolates of Bifidobacterium spp. were obtained from 55 (3%) children, 67 isolates of Eubacterium spp. from 65 (3%) children and 41 isolates of Lactobacillus spp. from 40 (2%) children. Most Bifidobacterium isolates were from chronic otitis media, abscesses, peritonitis, aspiration pneumonia and paronychia. Most Eubacterium isolates were from abscesses, peritonitis, decubitus ulcers and bites. Lactobacillus spp. were mainly isolated from abscesses, aspiration pneumonia, bacteraemia and conjunctivitis. Most (> 90%) infections from which these species were isolated were polymicrobial and yielded a mixture of aerobic and anaerobic bacteria. The organisms most commonly isolated with the non-sporing anaerobic gram-positive rods were Peptostreptococcus spp., Bacteroides spp., pigmented Prevotella and Porphyromonas spp., Fusobacterium spp., Staphylococcus aureus and Escherichia coli. Most Bacteroides spp. and E. coli were isolated from intra-abdominal infection and skin and soft tissue infection around the rectal area, whereas most Prevotella, Porphyromonas and Fusobacterium isolates were from oropharyngeal, pulmonary and head and neck sites. The predisposing conditions associated with the isolation of non-sporing anaerobic gram-positive rods were previous surgery, malignancy, steroid therapy and immunodeficiency. Antimicrobial therapy was given to 149 (83%) of the 160 patients, in conjunction with surgical drainage or correction of pathology in 89 (56%).

Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences

PubMed Central

Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao

2016-01-01

Background and objectives Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. Design, setting, participants, & measurements In this single–center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Results Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3–62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0–65.8 days versus 27.5; IQR, 23.0–35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8–60.5 months versus 55.8; IQR, 40.4–71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively. Conclusions S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study. PMID:27269302

Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences.

PubMed

Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao; Szeto, Cheuk Chun

2016-07-07

Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. In this single-center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3-62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0-65.8 days versus 27.5; IQR, 23.0-35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8-60.5 months versus 55.8; IQR, 40.4-71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively. S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study. Copyright © 2016 by the American Society of Nephrology.

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

PubMed

Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

2018-01-16

Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non- albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans / S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis / S. aureus -mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis -induced protection. C. dubliniensis / S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1 hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1 + cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans / S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of trained innate immunity. IMPORTANCE Polymicrobial intra-abdominal infections are clinically devastating infections with high mortality rates, particularly those involving fungal pathogens, including Candida species. Even in patients receiving aggressive antimicrobial therapy, mortality rates remain unacceptably high. There are no available vaccines against IAI, which is complicated by the polymicrobial nature of the infection. IAI leads to lethal systemic inflammation (sepsis), which is difficult to target pharmacologically, as components of the inflammatory response are also needed to control the infection. Our studies demonstrate that prior inoculation with low-virulence Candida species provides strong protection against subsequent lethal infection with C. albicans and S. aureus Surprisingly, protection is long-lived but not mediated by adaptive (specific) immunity. Instead, protection is dependent on cells of the innate immune system (nonspecific immunity) and provides protection against other virulent Candida species. This discovery implies that a form of trained innate immunity may be clinically effective against polymicrobial IAI. Copyright © 2018 Lilly et al.

[Peritonitis following gastroduodenal ulcer perforation disease in children: report of 4 cases].

PubMed

Ndour, O; Bansouda, J; Fall, A F; Alumeti, D M; Diouf, C; Ngom, G; Ndoye, M

2012-10-01

Peritonitis due to gastroduodenal ulcer perforation disease is a rare entity in pediatric surgery. In Senegal, no study has been dedicated to ulcer complications in children. The aim of this study was to describe the epidemiology, diagnosis, and treatment of perforated peptic ulcer in patients less than 15 years old. This retrospective study was conducted in the Surgical Emergencies and Paediatric Surgery Department at Aristide Le Dantec University Hospital Center in Dakar, Senegal, during a period of 11 years (January 1999 to December 2010). We found 4 children who presented perforated gastroduodenal ulcer: 3 females and 1 male. The average age of these patients was 9 years (range, 7-14 years). No family history was found. We noted 3 cases of perforated duodenal ulcer and one perforated gastric ulcer. The clinical diagnosis was suspected based on a peritoneal irritation syndrome. A plain x-ray of the abdomen was taken in all patients, which objectified a pneumoperitoneum image in 3 cases. The leukocytosis was constant. Treatment in all patients consisted on pre-, intra-, and postoperative intensive care, supra- and infraumbilical midline laparotomy, which allowed us to perform a debridement-suture of the gap followed by epiploplasty and extensive washing with lukewarm physiologic serum. Adjuvant therapy based on anti-ulcer and antibiotic therapy was initiated. Bacteriological examination of peritoneal fluid isolated a polymicrobial flora. Helicobacter pylori was not isolated. Histological examination of the biopsied perforation edges showed a benign ulcer in all cases. The follow-up endoscopy was performed 4 weeks after surgery and showed cicatrization of the ulcer in all patients. After a mean of 2 years, no recurrence was noted. The gastric or duodenal ulcer in children is rare. It is often discovered at the stage of perforation, a complication for which the essential treatment is surgery. Routine screening would certainly help to reduce the risk of this complication. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo

PubMed Central

Perez, Antonia C.; Pang, Bing; King, Lauren B.; Tan, Li; Murrah, Kyle A.; Reimche, Jennifer L.; Wren, John T.; Richardson, Stephen H.; Ghandi, Uma; Swords, W. Edward

2014-01-01

Otitis media is an extremely common pediatric ailment caused by opportunists that reside within the nasopharynx. Inflammation within the upper airway can promote ascension of these opportunists into the middle ear chamber. Otitis media can be chronic/recurrent in nature, and a wealth of data indicates that in these cases the bacteria persist within biofilms. Epidemiological data demonstrates most cases of otitis media are polymicrobial, which may have significant impact on antibiotic resistance. In this study, we used in vitro biofilm assays and rodent infection models to examine the impact of polymicrobial infection with Moraxella catarrhalis and Streptococcus pneumoniae (pneumococcus) on biofilm resistance to antibiotic treatment and persistence in vivo. Consistent with prior work, M. catarrhalis conferred beta-lactamase dependent passive protection from beta-lactam killing to pneumococci within polymicrobial biofilms. Moreover, pneumococci increased resistance of M. catarrhalis to macrolide killing in polymicrobial biofilms. However, pneumococci increased colonization in vivo by M. catarrhalis in a quorum signal-dependent manner. We also found that co-infection with M. catarrhalis affects middle ear ascension of pneumococci in both mice and chinchillas. Therefore, we conclude that residence of M. catarrhalis and pneumococci within the same biofilm community significantly impacts resistance to antibiotic treatment and bacterial persistence in vivo. PMID:24391058

Polymicrobial periodontal pathogens transcriptomes in calvarial bone and soft tissue

PubMed Central

Bakthavatchalu, Vasudevan; Meka, Archana; Mans, Jeffrey J.; Sathishkumar, Sabapathi; Lopez, M. Cecilia; Bhattacharyya, Indraneel; Boyce, Brendan F.; Baker, Henry V.; Lamont, Richard J.; Ebersole, Jeffrey L.; Kesavalu, L.

2011-01-01

Summary Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are consistently associated with adult periodontitis. This study sought to document the host transcriptome to a P. gingivalis, T. denticola, and T. forsythia challenge as a polymicrobial infection using a murine calvarial model of acute inflammation and bone resorption. Mice were infected with P. gingivalis, T. denticola, and T. forsythia over the calvaria, after which the soft tissues and calvarial bones were excised. A Murine GeneChip® array analysis of transcript profiles showed that 6997 genes were differentially expressed in calvarial bones (P < 0.05) and 1544 genes were differentially transcribed in the inflamed tissues after the polymicrobial infection. Of these genes, 4476 and 1035 genes in the infected bone and tissues were differentially expressed by upregulation. Biological pathways significantly impacted by the polymicrobial infection in calvarial bone included leukocyte transendothelial migration (LTM), cell adhesion molecules, adherens junction, major histocompatibility complex antigen, extracellular matrix-receptor interaction (ECM), and antigen processing and presentation resulting in inflammatory/cytokine/chemokine transcripts stimulation in bone and soft tissue. Intense inflammation and increased activated osteoclasts was observed in calvarias compared to sham-infected controls. Quantitative real-time RT-PCR analysis confirmed mRNA level of selected genes corresponded with the microarray expression. The polymicrobial infection regulated several LTM and extracellular membrane (ECM) pathway genes in a manner distinct from monoinfection with P. gingivalis, T. denticola, or T. forsythia. To our knowledge, this is the first definition of the polymicrobial induced transcriptome in calvarial bone and soft tissue in response to periodontal pathogens. PMID:21896157

Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection

PubMed Central

Pastar, Irena; Nusbaum, Aron G.; Gil, Joel; Patel, Shailee B.; Chen, Juan; Valdes, Jose; Stojadinovic, Olivera; Plano, Lisa R.; Tomic-Canic, Marjana; Davis, Stephen C.

2013-01-01

Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections. PMID:23451098

Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo.

PubMed

Perez, Antonia C; Pang, Bing; King, Lauren B; Tan, Li; Murrah, Kyle A; Reimche, Jennifer L; Wren, John T; Richardson, Stephen H; Ghandi, Uma; Swords, W Edward

2014-04-01

Otitis media (OM) is an extremely common pediatric ailment caused by opportunists that reside within the nasopharynx. Inflammation within the upper airway can promote ascension of these opportunists into the middle ear chamber. OM can be chronic/recurrent in nature, and a wealth of data indicates that in these cases, the bacteria persist within biofilms. Epidemiological data demonstrate that most cases of OM are polymicrobial, which may have significant impact on antibiotic resistance. In this study, we used in vitro biofilm assays and rodent infection models to examine the impact of polymicrobial infection with Moraxella catarrhalis and Streptococcus pneumoniae (pneumococcus) on biofilm resistance to antibiotic treatment and persistence in vivo. Consistent with prior work, M. catarrhalis conferred beta-lactamase-dependent passive protection from beta-lactam killing to pneumococci within polymicrobial biofilms. Moreover, pneumococci increased resistance of M. catarrhalis to macrolide killing in polymicrobial biofilms. However, pneumococci increased colonization in vivo by M. catarrhalis in a quorum signal-dependent manner. We also found that co-infection with M. catarrhalis affects middle ear ascension of pneumococci in both mice and chinchillas. Therefore, we conclude that residence of M. catarrhalis and pneumococci within the same biofilm community significantly impacts resistance to antibiotic treatment and bacterial persistence in vivo. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Nonencapsulated Streptococcus pneumoniae causes otitis media during single-species infection and during polymicrobial infection with nontypeable Haemophilus influenzae

PubMed Central

Murrah, Kyle A.; Pang, Bing; Richardson, Stephen; Perez, Antonia; Reimche, Jennifer; King, Lauren; Wren, John; Swords, W. Edward

2014-01-01

Streptococcus pneumoniae strains lacking capsular polysaccharide have been increasingly reported in carriage and disease contexts. Since most cases of otitis media involve more than one bacterial species, we aimed to determine the capacity of a nonencapsulated S. pneumoniae clinical isolate to induce disease in the context of a single-species infection and as a polymicrobial infection with nontypeable Haemophilus influenzae. Using the chinchilla model of otitis media, we found that nonencapsulated S. pneumoniae colonizes the nasopharynx following intranasal inoculation, but does not readily ascend into the middle ear. However, when we inoculated nonencapsulated S. pneumoniae directly into the middle ear, the bacteria persisted for two weeks post-inoculation and induced symptoms consistent with chronic otitis media. During coinfection with nontypeable H. influenzae, both species persisted for one week and induced polymicrobial otitis media. We also observed that nontypeable H. influenzae conferred passive protection from killing by amoxicillin upon S. pneumoniae from within polymicrobial biofilms in vitro. Therefore, based on these results, we conclude that nonencapsulated pneumococci are a potential causative agent of chronic/recurrent otitis media, and can also cause mutualistic infection with other opportunists, which could complicate treatment outcomes. PMID:26014114

A study on the information-motivation-behavioural skills model among Chinese adults with peritoneal dialysis.

PubMed

Chang, Tian-Ying; Zhang, Yi-Lin; Shan, Yan; Liu, Sai-Sai; Song, Xiao-Yue; Li, Zheng-Yan; Du, Li-Ping; Li, Yan-Yan; Gao, Douqing

2018-05-01

To examine whether the information-motivation-behavioural skills model could predict self-care behaviour among Chinese peritoneal dialysis patients. Peritoneal dialysis is a treatment performed by patients or their caregivers in their own home. It is important to implement theory-based projects to increase the self-care of patients with peritoneal dialysis. The information-motivation-behavioural model has been verified in diverse populations as a comprehensive, effective model to guide the design, implementation and evaluation of self-care programmes. A cross-sectional, observational study. A total of 201 adults with peritoneal dialysis were recruited at a 3A grade hospital in China. Participant data were collected on demographics, self-care information (knowledge), social support (social motivation), self-care attitude (personal motivation), self-efficacy (behaviour skills) and self-care behaviour. We also collected data on whether the recruited patients had peritoneal dialysis-associated peritonitis from electronic medical records. Measured variable path analysis was performed using mplus 7.4 to identify the information-motivation-behavioural model. Self-efficacy, information and social motivation predict peritoneal dialysis self-care behaviour directly. Information and personal support affect self-care behaviour through self-efficacy, whereas peritoneal dialysis self-care behaviour has a direct effect on the prevention of peritoneal dialysis-associated peritonitis. The information-motivation-behavioural model is an appropriate and applicable model to explain and predict the self-care behaviour of Chinese peritoneal dialysis patients. Poor self-care behaviour among peritoneal dialysis patients results in peritoneal dialysis-associated peritonitis. The findings suggest that self-care education programmes for peritoneal dialysis patients should include strategies based on the information-motivation-behavioural model to enhance knowledge, motivation and behaviour skills to change or maintain self-care behaviour. © 2018 John Wiley & Sons Ltd.

Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis.

PubMed

Gong, Yu; Zou, Lin; Cen, Dongzhi; Chao, Wei; Chen, Dunjin

2016-12-01

Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens. Results CLP-induced polymicrobial sepsis specifically attenuated both the gene and protein expression of SARM in the spleens. Moreover, the attenuation of SARM expression synchronized with splenocyte apoptosis, as evidenced by increased caspase 3 cleavage and ATP depletion. Conclusions These findings suggest that SARM is a potential regulator of sepsis-induced splenocyte apoptosis.

Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.

PubMed

Armbruster, Chelsie E; Hong, Wenzhou; Pang, Bing; Weimer, Kristin E D; Juneau, Richard A; Turner, James; Swords, W Edward

2010-07-06

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

Nonencapsulated Streptococcus pneumoniae causes otitis media during single-species infection and during polymicrobial infection with nontypeable Haemophilus influenzae.

PubMed

Murrah, Kyle A; Pang, Bing; Richardson, Stephen; Perez, Antonia; Reimche, Jennifer; King, Lauren; Wren, John; Swords, W Edward

2015-07-01

Streptococcus pneumoniae strains lacking capsular polysaccharide have been increasingly reported in carriage and disease contexts. Since most cases of otitis media involve more than one bacterial species, we aimed to determine the capacity of a nonencapsulated S. pneumoniae clinical isolate to induce disease in the context of a single-species infection and as a polymicrobial infection with nontypeable Haemophilus influenzae. Using the chinchilla model of otitis media, we found that nonencapsulated S. pneumoniae colonizes the nasopharynx following intranasal inoculation, but does not readily ascend into the middle ear. However, when we inoculated nonencapsulated S. pneumoniae directly into the middle ear, the bacteria persisted for two weeks post-inoculation and induced symptoms consistent with chronic otitis media. During coinfection with nontypeable H. influenzae, both species persisted for one week and induced polymicrobial otitis media. We also observed that nontypeable H. influenzae conferred passive protection from killing by amoxicillin upon S. pneumoniae from within polymicrobial biofilms in vitro. Therefore, based on these results, we conclude that nonencapsulated pneumococci are a potential causative agent of chronic/recurrent otitis media, and can also cause mutualistic infection with other opportunists, which could complicate treatment outcomes. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling

PubMed Central

Armbruster, Chelsie E.; Hong, Wenzhou; Pang, Bing; Weimer, Kristin E. D.; Juneau, Richard A.; Turner, James; Swords, W. Edward

2010-01-01

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm. PMID:20802829

Development and characterisation of a novel three-dimensional inter-kingdom wound biofilm model.

PubMed

Townsend, Eleanor M; Sherry, Leighann; Rajendran, Ranjith; Hansom, Donald; Butcher, John; Mackay, William G; Williams, Craig; Ramage, Gordon

2016-11-01

Chronic diabetic foot ulcers are frequently colonised and infected by polymicrobial biofilms that ultimately prevent healing. This study aimed to create a novel in vitro inter-kingdom wound biofilm model on complex hydrogel-based cellulose substrata to test commonly used topical wound treatments. Inter-kingdom triadic biofilms composed of Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus were shown to be quantitatively greater in this model compared to a simple substratum when assessed by conventional culture, metabolic dye and live dead qPCR. These biofilms were both structurally complex and compositionally dynamic in response to topical therapy, so when treated with either chlorhexidine or povidone iodine, principal component analysis revealed that the 3-D cellulose model was minimally impacted compared to the simple substratum model. This study highlights the importance of biofilm substratum and inclusion of relevant polymicrobial and inter-kingdom components, as these impact penetration and efficacy of topical antiseptics.

Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

PubMed Central

Yasuda, Hideo; Leelahavanichkul, Asada; Tsunoda, Shinichiro; Dear, James W.; Takahashi, Yoshiyuki; Ito, Shuichi; Hu, Xuzhen; Zhou, Hua; Doi, Kent; Childs, Richard; Klinman, Dennis M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development. PMID:18305095

Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1

PubMed Central

Jin, Liliang; Batra, Sanjay

2017-01-01

Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP) and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET) formation, and NET-mediated killing in response to both Gram-negative (E. coli) and Gram-positive (Staphylococcus aureus) pathogens. As compared with WT (C57Bl/6) mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1) in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis). Recombinant CXCL1 (rCXCL1) administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis. PMID:28922428

Assessment of Polymicrobial Infections in Ticks in New York State

PubMed Central

Tokarz, Rafal; Jain, Komal; Bennett, Ashlee; Briese, Thomas

2010-01-01

Abstract Ixodes scapularis ticks are clinically important hematophagous vectors. A single tick bite can lead to a polymicrobial infection. We determined the prevalence of polymicrobial infection with Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan virus in 286 adult ticks from the two counties in New York State where Lyme disease is endemic, utilizing a MassTag multiplex polymerase chain reaction assay. Seventy-one percent of the ticks harbored at least one organism; 30% had a polymicrobial infection. Infections with three microbes were detected in 5% of the ticks. One tick was infected with four organisms. Our results show that coinfection is a frequent occurrence in ticks in the two counties surveyed. PMID:19725770

Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip.

PubMed

Bozhkova, Svetlana; Tikhilov, Rashid; Labutin, Dmitry; Denisov, Alexey; Shubnyakov, Igor; Razorenov, Vadim; Artyukh, Vasilii; Rukina, Anna

2016-12-01

The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery. A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups-135 with monomicrobial and 54 with polymicrobial infection. Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m 2 (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0-10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0-27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18-16.37; p = 0.03). Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful. Level III, therapeutic study.

Model systems for the study of Enterococcal colonization and infection

PubMed Central

Goh, H. M. Sharon; Yong, M. H. Adeline; Chong, Kelvin Kian Long

2017-01-01

ABSTRACT Enterococcus faecalis and Enterococcus faecium are common inhabitants of the human gastrointestinal tract, as well as frequent opportunistic pathogens. Enterococci cause a range of infections including, most frequently, infections of the urinary tract, catheterized urinary tract, bloodstream, wounds and surgical sites, and heart valves in endocarditis. Enterococcal infections are often biofilm-associated, polymicrobial in nature, and resistant to antibiotics of last resort. Understanding Enterococcal mechanisms of colonization and pathogenesis are important for identifying new ways to manage and intervene with these infections. We review vertebrate and invertebrate model systems applied to study the most common E. faecalis and E. faecium infections, with emphasis on recent findings examining Enterococcal-host interactions using these models. We discuss strengths and shortcomings of each model, propose future animal models not yet applied to study mono- and polymicrobial infections involving E. faecalis and E. faecium, and comment on the significance of anti-virulence strategies derived from a fundamental understanding of host-pathogen interactions in model systems. PMID:28102784

Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

PubMed Central

Lee, Chan-Ho; Yoon, Seong-Jin; Lee, Sun-Mee

2012-01-01

Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders. PMID:23168580

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Wisniewska, J; Pawlaczyk, K; Kuzlan-Pawlaczyk, M; Filas, V; Breborowicz, A; Oreopoulos, D G

2001-03-01

Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.

The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection.

PubMed

Armbruster, Chelsie E; Smith, Sara N; Johnson, Alexandra O; DeOrnellas, Valerie; Eaton, Kathryn A; Yep, Alejandra; Mody, Lona; Wu, Weisheng; Mobley, Harry L T

2017-02-01

Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria. Copyright © 2017 American Society for Microbiology.

The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection

PubMed Central

Smith, Sara N.; Johnson, Alexandra O.; DeOrnellas, Valerie; Eaton, Kathryn A.; Yep, Alejandra; Mody, Lona; Wu, Weisheng

2016-01-01

ABSTRACT Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria. PMID:27895127

Experimental animal models of encapsulating peritoneal sclerosis.

PubMed

Hoff, Catherine M

2005-04-01

Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious complication of long-term peritoneal dialysis. The cause of EPS is unclear, but the low incidence suggests that it is most likely multifactorial. The elucidation of developmental pathways and predictive markers of EPS would facilitate the identification and management of high-risk patients. Animal models are often used to define pathways of disease progression and to test strategies for treatment and prevention in the patient population. Ideally such models could help to define the cause of EPS and its developmental pathways, to facilitate the identification of contributing factors and predictive markers, and to provide a system to test therapeutic strategies. Researchers have studied several rodent models of EPS that rely on chronic chemical irritation (for example, bleach, low-pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and abdominal encapsulation. Development in all models is progressive, with inflammation giving way to peritoneal fibrosis or sclerosis with accumulating membrane damage, culminating in cocoon formation. Microscopic findings are similar to those proposed as diagnostic criteria for clinical EPS: an initial inflammatory infiltrate and submesothelial thickening, collagen deposition, and activation and proliferation of peritoneal fibroblasts. The potential to block progression of peritoneal sclerosis in these models by anti-inflammatory, antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin-angiotensin system have been demonstrated. Animal models based on clinically relevant risk factors (for example, uremia, peritonitis, and long-term exposure to dialysis solutions) now represent the next step in model development.

Exogenous C3 protein enhances the adaptive immune response to polymicrobial sepsis through down-regulation of regulatory T cells.

PubMed

Yuan, Yujie; Ren, Jianan; Cao, Shougen; Zhang, Weiwei; Li, Jieshou

2012-01-01

The role of complement system in bridging innate and adaptive immunity has been confirmed in various invasive pathogens. It is still obscure how complement proteins promote T cell-mediated immune response during sepsis. The aim of this study is to investigate the role of exogenous C3 protein in the T-cell responses to sepsis. Sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type C57BL/6 mice, sham-operated mice for control. Human purified C3 protein (HuC3, 1 mg) was intraperitoneally injected at 6 h post-surgery, with 200 μl phosphate-buffered saline as control. The levels of C3 and cytokines, the expression of FOXP3 and NF-κB, and the percentages of CD4(+) T-cell subsets were compared among the groups at given time points. The polymicrobial sepsis produced considerable release of TNF-α and IL-10, and caused complement C3 exhaustion. Exogenous C3 administration markedly improved the 48 h survival rate, as compared with nontreatment (40% vs. 5%, P<0.01). The expression of FOXP3 protein was increased during sepsis, but can be suppressed by HuC3 administration. A single injection of HuC3 postponed the decline of differentiated Th1 cells, and depressed the activation of Th2/Th17 cells. Besides, the Th1-Th2 shift in late stage of sepsis can be controlled under C3 supplementation. The suppression of NF-κB pathway might be related to the appearance of immunocompromise. The study confirmed the important role of exogenous C3 in up-regulation of adaptive immune response to sepsis. The complement pathway would be a pivotal target for severe sepsis management. Copyright © 2011 Elsevier B.V. All rights reserved.

Center-Specific Factors Associated with Peritonitis Risk-A Multi-Center Registry Analysis.

PubMed

Nadeau-Fredette, Annie-Claire; Johnson, David W; Hawley, Carmel M; Pascoe, Elaine M; Cho, Yeoungjee; Clayton, Philip A; Borlace, Monique; Badve, Sunil V; Sud, Kamal; Boudville, Neil; McDonald, Stephen P

♦ Previous studies have reported significant variation in peritonitis rates across dialysis centers. Limited evidence is available to explain this variability. The aim of this study was to assess center-level predictors of peritonitis and their relationship with peritonitis rate variations. ♦ All incident peritoneal dialysis (PD) patients treated in Australia between October 2003 and December 2013 were included. Data were accessed through the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was peritonitis rate, evaluated in a mixed effects negative binomial regression model. Peritonitis-free survival was assessed as a secondary outcome in a Cox proportional hazards model. ♦ Overall, 8,711 incident PD patients from 51 dialysis centers were included in the study. Center-level predictors of lower peritonitis rates included smaller center size, high proportion of PD, low peritoneal equilibration test use at PD start, and low proportion of hospitalization for peritonitis. In contrast, a low proportion of automated PD exposure, high icodextrin exposure and low or high use of antifungal prophylaxis at the time of peritonitis were associated with a higher peritonitis rate. Similar results were obtained for peritonitis-free survival. Overall, accounting for center-level characteristics appreciably decreased peritonitis variability among dialysis centers (p = 0.02). ♦ This study identified specific center-level characteristics associated with the variation in peritonitis risk. Whether these factors are directly related to peritonitis risk or surrogate markers for other center characteristics is uncertain and should be validated in further studies. Copyright © 2016 International Society for Peritoneal Dialysis.

New Insights into Therapeutic Strategies for the Treatment of Peritoneal Fibrosis: Learning from Histochemical Analyses of Animal Models

PubMed Central

Kitamura, Mineaki; Nishino, Tomoya; Obata, Yoko; Ozono, Yoshiyuki; Koji, Takehiko; Kohno, Shigeru

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a fatal complication that can occur in patients undergoing long-term peritoneal dialysis. It is characterized by bowel obstruction and marked sclerotic thickening of the peritoneal membrane. Although the mechanisms underlying the development of EPS are complex, angiogenesis, inflammation, and peritoneal fibrosis are known to be essential factors. Now, several animal models that exhibit EPS have pathophysiology similar to that of human EPS and have been proposed for use in research to provide insights into it. Recent histochemical methods also help us to understand the pathophysiology of EPS. Advances in basic research based on the findings in those animal models have enabled the development of several strategies for the prevention and treatment of EPS. We describe here interventional studies in some animal models for peritoneal fibrosis, one of the histological disorders findings characteristic to EPS, and we highlight the need for a sophisticated animal model that closely resembles human conditions. PMID:25392567

Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

PubMed

Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-04-01

Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.

Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis

PubMed Central

Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2007-01-01

Targeted Interleukin (IL)-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild type (WT) littermates (n=127) were subjected to cecal ligation and puncture with a 27-gauge needle. Seven-day survival was 45% in transgenic animals and 30% in WT animals (p≤0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals, regardless of whether they expressed the transgene. Local parameters of injury including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines and stimulated cytokines from intraepithelial lymphocytes were similar between transgenic and wildtype mice. However, in stimulated splenocytes, pro-inflammatory cytokines MCP-1 (189 ± 43 pg/ml vs. 40 ± 8 pg/ml) and IL-6 (116 ± 28 pg/ml vs. 34 ± 9 pg/ml) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (p<0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the two groups as were circulating LPS levels. Transgenic mice also had lower white blood cell counts, associated with lower absolute neutrophil counts (0.5 ± 0.1 103/mm3 vs. 1.0 ± 0.2 103/mm3, p<0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

Periprosthetic joint infection by Propionibacterium acnes: Clinical differences between monomicrobial versus polymicrobial infection.

PubMed

Figa, Raúl; Muñetón, David; Gómez, Lucía; Matamala, Alfredo; Lung, Mayli; Cuchi, Eva; Corona, Pablo S

2017-04-01

To compare a series of monomicrobial Propionibacterium acnes (P. acnes) knee and hip periprosthetic joint infection (PJI) cases with cases of polymicrobial PJI which included P. acnes. We hypothesized that the presence of a polymicrobial P. acnes infection would lead to worse outcomes than those in cases of monomicrobial P. acnes PJI. Retrospective multicentre study. All patients with hip or knee PJIs including P. acnes diagnosed from August-2002 to July-2013 in two university hospitals were included. We collected demographic data, McPherson classification, local signs of infection (swelling or wound drainage), laboratory and histological data, surgical management, antibiotic treatment and outcomes. Data were compared between two groups: cases of monomicrobial P. acnes PJI, and cases of polymicrobial PJI involving P. acnes. Thirty-eight patients who presented with 38 PJIs were included; median age was 71 (IQR:62.5-79); 21 were men (55%); median follow-up was 42 months (IQR:17.5-58). Local signs of infection were present in 14 patients (36.8%); ESR>30 mm/h in 14 patients (36.8%); CRP>1 mg/dl in 15 patients (39.5%); 11 out of 25 patients (44%) had positive preoperative cultures from joint aspiration. Positive histologic studies (Feldman's criteria) were found in 5 out of 28 patients (17.8%). Twenty-four patients (63%) had monomicrobial PJIs; 14 patients (37%) had polymicrobial PJIs. There were no significant outcome differences between monomicrobial and polymicrobial PJIs cases; overall, the success rates were 79.2% and 85.7% respectively (P > 0.05). We did not find any significant differences between monomicrobial and polymicrobial P. acnes PJI outcomes. ESR, CRP and histologic study are established parameters for diagnosing PJI which did not prove useful in P. acnes PJI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can the three pore model correctly describe peritoneal transport of protein?

PubMed

Waniewski, Jacek; Poleszczuk, Jan; Antosiewicz, Stefan; Baczynński, Daniel; Gałach, Magda; Pietribiasi, Mauro; Wanńkowicz, Zofia

2014-01-01

The three pore model (3PM) includes large pores for the description of protein leak to the peritoneal cavity during peritoneal dialysis. However, the reliability of this description has been not fully tested against clinical data yet. Peritoneal transport parameters were estimated using 3PM, extended 3p model (with estimation of fraction of large pores, ext3PM), ext3PM with modified size of pores and proteins (mext3PM), and simplified two pore (2PM, small and ultrasmall pores) models for 32 patients on peritoneal dialysis investigated using the sequential peritoneal equilibration test (consecutive peritoneal equilibration test [PET]: glucose 2.27%, 4 h, and miniPET: glucose 3.86%, 1 h). Urea, creatinine, glucose, sodium, phosphate, albumin, and IgM concentrations were measured in dialysis fluid and plasma. Ext3PM and mext3PM, with large pore fraction of about 0.14, provided a good description of fluid and small solute kinetics, but their predictions for albumin transport were less accurate. Two pore model precisely described the data on fluid and small solute transport. The 3p models could not describe the diffusive-convective transport of albumin as precisely as the transport of fluid, small solutes, and IgM. The 2p model (not applicable for proteins) was an efficient tool for modeling fluid and small solute transport.

Animal models in peritoneal dialysis.

PubMed

Nikitidou, Olga; Peppa, Vasiliki I; Leivaditis, Konstantinos; Eleftheriadis, Theodoros; Zarogiannis, Sotirios G; Liakopoulos, Vassilios

2015-01-01

Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Comparison of three chronic dialysis models.

PubMed

Peng, W X; Guo, Q Y; Liu, S M; Liu, C Z; Lindholm, B; Wang, T

2000-01-01

The chronic peritoneal dialysis model is important for understanding the pathophysiology of peritoneal transport and for studying biocompatibility of peritoneal dialysis solutions. In this study, we compared three different chronic peritoneal dialysis models. A peritoneal catheter was placed in 23 male Sprague-Dawley rats, 12 of which had an intact omentum (model 1) and 11 of which received an omentectomy (model 2). Seven other rats, without a catheter, received a daily intraperitoneal injection (model 3). Each rat received a daily infusion of 25 mL of 3.86% glucose dialysis solution either through the catheter (models 1 and 2) or through injection (model 3) for 4 weeks. Then, a 4-hour dwell study using 3.86% glucose solution with an intraperitoneal volume marker and frequent dialysate and blood sampling was performed in each rat. The intraperitoneal volume was significantly lower in all the dialysis groups as compared to a control group (n = 6) in which the rats had no chronic dialysate exposure. The peritoneal fluid absorption rate, as well as the direct lymphatic absorption rate, was significantly higher in the three dialysis groups as compared to the control group. In general, no significant differences were seen in any of the parameters among the three dialysis models. Owing to catheter obstruction, three rats in model 1 and four rats in model 2 were lost during dialysis. Histological examination showed no significant differences among the three dialysis groups. Our results suggest that omentectomy may not be necessary in the chronic peritoneal dialysis model when using dialysate infusion and no drainage. Based on the present study, we think that perhaps model 1 may be the method of choice to test new peritoneal dialysis solutions. However, owing to its simplicity, model 3 could also be used if great care is taken to avoid puncturing the intestine or injecting into the abdominal wall.

The Negative Impact of Early Peritonitis on Continuous Ambulatory Peritoneal Dialysis Patients

PubMed Central

Hsieh, Yao-Peng; Wang, Shu-Chuan; Chang, Chia-Chu; Wen, Yao-Ko; Chiu, Ping-Fang; Yang, Yu

2014-01-01

♦ Background: Peritonitis rate has been reported to be associated with technique failure and overall mortality in previous literatures. However, information on the impact of the timing of the first peritonitis episode on continuous ambulatory peritoneal dialysis (CAPD) patients is sparse. The aim of this research is to study the influence of time to first peritonitis on clinical outcomes, including technique failure, patient mortality and dropout from peritoneal dialysis (PD). ♦ Methods: A retrospective observational cohort study was conducted over 10 years at a single PD unit in Taiwan. A total of 124 patients on CAPD with at least one peritonitis episode comprised the study subjects, which were dichotomized by the median of time to first peritonitis into either early peritonitis patients or late peritonitis patients. Cox proportional hazard model was used to analyze the correlation of the timing of first peritonitis with clinical outcomes. ♦ Results: Early peritonitis patients were older, more diabetic and had lower serum levels of creatinine than the late peritonitis patients. Early peritonitis patients were associated with worse technique survival, patient survival and stay on PD than late peritonitis patients, as indicated by Kaplan-Meier analysis (log-rank test, p = 0.04, p < 0.001, p < 0.001, respectively). In the multivariate Cox regression model, early peritonitis was still a significant predictor for technique failure (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.30 - 0.98), patient mortality (HR, 0.34; 95% CI, 0.13 - 0.92) and dropout from PD (HR, 0.50; 95% CI, 0.30 - 0.82). In continuous analyses, a 1-month increase in the time to the first peritonitis episode was associated with a 2% decreased risk of technique failure (HR, 0.98; 95% CI, 0.97 - 0.99), a 3% decreased risk of patient mortality (HR, 0.97; 95% CI, 0.95 - 0.99), and a 2% decreased risk of dropout from PD (HR, 98%; 95% CI, 0.97 - 0.99). Peritonitis rate was inversely correlated with time to first peritonitis according to the Spearman analysis (r = -0.64, p < 0.001). ♦ Conclusions: Time to first peritonitis is significantly correlated with clinical outcomes of peritonitis patients with early peritonitis patients having poor prognosis. Patients with shorter time to first peritonitis were prone to having a higher peritonitis rate. PMID:24497590

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

PubMed

Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

2016-03-03

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients.

PubMed

Waniewski, Jacek; Antosiewicz, Stefan; Baczynski, Daniel; Poleszczuk, Jan; Pietribiasi, Mauro; Lindholm, Bengt; Wankowicz, Zofia

2016-01-01

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 females; age 60 (21-87) years; median time on PD 19 (3-100) months) underwent sequential peritoneal equilibration test. Dialysis vintage and patient age did not correlate. Estimation of parameters of the two-pore model of peritoneal transport was performed. The estimated fluid transport parameters, including hydraulic permeability (LpS), fraction of ultrasmall pores (α u), osmotic conductance for glucose (OCG), and peritoneal absorption, were generally independent of solute transport parameters (diffusive mass transport parameters). Fluid transport parameters correlated whereas transport parameters for small solutes and proteins did not correlate with dialysis vintage and patient age. Although LpS and OCG were lower for older patients and those with long dialysis vintage, αu was higher. Thus, fluid transport parameters--rather than solute transport parameters--are linked to dialysis vintage and patient age and should therefore be included when monitoring processes linked to ageing of the peritoneal membrane.

Effects of natural honey on polymicrobial culture of various human pathogens

PubMed Central

Al-Waili, Faiza S.; Akmal, Mohammed; Ali, Amjed; Salom, Khelod Y.; Al Ghamdi, Ahmad A.

2012-01-01

Introduction Honey has a wide range of antimicrobial activity. All previous studies have considered honey's effect on a single microbe. The present study investigated activity of honey towards a high dose of single or polymicrobial culture. Material and methods 10 µl specimens of Staphylococcus aureus (S. aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli) and Candida albicans (C. albicans) were cultured in 10 ml of 10-100% (wt/v) honey diluted in broth. Six types of polymicrobial microbial cultures were prepared by culturing the isolates with each other onto broth (control) and broth containing various concentrations of honey (10-100% wt/v). Microbial growth was assessed on solid plate media after 24 h incubation. Results Honey (30-70%) prevents growth of 10 µl specimens of all the isolates. Greater reduction in growth of E. coli was observed when cultured with S. aureus. Culturing of S. aureus with S. pyogenes, C. albicans, or E. coli increased its sensitivity to honey. S. aureus and S. pyogenes increased sensitivity of C. albicans to honey while E. coli and C. albicans decreased sensitivity of S. pyogenes. Conclusions It might be concluded that honey prevents and inhibits growth of single and polymicrobial pathogenic cultures. Polymicrobial culture affects growth of the isolates and increases their sensitivity to honey. PMID:24904656

Effects of natural honey on polymicrobial culture of various human pathogens.

PubMed

Al-Waili, Noori S; Al-Waili, Faiza S; Akmal, Mohammed; Ali, Amjed; Salom, Khelod Y; Al Ghamdi, Ahmad A

2014-05-12

Honey has a wide range of antimicrobial activity. All previous studies have considered honey's effect on a single microbe. The present study investigated activity of honey towards a high dose of single or polymicrobial culture. 10 µl specimens of Staphylococcus aureus (S. aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli) and Candida albicans (C. albicans) were cultured in 10 ml of 10-100% (wt/v) honey diluted in broth. Six types of polymicrobial microbial cultures were prepared by culturing the isolates with each other onto broth (control) and broth containing various concentrations of honey (10-100% wt/v). Microbial growth was assessed on solid plate media after 24 h incubation. Honey (30-70%) prevents growth of 10 µl specimens of all the isolates. Greater reduction in growth of E. coli was observed when cultured with S. aureus. Culturing of S. aureus with S. pyogenes, C. albicans, or E. coli increased its sensitivity to honey. S. aureus and S. pyogenes increased sensitivity of C. albicans to honey while E. coli and C. albicans decreased sensitivity of S. pyogenes. It might be concluded that honey prevents and inhibits growth of single and polymicrobial pathogenic cultures. Polymicrobial culture affects growth of the isolates and increases their sensitivity to honey.

Laparoscopy and tribology: the effect of laparoscopic gas on peritoneal fluid.

PubMed

Ott, D E

2001-02-01

To assess the changes in viscosity of peritoneal fluid during laparoscopic exposure to CO2 insufflation. Analysis and mathematic modeling of peritoneal fluid viscosity in vivo and in vitro as a result of exposure to unconditioned CO2 (Canadian Task Force classification II-2). Medical school university research laboratory and hospital. Peritoneal fluid from 45 women. Peritoneal fluid was obtained at laparoscopy before insufflation and tested for viscosity after exposure to currently used raw dry unconditioned CO2. Peritoneal fluid viscosity was tested by viscometric methods and mathematic modeling. Initial viscosity of peritoneal fluid before gas exposure was 1.425 centipoise (cP). Viscosity measurements were obtained at 20-second intervals for gas flows of 1 and 3 L/minute. Increases in viscosity occur rapidly, and by 200 seconds it was 59 cP and 98 cP for 1 and 3 L flow rates, respectively. Very dry CO2 for laparoscopy causes peritoneal fluid viscosity to increase dramatically. (J Am Assoc Gynecol Laparosc 8(1):117-123, 2001)

Centre characteristics associated with the risk of peritonitis in peritoneal dialysis: a hierarchical modelling approach based on the data of the French Language Peritoneal Dialysis Registry.

PubMed

Béchade, Clémence; Guillouët, Sonia; Verger, Christian; Ficheux, Maxence; Lanot, Antoine; Lobbedez, Thierry

2017-06-01

This study investigated the centre effect on the risk of peritonitis in peritoneal dialysis (PD) patients. This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analysed 5017 incident patients starting PD between January 2008 and December 2012 in 127 PD centres. The end of the observation period was 1 January 2014. The event of interest was the first peritonitis episode. The analysis was performed with a multilevel Cox model and a Fine and Gray model. Among the 5017 patients, 3190 peritonitis episodes occurred in 1796 patients. There was significant heterogeneity between centres (variance of the random effect: 0.11). The variance of the centre effect was reduced by 9% after adjusting for patient characteristics and by 35% after adjusting on centre covariate. In the multivariate analysis with a multilevel Cox model, centre with a nurse specialized in PD or centre providing home visits before dialysis initiation decreased the centre effect on peritonitis. Patients treated in centres with a nurse specialized in PD or in centres providing home visits before dialysis initiation had a lower risk of peritonitis [cause-specific hazard ratio (cs-HR): 0.75 (95% confidence interval, CI, 0.67-0.83) and cs-HR: 0.87 (95% CI 0.76-0.97), respectively]. The data show that neither centre type nor centre volume influenced peritonitis risk. In the competing risk analysis, centre with a nurse specialized in PD and centre with home visits had a protective effect on peritonitis [sub-distribution HR (sd-HR): 0.77 (95% CI 0.70-0.85) and sd-HR: 0.85 (95% CI 0.77-0.94), respectively]. There is a significant centre effect on the risk of peritonitis that can be decreased by home visits before dialysis initiation and by the presence of a nurse specialized in PD. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury.

PubMed

Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yasuhiro; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryosuke; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

2015-09-01

Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (P<0.05) and day 50 after reduction of inflammation (P<0.01), indicating that the 7.5% icodextrin peritoneal equilibration test identifies changes in lymphangiogenesis. The solute transport rate was not affected by suppression of lymphangiogenesis. In human peritoneal dialysis patients, the dialysate to plasma ratio of creatinine positively correlated with the dialysate VEGF-D concentration (P<0.001). VEGF-D mRNA was significantly higher in the peritoneal membranes of patients with ultrafiltration failure, indicating that VEGF-D is involved in the development of lymphangiogenesis in peritoneal dialysis patients. These results indicate that VEGFR-3 is a new target to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

PubMed Central

Nash, Evelyn E.; Peters, Brian M.; Fidel, Paul L.

2015-01-01

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model of Candida albicans-Staphylococcus aureus intra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement for C. albicans morphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether other Candida species that are unable to form hyphae are as virulent as C. albicans during polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida (NAC) species with various morphologies and C. albicans transcription factor mutants (efg1/efg1 and cph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed that S. aureus coinoculated with C. krusei or C. tropicalis was highly lethal, similar to C. albicans, while S. aureus-C. dubliniensis, S. aureus-C. parapsilosis, and S. aureus-C. glabrata coinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation with C. albicans strains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that select Candida species, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2 acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability of C. albicans to induce mortality from an intra-abdominal polymicrobial infection. PMID:26483410

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus.

PubMed

Nash, Evelyn E; Peters, Brian M; Fidel, Paul L; Noverr, Mairi C

2016-01-01

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model of Candida albicans-Staphylococcus aureus intra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement for C. albicans morphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether other Candida species that are unable to form hyphae are as virulent as C. albicans during polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida (NAC) species with various morphologies and C. albicans transcription factor mutants (efg1/efg1 and cph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed that S. aureus coinoculated with C. krusei or C. tropicalis was highly lethal, similar to C. albicans, while S. aureus-C. dubliniensis, S. aureus-C. parapsilosis, and S. aureus-C. glabrata coinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation with C. albicans strains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that select Candida species, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2 acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability of C. albicans to induce mortality from an intra-abdominal polymicrobial infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans

PubMed Central

2013-01-01

Background Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity. Results Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse. Conclusions Mixed-species biofilms are enhanced and associated with increased S. epidermidis-specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S. epidermidis and C. albicans. PMID:24228850

Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans.

PubMed

Pammi, Mohan; Liang, Rong; Hicks, John; Mistretta, Toni-Ann; Versalovic, James

2013-11-14

Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity. Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse. Mixed-species biofilms are enhanced and associated with increased S. epidermidis-specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S. epidermidis and C. albicans.

Alloiococcus otitidis Forms Multispecies Biofilm with Haemophilus influenzae: Effects on Antibiotic Susceptibility and Growth in Adverse Conditions.

PubMed

Chan, Chun L; Richter, Katharina; Wormald, Peter-John; Psaltis, Alkis J; Vreugde, Sarah

2017-01-01

Otitis media with effusion (OME) is a biofilm driven disease and commonly accepted otopathogens, such as Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis , have been demonstrated to form polymicrobial biofilms within the middle ear cleft. However, Alloiococcus otitidis ( A. otitidis ), which is one of the most commonly found bacteria within middle ear aspirates of children with OME, has not been described to form biofilms. The aim of this study was to investigate whether A. otitidis can form biofilms and investigate the impact on antibiotic susceptibility and survivability in polymicrobial biofilms with H. influenzae in vitro . The ability of A. otitidis to form single-species and polymicrobial biofilms with H. influenzae was explored. Clinical and commercial strains of A. otitidis and H. influenzae were incubated in brain heart infusion with and without supplementation. Biofilm was imaged using confocal laser scanning microscopy and scanning electron microscopy. Quantification of biofilm biomass and viable bacterial number was assessed using crystal violet assays and viable cell counting in both optimal growth conditions and in adverse growth conditions (depleted media and sub-optimal growth temperature). Antimicrobial susceptibility and changes in antibiotic resistance of single-species and multi-species co-culture were assessed using a microdilution method to assess minimal bactericidal concentration and E-test for amoxicillin and ciprofloxacin. A. otitidis formed single-species and polymicrobial biofilms with H. influenzae . Additionally, whilst strain dependent, combinations of polymicrobial biofilms decreased antimicrobial susceptibility, albeit a small magnitude, in both planktonic and polymicrobial biofilms. Moreover, A. otitidis promoted H. influenzae survival by increasing biofilm production in depleted media and at suboptimal growth temperature. Our findings suggest that A. otitidis may play an indirect pathogenic role in otitis media by altering H. influenzae antibiotic susceptibility and enhancing growth under adverse conditions.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients: A retrospective study.

PubMed

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-12-01

Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients' technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients.This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes.During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality.We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality.These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients

PubMed Central

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-01-01

Abstract Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients’ technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients. This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes. During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality. We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality. These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes. PMID:27930566

The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions.

PubMed

ter Wee, P M; Beelen, R H J; van den Born, J

2003-12-01

The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions. Patients treated with peritoneal dialysis (PD) are at risk for development of ultrafiltration failure and peritonitis. These two significant complications can result in the termination of PD treatment. The relative unphysiologic composition of the currently used standard peritoneal dialysis fluids (PDF) is considered to be a major cause for the development of morphologic changes of the peritoneal membrane, ultimately resulting in ultrafiltration failure and probably contributing to changes in local defense mechanisms with the associated increased risk of peritonitis. In recent years, a major research focus has become the development of new and improved PD solutions. This has resulted in the development of an amino-acid-based PDF, a glucose polymer-based PDF, and several bicarbonate-buffered PDF. Typically, the first phase of biocompatibility testing of new PD solutions involves in vitro testing, employing isolated cells such as peritoneal macrophages or cell culture systems using human peritoneal mesothelial cells. The results of such evaluations are useful in providing insights into the biocompatibility performance of any given formulation, but suffer from several disadvantages, which can be better addressed using animal models. In vivo studies using animals permit the analysis of biocompatibility under conditions that allow for cell-to-cell interactions and dynamic changes in solution composition that more closely mimic the clinical situation. In this paper, we will review the use of animal models for the study of PDF biocompatibility and their application to the assessment of bicarbonate-buffered PDF.

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients

PubMed Central

Waniewski, Jacek; Antosiewicz, Stefan; Baczynski, Daniel; Poleszczuk, Jan; Pietribiasi, Mauro; Lindholm, Bengt; Wankowicz, Zofia

2016-01-01

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 females; age 60 (21–87) years; median time on PD 19 (3–100) months) underwent sequential peritoneal equilibration test. Dialysis vintage and patient age did not correlate. Estimation of parameters of the two-pore model of peritoneal transport was performed. The estimated fluid transport parameters, including hydraulic permeability (LpS), fraction of ultrasmall pores (α u), osmotic conductance for glucose (OCG), and peritoneal absorption, were generally independent of solute transport parameters (diffusive mass transport parameters). Fluid transport parameters correlated whereas transport parameters for small solutes and proteins did not correlate with dialysis vintage and patient age. Although LpS and OCG were lower for older patients and those with long dialysis vintage, αu was higher. Thus, fluid transport parameters—rather than solute transport parameters—are linked to dialysis vintage and patient age and should therefore be included when monitoring processes linked to ageing of the peritoneal membrane. PMID:26989432

Effect of assistance on peritonitis risk in diabetic patients treated by peritoneal dialysis: report from the French Language Peritoneal Dialysis Registry.

PubMed

Benabed, Anais; Bechade, Clemence; Ficheux, Maxence; Verger, Christian; Lobbedez, Thierry

2016-04-01

Diabetic patients treated by peritoneal dialysis (PD) have been reported to be at an increased risk of peritonitis. This has been attributed to impairment in host defense, visual impairment, disability and muscle wasting, which could compromise ability to safely perform catheter connections. This study aimed to evaluate whether assisted PD is associated with a lower risk of peritonitis in diabetic patients. This was a retrospective study based on data from the French Language Peritoneal Dialysis Registry. We included diabetic patients starting PD between 1 January 2002 and 31 December 2012. The end of the observation period was 31 December 2013. Using complementary regression analysis (Fine and Gray, Hurdle models), we assessed the relationship between peritonitis occurrence, peritonitis number over time and the type of assisted PD. Of the 3598 diabetic patients, there were 2040 patients on nurse-assisted PD. These patients were older, more comorbid and more frequently on continuous ambulatory peritoneal dialysis (CAPD). In the multivariate analysis, nurse assistance was associated with a reduced risk of peritonitis in the Fine and Gray [subdistribution hazard ratio: 0.78 (95% confidence interval, CI, 0.68-0.89)] and in the first component of the Hurdle models [rate ratio: 0.82 (95% CI 0.71-0.93)], but not a lower incidence of peritonitis after an initial episode [rate ratio: 0.82 (95% CI 0.95-1.38)]. Transplant failure, glomerulonephritis and CAPD were associated with an increased risk. In France, nurse-assisted PD is associated with a lower risk of peritonitis in diabetic patients treated by PD but not a lower incidence of peritonitis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Sequential peritoneal equilibration test: a new method for assessment and modelling of peritoneal transport.

PubMed

Galach, Magda; Antosiewicz, Stefan; Baczynski, Daniel; Wankowicz, Zofia; Waniewski, Jacek

2013-02-01

In spite of many peritoneal tests proposed, there is still a need for a simple and reliable new approach for deriving detailed information about peritoneal membrane characteristics, especially those related to fluid transport. The sequential peritoneal equilibration test (sPET) that includes PET (glucose 2.27%, 4 h) followed by miniPET (glucose 3.86%, 1 h) was performed in 27 stable continuous ambulatory peritoneal dialysis patients. Ultrafiltration volumes, glucose absorption, ratio of concentration in dialysis fluid to concentration in plasma (D/P), sodium dip (Dip D/P Sodium), free water fraction (FWF60) and the ultrafiltration passing through small pores at 60 min (UFSP60), were calculated using clinical data. Peritoneal transport parameters were estimated using the three-pore model (3p model) and clinical data. Osmotic conductance for glucose was calculated from the parameters of the model. D/P creatinine correlated with diffusive mass transport parameters for all considered solutes, but not with fluid transport characteristics. Hydraulic permeability (L(p)S) correlated with net ultrafiltration from miniPET, UFSP60, FWF60 and sodium dip. The fraction of ultrasmall pores correlated with FWF60 and sodium dip. The sequential PET described and interpreted mechanisms of ultrafiltration and solute transport. Fluid transport parameters from the 3p model were independent of the PET D/P creatinine, but correlated with fluid transport characteristics from PET and miniPET.

Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

PubMed

Neu, Alicia M; Richardson, Troy; Lawlor, John; Stuart, Jayne; Newland, Jason; McAfee, Nancy; Warady, Bradley A

2016-06-01

The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection.

PubMed

Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E

2017-07-01

We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Pelvic inflammatory disease.

PubMed

Soper, David E

2010-08-01

Pelvic inflammatory disease (PID) is an infection-caused inflammatory continuum from the cervix to the peritoneal cavity. Most importantly, it is associated with fallopian tube inflammation, which can lead to infertility, ectopic pregnancy, and chronic pelvic pain. The microbial etiology is linked to sexually transmitted microorganisms, including Chlamydia trachomatis, Neisseria gonorrheae, Mycoplasma genitalium, and bacterial vaginosis-associated microorganisms, predominantly anaerobes. Pelvic pain and fever are commonly absent in women with confirmed PID. Clinicians should consider milder symptoms such as abnormal vaginal discharge, metrorrhagia, postcoital bleeding, and urinary frequency as potential symptoms associated with the disease, particularly in women at risk of sexually transmitted infection. The diagnosis of PID is based on the findings of lower genital tract inflammation associated with pelvic organ tenderness. The outpatient treatment of mild-to-moderate PID should include tolerated antibiotic regimens with activity against the commonly isolated microorganisms associated with PID and usually consists of an extended spectrum cephalosporin in conjunction with either doxycycline or azithromycin. Clinically severe PID should prompt hospitalization and imaging to rule out a tuboovarian abscess. Parenteral broad-spectrum antibiotic therapy with activity against a polymicrobial flora, particularly gram-negative aerobes and anaerobes, should be implemented. Screening for and treatment of Chlamydia infection can prevent PID.

From metabolism to ecology: cross-feeding interactions shape the balance between polymicrobial conflict and mutualism

PubMed Central

Estrela, Sylvie; Trisos, Christopher H.; Brown, Sam P.

2012-01-01

Polymicrobial interactions are widespread in nature, and play a major role in maintaining human health and ecosystems. Whenever one organism uses metabolites produced by another organism as energy or nutrient sources, this is called cross-feeding. The ecological outcomes of cross-feeding interactions are poorly understood and potentially diverse: mutualism, competition, exploitation or commensalism. A major reason for this uncertainty is the lack of theoretical approaches linking microbial metabolism to microbial ecology. To address this issue, we explore the dynamics of a one-way interspecific cross-feeding interaction, in which food can be traded for a service (detoxification). Our results show that diverse ecological interactions (competition, mutualism, exploitation) can emerge from this simple cross-feeding interaction, and can be predicted by the metabolic, demographic and environmental parameters that govern the balance of the costs and benefits of association. In particular, our model predicts stronger mutualism for intermediate by-product toxicity because the resource-service exchange is constrained to the service being neither too vital (high toxicity impairs resource provision) nor dispensable (low toxicity reduces need for service). These results support the idea that bridging microbial ecology and metabolism is a critical step towards a better understanding of the factors governing the emergence and dynamics of polymicrobial interactions. PMID:23070318

Diverticular Pylephlebitis and Polymicrobial Septicemia.

PubMed

Ram, Pradhum; Lapumnuaypol, Kamolyut; Punjabi, Chitra

2017-01-01

Diverticulitis primarily affects the sigmoid colon and is often complicated by intra-abdominal abscesses and fistulas. Rarely, however, mesenteric venous thrombosis has been known to occur. Optimal management is still unclear. We report the first case of polymicrobial sepsis resulting from diverticular pylephlebitis, managed successfully with bowel rest, antibiotics, and anticoagulation.

A contemporary approach to the prevention of peritoneal dialysis-related peritonitis in children: the role of improvement science.

PubMed

Redpath Mahon, Allison; Neu, Alicia M

2017-08-01

Peritonitis is a leading cause of hospitalizations, morbidity, and modality change in pediatric chronic peritoneal dialysis (CPD) patients. Despite guidelines published by the International Society for Peritoneal Dialysis aimed at reducing the risk of peritonitis, registry data have revealed significant variability in peritonitis rates among centers caring for children on CPD, which suggests variability in practice. Improvement science methods have been used to reduce a variety of healthcare-associated infections and are also being applied successfully to decrease rates of peritonitis in children. A successful quality improvement program with the goal of decreasing peritonitis will not only include primary drivers directly linked to the outcome of peritonitis, but will also direct attention to secondary drivers that are important for the achievement of primary drivers, such as health literacy and patient and family engagement strategies. In this review, we describe a comprehensive improvement science model for the reduction of peritonitis in pediatric patients on CPD.

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

PubMed

Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

2015-12-01

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

[Inhibition of peritoneal bacterial adhesion using oligosaccharides. An experimental model of peritonitis in rats].

PubMed

Sielezneff, I; Mallet, M N; Berthezene, P; Sastre, B; Dagorn, J C

1999-04-01

Peritoneal colonization is a crucial event in the pathogenesis of peritonitis and its local complications. Adherence to the serosal mesothelium is mediated in a number of microorganisms derived from the digestive tract (especially E. coli) by type-1 fimbriae which have an oligosaccharide specificity. To evaluate the effect of repeated peritoneal washes with saline solution and oligosaccharides on E. coli peritoneal adherence in a rat peritonitis model. Sixty rats were randomized in 3 groups of 20. E. coli was inoculated at a constant concentration of 10(8)/mL per 100 g of weight. Then, peritoneal washes were achieved daily during three consecutive days (D1, D2, D3), with saline solution in Group I (control group), Methyl alpha-D-Mannoside (MADM) in Group II, and p-Nitro-phenyl alpha-D-Mannoside (pNADM) in Group III. Peritoneal samples were obtained before and after lavage at D1, D2, and D3. Microbial recovery was expressed as cfu/mg of tissue, and converted into a percentage of the initial value. A 10% threshold defined efficiency of the wash (inhibition of adherence for 90% of bacteries). Compared with data from Group I, E. coli peritoneal adherence was significantly lower after washes in Group III (D1: p = 0.03; D2: p = 0.009; D3: p = 0.003). Repeated washes were more efficient in Group III than in Group II (D1: p = 0.1; D2: p = 0.5; D3: p = 0.001). These results suggest that the addition of oligosaccharides, especially of pNADM, reduces the peritoneal adherence of E. coli when a peritoneal wash is performed for peritonitis.

Thalidomide suppresses sclerosing encapsulating peritonitis in a rat experimental model.

PubMed

Mondello, Stefania; Mazzon, Emanuela; Di Paola, Rosanna; Crisafulli, Concetta; Mondello, Paolo; Buemi, Michele; Aloisi, Carmelo; Cuzzocrea, Salvatore

2009-09-01

Peritoneal dialysis is an alternative treatment of patients with end-stage renal disease. Sclerosing encapsulating peritonitis is a life-threatening complication of continuous ambulatory peritoneal dialysis. The aim of the present study was to evaluate the effect of thalidomide, which is used for the treatment of various inflammatory and autoimmune diseases, on the development of sclerosing encapsulating peritonitis induced by chlorhexidine gluconate (CG). A peritoneal fibrosis model was established using rats treated intraperitoneally with injections of CG. Thalidomide was administered orally at a dose of 100 mg/kg three times per week. When compared with CG-treated rats, thalidomide (100 mg/kg orally)-treated mice subjected to CG-induced peritoneal fibrosis experienced a significantly lower rate in the extent and severity of histological signs of peritoneal injury. Thalidomide also caused a substantial reduction of 1) the rise in myeloperoxidase activity (mucosa); 2) the expression in the tissue of TNF-alpha, IL-1beta, transforming growth factor-beta, and vascular endothelial growth factor; 3) the increase in staining (immunohistochemistry) for nitrotyrosine and for poly(ADP ribose), as well as 4) the nuclear factor-kappaB activation caused by CG in the peritoneum. Thus, thalidomide treatment reduces the degree of peritoneal fibrosis caused by CG. We propose that this evidence may help clarify the potential therapeutic actions of thalidomide in patients with peritoneal fibrosis.

Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

PubMed Central

Hsieh, Yao-Peng; Chang, Chia-Chu; Wen, Yao-Ko; Chiu, Ping-Fang; Yang, Yu

2014-01-01

♦ Objective: Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes. ♦ Methods: Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality. ♦ Results: The peritonitis rate was 0.196 episodes per patient-year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free (p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD (p = 0.03). ♦ Conclusions: The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified. PMID:24084840

Therapeutic Effects of S-Petasin on Disease Models of Asthma and Peritonitis

PubMed Central

Lee, Kyoung-Pil; Kang, Saeromi; Noh, Min-Soo; Park, Soo-Jin; Kim, Jung-Min; Chung, Hae Young; Je, Nam Kyung; Lee, Young-Geun; Choi, Young-Whan; Im, Dong-Soon

2015-01-01

To explore the anti-allergic and anti-inflammatory effects of extracts of Petasites genus, we studied the effects of s-petasin, a major sesquiterpene from Petasites formosanus (a butterbur species) on asthma and peritonitis models. In an ovalbumin-induced mouse asthma model, s-petasin significantly inhibited the accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar fluids. S-petasin inhibited the antigen-induced degranulation of β-hexosamidase but did not inhibit intracellular Ca2+ increase in RBL-2H3 mast cells. S-petasin inhibited the LPS induction of iNOS at the RNA and protein levels in mouse peritoneal macrophages. Furthermore, s-petasin inhibited the production of NO (the product of iNOS) in a concentration-dependent manner in the macrophages. Furthermore, in an LPS-induced mouse model of peritonitis, s-petasin significantly inhibited the accumulation of polymorpho nuclear and mononuclear leukocytes in peritoneal cavity. This study shows that s-petasin in Petasites genus has therapeutic effects on allergic and inflammatory diseases, such as, asthma and peritonitis through degranulation inhibition in mast cells, suppression of iNOS induction and production of NO in macrophages, and suppression of inflammatory cell accumulation. PMID:25593643

Use of dynamic weight bearing as a novel end-point for the assessment of abdominal pain in the LPS-induced peritonitis model in the rat.

PubMed

Gruen, Michael; Laux-Biehlmann, Alexis; Zollner, Thomas M; Nagel, Jens

2014-07-30

Chronic pelvic pain (CPP) is defined as long-lasting and severe pelvic pain persisting over six months in cyclic or non-cyclic chronic manner. Various pathologic conditions like endometriosis, abdominal infections, intra-peritoneal adhesions or infection, underlie CPP which is often the leading symptom of the associated diseases. Pharmacological approaches addressing CPP are hampered by the absence of a straight-forward, objective, and reliable method for the assessment of CPP in rodents. In the presented study, the dynamic weight bearing system (DWB) was employed for the first time for the evaluation of pelvic pain in a rat model of LPS-induced peritonitis. Rats were pretreated with the COX-2 inhibitor rofecoxib and PGE2 levels were evaluated in peritoneal lavage. DWB analysis revealed that rats treated with LPS showed a relief posture by a significantly increased weight distribution to the front when compared to vehicle-treated animals. This effect was prevented by rofecoxib treatment indicating the sensitivity of the model for pelvic pain related to peritonitis. Analysis of the PGE2 levels in the peritoneal fluid indicated a correlation with the relief posture intensity. In contrast to others weight bearing approaches, the use of DWB allows evaluation of spontaneous posture changes as a consequence of pelvic pain. Taken together, we were able to show, that DWB combined with LPS-induced peritonitis may deliver a new reliable animal model addressing pelvic pain with high construct validity (peritoneal inflammation), and face validity (pain related relief posture). Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of polymicrobial biofilms in catheter-associated urinary tract infections.

PubMed

Azevedo, Andreia S; Almeida, Carina; Melo, Luís F; Azevedo, Nuno F

2017-08-01

Recent reports have demonstrated that most biofilms involved in catheter-associated urinary tract infections are polymicrobial communities, with pathogenic microorganisms (e.g. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and uncommon microorganisms (e.g. Delftia tsuruhatensis, Achromobacter xylosoxidans) frequently co-inhabiting the same urinary catheter. However, little is known about the interactions that occur between different microorganisms and how they impact biofilm formation and infection outcome. This lack of knowledge affects CAUTIs management as uncommon bacteria action can, for instance, influence the rate at which pathogens adhere and grow, as well as affect the overall biofilm resistance to antibiotics. Another relevant aspect is the understanding of factors that drive a single pathogenic bacterium to become prevalent in a polymicrobial community and subsequently cause infection. In this review, a general overview about the IMDs-associated biofilm infections is provided, with an emphasis on the pathophysiology and the microbiome composition of CAUTIs. Based on the available literature, it is clear that more research about the microbiome interaction, mechanisms of biofilm formation and of antimicrobial tolerance of the polymicrobial consortium are required to better understand and treat these infections.

Basic mechanisms and clinical implications of peritoneal fibrosis.

PubMed

Margetts, Peter J; Bonniaud, Philippe

2003-01-01

We have stressed the role of certain growth factors and cytokines in peritoneal fibrosis, including TGFbeta, TIMP-1, and inflammatory cytokines, especially IL-1beta. Recent research highlights the myofibroblast-like transformation of mesothelial cells as a central initiating event in peritoneal fibrosis. The induction, survival, and apoptosis of the myofibroblast cell population likely dictate the nature of the fibrogenic response. The accumulation of collagen occurs in a nondegradative environment, and collagenases and their inhibitors have a role in the maintenance of fibrosis. Fibrosis appears to be a ubiquitous response of peritoneal tissues to the damaging effects of uremia, bioincompatible dialysate, recurrent infection, and inflammation. Recent research has focused on the induction of angiogenesis, as this appears to correlate with increased solute transport and peritoneal membrane ultrafiltration failure. Fibrosis may play an integral part in peritoneal membrane dysfunction in several aspects. Angiogenesis may be induced as part of the fibrotic response, as many key fibrogenic cytokines are also strongly angiogenic. Fibrotic tissue may support and preserve angiogenesis. Changes in the interstitium may have a direct effect on the hydrodynamic properties of the peritoneum and may directly influence fluid movement. In its most extreme form, fibrosis manifests as the rare but devastating EPS. Peritoneal biopsy studies have identified a high prevalence of peritoneal fibrosis in PD patients. Research into peritoneal fibrosis will be enhanced by new animal models where the role of various cytokines and growth factors, cellular processes, and matrix interactions can be studied. With these models, the role of fibrosis in alteration of peritoneal membrane function can be better assessed. Clinical trials to assess the role of prevention of peritoneal injury using biocompatible solutions and treatments targeted directly at peritoneal fibrosis will be important, but challenging to design and carry out.

Searching for new strategies against polymicrobial biofilm infections: guanylated polymethacrylates kill mixed fungal/bacterial biofilms.

PubMed

Qu, Yue; Locock, Katherine; Verma-Gaur, Jiyoti; Hay, Iain D; Meagher, Laurence; Traven, Ana

2016-02-01

Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of diverse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with monomicrobial biofilms. Here, we address this therapeutic gap by assessing the potential of a new class of antimicrobial agents, guanylated polymethacrylates, in the treatment of polymicrobial biofilms built by two prominent human pathogens, the fungus Candida albicans and the bacterium Staphylococcus aureus. We used imaging and quantitative methods to test the antibiofilm efficacy of guanylated polymethacrylates, a new class of drugs that structurally mimic antimicrobial peptides. We further compared guanylated polymethacrylates with first-line antistaphylococcal and anti-Candida agents used as combinatorial therapy against polymicrobial biofilms. Guanylated polymethacrylates were highly effective as a sole agent, killing both C. albicans and S. aureus when applied to established polymicrobial biofilms. Furthermore, they outperformed multiple combinations of current antimicrobial drugs, with one of the tested compounds killing 99.98% of S. aureus and 82.2% of C. albicans at a concentration of 128 mg/L. The extracellular biofilm matrix provided protection, increasing the MIC of the polymethacrylates by 2-4-fold when added to planktonic assays. Using the C. albicans bgl2ΔΔ mutant, we implicate matrix polysaccharide β-1,3 glucan in the mechanism of protection. Data for two structurally distinct polymers suggest that this mechanism could be minimized through chemical optimization of the polymer structure. Finally, we demonstrate that a potential application for these polymers is in antimicrobial lock therapy. Guanylated polymethacrylates are a promising lead for the development of an effective monotherapy against C. albicans/S. aureus polymicrobial biofilms. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Host-to-host variation of ecological interactions in polymicrobial infections

NASA Astrophysics Data System (ADS)

Mukherjee, Sayak; Weimer, Kristin E.; Seok, Sang-Cheol; Ray, Will C.; Jayaprakash, C.; Vieland, Veronica J.; Swords, W. Edward; Das, Jayajit

2015-02-01

Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

Characterization of a Polymicrobial Dermal Infection in a Peninsular Pronghorn ( Antilocapra americana peninsularis) in Baja California, Mexico.

PubMed

Velez, Patricia; Romero, Lucía; Lopez-Tello, Jamvier; Callejas-Negrete, Olga A; Riquelme, Meritxell

2018-04-01

  In situ conservation efforts are assisting the recovery of free-ranging populations of the endangered peninsular pronghorns ( Antilocapra americana peninsularis) at the Vizcaino Biosphere Reserve, Baja California Sur, Mexico. We detected a polymicrobial dermal infection. Etiologic agents were identified as a keratinophilic dermatomycete and opportunistic pathogenic bacteria.

Exposure to pairs of Aeromonas strains enhances virulence in the Caenorhabditis elegans infection model

USDA-ARS?s Scientific Manuscript database

Aeromonad virulence remains poorly understood, and is difficult to predict from strain characteristics. In addition, infections are often polymicrobial (i.e., are mixed infections), and 5 -10% of such infections include two distinct aeromonads, which has an unknown impact on virulence. In this work,...

Comparing Mortality of Peritoneal and Hemodialysis Patients in the First 2 Years of Dialysis Therapy: A Marginal Structural Model Analysis

PubMed Central

Lukowsky, Lilia R.; Mehrotra, Rajnish; Kheifets, Leeka; Arah, Onyebuchi A.; Nissenson, Allen R.

2013-01-01

Summary Background and objectives There are conflicting research results about the survival differences between hemodialysis and peritoneal dialysis, especially during the first 2 years of dialysis treatment. Given the challenges of conducting randomized trials, differential rates of modality switch and transplantation, and time-varying confounding in cohort data during the first years of dialysis treatment, use of novel analytical techniques in observational cohorts can help examine the peritoneal dialysis versus hemodialysis survival discrepancy. Design, setting, participants, & measurements This study examined a cohort of incident dialysis patients who initiated dialysis in DaVita dialysis facilities between July of 2001 and June of 2004 and were followed for 24 months. This study used the causal modeling technique of marginal structural models to examine the survival differences between peritoneal dialysis and hemodialysis over the first 24 months, accounting for modality change, differential transplantation rates, and detailed time-varying laboratory measurements. Results On dialysis treatment day 90, there were 23,718 incident dialysis—22,360 hemodialysis and 1,358 peritoneal dialysis—patients. Incident peritoneal dialysis patients were younger, had fewer comorbidities, and were nine and three times more likely to switch dialysis modality and receive kidney transplantation over the 2-year period, respectively, compared with hemodialysis patients. In marginal structural models analyses, peritoneal dialysis was associated with persistently greater survival independent of the known confounders, including dialysis modality switch and transplant censorship (i.e., death hazard ratio of 0.52 [95% confidence limit 0.34–0.80]). Conclusions Peritoneal dialysis seems to be associated with 48% lower mortality than hemodialysis over the first 2 years of dialysis therapy independent of modality switches or differential transplantation rates. PMID:23307879

Comparing mortality of peritoneal and hemodialysis patients in the first 2 years of dialysis therapy: a marginal structural model analysis.

PubMed

Lukowsky, Lilia R; Mehrotra, Rajnish; Kheifets, Leeka; Arah, Onyebuchi A; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

2013-04-01

There are conflicting research results about the survival differences between hemodialysis and peritoneal dialysis, especially during the first 2 years of dialysis treatment. Given the challenges of conducting randomized trials, differential rates of modality switch and transplantation, and time-varying confounding in cohort data during the first years of dialysis treatment, use of novel analytical techniques in observational cohorts can help examine the peritoneal dialysis versus hemodialysis survival discrepancy. This study examined a cohort of incident dialysis patients who initiated dialysis in DaVita dialysis facilities between July of 2001 and June of 2004 and were followed for 24 months. This study used the causal modeling technique of marginal structural models to examine the survival differences between peritoneal dialysis and hemodialysis over the first 24 months, accounting for modality change, differential transplantation rates, and detailed time-varying laboratory measurements. On dialysis treatment day 90, there were 23,718 incident dialysis-22,360 hemodialysis and 1,358 peritoneal dialysis-patients. Incident peritoneal dialysis patients were younger, had fewer comorbidities, and were nine and three times more likely to switch dialysis modality and receive kidney transplantation over the 2-year period, respectively, compared with hemodialysis patients. In marginal structural models analyses, peritoneal dialysis was associated with persistently greater survival independent of the known confounders, including dialysis modality switch and transplant censorship (i.e., death hazard ratio of 0.52 [95% confidence limit 0.34-0.80]). Peritoneal dialysis seems to be associated with 48% lower mortality than hemodialysis over the first 2 years of dialysis therapy independent of modality switches or differential transplantation rates.

Transcriptome Analysis of Porphyromonas gingivalis and Acinetobacter baumannii in Polymicrobial Communities.

PubMed

Miller, Daniel P; Wang, Qian; Weinberg, Aaron; Lamont, Richard J

2018-06-25

Acinetobacter baumannii is a nosocomial, opportunistic pathogen that causes several serious conditions such as meningitis, septicemia, endocarditis and pneumonia. It can be found in the oral biofilm, which may be a reservoir for pneumonia and chronic obstructive pulmonary disease. Subgingival colonization by A. baumannii is associated with chronic and aggressive periodontitis as well as refractory periodontal disease. Porphyromonas gingivalis, a keystone periodontal pathogen localized to subgingival plaque, is also implicated in several chronic conditions including aspiration pneumonia. While both bacteria are found together in subgingival plaque and can cause multiple polymicrobial infections, nothing is known about the interactions between these two important human pathogens. In this study, we used RNA sequencing to understand the transcriptional response of both species as they adapt to heterotypic communities. Among the differentially regulated genes were those encoding a number of important virulence factors for both species including adhesion, biofilm formation, and protein secretion. Additionally, the presence of A. baumannii increased the abundance of P. gingivalis in model dual species communities Collectively these results suggest that both P. gingivalis and A. baumannii adapt to each other and have synergistic potential for increased pathogenicity. In identifying the mechanisms that promote pathogenicity and refractory disease, novel approaches to mitigate polymicrobial synergistic interactions may be developed to treat or prevent associated diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Establishment and characterization of intraperitoneal xenograft models by co-injection of human tumor cells and extracellular matrix gel

PubMed Central

YAO, YUQIN; ZHOU, YONGJUN; SU, XIAOLAN; DAI, LEI; YU, LIN; DENG, HONGXIN; GOU, LANTU; YANG, JINLIANG

2015-01-01

Establishing a feasible intraperitoneal (i.p.) xenograft model in nude mice is a good strategy to evaluate the antitumor effect of drugs in vivo. However, the manipulation of human cancer cells in establishing a stable peritoneal carcinomatosis model in nude mice is problematic. In the present study, the ovarian and colorectal peritoneal tumor models were successfully established in nude mice by co-injection of human tumor cells and extracellular matrix gel. In ovarian tumor models, the mean number tumor nodes was significantly higher in the experimental group (intraperitoneal tumor cell co-injection with ECM gel) compared with the PBS control group on the 30th day (21.0±3.0 vs. 3.6±2.5; P<0.05). The same results were observed in the colorectal peritoneal tumor models on the 28th day. The colorectal peritoneal tumor model was further used to evaluate the chemotherapy effect of irinotecan (CPT-11). The mean weight of peritoneal tumor nodes in CPT-11 treatment group was significantly less than that of the control group (0.81±0.16 vs. 2.18±0.21 g; P<0.05). The results confirmed the value of these i.p. xenograft models in nude mice as efficient and feasible tools for preclinical evaluation. PMID:26788149

Detection of disseminated peritoneal tumors by fluorescein diacrylate in mice

NASA Astrophysics Data System (ADS)

Harada, Yoshinori; Furuta, Hirokazu; Murayama, Yasutoshi; Dai, Ping; Fujikawa, Yuta; Urano, Yasuteru; Nagano, Tetsuo; Morishita, Koki; Hasegawa, Akira; Takamatsu, Tetsuro

2009-02-01

Tumor invasion to the peritoneum is a poor prognostic factor in cancer patients. Accurate diagnosis of disseminated peritoneal tumors is essential to accurate cancer staging. To date, peritoneal washing cytology during laparotomy has been used for diagnosis of peritoneal dissemination of gastrointestinal cancer, but its sensitivity has not been satisfactory. Thus, a more direct approach is indispensable to detect peritoneal dissemination in vivo. Fluorescein diacrylate (FDAcr) is an esterase-sensitive fluorescent probe derived from fluorescein. In cancer cells, fluorescent fluorescein generated by exogenous application of FDAcr selectively deposits owing to its stronger hydrolytic enzyme activity and its lower leakage rate. We examined whether FDAcr can specifically detect disseminated peritoneal tumors in athymic nude mouse models. Intraperitoneally administered FDAcr revealed disseminated peritoneal microscopic tumors not readily recognized on white-light imaging. These results suggest that FDAcr is a useful probe for detecting disseminated peritoneal tumors.

Water and solute transport across the peritoneal membrane.

PubMed

Morelle, Johann; Devuyst, Olivier

2015-09-01

We review the molecular mechanisms of peritoneal transport and discuss how a better understanding of these mechanisms is relevant for dialysis therapy. Peritoneal dialysis involves diffusion and osmosis through the highly vascularized peritoneal membrane. Computer simulations, expression studies and functional analyses in Aqp1 knockout mice demonstrated the critical role of the water channel aquaporin-1 (AQP1) in water removal during peritoneal dialysis. Pharmacologic regulation of AQP1, either through increased expression or gating, is associated with increased water transport in rodent models of peritoneal dialysis. Water transport is impaired during acute peritonitis, despite unchanged expression of AQP1, resulting from the increased microvascular area that dissipates the osmotic gradient across the membrane. In long-term peritoneal dialysis patients, the fibrotic interstitium also impairs water transport, resulting in ultrafiltration failure. Recent data suggest that stroke and drug intoxications might benefit from peritoneal dialysis and could represent novel applications of peritoneal transport in the future. A better understanding of the regulation of osmotic water transport across the peritoneum offers novel insights into the role of water channels in microvascular endothelia, the functional importance of structural changes in the peritoneal interstitium and the transport of water and solutes across biological membranes in general.

Polymicrobial biofilm formation by Candida albicans, Actinomyces naeslundii, and Streptococcus mutans is Candida albicans strain and medium dependent.

PubMed

Arzmi, Mohd Hafiz; Alnuaimi, Ali D; Dashper, Stuart; Cirillo, Nicola; Reynolds, Eric C; McCullough, Michael

2016-11-01

Oral biofilms comprise of extracellular polysaccharides and polymicrobial microorganisms. The objective of this study was to determine the effect of polymicrobial interactions of Candida albicans, Actinomyces naeslundii, and Streptococcus mutans on biofilm formation with the hypotheses that biofilm biomass and metabolic activity are both C. albicans strain and growth medium dependent. To study monospecific biofilms, C. albicans, A. naeslundii, and S. mutans were inoculated into artificial saliva medium (ASM) and RPMI-1640 in separate vials, whereas to study polymicrobial biofilm formation, the inoculum containing microorganisms was prepared in the same vial prior inoculation into a 96-well plate followed by 72 hours incubation. Finally, biofilm biomass and metabolic activity were measured using crystal violet and XTT assays, respectively. Our results showed variability of monospecies and polymicrobial biofilm biomass between C. albicans strains and growth medium. Based on cut-offs, out of 32, seven RPMI-grown biofilms had high biofilm biomass (HBB), whereas, in ASM-grown biofilms, 14 out of 32 were HBB. Of the 32 biofilms grown in RPMI-1640, 21 were high metabolic activity (HMA), whereas in ASM, there was no biofilm had HMA. Significant differences were observed between ASM and RPMI-grown biofilms with respect to metabolic activity (P <01). In conclusion, biofilm biomass and metabolic activity were both C. albicans strain and growth medium dependent. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polymicrobial Infective Endocarditis: Clinical Features and Prognosis

PubMed Central

García-Granja, Pablo Elpidio; López, Javier; Vilacosta, Isidre; Ortiz-Bautista, Carlos; Sevilla, Teresa; Olmos, Carmen; Sarriá, Cristina; Ferrera, Carlos; Gómez, Itziar; Román, José Alberto San

2015-01-01

Abstract To describe the profile of left-sided polymicrobial endocarditis (PE) and to compare it with monomicrobial endocarditis (ME). Among 1011 episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers, between January 1, 1996 and December 31, 2014, 60 were polymicrobial (5.9%), 821 monomicrobial (81.7%), and in 123 no microorganism was detected (12.2%). Seven patients (0.7%) were excluded from the analysis because contamination of biologic tissue could not be discarded. The authors described the clinical, microbiologic, echocardiographic, and outcome of patients with PE and compared it with ME. Mean age was 64 years SD 16 years, 67% were men and 30% nosocomial. Diabetes mellitus (35%) were the most frequent comorbidities, fever (67%) and heart failure (43%) the most common symptoms at admission. Prosthetic valves (50%) were the most frequent infection location and coagulase-negative Staphylococci (48%) and enterococci (37%) the leading etiologies. The most repeated combination was coagulase-negative Staphylococci with enterococci (n = 9). Polymicrobial endocarditis appeared more frequently in patients with underlying disease (70% versus 56%, P = 0.036), mostly diabetics (35% versus 24%, P = 0.044) with previous cardiac surgery (15% versus 8% P = 0.049) and prosthetic valves (50% versus 37%, P = 0.038). Coagulase-negative Staphylococci, enterococci, Gram-negative bacilli, anaerobes, and fungi were more frequent in PE. No differences on age, sex, symptoms, need of surgery, and in-hospital mortality were detected. Polymicrobial endocarditis represents 5.9% of episodes of left-sided endocarditis in our series. Despite relevant demographic and microbiologic differences between PE and ME, short-term outcome is similar. PMID:26656328

Prosthetic joint infection-a devastating complication of hemiarthroplasty for hip fracture.

PubMed

Guren, Ellen; Figved, Wender; Frihagen, Frede; Watne, Leiv Otto; Westberg, Marianne

2017-08-01

Background and purpose - Hemiarthroplasty is the most common treatment in elderly patients with displaced femoral neck fracture. Prosthetic joint infection (PJI) is a feared complication. The infection rate varies in the literature, and there are limited descriptive data available. We investigated the characteristics and outcome of PJI following hemiarthroplasty over a 15-year period. Patients and methods - Patients with PJI were identified among 519 patients treated with hemiarthroplasty for a femoral neck fracture at Oslo University Hospital between 1998 and 2012. We used prospectively registered data from previous studies, and recorded additional data from the patients' charts when needed. Results - Of the 519 patients, we identified 37 patients (6%) with early PJI. 20 of these 37 patients became free of infection. Soft tissue debridement and retention of implant was performed in 35 patients, 15 of whom became free of infection with an intact arthroplasty. The 1-year mortality rate was 15/37. We found an association between 1-year mortality and treatment failure (p = 0.001). Staphylococcus aureus and polymicrobial infection were the most common microbiological findings, each accounting for 14 of the 37 infections. Enterococcus spp. was found in 9 infections, 8 of which were polymicrobial. There was an association between polymicrobial infection and treatment failure, and between polymicrobial infection and 1-year mortality. Interpretation - PJI following hemiarthroplasty due to femoral neck fracture is a devastating complication in the elderly. We found a high rate of polymicrobial PJIs frequently including Enterococcus spp, which is different from what is common in PJI after elective total hip arthroplasty.

The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients.

PubMed

Ye, Hongjian; Zhou, Qian; Fan, Li; Guo, Qunying; Mao, Haiping; Huang, Fengxian; Yu, Xueqing; Yang, Xiao

2017-06-05

Results concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up. This retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality. A total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years. Peritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.

The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related Peritonitis.

PubMed

Hautem, Nicolas; Morelle, Johann; Sow, Amadou; Corbet, Cyril; Feron, Olivier; Goffin, Eric; Huaux, François; Devuyst, Olivier

2017-07-01

Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1 β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1 β The potential roles of the NLRP3 inflammasome and IL-1 β in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1 β in the dialysate. In mice, lipopolysaccharide- or Escherichia coli -induced peritonitis led to IL-1 β release in the peritoneal membrane. The genetic deletion of Nalp3 , which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1 β treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1 β receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1 β release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1 β axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis. Copyright © 2017 by the American Society of Nephrology.

Microbiology of Peritonitis in Peritoneal Dialysis Patients with Multiple Episodes

PubMed Central

Nessim, Sharon J.; Nisenbaum, Rosane; Bargman, Joanne M.; Jassal, Sarbjit V.

2012-01-01

♦ Background: Peritoneal dialysis (PD)–associated peritonitis clusters within patients. Patient factors contribute to peritonitis risk, but there is also entrapment of organisms within the biofilm that forms on PD catheters. It is hypothesized that this biofilm may prevent complete eradication of organisms, predisposing to multiple infections with the same organism. ♦ Methods: Using data collected in the Canadian multicenter Baxter POET (Peritonitis, Organism, Exit sites, Tunnel infections) database from 1996 to 2005, we studied incident PD patients with 2 or more peritonitis episodes. We determined the proportion of patients with 2 or more episodes caused by the same organism. In addition, using a multivariate logistic regression model, we tested whether prior peritonitis with a given organism predicted the occurrence of a subsequent episode with the same organism. ♦ Results: During their time on PD, 558 patients experienced 2 or more peritonitis episodes. Of those 558 patients, 181 (32%) had at least 2 episodes with the same organism. The organism most commonly causing repeat infection was coagulase-negative Staphylococcus (CNS), accounting for 65.7% of cases. Compared with peritonitis caused by other organisms, a first CNS peritonitis episode was associated with an increased risk of subsequent CNS peritonitis within 1 year (odds ratio: 2.1; 95% confidence interval: 1.5 to 2.8; p < 0.001). Among patients with repeat CNS peritonitis, 48% of repeat episodes occurred within 6 months of the earlier episode. ♦ Conclusions: In contrast to previous data, we did not find a high proportion of patients with multiple peritonitis episodes caused by the same organism. Coagulase-negative Staphylococcus was the organism most likely to cause peritonitis more than once in a given patient, and a prior CNS peritonitis was associated with an increased risk of CNS peritonitis within the subsequent year. PMID:22215659

Concomitant bidirectional transport during peritoneal dialysis can be explained by a structured interstitium

PubMed Central

Waniewski, Jacek; Flessner, Michael F.; Lindholm, Bengt

2016-01-01

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data. PMID:26945084

Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis.

PubMed

Alcayaga-Miranda, Francisca; Cuenca, Jimena; Martin, Aldo; Contreras, Luis; Figueroa, Fernando E; Khoury, Maroun

2015-10-16

Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB enhance survival in CLP-induced sepsis by acting on multiples targets. MenSCs thus constitute a feasible approach for the future clinical treatment of sepsis.

Is Peritonitis Risk Increased in Elderly Patients on Peritoneal Dialysis? Report from the French Language Peritoneal Dialysis Registry (RDPLF).

PubMed

Duquennoy, Simon; Béchade, Clémence; Verger, Christian; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

2016-01-01

♦ This study was carried out to examine whether or not elderly patients on peritoneal dialysis (PD) had an increased risk of peritonitis. ♦ This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analyzed 8,396 incident patients starting PD between January 2003 and December 2010. The end of the observation period was 31 December 2012. Patients were separated into 2 age groups: up to 75 and over of 75 years old. ♦ Among 8,396 patients starting dialysis there were 3,173 patients older than 75. When using a Cox model, no association was found between age greater than 75 years and increased risk of peritonitis (hazard ratio [HR]: 0.97 [0.88 - 1.07]). Diabetes (HR: 1.14 [1.01 - 1.28] and continuous ambulatory PD (HR: 1.13 [1.04 - 1.23]) were significantly associated with a higher risk of peritoneal infection whereas nurse-assisted PD was associated with a lower risk of peritonitis (HR: 0.85 [0.78 - 0.94]. In the analysis restricted to the 3,840 self-care PD patients, there was no association between age older than 75 years and risk of peritonitis. ♦ The risk of peritonitis is not increased in elderly patients on PD in a country where assisted PD is available. Copyright © 2016 International Society for Peritoneal Dialysis.

Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

PubMed

Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

PubMed Central

van Diepen, Anouk T.N.; van Esch, Sadie; Struijk, Dirk G.; Krediet, Raymond T.

2015-01-01

♦ Objective: Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection. ♦ Participants: We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared. ♦ Main outcome measurements: SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes. ♦ Results: Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04. ♦ Conclusions: The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state. PMID:24711641

Association of Enterococcus spp. with Severe Combat Extremity Injury, Intensive Care, and Polymicrobial Wound Infection.

PubMed

Heitkamp, Rae A; Li, Ping; Mende, Katrin; Demons, Samandra T; Tribble, David R; Tyner, Stuart D

2018-01-01

Combat-related extremity wound infections can complicate the recovery of injured military personnel. The Enterococcus genus contains both commensal and pathogenic bacteria found in many combat wounds. We describe the patient population susceptible to Enterococcus infection, the characteristics of Enterococcus spp. isolated from combat-related wounds, and the microbiological profile of Enterococcus-positive wounds. Patient and culture data were obtained from the Trauma Infectious Disease Outcomes Study. Subjects were divided into a case group with enterococcal extremity wound infections and a comparator group with wound infections caused by other micro-organisms. Case and comparator subjects had similar patterns of injury and infection. Case subjects had higher Injury Severity Scores (33 vs. 30; p < 0.001), longer hospitalization at U.S. facilities (55 vs. 40 days; p = 0.004), and required more large-volume blood transfusions (>20 units) within 24 h post-injury (53% vs. 30%; p < 0.001). Approximately 60% of case subjects had three or more infections, and 91% had one or more polymicrobial infections, compared with 43% and 50%, respectively, in the comparator group. The thigh was the most common site of Enterococcus spp. isolation, contributing 50% of isolates. Enterococcus faecium was the predominant species isolated from case-group infections overall (66%), as well as in polymicrobial infections (74%). Frequent co-colonizing microbes in polymicrobial wound infections with Enterococcus were other ESKAPE pathogens (64%) (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae [and Escherichia coli], Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and fungi (35%). The specific pathogenicity of Enterococcus relative to other pathogens in polymicrobial wounds is unknown. Identifying strain-specific outcomes and investigating the interactions of Enterococcus strains with other wound pathogens could provide additional tools and strategies for infection mitigation in combat-related wounds.

Hydration status measured by BCM: A potential modifiable risk factor for peritonitis in patients on peritoneal dialysis.

PubMed

Santhakumaran, Territa; Samad, Nasreen; Fan, Stanley L

2016-05-01

Peritoneal dialysis peritonitis and fluid overhydration (OH) are frequent problems in peritoneal dialysis. The latter can cause gut wall oedema or be associated with malnutrition. Both may lead to increased peritonitis risk. We wished to determine if OH is an independent risk factor for peritonitis (caused by enteric organisms). Retrospectively study of patients with >2 bioimpedance assessments (Body Composition Monitor). We compared peritonitis rates of patients with above or below the median time-averaged hydration parameter (OH/extracellular water, OH/ECW). Multivariate analysis was performed to determine independent risk factors for peritonitis by enteric organism. We studied 580 patients. Peritonitis was experienced by 28% patients (followed up for an average of 17 months). The overall peritonitis rate was 1:34 patient months. Patients with low OH/ECW values had significantly lower rates of peritonitis from enteric organisms than overhydrated patients (incident rate ratio 1.53, 95% confidence interval 1.38-1.70, P < 0.001). Hydration remained an independent predictor of peritonitis from enteric organisms when multivariate model included demographic parameters (odds ratio for a 1% increment of OH/ECW was 1.05; 95% confidence interval 1.01-1.10, P < 0.02). However, including biochemical parameters of malnutrition reduced the predictive power of overhydration. We found an association between overhydration and increased rates of peritonitis. While this may partly be due to the high co-morbidity of patients (advanced age and diabetes), on multivariate analysis, only inclusion of nutritional parameters reduced this association. It remains to be determined if overhydration will prove to be a modifiable risk factor for peritonitis or whether malnutrition will prove to be more important. © 2015 Asian Pacific Society of Nephrology.

Administration of Intravenous Inf liximab for Prevention of Peritoneal Adhesions Formation in Rats.

PubMed

Nikeghbalian, Saman; Vafaei, Homeira; Moradian, Farid; Kazemi, Kourosh; Tanideh, Nader; Shayan, Leila; Nikeghbalian, Zahra

2015-07-01

To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. This was an experimental study being performed in animal laboratory of Shiraz University of Medical Sciences during 2012. Sixty albino rats were randomly assigned in to three groups by Random Design Method. The first group received single infliximab injection (n=20), the second one received double infliximab injection (n=20) and the third received nothing (n=20), after receiving intra-peritoneal injection of talc for induction of peritoneal adhesions. All the animals were sacrificed after 6 weeks and the peritoneal adhesions were evaluated according to Nair classification. We observed that the mean adhesion grade was lower in those who received double dose of infliximib when compared to single dose and controls. However the difference did not reach a significant value (p=0.178). The grade of peritoneal adhesion was also comparable between the three study groups (p=0.103). The mean number of 1st WBC count was also comparable between three study groups (p=0.382). We observed that 2nd WBC count was also comparable between two study groups (p=0.317). Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat.

The PPARβ/δ agonist GW501516 attenuates peritonitis in peritoneal fibrosis via inhibition of TAK1-NFκB pathway in rats.

PubMed

Su, Xuesong; Zhou, Guangyu; Wang, Yanqiu; Yang, Xu; Li, Li; Yu, Rui; Li, Detian

2014-06-01

Peritoneal fibrosis is a common consequence of long-term peritoneal dialysis (PD), and peritonitis is a factor in its onset. Agonist-bound peroxisome proliferator-activated receptors (PPARs) function as key regulators of energy metabolism and inflammation. Here, we examined the effects of PPARβ/δ agonist GW501516 on peritonitis in a rat peritoneal fibrosis model. Peritoneal fibrosis secondary to inflammation was induced into uremic rats by daily injection of Dianeal 4.25% PD solutions along with six doses of lipopolysaccharide before commencement of GW501516 treatment. Normal non-uremic rats served as control, and all rats were fed with a control diet or a GW501516-containing diet. Compared to control group, exposure to PD fluids caused peritoneal fibrosis that was accompanied by increased mRNA levels of monocyte chemoattractant protein-1, tumor necrotic factor-α, and interleukin-6 in the uremic rats, and these effects were prevented by GW501516 treatment. Moreover, GW501516 was found to attenuate glucose-stimulated inflammation in cultured rat peritoneal mesothelial cells via inhibition of transforming growth factor-β-activated kinase 1 (TAK1), and nuclear factor kappa B (NFκB) signaling pathway (TAK1-NFκB pathway), a main inflammation regulatory pathway. In conclusion, inhibition of TAK1-NFκB pathway with GW501516 may represent a novel therapeutic approach to ameliorate peritonitis-induced peritoneal fibrosis for patients on PD.

Does the risk of peritoneal dialysis-associated peritonitis vary by time on treatment?

PubMed

Perl, Jeffrey; Parpia, Sameer; Nessim, Sharon J

2016-04-01

Early retraining of patients/caregivers at 3 months after peritoneal dialysis (PD) initiation is recommended to prevent peritonitis. We sought to better understand if the risk of peritonitis was highest early after the initiation of PD and if the risk varied by time on therapy and by organism. Using the multicenter Canadian Baxter POET database, we studied 4,247 incident PD patients. Time on dialysis was divided into 3-month intervals over the first 2 years on PD, with 0 - 3 months serving as the reference period. After creating several organism categories (all organisms, coagulase-negative staphylococcus (CNS), Staphylococcus aureus, streptococcus, Gramnegative, culture-negative, and yeast), time to first peritonitis was analyzed by Kaplan-Meier analysis and using smooth hazard plots. The risk of peritonitis for each of these categories over time was then analyzed in a multivariable model after adjusting for potential confounding variables. The overall risk of peritonitis (all organisms) was greatest in the first 3 months on PD compared with all subsequent 3-month intervals (p = 0.001). Organism-specific analyses revealed an increased risk of culture-negative peritonitis in the first 3 months (p < 0.001) but no increased risk of CNS peritonitis or any of the other pre-specified organism categories. The overall risk of peritonitis was greatest in the first 3 months on PD and was largely driven by an increased risk of culture-negative peritonitis but not by CNS. Better understanding of this increased early peritonitis risk is warranted in order to develop strategies aimed at its prevention.

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses – A First-In-Man Trial

PubMed Central

Boehm, Michael; Herzog, Rebecca; Gruber, Katharina; Lichtenauer, Anton Michael; Kuster, Lilian; Csaicsich, Dagmar; Gleiss, Andreas; Alper, Seth L.; Aufricht, Christoph; Vychytil, Andreas

2016-01-01

Background Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. Methods In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protein 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellular stress responses, complemented by metabolomics and functional immunocompetence assays. Results AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shock protein expression (effect 1.51-fold, CI 1.07–2.14; p = 0.022), without changes in peritoneal ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation. Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulated cytokine release from healthy donor peripheral blood monocytes. In patients with a history of peritonitis (5 of 20), AlaGln supplementation decreased dialysate interleukin-8 levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokine release in a mouse model of PD-associated peritonitis. Conclusion We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellular stress responses with attenuation of sterile inflammation, and may improve peritoneal host-defense in the setting of PD. PMID:27768727

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

PubMed

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Neighborhood Socioeconomic Status and Barriers to Peritoneal Dialysis: A Mixed Methods Study

PubMed Central

Perzynski, Adam T.; Austin, Peter C.; Wu, C. Fangyun; Lawless, Mary Ellen; Paterson, J. Michael; Quinn, Rob R.; Sehgal, Ashwini R.; Oliver, Matthew James

2013-01-01

Summary Background and objectives The objective of this study was to evaluate the association between neighborhood socioeconomic status and barriers to peritoneal dialysis eligibility and choice. Design, setting, participants, & measurements This study was a mixed methods parallel design study using quantitative and qualitative data from a prospective clinical database of ESRD patients. The eligibility and choice cohorts were assembled from consecutive incident chronic dialysis patients entering one of five renal programs in the province of Ontario, Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was measured as median household income and percentage of residents with at least a high school education using Statistics Canada dissemination area-level data. Multivariable models described the relationship between socioeconomic status and likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal dialysis eligibility and choice were classified into qualitative categories using the thematic constant comparative approach. Results The peritoneal dialysis eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of patients were deemed eligible for peritoneal dialysis, and 46% of eligible patients chose peritoneal dialysis. Socioeconomic status was not a significant predictor of peritoneal dialysis eligibility or choice in this study. Qualitative analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower- versus higher-income Statistics Canada dissemination areas cited built environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and family or social support barriers (8.3% versus 3.5%) more frequently. Conclusions Peritoneal dialysis eligibility and choice were not associated with socioeconomic status. However, socioeconomic status may influence specific barriers to peritoneal dialysis choice. Additional studies to determine the effect of targeting interventions to specific barriers to peritoneal dialysis choice in low socioeconomic status patients on peritoneal dialysis use are needed. PMID:23970135

Neighborhood socioeconomic status and barriers to peritoneal dialysis: a mixed methods study.

PubMed

Prakash, Suma; Perzynski, Adam T; Austin, Peter C; Wu, C Fangyun; Lawless, Mary Ellen; Paterson, J Michael; Quinn, Rob R; Sehgal, Ashwini R; Oliver, Matthew James

2013-10-01

The objective of this study was to evaluate the association between neighborhood socioeconomic status and barriers to peritoneal dialysis eligibility and choice. This study was a mixed methods parallel design study using quantitative and qualitative data from a prospective clinical database of ESRD patients. The eligibility and choice cohorts were assembled from consecutive incident chronic dialysis patients entering one of five renal programs in the province of Ontario, Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was measured as median household income and percentage of residents with at least a high school education using Statistics Canada dissemination area-level data. Multivariable models described the relationship between socioeconomic status and likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal dialysis eligibility and choice were classified into qualitative categories using the thematic constant comparative approach. The peritoneal dialysis eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of patients were deemed eligible for peritoneal dialysis, and 46% of eligible patients chose peritoneal dialysis. Socioeconomic status was not a significant predictor of peritoneal dialysis eligibility or choice in this study. Qualitative analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower- versus higher-income Statistics Canada dissemination areas cited built environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and family or social support barriers (8.3% versus 3.5%) more frequently. Peritoneal dialysis eligibility and choice were not associated with socioeconomic status. However, socioeconomic status may influence specific barriers to peritoneal dialysis choice. Additional studies to determine the effect of targeting interventions to specific barriers to peritoneal dialysis choice in low socioeconomic status patients on peritoneal dialysis use are needed.

Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation.

PubMed

Oliveira, Felipe L; Bernardes, Emerson S; Brand, Camila; dos Santos, Sofia N; Cabanel, Mariana P; Arcanjo, Kátia D; Brito, José M; Borojevic, Radovan; Chammas, Roger; El-Cheikh, Márcia C

2016-02-01

Galectin-3 is a β-galactoside-binding protein with an inhibitory role in B cell differentiation into plasma cells in distinct lymphoid tissues. We use a model of chronic schistosomiasis, a well-characterized experimental disease hallmarked by polyclonal B cell activation, in order to investigate the role of galectin-3 in controlling IgA production through peritoneal B1 cells. Chronically infected, galectin-3-deficient mice (Lgals3(-/-)) display peritoneal fluid hypercellularity, increased numbers of atypical peritoneal IgM(+)/IgA(+) B1a and B1b lymphocytes and histological disturbances in plasma cell niches when compared with Lgals3(+/+) mice. Similar to our infection model, peritoneal B1 cells from uninfected Lgals3(-/-) mice show enhanced switching to IgA after in vitro treatment with interleukin-5 plus transforming growth factor-β (IL-5 + TGF-β1). A higher number of IgA(+) B1a lymphocytes was found in the peritoneal cavity of Lgals3(-/-)-uninfected mice at 1 week after i.p. injection of IL-5 + TGF-β1; this correlates with the increased levels of secreted IgA detected in the peritoneal fluid of these mice after cytokine treatment. Interestingly, a higher number of degranulated mast cells is present in the peritoneal cavity of uninfected and Schistosoma mansoni-infected Lgals3(-/-) mice, indicating that, at least in part, mast cells account for the enhanced differentiation of B1 into IgA-producing B cells found in the absence of galectin-3. Thus, a novel role is revealed for galectin-3 in controlling the expression of surface IgA by peritoneal B1 lymphocytes; this might have important implications for manipulating the mucosal immune response.

[Antimicrobial treatment of polymicrobial infections].

PubMed

Pavlović, Milorad; Nikolić, Jelena

2010-01-01

Polymicrobial infections are concomitant or successive infections caused by two or more microorganisms at the same site. The most common types of these infections include orofacial, gastro-intestinal, pelvic (PID) infections, solid organ abscesses (brain, liver, lungs), chronic infections (sinusitis, mastoiditis), skin and soft tissue infections ("diabetic foot", cellulitis, necrotic fasciitis), sepsis. The most important clues in the therapeutic choice include isolation of the causative agents and empirical data concerning the most common microorganisms of'the affected region. The sensitivity of the most common anaerobic pathogen in polymicrobial infections--B.fragillis, is closely monitored, and according to the latest data it is maintained as such to metronidazole, carbapenems. aminopenicillins with beta-lactamase inhibitors and tigecycline, fluoroquinolones. However it must be emphasized that antimicrobial therapy represents only one aspect of the treatment in this type of infections, and can not replace a more adequate multi-disciplinary approach, which often includes surgical treatment.

A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients.

PubMed

Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Duan, Kangmin; Norgaard, Jens C; Surette, Michael G

2008-09-30

Lung disease is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. A modest number of bacterial pathogens have been correlated with pulmonary function decline; however, microbiological and molecular evidence suggests that CF airway infection is polymicrobial. To obtain a more complete assessment of the microbial community composition and dynamics, we undertook a longitudinal study by using culture-independent and microbiological approaches. In the process, we demonstrated that within complex and dynamic communities, the Streptococcus milleri group (SMG) can establish chronic pulmonary infections and at the onset of 39% of acute pulmonary exacerbations, SMG is the numerically dominant pathogen. We report the comprehensive polymicrobial community dynamics of a CF lung infection in a clinically relevant context. If a given organism, such as Pseudomonas aeruginosa, becomes resistant to antibiotic therapy, an alternative treatment avenue may mediate the desired clinical response by effectively managing the composition of the microbial community.

Administration of honey to prevent peritoneal adhesions in a rat peritonitis model.

PubMed

Yuzbasioglu, Mehmet Fatih; Kurutas, Ergul Belge; Bulbuloglu, Ertan; Goksu, Mustafa; Atli, Yalcin; Bakan, Vedat; Kale, Ilhami Taner

2009-02-01

We investigated the effects of intraperitoneal honey on the development of postoperative intra-abdominal adhesions and oxidative stress in a model of bacterial peritonitis. Bacterial peritonitis was induced in 18 rats by cecal ligation and puncture. The rats were randomly assigned to three groups. Group 1 (n=6) received honey intraperitoneally, group 2 (n=6) received 5% dextrose intraperitoneally, and the third group received no fluid or medicine intraperitoneally one day after cecal ligation and puncture procedure. All animals were killed 14 days later so we could assess the adhesion score. Tissue antioxidant levels were measured in 1-g tissue samples taken from the abdominal wall. Adhesion scores of honey treated group were significantly lower according to the control group (P<0.05) and statistically significant. Adhesion scores of honey were lower from 5% dextrose but not statistically significant (P>0.05). Malondialdehyde values of honey group were significantly lower from the control group (P<0.05) and levels in 5% dextrose group was higher than the honey group. Catalase levels were high in control and 5% dextrose groups. Superoxide dismutase levels were higher in the control group than the honey group (statistically significant). Intraperitoneal honey decreased the formation of postoperative intra-abdominal adhesions without compromising wound healing in this bacterial peritonitis rat model. Honey also decreased the oxidative stress during peritonitis.

Development and Application of a Polymicrobial in vitro Wound Biofilm Model

PubMed Central

Woods, Jeremy; Boegli, Laura; Kirker, Kelly R.; Agostinho, Alessandra M.; Durch, Amanda M.; Pulcini, Elinor deLancey; Stewart, Philip S.; James, Garth A.

2012-01-01

Aims The goal of this investigation was to develop an in vitro, polymicrobial, wound biofilm capable of supporting the growth of bacteria with variable oxygen requirements. Methods and Results The strict anaerobe Clostridium perfringens was isolated by cultivating wound homogenates using the drip-flow reactor, and a three-species biofilm model was established using methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and C. perfringens in the colony-drip-flow reactor model. Plate counts revealed that MRSA, P. aeruginosa, and C. perfringens grew to 7.39±0.45, 10.22±0.22, and 7.13±0.77 log CFU per membrane, respectively. The three-species model was employed to evaluate the efficacy of two antimicrobial dressings, Curity™ AMD and Acticoat™, compared to sterile gauze controls. Microbial growth on Curity™ AMD and gauze were not significantly different, for any species, whereas Acticoat™ was found to significantly reduce growth for all three species. Conclusions Using the Colony-DFR, a three-species biofilm was successfully grown, and the biofilms displayed a unique structure consisting of distinct layers that appeared to be inhabited exclusively or predominantly by a single species. Significance and Impact of Study The primary accomplishment of this study was the isolation and growth of an obligate anaerobe in an in vitro model without establishing an artificially anaerobic environment. PMID:22353049

Sepsis-induced expansion of granulocytic myeloid-derived suppressor cells promotes tumour growth through Toll-like receptor 4.

PubMed

Llitjos, Jean-François; Auffray, Cédric; Alby-Laurent, Fanny; Rousseau, Christophe; Merdji, Hamid; Bonilla, Nelly; Toubiana, Julie; Belaïdouni, Nadia; Mira, Jean-Paul; Lucas, Bruno; Chiche, Jean-Daniel; Pène, Frédéric

2016-08-01

Severe sepsis remains a frequent and dreaded complication in cancer patients. Beyond the often fatal short-term outcome, the long-term sequelae of severe sepsis may also impact directly on the prognosis of the underlying malignancy in survivors. The immune system is involved in all stages of tumour development, in the detection of transforming and dying cells and in the prevention of tumour growth and dissemination. In fact, the profound and sustained immune defects induced by sepsis may constitute a privileged environment likely to favour tumour growth. We investigated the impact of sepsis on malignant tumour growth in a double-hit animal model of polymicrobial peritonitis, followed by subcutaneous inoculation of MCA205 fibrosarcoma cells. As compared to their sham-operated counterparts, post-septic mice exhibited accelerated tumour growth. This was associated with intratumoural accumulation of CD11b(+) Ly6G(high) polymorphonuclear cells (PMNs) that could be characterized as granulocytic myeloid-derived suppressor cells (G-MDSCs). Depletion of granulocytic cells in post-septic mice inhibited the sepsis-enhanced tumour growth. Toll-like receptor (TLR)-4 (Tlr4) and Myd88 deficiencies prevented sepsis-induced expansion of G-MDSCs and tumour growth. Our results demonstrate that the myelosuppressive environment induced by severe bacterial infections promotes malignant tumour growth, and highlight a critical role of CD11b(+) Ly6G(high) G-MDSCs under the control of TLR-dependent signalling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The effect of Kombucha on post-operative intra-abdominal adhesion formation in rats.

PubMed

Maghsoudi, Hemmat; Mohammadi, Hussein Benagozar

2009-04-01

Peritoneal adhesions are fibrous bands of tissues formed between organs that are normally separated and/or between organs and the internal body wall after peritoneal injury. The aim of the study was to investigate the effect of intra-peritoneal administration of Kombucha on intra-peritoneal adhesions. Eighty Wistar rats were subjected to standardized lesion by scraping model and were randomly divided into two groups. Group I received no treatment, and Group II received 15 ml of Kombucha solution intra-peritoneally. On the post-operative 14th day adhesion intensity score, inflammatory cell reaction and number of adhesion bands were determined. In the control group, there were no rats with grade 0 and I adhesions. In the group II, there were 26 rats (78.8%) with grade 0-2 adhesions. Adhesion intensity was significantly less in group II (P<0.0001). Number of adhesion bands was significantly less in group II (P<0.001). It was concluded that intra-peritoneal administration of Kombucha might be useful for preventing peritoneal adhesions.

P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3

PubMed Central

Deng, Lulu; Li, Qin; Lin, Guixian; Huang, Dan; Zeng, Xuxin; Wang, Xinwei; Li, Ping; Jin, Xiaobao; Zhang, Haifeng; Li, Chunmei; Chen, Lixin; Wang, Liwei; Huang, Shulin; Shao, Hongwei; Xu, Bin; Mao, Jianwen

2016-01-01

P-glycoprotein (P-gp) is encoded by the multidrug resistance (MDR1) gene and is well studied as a multi-drug resistance transporter. Peritoneal adhesion formation following abdominal surgery remains an important clinical problem. Here, we found that P-gp was highly expressed in human adhesion fibroblasts and promoted peritoneal adhesion formation in a rodent model. Knockdown of P-gp expression by intraperitoneal injection of MDR1-targeted siRNA significantly reduced both the peritoneal adhesion development rate and adhesion grades. Additionally, we found that operative injury up-regulated P-gp expression in peritoneal fibroblasts through the TGF-β1/Smad signaling pathway and histone H3 acetylation. The overexpression of P-gp accelerated migration and proliferation of fibroblasts via volume-activated Cl- current and cell volume regulation by enhancing phosphorylation of the chloride channel-3. Therefore, P-gp plays a critical role in postoperative peritoneal adhesion formation and may be a valuable therapeutic target for preventing the formation of peritoneal adhesions. PMID:26877779

Effects of parecoxib on the prevention of postoperative peritoneal adhesions in rats.

PubMed

Arung, Willy; Jehaes, François; Cheramy, Jean-Paul; Defraigne, Jean-Olivier; Meurisse, Michel; Honoré, Pierre; Drion, Pierre; Detry, Olivier

2013-12-01

No systemic preventive therapy has been successful in inhibiting the development of postoperative peritoneal adhesions (PPAs). The aim of this study was to evaluate the potential effects of 5 day administration of parecoxib, on PPA prevention and on suture or wound healing in rats. In a model of PPAs induced by peritoneal electrical burn, 30 rats were randomized into 3 groups according to parecoxib administration route (control; intraperitoneal (IP); intramuscular (IM)). Plasma and peritoneal levels of PAI-1 and tPA were measured at T0, after 90 min of surgery (T90), and on postoperative day 10 (D10). In a cecum resection model, 20 rats were randomized into two groups (control and IP parecoxib), and abdominal wound healing and suture leakage were assessed at D10. In both models, PPAs were evaluated quantitatively and qualitatively on D10. Administration of parecoxib significantly decreased the quantity (p < .05) and the severity (p < .01) of PPAs in both models. In addition, parecoxib administration did not cause healing defects or infectious complications in the two models. In the peritoneal burn model, IP or IM parecoxib administration inhibited the increase of postoperative plasma and peritoneum PAI-1 levels, an increase that was observed in the control group (p < .01). No anastomosis leakage could be demonstrated in both groups in the cecum resection model. This study showed that, in these rat models, parecoxib might reduce PPA formation. Confirmation of the safety of parecoxib on intestinal anastomoses is required and should be investigated in further animal models.

Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice.

PubMed

Sun, Weidong; Liu, Chang; Zhang, Yaqi; Qiu, Xia; Zhang, Li; Zhao, Hongxia; Rong, Yi; Sun, Yun

2017-02-15

Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of Prophylactic Antibiotics at Peritoneal Catheter Insertion on Early Peritonitis: Data from the Catheter Section of the French Language Peritoneal Dialysis Registry.

PubMed

Lanot, Antoine; Lobbedez, Thierry; Bechade, Clémence; Verger, Christian; Fabre, Emmanuel; Dratwa, Max; Vernier, Isabelle

2016-01-01

International guidelines recommend the use of a prophylactic antibiotic before the peritoneal dialysis (PD) catheter can be inserted. The main objective of this study was to assess whether this practice is associated with a lower risk of early peritonitis and to estimate the magnitude of the centre effect. A retrospective, multi-centric study was conducted, in which data from the French Language Peritoneal Dialysis Registry was analysed. Patients were separated into 2 groups based on whether or not prophylactic antibiotics were used prior to catheter placement. Out of the 2,014 patients who had a PD catheter placed between February 1, 2012 and December 31, 2014, 1,105 were given a prophylactic antibiotic. In a classical logit model, the use of prophylactic antibiotics was found to protect the individual against the risk of early peritonitis (OR 0.67, 95% CI 0.49-0.92). However, this association lost significance in a mixed logistic regression model with centre as a random effect: OR 0.73 (95% CI 0.48-1.09). Covariates associated with the risk of developing early peritonitis were age over 65: OR 0.73 (95% CI 0.39-0.85), body mass index over 35 kg/m2: OR 1.99 (95% CI 1.13-3.47), transfer to PD due to graft failure: OR 2.24 (95% CI 1.22-4.11), assisted PD: OR 1.96 (95% CI 1.31-2.93), and the use of the Moncrief technique: OR 3.07 (95% CI 1.85-5.11). There is a beneficial effect of prophylactic antibiotic used prior to peritoneal catheter placement, on the occurence of early peritonitis. However, the beneficial effect could be masked by a centre effect. © 2016 S. Karger AG, Basel.

Impact of Host Age and Parity on Susceptibility to Severe Urinary Tract Infection in a Murine Model

PubMed Central

Kline, Kimberly A.; Schwartz, Drew J.; Gilbert, Nicole M.; Lewis, Amanda L.

2014-01-01

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10–100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups. PMID:24835885

Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

PubMed

Kline, Kimberly A; Schwartz, Drew J; Gilbert, Nicole M; Lewis, Amanda L

2014-01-01

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10-100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups.

Computerized urea kinetic modeling to prescribe and monitor delivered Kt/V (pKt/V, dKt/V) in peritoneal dialysis. Fresenius Randomized Dialysis Prescriptions and Clinical Outcome Study (RDP/CO).

PubMed

Gotch, F A; Lipps, B J; Keen, M L; Panlilio, F

1996-01-01

A computerized urea kinetic model of peritoneal urea transport (PACK-PD) has been developed and used to calculate prescription parameters which would result in the prescribed weekly peritoneal urea clearance (pKpt/V) required to achieve levels of weekly summed renal + peritoneal urea clearance (pKprt/ V) targeted at 1.75 and 2.16. Baseline kinetic data were obtained and analyzed with PACK-PD on 88 patients, and the program then used these data to calculate the required pKpt/V and subsequently the delivered Kpt/V (dKpt/V) from the dialysate collections. A total of 108 prescriptions were written and compared to dKpt/V measured over one to 24 months in the 88 patients. Both continuous ambulatory peritoneal dialysis and automated peritoneal dialysis (APD) were studied (APD consisted of PD+ with one or two diurnal and two to four nocturnal cycler exchanges). The correlation of dKpt/V to pKpt/V showed r = 0.93 with 95% confidence limits (CL) on agreement of +/-20% over a range of pKpt/V 0.52-2.55. The 95% CL on (dKpt/V-pKpt/V) were +/-0.30. We concluded: (1) that the prescription can be modeled as reliably in peritoneal dialysis as in hemodialysis (HD) where dKt/V and pKt/V agree to +/-25%, (2) that any individual weekly dKpt/V may vary as much as 0.3-0.4 from pKpt/V, and (3) that frequent measurement of dKpt/V and adjustment of pKpt/V as needed are required (as in HD) to control mean dKpt/V to within +/-10% of mean pKpt/V.

The genetic background of hypertensive, septic rats determines outcome improvement with antibiotic and G-CSF prophylaxis.

PubMed

Bauhofer, Artur; Tischer, Bjirn; Middeke, Martin; Plaul, Ulrike; Lorenz, Wilfried; Torossian, Alexander

2003-10-01

Hypertension is proposed as a risk factor among others (high age, diabetes mellitus, and pre- and intraoperative bleeding) for adverse outcomes, such as severe infections, leading to sepsis and to multiple organ failure as the most deleterious complication. Hypertension was modeled with spontaneous hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats and the infective complication by polymicrobial, peritoneal contamination, and infection (PCI). The concept of clinic modeling randomized trials was used to simulate clinical complexity, including a relevant antibiotic prophylaxis in combination with granulocyte-colony stimulating factor (G-CSF) and clinical trial conditions. Outcome parameters were: survival, systemic cytokines (protein), and organ-specific cytokine levels (mRNA). With low complexity (no prophylaxis), 28% of the animals in the Wistar and 50% in the SHR group survived (P=0.17). Tumor necrosis factor-alpha levels were lower in the liver of SHR vs. Wistar rats with PCI (P<0.01). The anti-inflammatory cytokine interleukin (IL)-10 was expressed on a higher level in SHR with PCI compared with Wistar rats (P<0.01). With increased complexity (antibiotic and G-CSF prophylaxis) the survival rate was increased from 50% in Wistar rats to 89% in SHR (P<0.01) and the mRNA expression of IL-6 was decreased in the kidney of SHR (P<0.05). Survival rate was 44% in the DS rats vs. 67% of the Wistar rats (P=0.18). The mRNA expression of tumor necrosis factor-alpha and IL-10 was reduced (P<0.01) by pretreatment in the liver of DS rats with PCI. The hypertensive, genetically distinct SHR and DS rats express different patterns of pro- and anti-inflammatory cytokine levels after PCI. G-CSF and antibiotic prophylaxis increases only in SHR survival and decreases IL-6 mRNA expression in the kidney significantly.

The Association Between Glucose Exposure and the Risk of Peritonitis in Peritoneal Dialysis Patients.

PubMed

van Diepen, Anouk T N; van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

♦ Little or no clinical evidence is available on the association between glucose exposure and peritoneal host defense in peritoneal dialysis (PD) patients. The objective of the present study was to quantify the exposure to glucose during the first year on PD and investigate the association with subsequent peritonitis. ♦ We analyzed prospectively collected demographic and peritonitis data from incident adult PD patients between 1990 and 2010. For the present study, we conducted a review of both in- and outpatient medical records of all patients to obtain their day-to-day dialysis schemes during the first year on PD. From these data, the average exposure to glucose was quantified. The exposure was stratified into low- and high-glucose groups based on the median, analyzed per standard deviation and in quartiles. Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HRs) and 95% confidence intervals for the association between glucose exposure and peritonitis. Adjustments were made for age, sex, primary kidney disease, diabetes mellitus, Davies comorbidity score and the treatment period. ♦ In total, 230 patients were included in the study of whom 151 (66%) experienced a first peritonitis episode. The median follow-up time was 2.6 years (interquartile range [IQR]: 1.9 - 3.8) in the low-glucose group and 3.1 (IQR: 2.1 - 4.2) in the high-glucose group. After adjustment for confounding factors, no association between high glucose exposure and the risk of peritonitis was found (HR: 0.81; 0.55 - 1.17). No association was present when glucose exposure was analyzed per standard deviation (SD) (HR: 0.98; 0.79 - 1.21) or patient quartiles were applied. No association was identified between glucose exposure and severe peritonitis, Staphylococcus aureus peritonitis, or a peritonitis episode that lasted more than 14 days. ♦ Exposure to glucose is not associated with an increased risk of peritonitis. The equilibrium between glycemic harm to peritoneal host defense and detrimental effects of glucose on invading microorganisms may determine the susceptibility to peritoneal infection. Copyright © 2016 International Society for Peritoneal Dialysis.

Lower education level is a major risk factor for peritonitis incidence in chronic peritoneal dialysis patients: a retrospective cohort study with 12-year follow-up.

PubMed

Chern, Yahn-Bor; Ho, Pei-Shan; Kuo, Li-Chueh; Chen, Jin-Bor

2013-01-01

Peritoneal dialysis (PD)-related peritonitis remains an important complication in PD patients, potentially causing technique failure and influencing patient outcome. To date, no comprehensive study in the Taiwanese PD population has used a time-dependent statistical method to analyze the factors associated with PD-related peritonitis. Our single-center retrospective cohort study, conducted in southern Taiwan between February 1999 and July 2010, used time-dependent statistical methods to analyze the factors associated with PD-related peritonitis. The study recruited 404 PD patients for analysis, 150 of whom experienced at least 1 episode of peritonitis during the follow-up period. The incidence rate of peritonitis was highest during the first 6 months after PD start. A comparison of patients in the two groups (peritonitis vs null-peritonitis) by univariate analysis showed that the peritonitis group included fewer men (p = 0.048) and more patients of older age (≥65 years, p = 0.049). In addition, patients who had never received compulsory education showed a statistically higher incidence of PD-related peritonitis in the univariate analysis (p = 0.04). A proportional hazards model identified education level (less than elementary school vs any higher education level) as having an independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using the Charlson comorbidity index (score >2 vs ≤2) showed borderline statistical significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053). A lower education level is a major risk factor for PD-related peritonitis independent of age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a comprehensive PD education program is crucial for PD patients with a lower education level.

Spontaneous fungal peritonitis: a rare but severe complication of liver cirrhosis.

PubMed

Gravito-Soares, Marta; Gravito-Soares, Elisa; Lopes, Sandra; Ribeiro, Graça; Figueiredo, Pedro

2017-09-01

Spontaneous bacterial peritonitis is the most common infectious complication in cirrhosis. Spontaneous fungal peritonitis is rare and remains unknown. In this work, spontaneous fungal peritonitis as well as risk factors and prognosis are characterized. A retrospective case-control study of 253 consecutive admissions by peritonitis in cirrhotic patients was carried out between 2006 and 2015. Comparison of patients with spontaneous fungal peritonitis (cases) and spontaneous bacterial peritonitis with positive microbiologic ascitic fluid culture (controls) was performed. Variables such as sociodemographic and clinical features, cirrhosis etiology, liver dysfunction scores, ascitic and laboratory parameters, invasive procedures, and prognosis were evaluated. Of the 231 patients, eight (3.5%) developed spontaneous fungal peritonitis, 62.5% of cases being coinfected with bacteria. Candida spp. was isolated in 87.5% of cases, mainly Candida albicans (37.5%) and C. krusei (25.0%). Patients with spontaneous fungal peritonitis had higher ascitic fluid lactate dehydrogenase (288.4±266.6 vs. 161.0±179.5; P=0.011), blood leukocyte count (15187.5±5432.3 vs. 10969.8±6949.5; P=0.028), blood urea nitrogen (69.8±3.1 vs. 36.3±25.5; P=0.001), higher number of invasive procedures (colonoscopy: 25.0 vs. 0.8%, P=0.001; urinary catheterization: 87.5 vs. 49.6%, P=0.038; nasogastric intubation: 87.5 vs. 26.9%, P=0.001), and longer duration of hospital stay (30.0±32.9 vs. 18.9±17.0 days; P=0.031). No statistical difference was found between the two groups for Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-sodium, and Child-Pugh scores. Spontaneous fungal peritonitis was associated with a worse prognosis, particularly severe sepsis/septic shock (87.5 vs. 42.8%, P=0.023), admission in the gastroenterology intensive care unit (87.5 vs. 24.4%; P=0.001), and overall (62.5 vs. 31.9%; P=0.039) or 30-day mortality (50.0 vs. 24.4%; P=0.034), with a mean diagnosis-death time of 17.6±11.5 days. Despite being a rare condition, spontaneous fungal peritonitis was associated with worse prognosis and higher mortality than SBP. The ascitic fluid lactate dehydrogenase, blood leukocyte count and urea nitrogen, invasive procedures, and longer admission time were independent risk factors for spontaneous fungal peritonitis.

An experimental infection model for Escherichia coli egg peritonitis in layer chickens.

PubMed

Chaudhari, Atul A; Kariyawasam, Subhashinie

2014-03-01

The present study describes an experimental infection model for avian pathogenic Escherichia coli (APEC)-induced egg peritonitis in layer chickens. First, a pilot study which consisted of two separate experiments was carried out to compare two routes of inoculations of APEC to induce peritonitis and to examine if the presence of egg yolk in the peritoneum would facilitate APEC-induced peritonitis. This study showed that the presence of egg yolk in the peritoneum facilitated the development of egg peritonitis when the APEC was inoculated via the intra-uterine (IU) route. Based on the results of the pilot study, 56-wk-old white leghorn hens were divided into two groups of five chickens, Group G (inoculated with E. coli APECO78 strain) and Group H (control). Both groups were inoculated with 2-3 ml of egg yolk via the intraperitoneal route (IP). Subsequently, hens in Group H were inoculated with only egg yolk whereas the hens in Group G were inoculated with 1 x 10(9) colony-forming units of APECO78 bacteria via the IU route. Parameters such as mortality, clinical signs (anorexia, depression, and egg production efficiency), gross lesion scores, bacterial loads in internal organs, and histopathology of ovary and oviduct were assessed to evaluate the success of the infection model. Group G showed 40% acute mortality, severe depression, and anorexia with markedly reduced egg production and developed peritonitis-associated lesions such as accumulation of yellowish caseous fluid in the peritoneum, salpingitis, and oophoritis. Histopathologically, ovarian and oviduct tissues from group G exhibited severe inflammatory changes such as infiltration of mononuclear cells and edema. Group G also showed significant bacterial loads in the peritoneum, ovary, and oviduct. Interestingly, deceased birds from group G had also developed mild perihepatitis and pericarditis with heavy bacterial loads in the internal organs. On the other hand, group H birds did not exhibit any of the clinical signs and remained healthy until the end of the experiment. To summarize, our results demonstrate that IP administration of egg yolk followed by IU inoculation of APECO78 induced peritonitis in laying hens. Experimental infection models are often required to understand the mechanisms of disease pathogenesis. Therefore, the present infection model will aid in the studies of pathogenesis of layer peritonitis caused by APEC and in evaluating vaccine candidates to control the disease.

Current Microbiology of Surgical Site Infections in Patients with Cancer: A Retrospective Review.

PubMed

Rolston, Kenneth V I; Nesher, Lior; Tarrand, Jeffrey T

2014-12-01

Patients with solid tumors frequently undergo surgical procedures and develop procedure-related infections. We sought to describe the current microbiologic spectrum of infections at various sites following common surgical procedures. This was a retrospective review of microbiologic data between January 2011 and February 2012. The sites studied were those associated with breast cancer surgery, thoracotomy, craniotomy, percutaneous endoscopic gastrostomy (PEG) tube insertion, and abdominal/pelvic surgery. Only patients with solid tumors were included. A total of 368 surgical site infections (SSIs) were identified (68 breast cancer related; 91 thoracotomy related; 45 craniotomy related; 75 PEG-tube insertion related; and 89 abdominal/pelvic surgery related). Of these, 58% were monomicrobial and 42% were polymicrobial. Overall, 85% of the 215 monomicrobial infections were caused by Gram-positive organisms and 13% by Gram-negative bacilli (GNB). Staphylococcus aureus was the predominant pathogen in monomicrobial infections (150 of 215, 70%). Sixty (40%) of these staphylococcal isolates were methicillin resistant (MRSA), and 65% had a vancomycin minimal inhibitory concentration (MIC) ≥1.0 µg/ml. Pseudomonas aeruginosa was the predominant GNB pathogen (19 of 27, 70%). Staphylococci were also the predominant pathogens in polymicrobial infections, while P. aeruginosa and Escherichia coli were the predominant GNB. Overall, 35% of isolates from polymicrobial infections were GNB. Cephalosporins (e.g., cefazolin) or amoxicillin/clavulanate was used most often for surgical prophylaxis, and 47% of organisms from monomicrobial infections (MRSA, P. aeruginosa) were resistant to them. A similar resistance pattern was observed in polymicrobial infections. Staphylococcus species were isolated most often from the sites studied. Polymicrobial infections (42%) and GNB monomicrobial infections (13%) were relatively frequent causes of SSIs. Many of these infections were caused by organisms that are resistant to agents commonly used for surgical prophylaxis. Additionally, 65% of staphylococcal isolates had a vancomycin MIC ≥1.0 µg/ml, suggesting the need for alternative therapeutic agents.

Selective Blocking of TNF Receptor 1 Attenuates Peritoneal Dialysis Fluid Induced Inflammation of the Peritoneum in Mice.

PubMed

Kälble, Florian; Damaske, Janine; Heide, Danijela; Arnold, Iris; Richter, Fabian; Maier, Olaf; Eisel, Ulrich; Scheurich, Peter; Pfizenmaier, Klaus; Zeier, Martin; Schwenger, Vedat; Ranzinger, Julia

2016-01-01

Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects.

The Association between Exit Site Infection and Subsequent Peritonitis among Peritoneal Dialysis Patients

PubMed Central

van Diepen, Anouk T.N.; Tomlinson, George A.

2012-01-01

Summary Background and objectives Peritonitis is the most common infectious complication seen in peritoneal dialysis (PD). Traditionally, exit site infection (ESI) has been thought to predispose PD patients to peritonitis, although the risks have not been quantified. This study aimed to quantify the risk of PD peritonitis after ESI. Design, setting, participants, & measurements Data from 203 clinically stable PD patients >18 years of age who were followed as part of a randomized controlled trial over 18 months were used to estimate the risk of developing peritonitis within 30 days of an ESI compared with individuals who did not have a recent ESI. Sensitivity analyses were performed at 15, 45, and 60 days. Results Patients were mostly male (64.5%) and Caucasian, with a mean age of 60.5±14.4 years. There were 44 ESIs and 87 peritonitis episodes during the 18-month study. Seven patients had an ESI followed by peritonitis within 30 days. Using a frailty model, patients who had an ESI had a significantly higher risk of developing peritonitis within 30 days, even if the ESI was appropriately treated. This risk was maximal early on and diminished with time, with hazard ratios (95% confidence interval) of 11.1 at 15 days (HR=11.1, 95% CI=4.9–25.1), 5.3 at 45 days (2.5–11.3), and 4.9 at 60 days (2.4–9.9). In 2.3% of patients, subsequent peritonitis was caused by the same organism as the previous ESI. Conclusions A strong association between a treated ESI and subsequent PD peritonitis was present up to 60 days after initial diagnosis. PMID:22745277

Risk Factors for the First Episode of Peritonitis in Southern Chinese Continuous Ambulatory Peritoneal Dialysis Patients

PubMed Central

Fan, Xiaoguang; Huang, Rong; Wang, Juan; Ye, Hongjian; Guo, Qunying; Yi, Chunyan; Lin, Jianxiong; Zhou, Qian; Shao, Fengmin; Yu, Xueqing; Yang, Xiao

2014-01-01

Background The first episode of peritonitis affects survival of the peritoneal membrane as a medium for dialysis as well as survival of patients. The aim of this study is to investigate risk factors associated with the first episode of peritonitis in Southern Chinese continuous ambulatory peritoneal dialysis (CAPD) patients. Methods This is a single-center, retrospective, cohort study. All incident CAPD patients from 1 January 2006 to 31 December 2010 were recruited, and followed up until their first episode of peritonitis or 31 December, 2012. Baseline demographic, socioeconomic, clinical and laboratory data were collected. Cox proportional model was used to determine the factors associated with the first episode of peritonitis. Results In a cumulative 30756.5 patient-months follow-up (the median vintage 26.1 months) of 1117 CAPD patients, 309(27.7%) patients presented the first episodes of peritonitis. The cumulative peritonitis-free survival was 86.2%, 78.1%, 71.4% and 57.8% at 1, 2, 3 and 5 year, respectively. The multivariate analysis showed that factors associated with risk for the first episode of peritonitis were elderly patients (>65 years) [hazard ratio (HR) = 1.427, 95% confidence interval (CI) = 1.051 to 1.938, P = 0.023], male(HR = 1.315, 95% CI = 1.028 to 1.684, P = 0.030), lower education level (HR = 1.446, 95% CI: 1.127 to 1.855, P = 0.004) and albumin <38g/L (HR = 1.425, 95% CI: 1.112 to 1.825, P = 0.005). Conclusions Older age, male, lower educational level and hypoalbuminemia at the commencement of PD were the risk factors associated with the first episode of peritonitis in Southern Chinese CAPD patients. PMID:25222609

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma.

PubMed

Mersch, Sabrina; Riemer, Jasmin C; Schlünder, Philipp M; Ghadimi, Markus P; Ashmawy, Hany; Möhlendick, Birte; Topp, Stefan A; Arent, Tanja; Kröpil, Patric; Stoecklein, Nikolas H; Gabbert, Helmut E; Knoefel, Wolfram T; Krieg, Andreas

2016-02-01

Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies.

Rational choice of peritoneal dialysis catheter.

PubMed

Dell'Aquila, Roberto; Chiaramonte, Stefano; Rodighiero, Maria Pia; Spanó, Emilia; Di Loreto, Pierluigi; Kohn, Catalina Ocampo; Cruz, Dinna; Polanco, Natalia; Kuang, Dingwei; Corradi, Valentina; De Cal, Massimo; Ronco, Claudio

2007-06-01

The peritoneal catheter should be a permanent and safe access to the peritoneal cavity. Catheter-related problems are often the cause of permanent transfer to hemodialysis (HD) in up to 20% of peritoneal dialysis (PD) patients; in some cases, these problems require a temporary period on HD. Advances in connectology have reduced the incidence of peritonitis, and so catheter-related complications during PD have become a major concern. In the last few years, novel techniques have emerged in the field of PD: new dialysis solutions, better connectology, and cyclers for automated PD. However, extracorporeal dialysis has continued to improve in terms of methods and patient survival, but PD has failed to do so. The main reason is that peritoneal access has remained problematical. The peritoneal catheter is the major obstacle to wide-spread use of PD. Overcoming catheter-related problems means giving a real chance to development of the peritoneal technique. Catheters should be as efficient, safe, and acceptable as possible. Since its introduction in the mid-1960s, the Tenckhoff catheter has not become obsolete: dozens of new models have been proposed, but none has significantly reduced the pre-dominance of the first catheter. No convincing prospective data demonstrate the superiority of any peritoneal catheter, and so it seems that factors other than choice of catheter are what affect survival and complication rates. Efforts to improve peritoneal catheter survival and complication rates should probably focus on factors other than the choice of catheter. The present article provides an overview of the characteristics of the best-known peritoneal catheters.

CD44 deficiency enhanced Streptococcus equi ssp. zooepidemicus dissemination and inflammation response in a mouse model.

PubMed

Fu, Qiang; Xiao, Pingping; Chen, Yaosheng; Wei, Zigong; Liu, Xiaohong

2017-12-01

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased. CD44 deficiency accelerated mortality, which was accompanied by increased peritoneal bacterial growth and dissemination to distant body sites. CD44 knock-out (KO) mice showed enhanced early inflammatory cell recruitment into the peritoneal fluid on S. zooepidemicus infection. In line with this, the expression of proinflammatory cytokines, chemokines in peritoneal exudate cells and peritoneal macrophages of CD44 KO mice were increased compared with those of WT mice. In addition, CD44 deficiency was associated with reduced expression of A20, a negative regulator in TLR signaling. Overall, the present study suggests that CD44 plays a protective role in antibacterial defense against S. zooepidemicus in mice. Copyright © 2017. Published by Elsevier Ltd.

Continuous ambulatory peritoneal dialysis is better than automated peritoneal dialysis as first-line treatment in renal replacement therapy.

PubMed

Li, Philip Kam-Tao; Chung, Kwok Yi; Chow, Kai Ming

2007-06-01

This article examines the roles of continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD) as first-line renal replacement therapy. To date, no high-quality large-scale randomized controlled studies have compared CAPD with APD as first-line therapy. However, a discussion on this issue is important so that nephrologists can decide and patients can have a choice of modality on which to start dialysis, especially in the context of health care economics. We review the literature and present Hong Kong as the model of a "CAPD first" policy, an appealing, cost-effective approach for any country. An ideal renal replacement therapy should provide optimal survival, lowest possible risk for comorbidity, highest level of quality of life, and equally important, acceptable cost to society. When we consider this subject in the context that all patients should be started on one first-line modality, the data suggest that a "CAPD first" policy has all these advantages, with APD probably having the edge only with regard to patient preference. The present review highlights preservation of residual renal function, removal and balancing of sodium, incidence of peritonitis, peritoneal membrane transport status, patient rehabilitation, and financial issues in demonstrating that a "CAPD first" policy is the model that should be adopted.

Acellular derivatives of mesenchymal stem cells prevent peritoneal adhesions in an animal model.

PubMed

Rojo, Daniel; Conget, Paulette

2018-03-01

Peritoneal adhesions are nonanatomical connections that bind organs to the abdominal wall or among them. They arise after peritoneal injury, which triggers an inflammatory response followed by a healing process that leads to fibrotic tissue formation. Mesenchymal stem cells and their secretion products, also referred to as acellular derivatives (ACDs), have anti-inflammatory, fibrinolytic, and antifibrogenic properties. The aim of this study was to determine the effect of intraoperative administration of ACD on the appearance, severity, and progression of peritoneal adhesions, in an animal model. Cecal erosions were mechanically induced in adult mice. Before closure, the vehicle, ACD, or Seprafilm was administered. Seven days later, the presence and grade of peritoneal adhesions were assessed macroscopically. One, 3, and 7 d after intervention, molecular and cellular markers of inflammation, fibrinolysis, and fibrogenesis were evaluated both locally and systemically. ACDs avoided the appearance of clinically relevant peritoneal adhesions. The vehicle had no effect, and Seprafilm reduced them inconsistently. The antiadhesive effect of ACD was associated with an early reduction of proinflammatory cytokine (tumor necrosis factor-alpha and interferon-gamma) secretion and leukocyte (polymorphonuclears, mononuclears, and macrophages) infiltration. High levels of D-dimer, low fibrin deposits, low myofibroblasts infiltration, and less fibrosis were also observed. ACD administered at the end of abdominal surgeries prevents the formation of peritoneal adhesions due to the modulation of inflammatory, fibrinolytic, and fibrogenic processes. Copyright © 2017 Elsevier Inc. All rights reserved.

New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

PubMed

Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

Definitions of differences and changes in peritoneal membrane water transport properties.

PubMed

Widerøe, T E; Smeby, L C; Dahl, K; Jörstad, S

1988-06-01

A survey is given comparing measurements of transperitoneal water transport in different clinical situations with analyses based on the so-called "pore theory." This model links the measured changes to physical alterations of the peritoneal membrane. The calculations include "equivalent pore radius," effective "membrane area" and diffusive length, the transport resistance of the unstirred dialysate layer, and the residual intraperitoneal volume after dialysate drainage. The clinical appearances include individual differences in transperitoneal transport characteristics, changes in transperitoneal transport over time on continuous ambulatory peritoneal dialysis (CAPD) and during peritonitis, the pharmacological effect on the transport properties, and the effect of peritoneal catheter dislocation on ultrafiltration capacity. The main conclusions are as follow: During CAPD treatment the measurement of intraperitoneal solute equilibration and "mass-transfer-area coefficients" for urea and creatinine is less sensitive than the measurement of ultrafiltration volume in revealing peritoneal membrane changes. Differences and changes found have mostly a combined physical explanation, but one is more or less dominant. Changes in peritoneal membrane area seem to be the most dominant cause of changes in transperitoneal transport during time on CAPD and when sodium nitroprusside was added to the peritoneal dialysate. Changes during peritonitis can be explained by changes in pore radius and depth. Individual differences can be explained by differences in "membrane" area and in resistance of the unstirred dialysate fluid. High residual dialysate volume can give rise to clinical problems and should be considered when placing the catheter in the peritoneal cavity.

The TGF-beta-induced gene product, betaig-h3: its biological implications in peritoneal dialysis.

PubMed

Park, Sun-Hee; Choi, Soon-Youn; Kim, Mi-Hyung; Oh, Eun-Joo; Ryu, Hye Myung; Kim, Chan-Duck; Kim, In-San; Kim, Yong-Lim

2008-01-01

TGF-beta is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-beta induces betaig-h3 in several cell lines, and betaig-h3 may be a marker for biologically active TGF-beta. However, no study has reported induction of betaig-h3 in human peritoneal mesothelial cells (HPMCs) or its involvement in PD-related peritoneal membrane changes. We used cultured HPMCs to investigate the biological roles of betaig-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in betaig-h3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model. In vitro, TGF-beta1 induced betaig-h3 in cultured HPMCs, and betaig-h3-mediated mesothelial cell adhesion occurred via alphavbeta3 integrin. betaig-h3 enhanced mesothelial cell adhesion and migration and, in part, wound healing during mesothelial cell injury. The animal study demonstrated that compared to the control group, betaig-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and betaig-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that betaig-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. betaig-h3 protein expression was higher in the dialysis group. In vitro, betaig-h3 induced by TGF-beta1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, betaig-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.

Polymicrobial Amniotic Fluid Infection with Mycoplasma/Ureaplasma and Other Bacteria Induces Severe Intra-Amniotic Inflammation Associated with Poor Perinatal Prognosis in Preterm Labor.

PubMed

Yoneda, Noriko; Yoneda, Satoshi; Niimi, Hideki; Ueno, Tomohiro; Hayashi, Shirou; Ito, Mika; Shiozaki, Arihiro; Urushiyama, Daichi; Hata, Kenichiro; Suda, Wataru; Hattori, Masahira; Kigawa, Mika; Kitajima, Isao; Saito, Shigeru

2016-02-01

To study the relationship between perinatal prognosis in cases of preterm labor (PTL) and polymicrobial infection in amniotic fluid (AF) and intra-amniotic (IA) inflammation using a highly sensitive and reliable PCR-based method. To detect prokaryotes using a nested PCR-based method, eukaryote-made thermostable DNA polymerase without bacterial DNA contamination was used in combination with bacterial universal primers. We collected AF aseptically from 118 PTL cases and 50 term subjects. The prevalence of microorganisms was 33% (39/118) by PCR and only 7.6% (9/118) by culture. PTL caused by a combination of positive Mycoplasma/Ureaplasma and other bacteria had significantly higher AF IL-8 levels and a significantly shorter amniocentesis-to-delivery interval. Our newly established PCR method is useful for detecting IA microorganisms. Polymicrobial infection with Mycoplasma/Ureaplasma and other bacteria induces severe IA inflammation associated with poor perinatal prognosis in PTL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A polymicrobial fungal outbreak in a regional burn center after Hurricane Sandy.

PubMed

Sood, Geeta; Vaidya, Dhananjay; Dam, Lisa; Grubb, Lisa M; Zenilman, Jonathan; Krout, Kelly; Khouri-Stevens, Zeina; Bennett, Richard; Blanding, Renee; Riedel, Stefan; Milner, Stephen; Price, Leigh Ann; Perl, Trish M

2018-03-30

To describe a polymicrobial fungal outbreak after Hurricane Sandy. An observational concurrent outbreak investigation and retrospective descriptive review. A regional burn intensive care unit that serves the greater Baltimore area, admitting 350-450 burn patients annually. Patients with burn injuries and significant dermatologic diseases such as toxic epidermal necrolysis who were admitted to the burn intensive care unit. An outbreak investigation and a retrospective review of all patients with non-candida fungal isolates from 2009-2016 were performed. A polymicrobial fungal outbreak in burn patients was temporally associated with Hurricane Sandy and associated with air and water permeations in the hospital facility. The outbreak abated after changes to facility design. Our results suggest a possible association between severe weather events like hurricanes and nosocomial fungal outbreaks. This report adds to the emerging literature on the effect of severe weather on healthcare-associated infections. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Polymicrobial bacteremia caused by Escherichia coli, Edwardsiella tarda, and Shewanella putrefaciens.

PubMed

Wang, I-Kuan; Lee, Ming-Hsun; Chen, Yu-Ming; Huang, Chiu-Ching

2004-09-01

Edwardsiella tarda, a member of Enterobacteriaceae, is found in freshwater and marine environments and in animals living in these environments. This bacterium is primarily associated with gastrointestinal diseases, and has been isolated from stool specimens obtained from persons with or without clinical infectious diseases. Shewanella putrefaciens, a saprophytic gram-negative rod, is rarely responsible for clinical syndromes in humans. Debilitated status and exposure to aquatic environments are the major predisposing factors for E. tarda or S. putrefaciens infection. A 61-year-old woman was febrile with diarrhea 8 hours after ingesting shark meat, and two sets of blood cultures grew Escherichia coli, E. tarda and S. putrefaciens at the same time. She was successfully treated with antibiotics. We present this rare case of polymicrobial bacteremia caused by E. coli, E. tarda and S. putrefaciens without underlying disease, which is the first found in Taiwan. This rare case of febrile diarrhea with consequent polymicrobial bacteremia emphasizes that attention should always be extended to these unusual pathogens.

Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

PubMed

Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-06-07

Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

Water transport across biological membranes: Overton, water channels, and peritoneal dialysis.

PubMed

Devuyst, O

2010-01-01

Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore predicted by the modelization of peritoneal transport. Proof-of-principle studies have shown that upregulation of the expression of AQP1 in peritoneal capillaries is reflected by increased water permeability and ultrafiltration, without affecting the osmotic gradient and the permeability for small solutes. Inversely, studies in Aqp1 mice have shown that haplo-insufficiency in AQP1 is reflected by significant attenuation of water transport. Recent studies have identified lead compounds that could act as agonists of aquaporins, as well as putative binding sites and potential mechanisms of gating the water channel. By modulating water transport, these pharmacological agents could have clinically relevant effects in targeting specific tissues or disease states. These studies on the peritoneal membrane also provide an experimental framework to investigate the role of water channels in the endothelium and various cell types.

Changes of peritoneal transport parameters with time on dialysis: assessment with sequential peritoneal equilibration test.

PubMed

Waniewski, Jacek; Antosiewicz, Stefan; Baczynski, Daniel; Poleszczuk, Jan; Pietribiasi, Mauro; Lindholm, Bengt; Wankowicz, Zofia

2017-10-27

Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

PubMed Central

Morelle, Johann; Sow, Amadou; Hautem, Nicolas; Bouzin, Caroline; Crott, Ralph

2015-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport. PMID:25636412

Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

PubMed

Song, Hua-Li; Zhang, Dong-Mei; Wen, Heng; Wang, Meng; Zhao, Na; Gao, Yu-Hua; Ding, Ni

2018-08-01

Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-inflammatory effect of a Nuphar lutea partially purified leaf extract in murine models of septic shock.

PubMed

Ozer, J; Levi, T; Golan-Goldhirsh, A; Gopas, J

2015-02-23

Various plant organs of Nuphar lutea (L.) SM. (Nymphaeaceae) are used in traditional medicine for the treatment of arthritis, fever, aches, pains and inflammation. The main purpose of this study was to determine the anti-inflammatory effect of Nuphar lutea leaf extract (NUP) in two septic shock models: (1) Survival of mice challenged with a lethal dose of LPS, determination of pro-inflammatory and anti-inflammatory cytokines in serum, as well as in peritoneal macrophages in cell culture. (2) The effect of NUP in a murine model of fecal-induced peritonitis. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. A significant average survival rate (60%) of LPS lethally-challenged mice was achieved by pre-treatment with NUP. In addition, NUP pre-treatment reduced nuclear NF-κB translocation in peritoneal macrophages. The production of pro-inflammatory cytokines, TNF-α, IL-6 and IL-12, in the sera of LPS-treated mice or in the supernatants of peritoneal macrophages stimulated with LPS for 2-6 h was also decreased by NUP. Pre-treatment with NUP caused a significant increase in the anti-inflammatory cytokine IL-10. The NUP pre-treatment reduced and delayed mortality in mice with fecal-induced peritonitis. Our studies also revealed that NUP pre-treatment induced a dose-dependent phosphorylation of ERK in peritoneal macrophages. Since most of the reports about the anti-inflammatory effect of Nuphar lutea refer to rhizome and root powder and extracts, it is important to clarify the effectiveness of leaf extract as a source for such activity. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bowel perforation detection using metabolic fluorescent chlorophylls

NASA Astrophysics Data System (ADS)

Han, Jung Hyun; Jo, Young Goun; Kim, Jung Chul; Choi, Sujeong; Kang, Hoonsoo; Kim, Yong-Chul; Hwang, In-Wook

2016-03-01

Thus far, there have been tries of detection of disease using fluorescent materials. We introduce the chlorophyll derivatives from food plants, which have longer-wavelength emissions (at >650 nm) than those of fluorescence of tissues and organs, for detection of bowel perforation. To figure out the possibility of fluorescence spectroscopy as a monitoring sensor of bowel perforation, fluorescence from organs of rodent models, intestinal and peritoneal fluids of rodent models and human were analyzed. In IVIS fluorescence image of rodent abdominal organ, visualization of perforated area only was possible when threshold of image is extremely finely controlled. Generally, both perforated area of bowel and normal bowel which filled with large amount of chlorophyll derivatives were visualized with fluorescence. The fluorescence from chlorophyll derivatives penetrated through the normal bowel wall makes difficult to distinguish perforation area from normal bowel with direct visualization of fluorescence. However, intestinal fluids containing chlorophyll derivatives from food contents can leak from perforation sites in situation of bowel perforation. It may show brighter and longer-wavelength regime emissions of chlorophyll derivatives than those of pure peritoneal fluid or bioorgans. Peritoneal fluid mixed with intestinal fluids show much brighter emissions in longer wavelength (at>650 nm) than those of pure peritoneal fluid. In addition, irrigation fluid, which is used for the cleansing of organ and peritoneal cavity, made of mixed intestinal and peritoneal fluid diluted with physiologic saline also can be monitored bowel perforation during surgery.

[Establishment of risk evaluation model of peritoneal metastasis in gastric cancer and its predictive value].

PubMed

Zhao, Junjie; Zhou, Rongjian; Zhang, Qi; Shu, Ping; Li, Haojie; Wang, Xuefei; Shen, Zhenbin; Liu, Fenglin; Chen, Weidong; Qin, Jing; Sun, Yihong

2017-01-25

To establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance. Clinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity. Among 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28.2%). Neutrophil/lymphocyte ratio (NLR) of 26 patients was ≥ 2.37(26/231, 11.3%). Multivariate analysis showed that Lauren classification (HR=8.95, 95%CI:1.32-60.59, P=0.025), CA125(HR=17.45, 95%CI:5.54-54.89, P=0.001), CA72-4(HR=20.06, 95%CI:5.05-79.68, P=0.001), and NLR (HR=4.16, 95%CI:1.17-14.75, P=0.032) were independent risk factors of peritoneal metastasis in gastric cancer. In the nomogram, the highest score was 241, including diffuse or mixed Lauren classification (54 score), CA125 ≥ 35 kU/L (66 score), CA72-4 ≥ 10 kU/L (100 score), and NLR ≥ 2.37 (21 score), which represented a highest risk of peritoneal metastasis (more than 90%). The AUC of nomogram was 0.912, which was superior than any single variable (AUC of Lauren classification: 0.678; AUC of CA125: 0.720; AUC of CA72-4: 0.792; AUC of NLR: 0.613, all P=0.000). The total score of nomogram increased according to the TNM stage, and was highest in the peritoneal metastasis group (F=49.1, P=0.000). When the cut-off value calculated by ROC analysis was set at 140, the model could best balanced the sensitivity (0.79) and the specificity (0.87). Only 5% of patients had peritoneal metastasis when their nomogram scores were lower than 140, while 58% of patients had peritoneal metastasis when their scores were ≥ 140(χ 2 =69.1, P=0.000). The risk evaluation model established with Lauren classification, CA125, CA72-4 and NLR can effectively predict the risk of peritoneal metastasis in gastric cancer, and provide the reference to preoperative staging and choice of therapeutic strategy.

Ultrasound criteria and guided fine-needle aspiration diagnostic yields in small animal peritoneal, mesenteric and omental disease.

PubMed

Feeney, Daniel A; Ober, Christopher P; Snyder, Laura A; Hill, Sara A; Jessen, Carl R

2013-01-01

Peritoneal, mesenteric, and omental diseases are important causes of morbidity and mortality in humans and animals, although information in the veterinary literature is limited. The purposes of this retrospective study were to determine whether objectively applied ultrasound interpretive criteria are statistically useful in differentiating among cytologically defined normal, inflammatory, and neoplastic peritoneal conditions in dogs and cats. A second goal was to determine the cytologically interpretable yield on ultrasound-guided, fine-needle sampling of peritoneal, mesenteric, or omental structures. Sonographic criteria agreed upon by the authors were retrospectively and independently applied by two radiologists to the available ultrasound images without knowledge of the cytologic diagnosis and statistically compared to the ultrasound-guided, fine-needle aspiration cytologic interpretations. A total of 72 dogs and 49 cats with abdominal peritoneal, mesenteric, or omental (peritoneal) surface or effusive disease and 17 dogs and 3 cats with no cytologic evidence of inflammation or neoplasia were included. The optimized, ultrasound criteria-based statistical model created independently for each radiologist yielded an equation-based diagnostic category placement accuracy of 63.2-69.9% across the two involved radiologists. Regional organ-associated masses or nodules as well as aggregated bowel and peritoneal thickening were more associated with peritoneal neoplasia whereas localized, severely complex fluid collections were more associated with inflammatory peritoneal disease. The cytologically interpretable yield for ultrasound-guided fine-needle sampling was 72.3% with no difference between species, making this a worthwhile clinical procedure. © 2013 Veterinary Radiology & Ultrasound.

Dialysate interleukin-6 predicts increasing peritoneal solute transport rate in incident peritoneal dialysis patients

PubMed Central

2014-01-01

Background Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. Methods The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). Results Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. Conclusion Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis. PMID:24410736

Polymicrobial Genital Gangrene (Fournier's Gangrene): Clinical, Microbiologic, and Therapeutic Features

PubMed Central

Thadepalli, Haragopal; Rao, Bhavani; Datta, Nand K.; Zinner, Norman

1982-01-01

The microbiologic and therapeutic aspects of polymicrobial genital gangrene (Fournier's gangrene) studied in nine patients are presented. Seven patients had both aerobic and anaerobic bacteria isolated from the site of infection; four had Bacteroides and two, Clostridia. Broad-spectrum penicillins such as ticarcillin, mezlocillin, and piperacillin, or combined clindamycin and gentamicin therapy were used. One patient died of fulminating infection and eight patients were cured of their infections. Anaerobic bacteria and appropriate antibiotic therapy should be considered in all patients with genital gangrene. ImagesFigure 1 PMID:7120464

Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract

PubMed Central

Kline, Kimberly A.; Lewis, Amanda L.

2015-01-01

Gram-positive bacteria are a common cause of urinary tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens: Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including Aerococcus, Corynebacterium, Actinobaculum, and Gardnerella. The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI. PMID:27227294

Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract.

PubMed

Kline, Kimberly A; Lewis, Amanda L

2016-04-01

Gram-positive bacteria are a common cause of urinary-tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens: Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including Aerococcus, Corynebacterium, Actinobaculum, and Gardnerella. The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI.

Periodontal Pathogens Invade Gingiva and Aortic Adventitia and Elicit Inflammasome Activation in αvβ6 Integrin-Deficient Mice

PubMed Central

Velsko, Irina M.; Chukkapalli, Sasanka S.; Rivera-Kweh, Mercedes F.; Zheng, Donghang; Aukhil, Ikramuddin; Lucas, Alexandra R.; Larjava, Hannu

2015-01-01

The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of the integrin β6−/− mouse model to study the causality. We investigated the ability of a polymicrobial consortium of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum to colonize the periodontium and induce local and systemic inflammatory responses. Polymicrobially infected Itgβ6−/− mice demonstrate greater susceptibility to gingival colonization/infection, with severe gingival inflammation, apical migration of the junctional epithelium, periodontal pocket formation, alveolar bone resorption, osteoclast activation, bacterial invasion of the gingiva, a greater propensity for the bacteria to disseminate hematogenously, and a strong splenic T cell cytokine response. Levels of atherosclerosis risk factors, including serum nitric oxide, oxidized low-density lipoprotein, serum amyloid A, and lipid peroxidation, were significantly altered by polybacterial infection, demonstrating an enhanced potential for atherosclerotic plaque progression. Aortic gene expression revealed significant alterations in specific Toll-like receptor (TLR) and nucleotide-binding domain- and leucine-rich-repeat-containing receptor (NLR) pathway genes in response to periodontal bacterial infection. Histomorphometry of the aorta demonstrated larger atherosclerotic plaques in Itgβ6−/− mice than in wild-type (WT) mice but no significant difference in atherosclerotic plaque size between mice with polybacterial infection and mice with sham infection. Fluorescence in situ hybridization demonstrated active invasion of the aortic adventitial layer by P. gingivalis. Our observations suggest that polybacterial infection elicits distinct aortic TLR and inflammasome signaling and significantly increases local aortic oxidative stress. These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well-characterized periodontal pathogens. PMID:26371120

Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer

PubMed Central

Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to near infrared (NIR) light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a 3D spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the anti-tumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs control in tumor volume changes at day 10; p=0.0001, NIR-PIT vs control in luciferase activity at day 4; p=0.0237), and the peritoneal model (NIR-PIT vs control in luciferase activity at day 7; p=0.0037). NIR-PIT provided effective cell killing in this HER2 positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors. PMID:25416790

Polymicrobial Biofilm Inhibition Effects of Acetate-Buffered Chitosan Sponge Delivery Device.

PubMed

Jennings, Jessica Amber; Beenken, Karen E; Parker, Ashley C; Smith, James Keaton; Courtney, Harry S; Smeltzer, Mark S; Haggard, Warren O

2016-04-01

Polymicrobial biofilm-associated implant infections present a challenging clinical problem. Through modifications of lyophilized chitosan sponges, degradable drug delivery devices for antibiotic solution have been fabricated for prevention and treatment of contaminated musculoskeletal wounds. Elution of amikacin, vancomycin, or a combination of both follows a burst release pattern with vancomycin released above minimum inhibitory concentration for Staphylococcus aureus for 72 h and amikacin released above inhibitory concentrations for Pseudomonas aeruginosa for 3 h. Delivery of a vancomycin, amikacin, or a combination of both reduces biofilm formation on polytetrafluoroethylene catheters in an in vivo model of contamination. Release of dual antibiotics from sponges is more effective at preventing biofilm formation than single-loaded chitosan sponges. Treatment of pre-formed biofilm with high-dose antibiotic release from chitosan sponges shows minimal reduction after 48 h. These results demonstrate infection-preventive efficacy for antibiotic-loaded sponges, as well as the need for modifications in the development of advanced materials to enhance treatment efficacy in removing established biofilm. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection.

PubMed

Marcatili, Paolo; Nielsen, Martin W; Sicheritz-Pontén, Thomas; Jensen, Tim K; Schafer-Nielsen, Claus; Boye, Mette; Nielsen, Morten; Klitgaard, Kirstine

2016-12-01

Polymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections. The strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease. The extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host's capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.

Pathogenesis of Proteus mirabilis Infection

PubMed Central

Armbruster, Chelsie E.; Mobley, Harry L. T.; Pearson, Melanie M.

2017-01-01

Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTI) that are often polymicrobial. These infections may be accompanied by urolithiasis, development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different fimbriae, most notably MR/P fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54 kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a “Dienes line”, develops due to the killing action of each strain’s type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending UTI or CAUTI using both single-species and polymicrobial models. Global gene expression studies carried out in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances. PMID:29424333

Synergistic Effects of Honey and Propolis toward Drug Multi-Resistant Staphylococcus Aureus, Escherichia Coli and Candida Albicans Isolates in Single and Polymicrobial Cultures

PubMed Central

AL-Waili, Noori; Al-Ghamdi, Ahmad; Ansari, Mohammad Javed; Al-Attal, Y.; Salom, Khelod

2012-01-01

Background: Propolis and honey are natural bee products with wide range of biological and medicinal properties. The study investigated antimicrobial activity of ethyl alcohol extraction of propolis collected from Saudi Arabia (EEPS) and from Egypt (EEPE), and their synergistic effect when used with honey. Single and polymicrobial cultures of antibiotic resistant human pathogens were tested. Material and methods; Staphylococcus aureus (S. aureus),), Escherichia coli (E. coli) and Candida albicans (C.albicans) were cultured in 10-100% (v/v) honey diluted in broth, or 0.08-1.0% (weight/volume) EEPS and EEPE diluted in broth. Four types of polymicrobial cultures were prepared by culturing the isolates with each other in broth (control) and broth containing various concentrations of honey or propolis. Microbial growth was assessed on solid plate media after 24 h incubation. Results; EEPS and EEPE inhibited antibiotic resistant E.coli, and S.aureus, and C.albicans in single and polymicrobial cultures. S.aureus became more susceptible when it was cultured with E.coli or C.albicans or when all cultured together. C.albicans became more susceptible when it was cultured with S.aureus or with E.coli and S. aureus together. The presence of ethyl alcohol or honey potentiated antimicrobial effect of propolis toward entire microbes tested in single or polymicrobial cultures. EEPS had lower MIC toward E.coli and C.albicans than EEPE. When propolis was mixed with honey, EEPS showed lower MIC than EEPE. In addition, honey showed lower MIC toward entire microbes when mixed with EEPS than when it was mixed with EEPE. Conclusion; 1) propolis prevents the growth of the microorganisms in single and mixed microbial cultures, and has synergistic effect when used with honey or ethyl alcohol, 2) the antimicrobial property of propolis varies with geographical origin, and 3) this study will pave the way to isolate active ingredients from honey and propolis to be further tested individually or in combination against human resistant infections. PMID:23136543

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT.

PubMed

Shi, Bowen; Lin, Huimin; Zhang, Miao; Lu, Wei; Qu, Ying; Zhang, Huan

2018-01-22

Gastric cancer remains fourth in cancer incidence worldwide with a five-year survival of only 20%-30%. Peritoneal metastasis is the most frequent type of metastasis that accompanies unresectable gastric cancer and is a definitive determinant of prognosis. Preventing and controlling the development of peritoneal metastasis could play a role in helping to prolong the survival of gastric cancer patients. A non-invasive and efficient imaging technique will help us to identify the invasion and metastasis process of peritoneal metastasis and to monitor the changes in tumor nodules in response to treatments. This will enable us to obtain an accurate description of the development process and molecular mechanisms of gastric cancer. We have recently described experiment using dual energy CT (DECT) and positron emission tomography/computed tomography (PET/CT) platforms for the detection and monitoring of gastric tumor metastasis in nude mice models. We have shown that weekly continuous monitoring with DECT and PET/CT can identify dynamic changes in peritoneal metastasis. The sFRP1-overexpression in gastric cancer mice models showed positive radiological performance, a higher FDG uptake and increasing enhancement, and the SUVmax (standardized uptake value) of nodules demonstrated an obvious alteration trend in response to targeted therapy of TGF-β1 inhibitor. In this article, we described the detailed non-invasive imaging procedures to conduct more complex research on gastric cancer peritoneal metastasis using animal models and provided representative imaging results. The use of non-invasive imaging techniques should enable us to better understand the mechanisms of tumorigenesis, monitor tumor growth, and evaluate the effect of therapeutic interventions for gastric cancer.

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

PubMed

Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

A Pathogenetic Role for Endothelin-1 in Peritoneal Dialysis-Associated Fibrosis

PubMed Central

Busnadiego, Oscar; Loureiro-Álvarez, Jesús; Sandoval, Pilar; Lagares, David; Dotor, Javier; Pérez-Lozano, María Luisa; López-Armada, María J.; Lamas, Santiago; López-Cabrera, Manuel

2015-01-01

In patients undergoing peritoneal dialysis (PD), chronic exposure to nonphysiologic PD fluids elicits low-grade peritoneal inflammation, leading to fibrosis and angiogenesis. Phenotype conversion of mesothelial cells into myofibroblasts, the so-called mesothelial-to-mesenchymal transition (MMT), significantly contributes to the peritoneal dysfunction related to PD. A number of factors have been described to induce MMT in vitro and in vivo, of which TGF-β1 is probably the most important. The vasoconstrictor peptide endothelin-1 (ET-1) is a transcriptional target of TGF-β1 and mediates excessive scarring and fibrosis in several tissues. This work studied the contribution of ET-1 to the development of peritoneal damage and failure in a mouse model of PD. ET-1 and its receptors were expressed in the peritoneal membrane and upregulated on PD fluid exposure. Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. Adenovirus-mediated overexpression of ET-1 induced MMT in human mesothelial cells in vitro and promoted the early cellular events associated with peritoneal dysfunction in vivo. Notably, TGF-β1–blocking peptides prevented these actions of ET-1. Furthermore, a positive reciprocal relationship was observed between ET-1 expression and TGF-β1 expression in human mesothelial cells. These results strongly support a role for an ET-1/TGF-β1 axis as an inducer of MMT and subsequent peritoneal damage and fibrosis, and they highlight ET-1 as a potential therapeutic target in the treatment of PD-associated dysfunction. PMID:25012164

A case of polymicrobial endocarditis caused by anaerobic organisms in an injection drug user.

PubMed

Oh, Seunghee; Havlen, Pamela R; Hussain, Nasir

2005-10-01

Endocarditis is a serious complication of injection drug use most commonly caused by Staphylococcus aureus. We report a case of tricuspid valve polymicrobial bacterial endocarditis in an injection drug user from 3 oral anaerobes: Actinomyces odontolytica, Veillonella species, and Prevotella melaninogenica. The patient was believed to have acquired these organisms from his habit of licking the needle in order to gauge the strength of the cocaine prior to injection. The patient was successfully treated with a 6-week course of penicillin G and metronidazole. This case demonstrates the importance of a detailed history in designing empiric therapy.

A novel patchwork model used in lecture and laboratory to teach the three-dimensional organization of mesenteries.

PubMed

Noël, Geoffroy P J C

2013-01-01

Anatomy teaching is seeing a decline in both lecture and laboratory hours across many medical schools in North America. New strategies are therefore needed to not only make anatomy teaching more clinically integrated, but also to implement new interactive teaching techniques to help students more efficiently grasp the complex organization of the human body. Among the difficult anatomical concepts that students struggle to understand, the anatomy of the peritoneal cavity with its complex projections of peritoneum could benefit strongly from new learning aids. In this report, an innovative teaching tool is presented to engage students during both lecture and laboratory, and help them build three-dimensional (3D) mental maps of peritoneal cavity. The model consists of a patchwork of mesenteries and gut made from colored cloth stitched together onto a T-shirt to denote the origin and outflow of each peritoneum projection. As the lecturer wears the life-size model, the students can appreciate the 3D organization of the peritoneal cavity on a living body. In addition, the T-shirt model can be used in parallel with dissection to ensure a strong reinforcement of the spatial understanding of the peritoneal cavity. Copyright © 2012 American Association of Anatomists.

Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration.

PubMed

Chang, Jee Suk; Kim, Kyung Hwan; Keum, Ki Chang; Noh, Sung Hoon; Lim, Joon Seok; Kim, Hyo Song; Rha, Sun Young; Lee, Yong Chan; Hyung, Woo Jin; Koom, Woong Sub

2016-12-01

To classify patients with nonmetastatic advanced gastric cancer who underwent D2-gastrectomy into prognostic groups based on peritoneal and systemic recurrence risks. Between 2004 and 2007, 1,090 patients with T3-4 or N+ gastric cancer were identified from our registry. Recurrence rates were estimated using a competing-risk analysis. Different prognostic groups were defined using recursive partitioning analysis (RPA). Median follow-up was 7 years. In the RPA-model for peritoneal recurrence risk, the initial node was split by T stage, indicating that differences between patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were 34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact on high-risk patients. The RPA model for systemic relapse incorporated N stage alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year cumulative incidences were 7.7% and 24.5%, respectively. We proposed risk stratification models of peritoneal and systemic recurrence in patients undergoing D2-gastrectomy. This classification could be used for stratification protocols in future studies evaluating adjuvant therapies such as preoperative chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry)

PubMed Central

Nadeau-Fredette, Annie-Claire; Hawley, Carmel M.; Pascoe, Elaine M.; Chan, Christopher T.; Clayton, Philip A.; Polkinghorne, Kevan R.; Boudville, Neil; Leblanc, Martine

2015-01-01

Background and objectives Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. Design, setting, participants, & measurements This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile–stratified model, and propensity score–matched model. Results The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank P<0.001). Using multivariable Cox proportional hazards analysis, home hemodialysis was associated with superior patient survival (hazard ratio for overall death, 0.47; 95% confidence interval, 0.38 to 0.59) as well as better on-treatment survival (hazard ratio for on-treatment death, 0.34; 95% confidence interval, 0.26 to 0.45), composite patient and technique survival (hazard ratio for death or technique failure, 0.34; 95% confidence interval, 0.29 to 0.40), and death-censored technique survival (hazard ratio for technique failure, 0.34; 95% confidence interval, 0.28 to 0.41). Similar results were obtained with the propensity score models as well as sensitivity analyses using competing risks models and different definitions for technique failure and lag period after modality switch, during which events were attributed to the initial modality. Conclusions Home hemodialysis was associated with superior patient and technique survival compared with peritoneal dialysis. PMID:26068181

Photoimmunotherapy of Gastric Cancer Peritoneal Carcinomatosis in a Mouse Model

PubMed Central

Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p<0.0001 vs. control) and GFP fluorescence intensity (flank model: at day 3, PIT treated vs. control p<0.01 and peritoneal disseminated model: at day 3 PIT treated vs. control, p<0.05). Cytotoxic effects in vitro were shown to be dependent on the light dose and caused necrotic cell rupture leading to GFP release and a decrease in fluorescence intensity in vitro. Thus, loss of GFP fluorescence served as a useful biomarker of cell necrosis after PIT. PMID:25401794

A rat hysteropexy model for evaluating adhesion formation and comparison of two different structured meshes.

PubMed

Gokmen-Karasu, Ayse Filiz; Aydin, Serdar; Sonmez, Fatma Cavide; Adanir, Ilknur; Ilhan, Gulsah; Ates, Seda

2017-11-01

Peritonization of mesh during sacrohysteropexy is generally advocated to prevent adhesions to the viscera; however, randomized clinical trials are lacking, and peritonization may not be completely possible in a laparoscopic hysteropexy procedure. Our main objective was to describe a basic experimental rat sacrohysteropexy model. We hypothesized that even when peritoneal closure was omitted, using composite mesh would result in less adhesions to the viscera. Twenty in-bred female virgin Wistar Hannover rats were used in this study. Standardized hysteropexy procedure and adhesion model is described step by step with two different mesh materials: polypropylene and a composite polyester. Mesh was anchored between the posterior cervix and anterior longitudinal ligament of the lumbar vertebrae. Macroscopic adhesion scores and histopathological tissue reaction was investigated. Macroscopically, the surface area involved in adhesions was similar between groups. However, adhesions in the polypropylene group were more dense, required sharp dissection for lysis, and yielded higher total macroscopic adhesion scores (p < 0.001). Histologically, a more pronounced host inflammatory response was encountered in the polyester group (p < 0.001). We describe a rat hysteropexy model and a previously established uterine adhesion model. Adhesion scores in the composite mesh group were lower, and bowel involvement was not seen. Our findings are promising, and further research investigating antiadhesive composite mesh use for hysterosacropexy would be appropriate, especially when peritoneal closure is omitted.

Use of Peritoneal Dialysis in AKI: A Systematic Review

PubMed Central

Chionh, Chang Yin; Soni, Sachin S.; Finkelstein, Fredric O.; Ronco, Claudio

2013-01-01

Summary Background and objectives The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. Design, setting, participants, & measurements MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. Results Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I2=73%, P=0.03). Conclusions There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area. PMID:23833316

Inhibition of peritoneal dissemination of colon cancer by hyperthermic CO2 insufflation: A novel approach to prevent intraperitoneal tumor spread

PubMed Central

Zhou, Houming; Zheng, Minhua

2017-01-01

Background The increasing use of laparoscopic surgery for advanced gastrointestinal cancer raises concerns about intra-peritoneal tumor spread. Prevention of peritoneal dissemination is extremely important but a preventive modality is lacking. The aim of this study was to examine a novel approach (hyperthermic CO2 insufflation, HT-CO2) for preventing peritoneal dissemination during laparoscopic surgery. Methods A peritoneal dissemination model was established in Balb/c nu/nu mice by intraperitoneal injection of human colon cancer cells (SW1116, 1×106). The mice (n = 48) were subsequently randomized into two groups and subjected to hyperthermic CO2 (43°C, >95% humidity, HT-CO2 group) or standard normothermic CO2 (21°C, <1% relative humidity, NT-CO2 group) insufflation for 3 hours. The mice were sacrificed 28 days later. The peritoneal dissemination was quantitatively analyzed by counting and weighing the peritoneal nodules. The port sites and ascites volume were measured. The peritoneal damage of HT-CO2 was histologically examined with light microscopy and scanning electron microscopy. Intra-abdominal adhesions were evaluated 4 weeks later. Results The number of peritoneal nodules in the HT-CO2 group was significantly less than that in the NT-CO2 group (10.21±3.72 vs. 67.12±5.49, P<0.01). The mean weight of metastatic tumors in the HT-CO2 group was significantly lower than that in the NT-CO2 group (0.31±0.10g vs. 2.16±0.31g, P<0.01). Massive ascites were found in the NT-CO2 group while significantly less ascites developed in HT-CO2- treated mice (8.26±0.31ml vs. 1.27±0.28ml, P<0.01). No port-site metastases were detected in the HT-CO2 group while the incidence of the NT-CO2 group was 12.5% (3/24). HT-CO2 subjection resulted in slight peritoneal damage; the peritoneum returned to normal within five days. No adhesions formed after HT-CO2 treatment. Conclusions HT-CO2 can suppress peritoneal dissemination of colon cancer cells and only causes slight and transient peritoneal damage. HT-CO2 may serve as a promising adjuvant treatment for preventing peritoneal dissemination in laparoscopic resection of advanced colorectal cancer. PMID:28207849

Inhibition of peritoneal dissemination of colon cancer by hyperthermic CO2 insufflation: A novel approach to prevent intraperitoneal tumor spread.

PubMed

Peng, Yuanfei; Yang, Hua; Ye, Qing; Zhou, Houming; Zheng, Minhua; Shi, Yinghong

2017-01-01

The increasing use of laparoscopic surgery for advanced gastrointestinal cancer raises concerns about intra-peritoneal tumor spread. Prevention of peritoneal dissemination is extremely important but a preventive modality is lacking. The aim of this study was to examine a novel approach (hyperthermic CO2 insufflation, HT-CO2) for preventing peritoneal dissemination during laparoscopic surgery. A peritoneal dissemination model was established in Balb/c nu/nu mice by intraperitoneal injection of human colon cancer cells (SW1116, 1×106). The mice (n = 48) were subsequently randomized into two groups and subjected to hyperthermic CO2 (43°C, >95% humidity, HT-CO2 group) or standard normothermic CO2 (21°C, <1% relative humidity, NT-CO2 group) insufflation for 3 hours. The mice were sacrificed 28 days later. The peritoneal dissemination was quantitatively analyzed by counting and weighing the peritoneal nodules. The port sites and ascites volume were measured. The peritoneal damage of HT-CO2 was histologically examined with light microscopy and scanning electron microscopy. Intra-abdominal adhesions were evaluated 4 weeks later. The number of peritoneal nodules in the HT-CO2 group was significantly less than that in the NT-CO2 group (10.21±3.72 vs. 67.12±5.49, P<0.01). The mean weight of metastatic tumors in the HT-CO2 group was significantly lower than that in the NT-CO2 group (0.31±0.10g vs. 2.16±0.31g, P<0.01). Massive ascites were found in the NT-CO2 group while significantly less ascites developed in HT-CO2- treated mice (8.26±0.31ml vs. 1.27±0.28ml, P<0.01). No port-site metastases were detected in the HT-CO2 group while the incidence of the NT-CO2 group was 12.5% (3/24). HT-CO2 subjection resulted in slight peritoneal damage; the peritoneum returned to normal within five days. No adhesions formed after HT-CO2 treatment. HT-CO2 can suppress peritoneal dissemination of colon cancer cells and only causes slight and transient peritoneal damage. HT-CO2 may serve as a promising adjuvant treatment for preventing peritoneal dissemination in laparoscopic resection of advanced colorectal cancer.

Assessment of intensive care unit‐acquired weakness in young and old mice: An E. coli septic peritonitis model

PubMed Central

Hoogland, Inge C.M.; Wieske, Luuk; Weber, Nina C.; Verhamme, Camiel; Schultz, Marcus J.; van Schaik, Ivo N.; Horn, Janneke

2015-01-01

ABSTRACT Introduction: There are few reports of in vivo muscle strength measurements in animal models of ICU‐acquired weakness (ICU‐AW). In this study we investigated whether the Escherichia coli (E. coli) septic peritonitis mouse model may serve as an ICU‐AW model using in vivo strength measurements and myosin/actin assays, and whether development of ICU‐AW is age‐dependent in this model. Methods: Young and old mice were injected intraperitoneally with E. coli and treated with ceftriaxone. Forelimb grip strength was measured at multiple time points, and the myosin/actin ratio in muscle was determined. Results: E. coli administration was not associated with grip strength decrease, neither in young nor in old mice. In old mice, the myosin/actin ratio was lower in E. coli mice at t = 48 h and higher at t = 72 h compared with controls. Conclusions: This E. coli septic peritonitis mouse model did not induce decreased grip strength. In its current form, it seems unsuitable as a model for ICU‐AW. Muscle Nerve 53: 127–133, 2016 PMID:26015329

Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

PubMed Central

Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

2016-01-01

Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model. PMID:27807506

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer.

PubMed

Kanda, Mitsuro; Shimizu, Dai; Tanaka, Haruyoshi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Iwata, Naoki; Niwa, Yukiko; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-03-01

To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.

Plexin-A4–semaphorin 3A signaling is required for Toll-like receptor– and sepsis-induced cytokine storm

PubMed Central

Wen, Haitao; Lei, Yu; Eun, So-Young

2010-01-01

Plexins and semaphorins are ligand–receptor pairs that serve as guidance molecules in the nervous system and play some roles in immunity. Plexins are similar to the Toll-like receptors (TLRs) in their evolutionary conservation from flies to mammals. By studying plexin-A4–deficient (Plxna4−/−) innate immune cells, in this study we show a novel influence of plexin-A4 on TLR signaling. Plxna4−/− cells exhibit defective inflammatory cytokine production upon activation by a spectrum of TLR agonists and bacteria. Plexin-A4 is required for TLR-induced activation of the small guanosine triphosphate hydrolase (GTPase) Rac1 (ras-related C3 botulinum toxin substrate 1). Rac1 activation is accompanied by JNK (c-Jun N-terminal kinase) and NF-κB activation, culminating in TLR-induced binding of NF-κB and AP-1 to the promoters of inflammatory cytokines. Plxna4−/− mice are remarkably resistant to TLR agonist–induced inflammation and polymicrobial peritonitis caused by cecal ligation and puncture. Administration of a ligand of plexin-A4, Sema3A (semaphorin 3A), exacerbates the cytokine storm caused by TLR agonists and bacterial sepsis. TLR engagement can induce Sema3A expression, thus completing an autocrine loop. These findings expand the role of plexins to TLR signaling and suggest plexin-A4 and Sema3A as new intervention points for treating sepsis. PMID:21098092

The impact of neutral-pH peritoneal dialysates with reduced glucose degradation products on clinical outcomes in peritoneal dialysis patients.

PubMed

Cho, Yeoungjee; Johnson, David W; Badve, Sunil V; Craig, Jonathan C; Strippoli, Giovanni F M; Wiggins, Kathryn J

2013-11-01

Neutral-pH peritoneal dialysates, with reduced glucose degradation products (GDPs), have been developed to reduce peritoneal membrane damage. Here our review evaluated the impact of these solutions on clinical outcomes using data from The Cochrane CENTRAL Registry, MEDLINE, Embase, and reference lists for randomized trials of biocompatible solutions. Summary estimates of effect were obtained using a random-effects model of 20 eligible trials encompassing 1383 patients. The quality of studies was generally poor, such that 13 studies had greater than a 20% loss to follow-up and only 3 trials reported adequate concealment of allocation. Use of neutral-pH dialysates with reduced GDPs resulted in larger urine volumes (7 trials; 520 patients; mean difference 126 ml/day, 95% CI 27-226), improved residual renal function after 12 months (6 trials; 360 patients; standardized mean difference 0.31, 95% confidence interval 0.10-0.52), and a trend to reduced inflow pain (1 trial; 58 patients; relative risk 0.51, 95% CI 0.24-1.08). However, there was no significant effect on body weight, hospitalization, peritoneal solute transport rate, peritoneal small-solute clearance, peritonitis, technique failure, patient survival, or adverse events. No significant harms were identified. Thus, based on generally poor quality trials, the use of neutral-pH peritoneal dialysates with reduced GDPs resulted in greater urine volumes and residual renal function after 12 months, but without other clinical benefits. Larger, better-quality studies are needed for accurate evaluation of the impact of these newer dialysates on patient-level hard outcomes.

Cardiovascular Performance with E. coli Challenges in a Canine Model of Human Sepsis

DTIC Science & Technology

1988-01-01

most severe peritonitis with volume loading. However, in response to volume, the the largest third space fluid loss (i.e., such animals should...in ESVI represent a greater third space loss from peritoneal in- in infected dogs, i.e., a decrease in contractility. Further- flammation and/or a

CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

PubMed

Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L

2017-01-01

Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

A Case of Polymicrobial Endocarditis due to Anaerobic Organisms in an Injection Drug User

PubMed Central

Oh, Seunghee; Havlen, Pamela R; Hussain, Nasir

2005-01-01

Endocarditis is a serious complication of injection drug use most commonly due to Staphylococcus aureus. We report a case of tricuspid valve polymicrobial bacterial endocarditis in an injection drug user from 3 oral anaerobes: Actinomyces odontolytica, Veillonella species, and Prevotella melaninogenica. The patient was believed to have acquired these organisms due to his habit of licking the needle in order to gauge the strength of the cocaine prior to injection. The patient was successfully treated with a 6-week course of penicillin G and metronidazole. This case demonstrates the importance of a detailed history in designing empiric therapy. PMID:16191149

The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds

PubMed Central

Duplantier, Allen J.; van Hoek, Monique L.

2013-01-01

Diabetic patients often have ulcers on their lower-limbs that are infected by multiple biofilm-forming genera of bacteria, and the elimination of the biofilm has proven highly successful in resolving such wounds in patients. To that end, antimicrobial peptides have shown potential as a new anti-biofilm approach. The single human cathelicidin peptide LL-37 has been shown to have antimicrobial and anti-biofilm activity against multiple Gram-positive and Gram-negative human pathogens, and have wound-healing effects on the host. The combination of the anti-biofilm effect and wound-healing properties of LL-37 may make it highly effective in resolving polymicrobially infected wounds when topically applied. Such a peptide or its derivatives could be a platform from which to develop new therapeutic strategies to treat biofilm-mediated infections of wounds. This review summarizes known mechanisms that regulate the endogenous levels of LL-37 and discusses the anti-biofilm, antibacterial, and immunological effects of deficient vs. excessive concentrations of LL-37 within the wound environment. Here, we review recent advances in understanding the therapeutic potential of this peptide and other clinically advanced peptides as a potential topical treatment for polymicrobial infected wounds. PMID:23840194

Primary bacterial peritonitis in dogs and cats: 24 cases (1990-2006).

PubMed

Culp, William T N; Zeldis, Tracy E; Reese, Michael S; Drobatz, Kenneth J

2009-04-01

To determine clinical characteristics of primary bacterial peritonitis (infection of the peritoneal cavity with no identifiable intraperitoneal source of infection) and compare characteristics of primary and secondary peritonitis in dogs and cats. Retrospective case series. 24 (primary peritonitis) and 60 (secondary peritonitis) client-owned dogs and cats. Data from medical records of dogs and cats with primary and secondary peritonitis were reviewed for descriptive information regarding primary peritonitis and for comparison between the 2 forms of peritonitis. 15 dogs and 9 cats met inclusion criteria for primary peritonitis, and 49 dogs and 11 cats met inclusion criteria for secondary peritonitis. The most common historical findings in dogs and cats with primary and secondary peritonitis were lethargy, vomiting, and anorexia. Dogs with secondary peritonitis more often developed peritoneal exudates than those with primary peritonitis, and dogs with primary peritonitis were more often infected with gram-positive bacteria than those with secondary peritonitis. No difference in outcome was detected between all animals with primary versus secondary peritonitis; however, dogs with secondary peritonitis treated with surgery were more commonly discharged than those with primary peritonitis treated with surgery. Differences in primary and secondary peritonitis related to historical, physical examination, and clinical laboratory findings; bacteriologic findings; peritoneal effusion characteristics; and outcome were detected. However, larger case numbers are needed before alternative recommendations, such as avoidance of surgery, can be made.

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

PubMed Central

Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

2018-01-01

ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of trained innate immunity. PMID:29339423

Molecular Determinants of the Thickened Matrix in a Dual-Species Pseudomonas aeruginosa and Enterococcus faecalis Biofilm

PubMed Central

Lee, Keehoon; Lee, Kang-Mu; Kim, Donggeun

2017-01-01

ABSTRACT Biofilms are microbial communities that inhabit various surfaces and are surrounded by extracellular matrices (ECMs). Clinical microbiologists have shown that the majority of chronic infections are caused by biofilms, following the introduction of the first biofilm infection model by J. W. Costerton and colleagues (J. Lam, R. Chan, K. Lam, and J. W. Costerton, Infect Immun 28:546–556, 1980). However, treatments for chronic biofilm infections are still limited to surgical removal of the infected sites. Pseudomonas aeruginosa and Enterococcus faecalis are two frequently identified bacterial species in biofilm infections; nevertheless, the interactions between these two species, especially during biofilm growth, are not clearly understood. In this study, we observed phenotypic changes in a dual-species biofilm of P. aeruginosa and E. faecalis, including a dramatic increase in biofilm matrix thickness. For clear elucidation of the spatial distribution of the dual-species biofilm, P. aeruginosa and E. faecalis were labeled with red and green fluorescence, respectively. E. faecalis was located at the lower part of the dual-species biofilm, while P. aeruginosa developed a structured biofilm on the upper part. Mutants with altered exopolysaccharide (EPS) productions were constructed in order to determine the molecular basis for the synergistic effect of the dual-species biofilm. Increased biofilm matrix thickness was associated with EPSs, not extracellular DNA. In particular, Pel and Psl contributed to interspecies and intraspecies interactions, respectively, in the dual-species P. aeruginosa and E. faecalis biofilm. Accordingly, targeting Pel and Psl might be an effective part of eradicating P. aeruginosa polymicrobial biofilms. IMPORTANCE Chronic infection is a serious problem in the medical field. Scientists have observed that chronic infections are closely associated with biofilms, and the vast majority of infection-causing biofilms are polymicrobial. Many studies have reported that microbes in polymicrobial biofilms interact with each other and that the bacterial interactions result in elevated virulence, in terms of factors, such as infectivity and antibiotic resistance. Pseudomonas aeruginosa and Enterococcus faecalis are frequently isolated pathogens in chronic biofilm infections. Nevertheless, while both bacteria are known to be agents of numerous nosocomial infections and can cause serious diseases, interactions between the bacteria in biofilms have rarely been examined. In this investigation, we aimed to characterize P. aeruginosa and E. faecalis dual-species biofilms and to determine the molecular factors that cause synergistic effects, especially on the matrix thickening of the biofilm. We suspect that our findings will contribute to the development of more efficient methods for eradicating polymicrobial biofilm infections. PMID:28842537

Molecular Determinants of the Thickened Matrix in a Dual-Species Pseudomonas aeruginosa and Enterococcus faecalis Biofilm.

PubMed

Lee, Keehoon; Lee, Kang-Mu; Kim, Donggeun; Yoon, Sang Sun

2017-11-01

Biofilms are microbial communities that inhabit various surfaces and are surrounded by extracellular matrices (ECMs). Clinical microbiologists have shown that the majority of chronic infections are caused by biofilms, following the introduction of the first biofilm infection model by J. W. Costerton and colleagues (J. Lam, R. Chan, K. Lam, and J. W. Costerton, Infect Immun 28:546-556, 1980). However, treatments for chronic biofilm infections are still limited to surgical removal of the infected sites. Pseudomonas aeruginosa and Enterococcus faecalis are two frequently identified bacterial species in biofilm infections; nevertheless, the interactions between these two species, especially during biofilm growth, are not clearly understood. In this study, we observed phenotypic changes in a dual-species biofilm of P. aeruginosa and E. faecalis , including a dramatic increase in biofilm matrix thickness. For clear elucidation of the spatial distribution of the dual-species biofilm, P. aeruginosa and E. faecalis were labeled with red and green fluorescence, respectively. E. faecalis was located at the lower part of the dual-species biofilm, while P. aeruginosa developed a structured biofilm on the upper part. Mutants with altered exopolysaccharide (EPS) productions were constructed in order to determine the molecular basis for the synergistic effect of the dual-species biofilm. Increased biofilm matrix thickness was associated with EPSs, not extracellular DNA. In particular, Pel and Psl contributed to interspecies and intraspecies interactions, respectively, in the dual-species P. aeruginosa and E. faecalis biofilm. Accordingly, targeting Pel and Psl might be an effective part of eradicating P. aeruginosa polymicrobial biofilms. IMPORTANCE Chronic infection is a serious problem in the medical field. Scientists have observed that chronic infections are closely associated with biofilms, and the vast majority of infection-causing biofilms are polymicrobial. Many studies have reported that microbes in polymicrobial biofilms interact with each other and that the bacterial interactions result in elevated virulence, in terms of factors, such as infectivity and antibiotic resistance. Pseudomonas aeruginosa and Enterococcus faecalis are frequently isolated pathogens in chronic biofilm infections. Nevertheless, while both bacteria are known to be agents of numerous nosocomial infections and can cause serious diseases, interactions between the bacteria in biofilms have rarely been examined. In this investigation, we aimed to characterize P. aeruginosa and E. faecalis dual-species biofilms and to determine the molecular factors that cause synergistic effects, especially on the matrix thickening of the biofilm. We suspect that our findings will contribute to the development of more efficient methods for eradicating polymicrobial biofilm infections. Copyright © 2017 American Society for Microbiology.

Peritoneal fluid transport in CAPD patients with different transport rates of small solutes.

PubMed

Sobiecka, Danuta; Waniewski, Jacek; Weryński, Andrzej; Lindholm, Bengt

2004-01-01

Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

The influences of a novel anti-adhesion device, thermally cross-linked gelatin film on peritoneal dissemination of tumor cells: The in vitro and in vivo experiments using murine carcinomatous peritonitis models.

PubMed

Miyamoto, Hiroe; Tsujimoto, Hiroyuki; Horii, Tsunehito; Ozamoto, Yuki; Ueda, Joe; Takagi, Toshitaka; Saitoh, Naoto; Hagiwara, Akeo

2017-10-10

To create anti-adhesive materials to be more effective and safer, we developed a thermally cross-linked gelatin film that showed superior anti-adhesive effects with excellent peritoneal regeneration. However, it may act as a convenient scaffold for tumor cell growth, thereby accelerating peritoneal dissemination when used in surgery for abdominal tumors. In this study, we tried to clarify this issue using mouse carcinomatous peritonitis models. First, we examined the in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell growth on each film was significantly lower than that of the control (no film). Next, we conducted the following in vivo experiments: After the parietal peritoneum was partially removed and covered with each film or without any film, mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells expressing NanoLuc luciferase gene. At 7 days after the operation, we measured the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells using in vivo imaging at the injured sites. There were no significant differences in the weight of the tumors and the NanoLuc activity among the three groups. We also observed the survival time of mice receiving the same operation and treatments. There was no significant difference in the survival time among the three groups. These results suggest that the gelatin film will likely not accelerate peritoneal dissemination as a convenient scaffold for tumor cell growth when used in surgery for abdominal tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

A comparison of the biocompatibility of phosphate-buffered saline and dianeal 3.86% in the rat model of peritoneal dialysis.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Breborowicz, A; Oreopoulos, D G

2001-01-01

Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can be considered an example of a biocompatible dialysis fluid. This study compared the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the rat. In an acute experiment, after catheter implantation, rats were infused on day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on day 7 again with PBS. When rats were injected with Dianeal 3.86%, the inflammatory reaction was suppressed as compared with PBS. The cell count was lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower (p < 0.01). In a chronic experiment, after catheter implantation, rats were dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a semiquantitative scale, macroscopic changes in the peritoneum were more severe in rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/- 2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both groups; but, in PBS-treated rats, the peritoneal interstitium contained more inflammatory cells and more new vessels. During the 1-hour PET, peritoneal permeability to water and solutes was comparable in the two groups. Despite a more physiologic composition, PBS is a less biocompatible peritoneal dialysis solutions than is standard, acidic, hypertonic dialysis solution.

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis

PubMed Central

Liappas, Georgios; González-Mateo, Guadalupe Tirma; Sánchez-Díaz, Raquel; Lazcano, Juan José; Lasarte, Sandra; Matesanz-Marín, Adela; Zur, Rafal; Ferrantelli, Evelina; Ramírez, Laura García; Aguilera, Abelardo; Fernández-Ruiz, Elena; Beelen, Robert H.J.; Selgas, Rafael; Sánchez-Madrid, Francisco

2016-01-01

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation. PMID:27151919

Peritoneal dialysis-related peritonitis: challenges and solutions

PubMed Central

Salzer, William L

2018-01-01

Peritoneal dialysis is an effective treatment modality for patients with end-stage renal disease. The relative use of peritoneal dialysis versus hemodialysis varies widely by country. Data from a 2004 survey reports the percentage of patients with end-stage renal disease treated with peritoneal dialysis to be 5%–10% in economically developed regions like the US and Western Europe to as much as 75% in Mexico. This disparity is probably related to the availability and access to hemodialysis, or in some cases patient preference for peritoneal over hemodialysis. Peritoneal dialysis-related peritonitis remains the major complication and primary challenge to the long-term success of peritoneal dialysis. Fifty years ago, with the advent of the Tenckhoff catheter, patients averaged six episodes of peritonitis per year on peritoneal dialysis. In 2016, the International Society for Peritoneal Dialysis proposed a benchmark of 0.5 episodes of peritonitis per year or one episode every 2 years. Despite the marked reduction in peritonitis over time, peritonitis for the individual patient is problematic. The mortality for an episode of peritonitis is 5% and is a cofactor for mortality in another 16% of affected patients. Prevention of peritonitis and prompt and appropriate management of peritonitis is essential for the long-term success of peritoneal dialysis in all patients. In this review, challenges and solutions are addressed regarding the pathogenesis, clinical features, diagnosis, treatment, and prevention of peritoneal dialysis-related peritonitis from the viewpoint of an infectious disease physician.

Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells.

PubMed

Pène, Frédéric; Courtine, Emilie; Ouaaz, Fatah; Zuber, Benjamin; Sauneuf, Bertrand; Sirgo, Gonzalo; Rousseau, Christophe; Toubiana, Julie; Balloy, Viviane; Chignard, Michel; Mira, Jean-Paul; Chiche, Jean-Daniel

2009-12-01

Depletion of dendritic cells (DC) in secondary lymphoid organs is a hallmark of sepsis-induced immune dysfunction. In this setting, we investigated if Toll-like receptor (TLR)-dependent signaling might modulate the maturation process and the survival of DC. Using a model of sublethal polymicrobial sepsis induced by cecal ligation and puncture, we investigated the quantitative and functional features of spleen DC in wild-type, TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. By 24 h, a decrease in the relative percentage of CD11c(high) spleen DC occurred in wild-type mice but was prevented in TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. In wild-type mice, sepsis dramatically affected both CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) subsets. In all three types of knockout mice studied, the CD11c(+) CD8alpha(+) subset followed a depletion pattern similar to that for wild-type mice. In contrast, the loss of CD11c(+) CD8alpha(-) cells was attenuated in TLR2(-/-) and TLR4(-/-) mice and completely prevented in TLR2(-/-) TLR4(-/-) mice. Accordingly, apoptosis of spleen DC was increased in septic wild-type mice and inhibited in knockout mice. In addition we characterized the functional features of spleen DC obtained from septic mice. As shown by increased expression of major histocompatibility complex class II and CD86, polymicrobial sepsis induced maturation of DC, with subsequent increased capacity to prime T lymphocytes, similarly in wild-type and knockout mice. In response to CpG DNA stimulation, production of interleukin-12 was equally impaired in DC obtained from wild-type and knockout septic mice. In conclusion, although dispensable for the DC maturation process, TLR2 and TLR4 are involved in the mechanisms leading to depletion of spleen DC following polymicrobial sepsis.

Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

PubMed

Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

2009-09-01

Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.

Differential activation of peritoneal cells by subcutaneous treatment of rats with cryptococcal antigens.

PubMed

Baronetti, José L; Chiapello, Laura S; Garro, Ana P; Masih, Diana T

2009-08-01

Previous studies in our laboratory have shown that the subcutaneous pretreatment of rats with heat-killed cells (HKC) of Cryptococcus neoformans emulsified in complete Freund adjuvant (CFA) promotes protective immunity against an intraperitoneal challenge with C. neoformans. In contrast, subcutaneous treatment with the capsular polysaccharide (PSC) emulsified in CFA exacerbates the cryptococcal infection. The purpose of this study was to analyze the mechanisms involved in these phenomena. Adherent peritoneal cells from rats treated with HKC-CFA showed upregulated ED2, CD80, and CD86 expression; an increase in the level of production of anticryptococcal metabolites; and the enhanced production of interleukin-12 (IL-12) in comparison with the findings for cells from rats treated with CFA-phosphate-buffered saline (PBS). Adherent peritoneal cells from rats treated with PSC-CFA, however, also presented upregulated ED2, CD80, and CD86 expression compared to the level of expression for peritoneal cells from controls, but these cells showed an increase in arginase activity and decreased levels of production of IL-12 and tumor necrosis factor (TNF) compared with the activity and levels of production by peritoneal cells from CFA-PBS-treated rats. In addition, treatment with HKC-CFA resulted in a rise in the phagocytic and anticryptococcal activities of adherent peritoneal cells compared to those for control rats. However, adherent peritoneal cells from rats treated with PSC-CFA presented a reduction in anticryptococcal activity in comparison with that for cells from animals treated with CFA-PBS. These results show the differential activation between adherent peritoneal cells from HKC-CFA- and PSC-CFA-treated rats, with this differential activation at the primary site of infection possibly being responsible, at least in part, for the phenomena of protection and exacerbation observed in our model.

Peritonitis - spontaneous bacterial

MedlinePlus

Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

Predictors of baseline peritoneal transport status in Australian and New Zealand peritoneal dialysis patients.

PubMed

Rumpsfeld, Markus; McDonald, Stephen P; Purdie, David M; Collins, John; Johnson, David W

2004-03-01

Factors that predict peritoneal transport status in peritoneal dialysis (PD) patients are poorly understood. The aim of the present study is to determine these factors in Australian and New Zealand incident PD patients. The study included all patients on the Australian and New Zealand Dialysis and Transplant Registry who started PD therapy between April 1, 1991, and March 31, 2002, and underwent a peritoneal equilibration test (PET) within the first 6 months. Predictors of peritoneal transport category and dialysate-plasma creatinine ratio at 4 hours (D-P Cr 4h) were assessed by multivariate ordinal logistic regression and multiple linear regression, respectively. A total of 3,188 patients were studied. Mean D-P Cr 4h was 0.69 +/- 0.13. High transport status was associated with older age (adjusted odds ratio [OR], 1.08 for each 10 years; 95% confidence interval [CI], 1.03 to 1.13), Maori and Pacific Islander racial origin (OR, 1.48; 95% CI, 1.13 to 1.94), and normal body mass index (BMI; < 18.5 kg/m2: OR, 0.90; 95% CI, 0.65 to 1.24; BMI of 18.5 to 25 kg/m2: OR, 1 [reference]; BMI of 25 to 30 kg/m2: OR, 0.81; 95% CI, 0.70 to 0.95; BMI > 30 kg/m2: OR, 0.71; 95% CI, 0.58 to 0.86), but was not independently predicted by sex, diabetes, other comorbid diseases, smoking, previous hemodialysis therapy or transplantation, or residual renal function. Similar results were found when peritoneal permeability was modeled as a continuous variable (D-P Cr 4h). In Australian and New Zealand PD patients, higher peritoneal transport status is independently associated with racial origin, older age, and lower BMI. The diversity of peritoneal transport characteristics in different ethnic populations suggests that additional validation of PET measurements in various racial groups and study of their relationship to patient outcomes are warranted.

The time for surgery of peritonitis associated with peritoneal dialysis.

PubMed

Mihalache, O; Bugă, C; Doran, H; Catrina, E; Bobircă, F; Andreescu, A; Mustățea, P; Pătrașcu, T

2016-01-01

Peritonitis is the main complication of peritoneal dialysis (PD) and also an important factor for raising the cost of the method to the level of hemodialysis. Associated with PD, peritonitis is responsible for the increase of morbidity and mortality of the procedure and, at the same time, the main cause of the technique failure. Severe and prolonged peritonitis or repeated episodes of peritonitis lead to ultrafiltration failure. Peritonitis treatment should aim for a rapid remission of inflammation in order to preserve the peritoneal membrane functional integrity. The treatment of PD peritonitis consists mainly of antibiotic therapy, surgical intervention not being usually required. However, it is of outmost importance to differentiate the so-called "catheter related" peritonitis from secondary peritonitis due to visceral lesions, in which the surgical treatment comes first. The confusion between secondary and "catheter related" peritonitis may lead to serious errors in choosing the correct treatment, endangering the patient's life. The differential diagnosis between a refractory or secondary peritonitis in a peritoneal dialyzed patient may be very difficult. In front of a refractory PD peritonitis, surgical exploration must not be delayed. Also we have to keep in mind that the aim of peritonitis treatment is the saving of the peritoneal membrane and not the catheter.

Amelioration of ischemic brain damage by peritoneal dialysis

PubMed Central

Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-01-01

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

European Training and Research in Peritoneal Dialysis--A Network to Deliver Scientific Peritoneal Dialysis Training to a New Generation of Researchers.

PubMed

Machowska, Anna; van Wier, Tanja; Aufricht, Christoph; Beelen, Rob; Rutherford, Peter

2015-01-01

Peritoneal dialysis (PD) utilization varies across countries, and of the factors that explain the variation, the scientific and clinical knowledge of health care professionals is potentially important. In this paper, we describe a European collaboration--between 8 academic PD research programs, a small-to-medium-sized enterprise, and a large PD product manufacturer--that received significant research funding from the EU commission to establish a training network. European Training and Research in Peritoneal Dialysis (EuTRiPD) is providing training to 12 PhD students who have moved within the European Union and are completing research training. The underlying structure and processes within EuTRiPD (http://www.eutripd. eu) are described, and the benefits of the collaborative approach are discussed. This model could be useful to other research groups and will assist in maintaining and growing scientific expertise in PD research.

Mueller-matrix of laser-induced autofluorescence of polycrystalline films of dried peritoneal fluid in diagnostics of endometriosis

NASA Astrophysics Data System (ADS)

Ushenko, Yuriy A.; Koval, Galina D.; Ushenko, Alexander G.; Dubolazov, Olexander V.; Ushenko, Vladimir A.; Novakovskaia, Olga Yu.

2016-07-01

This research presents investigation results of the diagnostic efficiency of an azimuthally stable Mueller-matrix method of analysis of laser autofluorescence of polycrystalline films of dried uterine cavity peritoneal fluid. A model of the generalized optical anisotropy of films of dried peritoneal fluid is proposed in order to define the processes of laser autofluorescence. The influence of complex mechanisms of both phase (linear and circular birefringence) and amplitude (linear and circular dichroism) anisotropies is taken into consideration. The interconnections between the azimuthally stable Mueller-matrix elements characterizing laser autofluorescence and different mechanisms of optical anisotropy are determined. The statistical analysis of coordinate distributions of such Mueller-matrix rotation invariants is proposed. Thereupon the quantitative criteria (statistic moments of the first to the fourth order) of differentiation of polycrystalline films of dried peritoneal fluid, group 1 (healthy donors) and group 2 (uterus endometriosis patients), are determined.

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

PubMed Central

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

Preclinical activity of melflufen (J1) in ovarian cancer.

PubMed

Carlier, Charlotte; Strese, Sara; Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P; Gullbo, Joachim

2016-09-13

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Preclinical activity of melflufen (J1) in ovarian cancer

PubMed Central

Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P.; Gullbo, Joachim

2016-01-01

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration. PMID:27528037

Perioperative Systemic Therapy and Surgery Versus Surgery Alone for Resectable Colorectal Peritoneal Metastases.

ClinicalTrials.gov

2017-05-05

Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer Metastatic; Peritoneal Carcinoma; Peritoneal Neoplasms; Peritoneal Cavity Cancer; Peritoneal Carcinomatosis; Peritoneal Metastases

Pathophysiological Changes to the Peritoneal Membrane during PD-Related Peritonitis: The Role of Mesothelial Cells

PubMed Central

Yung, Susan; Chan, Tak Mao

2012-01-01

The success of peritoneal dialysis (PD) is dependent on the structural and functional integrity of the peritoneal membrane. The mesothelium lines the peritoneal membrane and is the first line of defense against chemical and/or bacterial insult. Peritonitis remains a major complication of PD and is a predominant cause of technique failure, morbidity and mortality amongst PD patients. With appropriate antibiotic treatment, peritonitis resolves without further complications, but in some PD patients excessive peritoneal inflammatory responses lead to mesothelial cell exfoliation and thickening of the submesothelium, resulting in peritoneal fibrosis and sclerosis. The detrimental changes in the peritoneal membrane structure and function correlate with the number and severity of peritonitis episodes and the need for catheter removal. There is evidence that despite clinical resolution of peritonitis, increased levels of inflammatory and fibrotic mediators may persist in the peritoneal cavity, signifying persistent injury to the mesothelial cells. This review will describe the structural and functional changes that occur in the peritoneal membrane during peritonitis and how mesothelial cells contribute to these changes and respond to infection. The latter part of the review discusses the potential of mesothelial cell transplantation and genetic manipulation in the preservation of the peritoneal membrane. PMID:22577250

Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.

PubMed

Combet, S; Ferrier, M L; Van Landschoot, M; Stoenoiu, M; Moulin, P; Miyata, T; Lameire, N; Devuyst, O

2001-10-01

Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.

Differences in survival on peritoneal dialysis between oriental Asians and Caucasians: one center's experience.

PubMed

Wang, Tao; Tziviskou, Effie; Chu, Maggie; Bargman, Joanne; Jassal, Vanita; Vas, Stephen; Oreopoulos, Dimitrios G

2003-01-01

Recently it has been suggested that the survival of dialysis patients may differ among different races. Both registry data and data from Asian countries indicates that Asians on peritoneal dialysis may survive longer than their Caucasian counterparts. In the present study, we performed a detailed analysis of survival differences between oriental Asians and Caucasians on peritoneal dialysis in our multiethnic, multicultural program. Retrospectively we analyzed the survival data for patients who started peritoneal dialysis after January 1, 1996 and before December 31, 1999, in our hospital. They were followed for at least for two years. Excluded from the present analysis were those who survived for less than three months on peritoneal dialysis. The patient demographic characteristics, comorbidities, and residual renal function at the start of dialysis were collected. Indices for adequacy of dialysis were collected 1-3 months after the initiation of dialysis. Actuarial survival rates were determined by the Kaplan-Meier method. The Cox proportional hazards model was used to classify risk factors for a high mortality. There were 87 Caucasians and 29 Oriental Asian peritoneal dialysis patients. No differences were found in age, gender, primary renal disease, and residual renal function between the two groups. The Caucasians had significantly higher body surface area and urea volume and higher incidence of cardiovascular diseases. Even with slightly higher dialysis dose, the peritoneal creatinine clearance was significantly lower among the Caucasians than among Asians. There was no difference in the peritoneal D/P value between the two groups. However, compared to the Caucasians, the 24hr peritoneal fluid removal and total fluid removal volumes were significantly lower in the Asian patients. The one, two, three and four year survival rates were 95.8%, 91%, 86% and 80% for Asians and 91.3%, 78.1%, 64.7% and 54.1% for Caucasians. Significant predictors for a higher mortality were the presence of cardiovascular disease (42% increase in risk), Caucasians (39% increase in risk) and older age (37% increase in risk for age older than 65). Our study confirms that oriental Asians on peritoneal dialysis patients survive much longer than their Caucasian counterparts; this was partly due to the fact that Asian patients have less cardiovascular disease when they began peritoneal dialysis. Due to their smaller body size, the Asians tended to have a higher peritoneal small solute clearances despite their smaller dialysis doses, indicating that, to achieve the same solute clearance targets, Asians need a smaller dialysis dose compared to Caucasians.

Microbial keratitis following vegetative matter injury.

PubMed

Taneja, Mukesh; Ashar, Jatin N; Mathur, Anurag; Nalamada, Suma; Garg, Prashant

2013-04-01

The purpose of the present study was to analyze the microbiological profile of cases of keratitis following trauma with vegetative matter in a tertiary care center. A retrospective review of the medical records of 49 patients with keratitis following vegetative matter injury over a 3-month period was performed. All patients underwent corneal scraping for smears and inoculation onto various culture media. The microbiological profile was based on the smear and culture reports. For patients who were culture-negative, outcome after standard empirical antibacterial therapy as per hospital protocol was analyzed. Thirteen patients with corneal ulcers had fungal etiology, eight had bacterial etiology, and two had protozoal etiology, while 13 patients were polymicrobial and 13 were culture-negative. Polymicrobial infections were mainly bacterial (eight cases), and the remaining five cases had coexistent fungal and bacterial etiology. The treatment was directed to the specific organism and patients improved with medical or surgical therapy. Only a third of culture-negative cases showed fungal etiology on biopsy or histopathology after keratoplasty while a third showed improvement with therapy. Corneal infections following vegetative matter trauma show a varied etiological profile; however, bacterial and polymicrobial infections are more prevalent. Empirical anti-fungal therapy, as commonly practiced, must be avoided in cases with vegetative matter injury.

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

PubMed

Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

2016-01-01

The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Peritoneal dialysis: from bench to bedside and bedside to bench.

PubMed

Perl, Jeffrey; Bargman, Joanne M

2016-11-01

For patients with end-stage kidney disease unable to receive a kidney transplant, replacement of kidney function with dialysis is necessary to extend life. Peritoneal dialysis (PD) and hemodialysis (HD) are the two major forms of dialysis therapy. HD involves the passage of blood via an extracorporeal circuit whereby removal of small solutes, toxins, and water is achieved across a synthetic, semipermeable dialysis membrane. In contrast, in PD, the dialysis membrane is the highly vascularized internal lining of the peritoneal cavity. Intraperitoneal installation of hypertonic high glucose PD solution creates a transmembrane osmotic and diffusive gradient that facilitates water removal [ultrafiltration (UF)], convection, and diffusion of uremic toxins. Insight into the physiology of solute and water transport across the peritoneal membrane has been enhanced by the proposal of the ''three-pore model'' of peritoneal membrane transport. Transport characteristics and UF capacity of the peritoneal membrane vary among individuals, and deleterious changes in the membrane may ensue over time. The degree to which these changes are a direct consequence of the type and composition of currently available PD solutions, recurrent infectious episodes, genetic differences among individuals, or a combination thereof is the subject of intense study. Adverse consequences resulting from the systemic and local metabolic effects of intraperitoneal glucose exposure, infection of the PD fluid, PD catheter dysfunction, and patient burnout from self-care often limit the long-term success of the therapy. Research aimed at addressing these challenges will examine the use of more biocompatible PD solutions and strategies aimed at attenuating progressive peritoneal membrane injury. Copyright © 2016 the American Physiological Society.

Relationship of IgG, C3 and transferrin with opsonising and bacteriostatic activity of peritoneal fluid from CAPD patients and the incidence of peritonitis.

PubMed

McGregor, S J; Brock, J H; Briggs, J D; Junor, B J

1987-01-01

IgG, C3 and transferrin in peritoneal dialysis effluent of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were 1%-2% of those in serum. In contrast, the values in normal peritoneal fluid were not significantly different from those in serum. The three proteins correlated with each other in peritoneal dialysis effluent, but were independent of the amount in the corresponding patients' sera. There was also an overall inverse correlation between total protein in peritoneal dialysis effluent and time on CAPD during the first 6 months of treatment but not thereafter, which suggests that changes in membrane permeability occur during the early months. In peritoneal dialysis effluent, but not in normal peritoneal fluid, there was a correlation between opsonising capacity and IgG or C3 concentrations. An inverse correlation between opsonic activity of peritoneal dialysis effluent and frequency of peritonitis was also found. Peritoneal dialysis effluent permitted significantly faster multiplication of Staphylococcus epidermidis than sera or normal peritoneal fluid, and the growth rate correlated inversely with the transferrin levels in peritoneal dialysis effluent. Overall IgG, C3 and transferrin in peritoneal dialysis effluent are inadequate for optimal opsonising and bacteriostatic activity, and the peritoneal cavities of CAPD patients are therefore immunocompromised sites.

RhoA/Rho-kinase triggers epithelial-mesenchymal transition in mesothelial cells and contributes to the pathogenesis of dialysis-related peritoneal fibrosis

PubMed Central

Wang, Qinglian; Yang, Xiaowei; Xu, Ying; Shen, Zhenwei; Cheng, Hongxia; Cheng, Fajuan; Liu, Xiang; Wang, Rong

2018-01-01

Peritoneal fibrosis (PF) with associated peritoneal dysfunction is almost invariably observed in long-term peritoneal dialysis (PD) patients. Advanced glycation end products (AGEs) are pro-oxidant compounds produced in excess during the metabolism of glucose and are present in high levels in standard PD solutions. The GTPase RhoA has been implicated in PF, but its specific role remains poorly understood. Here, we studied the effects of RhoA/Rho-kinase signaling in AGEs-induced epithelial-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs), and evaluated morphological and molecular changes in a rat model of PD-related PF. Activation of RhoA/Rho-kinase and activating protein-1 (AP-1) was assessed in HPMCs using pull-down and electrophoretic mobility shift assays, respectively, while expression of transforming growth factor-β, fibronectin, α-smooth muscle actin, vimentin, N-cadherin, and E-cadherin expression was assessed using immunohistochemistry and western blot. AGEs exposure activated Rho/Rho-kinase in HPMCs and upregulated EMT-related genes via AP-1. These changes were prevented by the Rho-kinase inhibitors fasudil and Y-27632, and by the AP-1 inhibitor curcumin. Importantly, fasudil normalized histopathological and molecular alterations and preserved peritoneal function in rats. These data support the therapeutic potential of Rho-kinase inhibitors in PD-related PF. PMID:29581852

Peritoneal small solute transport rate is related to the malnutrition inflammation score in peritoneal dialysis patients.

PubMed

Sezer, Siren; Elsurer, Rengin; Afsar, Baris; Arat, Zubeyde; Ozdemir, Nurhan F; Haberal, Mehmet

2007-01-01

A high peritoneal membrane transport status and peritoneal albumin leakage are determinants of morbidity and mortality in patients receiving continuous ambulatory peritoneal dialysis. In this study, we analyzed the relationship between the malnutrition inflammation score, peritoneal transport status, and 24-hour peritoneal albumin leakage in patients receiving peritoneal dialysis. Sixty-six patients receiving peritoneal dialysis (male-female ratio 30/36; age 46.2 +/- 14.1 years; mean duration of peritoneal dialysis 32.4 +/- 23.9 months) who had experienced no attacks of peritonitis within the prior 6 months were included. The malnutrition inflammation score was positively correlated with the serum C-reactive protein concentration, dialysate/plasma creatinine ratio, and 24-hour peritoneal albumin leakage. Triceps and biceps skinfold thicknesses and serum concentrations of prealbumin, total cholesterol, and triglyceride were negatively correlated with the malnutrition inflammation score. Multiple linear regression analysis showed that the malnutrition inflammation score was independently associated with the dialysate/plasma creatinine ratio (p = 0.039) and 24-hour peritoneal albumin amount (p = 0.005). High peritoneal transport status and peritoneal albumin leakage are significantly associated with the malnutrition inflammation score. (c) 2007 S. Karger AG, Basel

The development and application of a molecular community profiling strategy to identify polymicrobial bacterial DNA in the whole blood of septic patients.

PubMed

Faria, M M P; Conly, J M; Surette, M G

2015-10-16

The application of molecular based diagnostics in sepsis has had limited success to date. Molecular community profiling methods have indicated that polymicrobial infections are more common than suggested by standard clinical culture. A molecular profiling approach was developed to investigate the propensity for polymicrobial infections in patients predicted to have bacterial sepsis. Disruption of blood cells with saponin and hypotonic shock enabled the recovery of microbial cells with no significant changes in microbial growth when compared to CFU/ml values immediately prior to the addition of saponin. DNA extraction included a cell-wall digestion step with both lysozyme and mutanolysin, which increased the recovery of terminal restriction fragments by 2.4 fold from diverse organisms. Efficiencies of recovery and limits of detection using Illumina sequencing of the 16S rRNA V3 region were determined for both viable cells and DNA using mock bacterial communities inoculated into whole blood. Bacteria from pre-defined communities could be recovered following lysis and removal of host cells with >97% recovery of total DNA present. Applying the molecular profiling methodology to three septic patients in the intensive care unit revealed microbial DNA from blood had consistent alignment with cultured organisms from the primary infection site providing evidence for a bloodstream infection in the absence of a clinical lab positive blood culture result in two of the three cases. In addition, the molecular profiling indicated greater diversity was present in the primary infection sample when compared to clinical diagnostic culture. A method for analyzing bacterial DNA from whole blood was developed in order to characterize the bacterial DNA profile of sepsis infections. Preliminary results indicated that sepsis infections were polymicrobial in nature with the bacterial DNA recovered suggesting a more complex etiology when compared to blood culture data.

Effectiveness and Safety of Tigecycline Compared with Other Broad-Spectrum Antimicrobials in Abdominal Solid Organ Transplant Recipients with Polymicrobial Intraabdominal Infections.

PubMed

Liebenstein, Tyler; Schulz, Lucas T; Viesselmann, Chris; Bingen, Emma; Musuuza, Jackson; Safdar, Nasia; Rose, Warren E

2017-02-01

Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad-spectrum therapies for polymicrobial IAIs in this population. Retrospective cohort study. Large academic medical center with multiple outpatient clinics. A total of 81 adult SOT recipients were included who were treated for confirmed or suspected polymicrobial IAIs from 2007-2012. Of these patients, 27 received tigecycline and 54 received comparator therapy with a broad-spectrum β-lactam (e.g., piperacillin-tazobactam, cefepime, or meropenem) with or without glycopeptide or lipopeptide gram-positive therapy (vancomycin or daptomycin) (comparator group). Patients in the comparator group were matched to tigecycline-treated patients based on transplant type (kidney, combined kidney-pancreas, combined kidney-liver, or solitary pancreas) in a 1:2 ratio (tigecycline-to-other broad-spectrum antibiotics). Data on patient demographics, comorbidities, and clinical variables were collected and compared by using bivariate analyses. Clinical outcomes-clinical cure, improvement or failure, and disease recurrence-as well as death within 1 year were analyzed by bivariate analyses and logistic regression. Clinical cure was lower in the tigecycline group versus the comparator group (40.7% vs 72.2%, p=0.008), but cure combined with improvement was similar between the two groups (85.2% vs 88.9%, p=0.724). Multiple logistic regression analysis showed that treatment with comparator antibiotics increased the odds of cure (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.15-12.27) and reduced the odds of treatment failure (OR 0.59, 95% CI 0.07-4.55) and death within 1 year (OR 0.79, 95% CI 0.22-2.86); however, patients receiving comparator antibiotics were more likely to have disease recurrence (OR 1.45, 95% CI 0.33-6.36). Patients receiving tigecycline experienced a higher rate of adverse events than those receiving comparator antibiotics (29.6% vs 9.3%, p=0.026). Patients receiving tigecycline were less likely to achieve optimal clinical outcomes and had more adverse events. Alternative regimens should be selected over tigecycline for the treatment of polymicrobial IAIs in abdominal SOT recipients until additional studies are completed to examine its role in this population. © 2016 Pharmacotherapy Publications, Inc.

Campylobacter jejuni: A rare agent in a child with peritoneal dialysis-related peritonitis.

PubMed

Tural Kara, Tugce; Yilmaz, Songul; Ozdemir, Halil; Birsin Ozcakar, Zeynep; Derya Aysev, Ahmet; Ciftci, Ergin; Ince, Erdal

2016-10-01

Peritonitis is a serious problem in children receiving peritoneal dialysis. Campylobacter jejuni is an unusual cause of peritonitis. A 10-year-old boy who had end stage renal failure due to atypical hemolytic uremic syndrome was admitted to our hospital with abdominal pain and fever. Peritoneal dialysis fluid was cloudy and microscopic examination showed abundant leukocytes. Intraperitoneal cefepime treatment was started. Campylobacter jejuni was isolated from peritoneal dialysis fluid culture and oral clarithromycin was added to the treatment. At the end of therapy, peritoneal fluid culture was negative. To our knowledge, C. jejuni peritonitis was not reported in children previously. Although C. jejuni peritonitis is rarely encountered in children, it should be considered as an etiologic factor for peritonitis. Sociedad Argentina de Pediatría.

Curvularia lunata, a rare fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD); a rare case report.

PubMed

Subramanyam, Haritha; Elumalai, Ramprasad; Kindo, Anupma Jyoti; Periasamy, Soundararajan

2016-01-01

Peritonitis is an inflammation of the peritoneum that occurs in patients with end-stage renal disease (ESRD) treated by peritoneal dialysis. Fungal peritonitis is a dreaded complication of peritoneal dialysis. Curvularia lunata is known to cause extra renal disease like endocarditis, secondary allergic bronchopulmonary aspergillosis and endophthalmitis. This case report presents a case of continuous ambulatory peritoneal dialysis peritonitis with this disease and its management. This case is of a 45-year-old man, presented with ESRD, secondary to diabetic nephropathy. After 3 months of hemodialysis the patient was put on continuous ambulatory peritoneal dialysis (CAPD). Local Examination at catheter site showed skin excoriation and purulent discharge. Further peritoneal dialysis (PD) fluid analysis showed neutrophilic leukocytosis and diagnosis of Curvularia lunata PD peritonitis.

Mycobacterial peritonitis: difference between non-tuberculous mycobacteria and Mycobacterium tuberculosis.

PubMed

Shu, C-C; Wang, J-T; Wang, J-Y; Yu, C-J; Lee, L-N

2012-03-01

Unlike tuberculous peritonitis, peritonitis due to non-tuberculous mycobacteria (NTM) has unclear clinical manifestations. This study aimed to clarify the clinical manifestations and laboratory results of NTM peritonitis and compare it to tuberculous peritonitis. This retrospective study was conducted from 2000 to 2008 in a medical centre in Taiwan. Patients with mycobacteria isolated from ascites were identified and compared according to causative pathogens (Mycobacterium tuberculosis or NTM). Those with NTM peritonitis were further classified into the 'probable' and 'possible' groups based on diagnostic evidence. Twenty-five patients with NTM peritonitis and 65 with tuberculous peritonitis were reviewed. Mycobacterium avium complex was the most common NTM pathogen (52%). There was no obvious difference between the 'probable' and 'possible' NTM peritonitis groups regarding age and laboratory data. Patients with NTM peritonitis and those with tuberculous peritonitis had no differences in age or gender but varied in symptoms and serum laboratory data. NTM peritonitis was 100% associated with underlying co-morbidities and had lower proportions of lymphocytes and albumin level in ascites. Twelve (48%) NTM peritonitis and 21 (32%) tuberculous peritonitis patients died during the 6-month follow-up. Anti-mycobacterial treatment, but not mycobacterial species, was correlated with better 6-month survival. In Taiwan, NTM is responsible for 28% of mycobacterial peritonitis cases, which have a poor prognosis if untreated. There are some differences in clinical manifestations between NTM and tuberculous peritonitis. NTM peritonitis should be considered in patients with peritonitis but without causative microorganisms identified other than NTM. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Knowledge, understanding and experiences of peritonitis amongst patients, and their families, undertaking peritoneal dialysis: A mixed methods study protocol.

PubMed

Baillie, Jessica; Gill, Paul; Courtenay, Molly

2018-01-01

This article is a report of a study protocol designed to examine patients' and families' knowledge and experiences of peritoneal dialysis-associated peritonitis. Peritonitis is a considerable problem for people using peritoneal dialysis, leading to antibiotics, hospitalization and decreased quality of life. For some patients, peritonitis requires changing renal replacement therapy and can be fatal. Peritonitis is distressing and some patients are unfamiliar with the signs and symptoms. Patients with better knowledge of peritonitis and adherence to peritoneal dialysis procedures have lower rates of peritonitis. Little is known about patients' and families' knowledge and experience of peritoneal dialysis-associated peritonitis in the United Kingdom. Ethical approval was gained in March 2017. To meet the study aim, a two-phase sequential explanatory mixed methods study is proposed. Phase One: An author-developed questionnaire will be sent to patients using peritoneal dialysis at five sites in England and Wales. Patients will be asked to consider inviting a relative to participate. The questionnaire will assess peritonitis knowledge and experience. Data will be analysed statistically. Phase Two: Semi-structured interviews will be conducted with a purposive sample of Phase One participants (n = 30) to explore their experiences of peritonitis in further depth. The data will be analysed thematically using Wolcott's (1994) approach. Data from the two phases will be synthesized to identify patients' and families' peritonitis information needs, to ensure they are appropriately supported to prevent, monitor, identify and report peritonitis. © 2017 John Wiley & Sons Ltd.

[Fungal peritonitis due to Rhodotorula mucilaginosa in a patient with automated peritoneal dialysis: Literature review].

PubMed

Verdugo, Fernando J; Briones, Eduardo; Porte, Lorena; Amaro, José; Fica, Alberto

2016-04-01

Fungal peritonitis is a major complication of peritoneal dialysis associated with high mortality. Most survivors have a high rate of abandonment of peritoneal dialysis. We report a case of fungal peritonitis due to an unusual agent. An 83 year-old woman, with a history of type 2 diabetes mellitus and multiple episodes of bacterial peritonitis associated to technical flaws in the implementation of automated peritoneal dialysis, was admitted due to abdominal pain and cloudy peritoneal fluid. Rhodotorula mucilaginosa was identified in the peritoneal fluid by MALDI-TOF. She was treated with catheter removal and oral posaconazole for 14 days showing clinical resolution and non-recurrence.

Peritonitis due to Curvularia inaequalis in an elderly patient undergoing peritoneal dialysis and a review of six cases of peritonitis associated with other Curvularia spp.

PubMed

Pimentel, Jason D; Mahadevan, Kumar; Woodgyer, Alan; Sigler, Lynne; Gibas, Connie; Harris, Owen C; Lupino, Michael; Athan, Eugene

2005-08-01

Fungal peritonitis due to Curvularia species in patients undergoing peritoneal dialysis is a very rare problem. We report a case of peritonitis caused by Curvularia inaequalis. This is the first report in the English literature of this species causing human infection. We also review the six previously reported cases of continuous ambulatory peritoneal dialysis peritonitis caused by other Curvularia species.

Desertification of the peritoneum by thin-film evaporation during laparoscopy.

PubMed

Ott, Douglas E

2003-01-01

To assess the effects of gas flow during insufflation on peritoneal fluid and peritoneal tissue regarding transient thermal behavior and thin-film evaporation. The effects of laparoscopic gas on peritoneal cell desiccation and peritoneal fluid thin-film evaporation were analyzed. Measurment of tissue and peritoneal fluid and analysis of gas flow dynamics during laparoscopy. High-velocity gas interface conditions during laparoscopic gas insufflation result in peritoneal surface temperature and decreases up to 20 degrees C/second due to rapid thin-film evaporation of the peritoneal fluid. Evaporation of the thin film of peritoneal fluid extends quickly to the peritoneal cell membrane, causing peritoneal cell desiccation, internal cytoplasmic stress, and disruption of the cell membrane, resulting in loss of peritoneal surface continuity and integrity. Changing the gas conditions to 35 degrees C and 95% humidity maintains normal peritoneal fluid thin-film characteristics, cellular integrity, and prevents evaporative losses. Cold, dry gas and the characteristics of the laparoscopic gas delivery apparatus cause local peritoneal damaging alterations by high-velocity gas flow with extremely dry gas, creating extreme arid surface conditions, rapid evaporative and hydrological changes, tissue desiccation, and peritoneal fluid alterations that contribute to the process of desertification and thin-film evaporation. Peritoneal desertification is preventable by preconditioning the gas to 35 degrees C and 95% humidity.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

PubMed

van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration. Copyright © 2016 International Society for Peritoneal Dialysis.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription.

PubMed

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 - 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. Copyright © 2016 International Society for Peritoneal Dialysis.

Increased incidence of urolithiasis and bacteremia during Proteus mirabilis and Providencia stuartii coinfection due to synergistic induction of urease activity.

PubMed

Armbruster, Chelsie E; Smith, Sara N; Yep, Alejandra; Mobley, Harry L T

2014-05-15

Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI.

Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant Microparticle Release

PubMed Central

Gerotziafas, Grigoris; Byrnes, Colleen; Hu, Xuzhen; Perez, Joelle; Lévi, Charlène; Placier, Sandrine; Letavernier, Emmanuel; Leelahavanichkul, Asada; Haymann, Jean-philippe; Elalamy, Ismail; Miller, Jeffrey L.; Star, Robert A.; Yuen, Peter S. T.; Baud, Laurent

2012-01-01

Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis. Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis. PMID:22268136

Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation.

PubMed

Danielski, Lucinéia Gainski; Giustina, Amanda Della; Goldim, Mariana Pereira; Florentino, Drielly; Mathias, Khiany; Garbossa, Leandro; de Bona Schraiber, Rosiane; Laurentino, Ana Olívia Martins; Goulart, Marina; Michels, Monique; de Queiroz, Karina Barbosa; Kohlhof, Markus; Rezin, Gislaine Tezza; Fortunato, Jucélia Jeremias; Quevedo, Joao; Barichello, Tatiana; Dal-Pizzol, Felipe; Coimbra, Roney S; Petronilho, Fabricia

2018-06-01

Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B 6 (vit B 6 ) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B 6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B 6 , CLP + saline, and CLP + vit B 6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B 6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B 6 exerts neuroprotective effects in acute and late consequences after sepsis.

Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis.

PubMed

Ramanathan, Kumaresan; Padmanabhan, Giri; Vijayaraghavan, Bhooma

2016-05-01

Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

Myths in peritoneal dialysis.

PubMed

Lee, Martin B; Bargman, Joanne M

2016-11-01

To clarify misconceptions about the feasibility and risks of peritoneal dialysis that unnecessarily limit peritoneal dialysis uptake or continuation in patients for whom peritoneal dialysis is the preferred dialysis modality. The inappropriate choice of haemodialysis as a result of these misconceptions contributes to low peritoneal dialysis penetrance, increases transfer from peritoneal dialysis to haemodialysis, increases expenditure on haemodialysis and compromises quality of life for these patients. Peritoneal dialysis is an excellent renal replacement modality that is simple, cost-effective and provides comparable clinical outcomes to conventional in-centre haemodialysis. Unfortunately, many patients are deemed unsuitable to start or continue peritoneal dialysis because of false or inaccurate beliefs about peritoneal dialysis. Here, we examine some of these 'myths' and critically review the evidence for and against each of them. We review the feasibility and risk of peritoneal dialysis in patients with prior surgery, ostomies, obesity and mesh hernia repairs. We examine the fear of mediastinitis with peritoneal dialysis after coronary artery bypass graft surgery and the belief that the use of hypertonic glucose dialysate causes peritoneal membrane failure. By clarifying common myths about peritoneal dialysis, we hope to reduce overly cautious practices surrounding this therapy.

Olprinone and colforsin daropate alleviate septic lung inflammation and apoptosis through CREB-independent activation of the Akt pathway.

PubMed

Oishi, Hirofumi; Takano, Ken-ichi; Tomita, Kengo; Takebe, Mariko; Yokoo, Hiroki; Yamazaki, Mitsuaki; Hattori, Yuichi

2012-07-01

Olprinone, a specific phosphodiesterase III inhibitor, and corforsin daropate, a direct adenylate cyclase activator, are now being used in critical conditions. We investigated whether their therapeutic use provides protection against septic acute lung injury (ALI) and mortality. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. Olprinone or colforsin daropate was continuously given through an osmotic pump that was implanted into the peritoneal cavity immediately following CLP. These treatments prevented the ALI development in CLP mice, as indicated by the findings that severe hypoxemia, increased pulmonary vascular permeability, and histological lung damage were strikingly remedied. Furthermore, continued administration of olprinone or colforsin daropate suppressed apoptosis induction in septic lungs and improved the survival of CLP mice. Olprinone and corforsin daropate enhanced Akt phosphorylation in septic lungs. Wortmannin, which inhibits the Akt upstream regulator phosphatidylinositol 3-kinase, abrogated the protective effects of olprinone and corforsin daropate on sepsis-associated lung inflammation and apoptosis. In vivo transfection of cyclic AMP response element binding protein (CREB) decoy oligodeoxynucleotide failed to negate the abilities of these agents to increase Akt phosphorylation and to inhibit IκBα degradation in septic lungs. These results demonstrate for the first time that CREB-independent Akt-mediated signaling is a critical mechanism contributing to the therapeutic effects of olprinone and corforsin daropate on septic ALI. Moreover, our data also suggest that these cyclic AMP-related agents, by blocking both nuclear factor-κB activation and apoptosis induction, may represent an effective therapeutic approach to the treatment of the septic syndrome.

French National Registry of Rare Peritoneal Surface Malignancies

ClinicalTrials.gov

2017-08-18

Rare Peritoneal Surface Malignancies; Pseudomyxoma Peritonei; Peritoneal Mesothelioma; Desmoplastic Small Round Cell Tumor; Psammocarcinoma; Primary Peritoneal Serous Carcinoma; Diffuse Peritoneal Leiomyomatosis; Appendiceal Mucinous Neoplasms

The Mutual Relationship Between Peritonitis and Peritoneal Transport.

PubMed

van Esch, Sadie; van Diepen, Anouk T N; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. Copyright © 2016 International Society for Peritoneal Dialysis.

Single Daily Icodextrin Exchange as Initial and Solitary Therapy.

PubMed

Agar, Baris U; Sloand, James A

2018-01-01

Incremental dialysis utilizes gradually increasing dialysis doses in response to declines in residual kidney function, and it is the preferred renal replacement therapy for patients who have just transitioned to end-stage renal disease (ESRD). Incremental peritoneal dialysis (PD) may impose fewer restrictions on patients' lifestyle, help attenuate lifetime peritoneal and systemic exposure to glucose and its degradation products, and minimize connections that could compromise the sterile fluid path. In this study, we utilized a 3-pore kinetic model to assess fluid and solute removal during single daily icodextrin treatments for patients with varying glomerular filtration rates (GFR). Single icodextrin exchanges of 8 to 16 hours using 2- and 2.5-L bag volumes were simulated for different patient transport types (i.e., high to low) to predict daily peritoneal ultrafiltration (UF), daily peritoneal sodium removal, and weekly total (peritoneal + residual kidney) Kt/V (Kt/V Total ) for patients with residual renal GFRs ranging from 0 to 15 mL/min/1.73 m 2 . Daily peritoneal UF varied from 359 to 607 mL, and daily peritoneal Na removal varied from 52 to 87 mEq depending on length of icodextrin exchange and bag volume. Both were effectively independent of patient transport type. All but very large patients (total body water [TBW] > 60 L) were predicted to achieve adequate dialysis (Kt/V Total ≥ 1.7) with a GFR of 10 mL/min/1.73 m 2 , and small patients (TBW: 30 L) were predicted to achieve adequate dialysis with a GFR of 6 mL/min/1.73 m 2 . A single daily icodextrin exchange can be tailored to augment urea, UF, and Na removal in patients with sufficient residual kidney function (RKF). A solitary icodextrin exchange may therefore be reasonable initial therapy for some incident ESRD patients. Copyright © 2018 International Society for Peritoneal Dialysis.

Lower Education Level Is a Risk Factor for Peritonitis and Technique Failure but Not a Risk for Overall Mortality in Peritoneal Dialysis under Comprehensive Training System

PubMed Central

Kim, Hyo Jin; Lee, Joongyub; Park, Miseon; Kim, Yuri; Lee, Hajeong; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Cho, Eun Jin; Ahn, Curie

2017-01-01

Background Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower education level on the development of peritonitis, technique failure, and overall mortality. Methods Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (912, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression. Results A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20–65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10–2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10–3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53–2.33; P = 0.788) or intent-to-treat analysis (P = 0.726). Conclusions Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD. PMID:28056058

Lower Education Level Is a Risk Factor for Peritonitis and Technique Failure but Not a Risk for Overall Mortality in Peritoneal Dialysis under Comprehensive Training System.

PubMed

Kim, Hyo Jin; Lee, Joongyub; Park, Miseon; Kim, Yuri; Lee, Hajeong; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Cho, Eun Jin; Ahn, Curie; Oh, Kook-Hwan

2017-01-01

Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower education level on the development of peritonitis, technique failure, and overall mortality. Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (912, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression. A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20-65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10-2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10-3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53-2.33; P = 0.788) or intent-to-treat analysis (P = 0.726). Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD.

A Rare Reason of Ileus in Renal Transplant Patients With Peritoneal Dialysis History: Encapsulated Peritoneal Sclerosis.

PubMed

Gökçe, Ali Murat; Özel, Leyla; İbişoğlu, Sevinç; Ata, Pınar; Şahin, Gülizar; Gücün, Murat; Kara, V Melih; Özdemir, Ebru; Titiz, M İzzet

2015-12-01

Encapsulating peritoneal sclerosis is a rare complication of long-term peritoneal dialysis ranging from moderate inflammation of peritoneal structures to severe sclerosing peritonitis and encapsulating peritoneal sclerosis. Complicated it, ileus may occur during or after peritoneal dialysis treatment or after kidney transplant. We sought to evaluate 3 posttransplant encapsulating peritoneal sclerosis through clinical presentation, radiologic findings, and outcomes. We analyzed 3 renal transplant patients with symptoms of encapsulating peritoneal sclerosis admitted posttransplant to our hospital with ileus between 2012 and 2013. Conservative treatment was applied to the patients whenever necessary to avoid surgery. One patient improved with medical therapy. Surgical treatment was delayed and we decided it as a last resort, in 2 cases with no response to conservative treatment for a long time. Finally, patients with peritoneal dialysis history should be searched carefully before renal transplant for intermittent bowel obstruction story.

No increase in small-solute transport in peritoneal dialysis patients treated without hypertonic glucose for fifty-four months.

PubMed

Pagniez, Dominique; Duhamel, Alain; Boulanger, Eric; Lessore de Sainte Foy, Celia; Beuscart, Jean-Baptiste

2017-08-31

Glucose is widely used as an osmotic agent in peritoneal dialysis (PD), but exerts untoward effects on the peritoneum. The potential protective effect of a reduced exposure to hypertonic glucose has never been investigated. The cohort of PD patients attending our center which tackled the challenge of a restricted use of hypertonic glucose solutions has been prospectively followed since 1992. Small-solute transport was assessed using an equivalent of the glucose peritoneal equilibration test after 6 months, and then every year. Study was stopped on July 1st, 2008, before use of biocompatible solutions. Repeated measures in patients treated with PD for 54 months were analyzed by using (1) the slopes of the linear regression for D 4 /D 0 ratios over time computed for each individual, and (2) a linear mixed model. In the study period, 44 patients were treated for a total of 2376 months, 2058 without hypertonic glucose. There was one episode of peritoneal infection every 18 patient-months. The mean of slopes of the linear regression for D 4 /D 0 ratios was found to be significantly positive (Student's test, p < .001) and the results of the mixed model reflected a similar significant increase for D 4 /D 0 ratios over time. These results reflected a significant decrease of small-solute transport. In this large series, minimizing the use of hypertonic glucose solutions was associated in patients on long term PD with an overall decrease of small-solute transport within 54 months, despite a high rate of peritoneal infection.

Prevention of gram-positive infections in peritoneal dialysis patients in Hong Kong: a cost-effectiveness analysis.

PubMed

Wong, Carlos; Luk, In-Wa; Ip, Margaret; You, Joyce H S

2014-04-01

Gram-positive bacteria are the major causative pathogens of peritonitis and exit site infection in patients undergoing peritoneal dialysis (PD). We investigated the cost-effectiveness of regular application of mupirocin at the exit site in PD recipients from the perspective of health care providers in Hong Kong. A decision tree was designed to simulate outcomes of incident PD patients with and without regular application of mupirocin over a 1-year period. Outcome measures included total direct medical costs, quality-adjusted life-years (QALYs) gained, and gram-positive infection-related mortality rate. Model inputs were derived from the literature. Sensitivity analyses evaluated the impact of uncertainty in all model variables. In a base case analysis, the mupirocin group had a higher expected QALY value (0.6496 vs 0.6456), a lower infection-related mortality rate (0.18% vs 1.64%), and a lower total cost per patient (US $258 vs $1661) compared with the control group. The rate of gram-positive peritonitis without mupirocin and the risk of gram-positive peritonitis with mupirocin were influential factors. In 10,000 Monte Carlo simulations, the mupirocin group had significantly lower associated costs, higher QALYs, and a lower mortality rate 99.9% of the time. Topical mupirocin appears to be a cost-effective preventive measure against gram-positive infection in incident patients undergoing PD. The cost-effectiveness of mupirocin is affected by the level of infection risk reduction and subject to resistance against mupirocin. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Peritoneal Cell-free DNA: an innovative method for determining acute cell damage in peritoneal membrane and for monitoring the recovery process after peritonitis.

PubMed

Virzì, Grazia Maria; Milan Manani, Sabrina; Brocca, Alessandra; Cantaluppi, Vincenzo; de Cal, Massimo; Pastori, Silvia; Tantillo, Ilaria; Zambon, Roberto; Crepaldi, Carlo; Ronco, Claudio

2016-02-01

Cell-free DNA (cfDNA) is present in the peritoneal effluent of stable peritoneal dialysis (PD) patients, but there are no data on cfDNA in PD patients with peritonitis. We investigated the variation of peritoneal cfDNA levels subsequent to peritonitis in PD patients. We enrolled 53 PD patients: 30 without any history of systemic inflammation or peritonitis in the last 3 months (group A) and 23 with acute peritonitis (group B). CfDNA was quantified in the peritoneal effluent. Peritoneal samples on days 1, 3, 10, 30 and until day 120 from the start of peritonitis were collected for white blood cells (WBC) count and cfDNA evaluation in group B. Quantitative analysis of cfDNA showed significantly higher levels in group B on day 1, 3, 10 and 30 compared with group A (p < 0.05). A significant positive correlation was observed between cfDNA concentration and WBC on day 1 (rho = 0.89) and day 3 (rho = 0.5) (both, p < 0.05). However, no significant correlation was observed between cfDNA and WBC on days 10 and 30. In group B, peritoneal cfDNA levels tended to progressively decline during follow-up of peritonitis. From this decreasing curve, we estimated that 49 days are necessary to reach the value of 51 genome equivalents (GE)/ml (75th percentile in controls) and 63 days to reach 31 GE/ml (median). Our results demonstrate that cfDNA increases in peritoneal effluent of PD patients with peritonitis and tends to progressively decline in step with peritonitis resolution and membrane repair process. Peritoneal cfDNA quantification could be an innovative method to determine acute damage and an inverse index of the repair process.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription

PubMed Central

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Background: Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Methods: Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Results: Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 – 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Conclusion: Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. PMID:26224788

Time Course of Peritoneal Function in Automated and Continuous Peritoneal Dialysis

PubMed Central

Michels, Wieneke M.; Verduijn, Marion; Parikova, Alena; Boeschoten, Elisabeth W.; Struijk, Dirk G.; Dekker, Friedo W.; Krediet, Raymond T.

2012-01-01

♦ Background and Objectives: In automated peritoneal dialysis (APD), a patient’s peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD—compared with that of CAPD—on peritoneal transport over 4 years. ♦ Design, Setting, Participants, and Measurements: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. ♦ Results: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. ♦ Conclusions: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups. PMID:22473037

Evidence for less irritation to the peritoneal membrane in rats dialyzed with solutions low in glucose degradation products.

PubMed

Wieczorowska-Tobis, Katarzyna; Brelinska, Renata; Witowski, Janusz; Passlick-Deetjen, Jutta; Schaub, Thomas P; Schilling, Holger; Breborowicz, Andrzej

2004-01-01

Acidic pH and the presence of glucose degradation products (GDP) are believed to compromise the biocompatibility of peritoneal dialysis fluids (PDF). The present study examines the effects of long-term exposure to GDP and low pH by comparing conventional PDF and a new, neutral pH, low GDP solution. All experiments were performed using a chronic infusion model of dialysis in nonuremic rats. The animals were treated for 6 weeks with 2 daily injections of 4.25% glucose-containing PDF. The following PDF were tested: CAPD3 (single-chamber bag, low pH, high GDP), CAPD3 pH 7.4 (single-chamber bag, neutral pH, high GDP), CAPD3-Balance (double-chamber bag, neutral pH, low GDP). All test solutions were obtained from Fresenius Medical Care, Bad Homburg, Germany. After 6 weeks of exposure, peritoneal permeability to water, urea, creatinine, glucose, and sodium, assessed by peritoneal equilibration test, was similar in all groups. However, compared to other PDF, dialysis with CAPD3-Balance was associated with reduced concentrations of protein and hyaluronan in the dialysate, decreased peritoneal eosinophilia, and reduced dialysate levels of chemokines CCL2/MCP-1 and CCL5/RANTES. Morphologic changes in the peritoneal membrane of CAPD3-Balance-treated animals were much less pronounced and included reduced vascular density, preservation of the mesothelial monolayer and intercellular junction, and no reduplication of the submesothelial basement membrane. A new generation of PDF with physiologic pH and low GDP level produce less irritation to the peritoneal membrane and better preserve its structural integrity. This effect seems to be related predominantly to minimized GDP concentrations.

The hallucinogenic diterpene salvinorin A inhibits leukotriene synthesis in experimental models of inflammation.

PubMed

Rossi, Antonietta; Pace, Simona; Tedesco, Federica; Pagano, Ester; Guerra, Germano; Troisi, Fabiana; Werner, Markus; Roviezzo, Fiorentina; Zjawiony, Jordan K; Werz, Oliver; Izzo, Angelo A; Capasso, Raffaele

2016-04-01

Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis

PubMed Central

Kemp, Anna; Clayton, Philip; Lim, Wai; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen P.; Wiggins, Kathryn J.; Bannister, Kym M.; Brown, Fiona G.; Johnson, David W.

2012-01-01

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4–8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days. PMID:22626818

The Role of the Omental Microenvironment in Ovarian Cancer Metastatic Colonization

DTIC Science & Technology

2012-08-01

and clinical disease . It is unusual as it contains milky spots, structures consisting of immune cells, stromal cells and structural elements...peritoneal disease . 15. SUBJECT TERMS Nothing Listed 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...the peritoneal fluid have access to and can potentially lodge within a variety of tissues (1,2). In both clinical disease and experimental models

Pathways of fluid transport and reabsorption across the peritoneal membrane.

PubMed

Asghar, R B; Davies, S J

2008-05-01

The three-pore model of peritoneal fluid transport predicts that once the osmotic gradient has dissipated, fluid reabsorption will be due to a combination of small-pore reabsorption driven by the intravascular oncotic pressure, and an underlying disappearance of fluid from the cavity by lymphatic drainage. Our study measured fluid transport by these pathways in the presence and absence of an osmotic gradient. Paired hypertonic and standard glucose-dwell studies were performed using radio-iodinated serum albumin as an intraperitoneal volume marker and changes in intraperitoneal sodium mass to determine small-pore versus transcellular fluid transport. Disappearance of iodinated albumin was considered to indicate lymphatic drainage. Variability in transcellular ultrafiltration was largely explained by the rate of small-solute transport across the membrane. In the absence of an osmotic gradient, fluid reabsorption occurred via the small-pore pathway, the rate being proportional to the small-solute transport characteristics of the membrane. In most cases, fluid removal from the peritoneal cavity by this pathway was faster than by lymphatic drainage. Our study shows that the three-pore model describes the pathways of peritoneal fluid transport well. In the presence of high solute transport, poor transcellular ultrafiltration was due to loss of the osmotic gradient and an enhanced small-pore reabsorption rate after this gradient dissipated.

The Mutual Relationship Between Peritonitis and Peritoneal Transport

PubMed Central

van Esch, Sadie; van Diepen, Anouk T.N.; Struijk, Dirk G.; Krediet, Raymond T.

2016-01-01

♦ Background: Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Methods: Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ Results: At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Conclusions: Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. PMID:25395498

The Association between Peritoneal Dialysis Modality and Peritonitis

PubMed Central

Johnson, David W.; McDonald, Stephen P.; Boudville, Neil; Borlace, Monique; Badve, Sunil V.; Sud, Kamal; Clayton, Philip A.

2014-01-01

Background and objectives There is conflicting evidence comparing peritonitis rates among patients treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). This study aims to clarify the relationship between peritoneal dialysis (PD) modality (APD versus CAPD) and the risk of developing PD-associated peritonitis. Design, setting, participants, & measurements This study examined the association between PD modality (APD versus CAPD) and the risks, microbiology, and clinical outcomes of PD-associated peritonitis in 6959 incident Australian PD patients between October 1, 2003, and December 31, 2011, using data from the Australia and New Zealand Dialysis and Transplant Registry. Median follow-up time was 1.9 years. Results Patients receiving APD were younger (60 versus 64 years) and had fewer comorbidities. There was no association between PD modality and time to first peritonitis episode (adjusted hazard ratio [HR] for APD versus CAPD, 0.98; 95% confidence interval [95% CI], 0.91 to 1.07; P=0.71). However, there was a lower hazard of developing Gram-positive peritonitis with APD than CAPD, which reached borderline significance (HR, 0.90; 95% CI, 0.80 to 1.00; P=0.05). No statistically significant difference was found in the risk of hospitalizations (odds ratio, 1.12; 95% CI, 0.93 to 1.35; P=0.22), but there was a nonsignificant higher likelihood of 30-day mortality (odds ratio, 1.33; 95% CI, 0.93 to 1.88; P=0.11) at the time of the first episode of peritonitis for patients receiving APD. For all peritonitis episodes (including subsequent episodes of peritonitis), APD was associated with lower rates of culture-negative peritonitis (incidence rate ratio [IRR], 0.81; 95% CI, 0.69 to 0.94; P=0.002) and higher rates of gram-negative peritonitis (IRR, 1.28; 95% CI, 1.13 to 1.46; P=0.01). Conclusions PD modality was not associated with a higher likelihood of developing peritonitis. However, APD was associated with a borderline reduction in the likelihood of a first episode of Gram-positive peritonitis compared with CAPD, and with lower rates of culture-negative peritonitis and higher rates of Gram-negative peritonitis. Peritonitis outcomes were comparable between both modalities. PMID:24626434

Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: a potential experimental tool to study molecular pathogenesis of endometriosis in humans.

PubMed

Banu, Sakhila K; Starzinski-Powitz, Anna; Speights, V O; Burghardt, Robert C; Arosh, Joe A

2009-05-01

To determine whether a mixed population of immortalized human endometriosis epithelial and stromal cells is able to induce peritoneal endometriosis in nude mice. Prospective experimental study. Human immortalized endometriosis epithelial and stromal cells were xenografted into ovariectomized nude mice. Macroscopically, the number of induced endometriosis-like lesions and their color were determined. Microscopically, histomorphology of endometriosis glands and their structure were analyzed, and comparisons were made with tissue from spontaneous endometriosis in women. College of Veterinary Medicine and Biomedical Sciences, Texas A&M University. Seven ovariectomized nude mice. Minimal invasive procedures were performed to administer estrogen pellets and transplant immortalized human endometriosis epithelial and stromal cells into nude mice. Peritoneal endometriosis-like lesions induced in nude mice were characterized and compared with spontaneous peritoneal endometriosis in women. Xenografts of human immortalized endometriosis epithelial and stromal cells into the peritoneal cavity of the recipient nude mice are able to proliferate, attach, invade, reorganize, and establish peritoneal endometriosis. Endometriosis glands at different stages of growth were present in induced endometriosis-like lesions. Proliferating cell nuclear antigen, metalloproteinase 2, estrogen receptor-alpha, cyclooxygenase-2, and prostaglandin E(2) receptors EP2 and EP4 proteins were expressed in both endometriosis glandular epithelial and stromal cells of the induced endometriosis-like lesions. This xenograft model could be used as a potential experimental tool to understand the molecular and cellular aspects of the pathogenesis of endometriosis in humans.

Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer.

PubMed

Lin, Been-Ren; Chang, Cheng-Chi; Chen, Robert Jeen-Chen; Jeng, Yung-Ming; Liang, Jin-Tung; Lee, Po-Huang; Chang, King-Jen; Kuo, Min-Liang

2011-05-15

Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients. ©2011 AACR.

The Role of NGAL in Peritoneal Dialysis Effluent in Early Diagnosis of Peritonitis: Case-Control Study in Peritoneal Dialysis Patients.

PubMed

Martino, Francesca; Scalzotto, Elisa; Giavarina, Davide; Rodighiero, Maria Pia; Crepaldi, Carlo; Day, Sonya; Ronco, Claudio

2015-01-01

Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis. A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p < 0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in PDE (p < 0.001) were all significantly different in patients with and without peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR 36.75 p < 0.001) were significantly associated with episodes of peritonitis. In multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001), 0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and peritoneal NGAL test increased the specificity (= 96%) of the single test. These results identify NGAL in peritoneal effluent as a reliable marker of peritonitis episodes in PD patients. Collectively, our findings demonstrate that the use of peritoneal NGAL cooperatively with current clinical diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool in PD-associated peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

ClinicalTrials.gov

2013-12-17

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

PubMed Central

Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender

2016-01-01

Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

An intra-abdominal abscess or "rind" as a consequence of peritoneal dialysis-associated pseudomonas peritonitis.

PubMed

Culpepper, R Michael; Gore, Sarah; Rutecki, Gregory W

2013-01-01

Abdominal CT imaging has defined characteristics of two pathological entities specific to peritoneal dialysis patients. Both are associated with serious peritoneal complications. One is comprised of ascites accompanied by septation and loculated fluid pockets as a complication of bacterial peritonitis. The other is the syndrome of encapsulating peritoneal sclerosis. We present the evolution of a single, thick-walled fluid collection as a consequence of relapsing Pseudomonas aeruginosa peritonitis. The entity had distinctive features differing from either of the two previously described entities, and to our knowledge, has not been described previously. Our patient's radiological evolution resembled the formation of a pleural or peritoneal "rind." Peritonitis, as a result of Pseudomonas aeruginosa , may lead to "rind" formation as described with empyemas and is distinct from previously described intra-abdominal pathologies in peritoneal dialysis patients.

Acute Peritonitis Caused by Staphylococcus capitis in a Peritoneal Dialysis Patient.

PubMed

Basic-Jukic, Nikolina

Acute peritonitis remains the most common complication of peritoneal dialysis (PD), with coagulase-negative staphylococci (CoNS) reported to account for more than 25% of peritonitis episodes (1). Staphylococcus capitis is a gram-positive, catalase-positive CoNS that was originally identified as a commensal on the skin of the human scalp (2). Advancement of microbiological technologies for bacterial identification enables diagnosis of previously unknown causes of acute peritonitis. This is the first reported case of acute peritonitis in a PD patient caused by S. capitis. Copyright © 2017 International Society for Peritoneal Dialysis.

[Infectious peritonitis in peritoneal dialysis: an over-emphasized complication].

PubMed

Vakilzadeh, N; Burnier, M; Halabi, G

2013-02-27

Peritoneal dialysis is an extrarenal epuration modality which uses physiological properties of peritoneum as a dialysis membrane. Despite the improvement of peritoneal dialysis techniques in the last ten years, peritonitis remains one of the most redoubt complications. Peritonitis may sometimes lead to technical failures, which need catheter removing, but rarely lead to death. Our retrospective study at the dialysis center of CHUV has analyzed factors which can predict this kind of complication. It calculates peritonitis rate and median peritonitis free-survival for different groups of patients. It also describes causatives organisms and their sensitivity to antibiotics.

Establishment of a multi-species biofilm model to evaluate chlorhexidine efficacy.

PubMed

Touzel, R E; Sutton, J M; Wand, M E

2016-02-01

Chronic infections, for example, diabetic foot ulcers, have a large impact in terms of patient morbidity and mortality. These wounds are characterized by complex polymicrobial communities of bacteria, which may include a number of difficult-to-eradicate multidrug-resistant pathogens. To establish a multi-species biofilm model to test the efficacy of chlorhexidine and chlorhexidine-containing formulas in eradication of polymicrobial biofilms. A Centers for Disease Control and Prevention bioreactor was used to establish a multi-species biofilm incorporating Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis with equal numbers of each pathogen. This model was used to test the effectiveness of chlorhexidine at controlling the pre-formed biofilm. Chlorhexidine digluconate (CHD) was added to the bioreactor at a range of concentrations. K. pneumoniae and P. aeruginosa survived within multi-species biofilms, up to and including 4% CHD, whereas S. aureus was reduced to below the level of detection at 1%. Wiping the biofilm-containing coupons from the bioreactor with chlorhexidine-containing medical wipes resulted in >3 to <4log10 reduction after 24h, for all species. When the coupons were embedded in a simulated wound bed, formed in an agar plate, CHD-containing medical dressings completely eliminated S. aureus (>8log10 reduction), but had minimal effect (<3log10) against the other species tested. The study demonstrates that the effectiveness of chlorhexidine may be limited in settings where it is required to act on multi-species biofilms. This may compromise the ability of chlorhexidine to control the infection and spread of these pathogens. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Exploiting Uptake of Nanoparticles by Phagocytes for Cancer Treatment.

PubMed

Sheen, Mee Rie; Fiering, Steven

2017-01-01

Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers. This basic approach can be modified as needed for different types of tumors and nanoparticles.

Characterization and identification of microbial communities in bovine necrotic vulvovaginitis.

PubMed

Shpigel, N Y; Adler-Ashkenazy, L; Scheinin, S; Goshen, T; Arazi, A; Pasternak, Z; Gottlieb, Y

2017-01-01

Bovine necrotic vulvovaginitis (BNVV) is a severe and potentially fatal disease of post-partum cows that emerged in Israel after large dairy herds were merged. While post-partum cows are commonly affected by mild vulvovaginitis (BVV), in BNVV these benign mucosal abrasions develop into progressive deep necrotic lesions leading to sepsis and death if untreated. The etiology of BNVV is still unknown and a single pathogenic agent has not been found. We hypothesized that BNVV is a polymicrobial disease where the normally benign vaginal microbiome is remodeled and affects the local immune response. To this end, we compared the histopathological changes and the microbial communities using 16S rDNA metagenetic technique in biopsies taken from vaginal lesions in post-partum cows affected by BVV and BNVV. The hallmark of BNVV was the formation of complex polymicrobial communities in the submucosal fascia and abrogation of neutrophil recruitment in these lesions. Additionally, there was a marked difference in the composition of bacterial communities in the BNVV lesions in comparison to the benign BVV lesions. This difference was characterized by the abundance of Bacteroidetes and lower total community membership in BNVV. Indicator taxa for BNVV were Parvimonas, Porphyromonas, unclassified Veillonellaceae, Mycoplasma and Bacteroidetes, whereas unclassified Clostridiales was an indicator for BVV. The results support a polymicrobial etiology for BNVV. Copyright © 2016 Elsevier Ltd. All rights reserved.

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens

PubMed Central

Annamanedi, Madhavi; Varma, Gajapati Y. N.; Anuradha, K.; Kalle, Arunasree M.

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections. PMID:28533769

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

PubMed

Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

Association Between Peritoneal Glucose Exposure and Peritonitis in Peritoneal Dialysis Patients: The balANZ Trial.

PubMed

Nataatmadja, Melissa; Cho, Yeoungjee; Pascoe, Elaine M; Darssan, Darsy; Hawley, Carmel M; Johnson, David W

2017-01-01

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and exposure to glucose has been shown to exert detrimental effects both locally, at the peritoneal membrane, and systemically. Moreover, high dialysate glucose exposure may predispose patients to an increased risk of peritonitis, perhaps as a result of impaired host defences, vascular disease, and damage to the peritoneal membrane. In this post-hoc analysis of a multicenter, multinational, open-label randomized controlled trial of neutral pH, low-glucose degradation product (GDP) versus conventional PD solutions ( bal ANZ trial), the relationship between peritonitis rates of low (< 123.1 g/day) versus high (≥ 123.1 g/day) dialysate glucose exposure was evaluated in 177 incident PD patients over a 2-year study period. Peritonitis rates were 0.44 episodes per patient-year in the low-glucose exposure group and 0.31 episodes per patient-year in the high-glucose exposure group, (incidence rate ratio [IRR] 0.69, p = 0.09). There was no significant association between dialysate glucose exposure and peritonitis-free survival on univariable analysis (high glucose exposure hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40 - 1.08) or on multivariable analysis (adjusted HR 0.64, 95% CI 0.39 - 1.05). Moreover, there was no relationship between peritoneal glucose exposure and type of organism causing peritonitis. Physician-rated severity of first peritonitis episodes was similar between groups, as was rate and duration of hospital admission. Overall, this study did not identify an association between peritoneal dialysate glucose exposure and peritonitis occurrence, severity, hospitalization, or outcomes. A further large-scale, prospective, randomized controlled trial evaluating patient-level outcomes is merited. Copyright © 2017 International Society for Peritoneal Dialysis.

Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

PubMed

Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

2014-12-10

The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti histaminic activity of cissus quadragularis.

PubMed

Begum, V H; Sadique, J

1999-01-01

Anti histaminic activity of cissus quadrangularis stem powder was carried out determining the histamine activity and histamine content in carrageenin induced rat paw swelling model and formalin induced peritonitis respectively. The crude powder at the dose of 100mg/1QQ00 gm exerted reduction to the maximum of 44% in the early hisamine phase swelling. Further it significantly reduced the histamine content in the peritoneal fluid. For comparison standard steroidal drug hydrocortisone and avil were used.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PubMed Central

Lee, Kyong Ok; Park, Se Jin; Kim, Ji Hong; Lee, Jae Seung; Kim, Pyung Kil

2013-01-01

Purpose Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. Materials and Methods We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. Results We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). Conclusion Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD. PMID:23709435

Antimicrobial susceptibility of clinically isolated anaerobic bacteria in a University Hospital Centre Split, Croatia in 2013.

PubMed

Novak, Anita; Rubic, Zana; Dogas, Varja; Goic-Barisic, Ivana; Radic, Marina; Tonkic, Marija

2015-02-01

Anaerobic bacteria play a significant role in many endogenous polymicrobial infections. Since antimicrobial resistance among anaerobes has increased worldwide, it is useful to provide local susceptibility data to guide empirical therapy. The present study reports recent data on the susceptibility of clinically relevant anaerobes in a University Hospital Centre (UHC) Split, Croatia. A total of 63 Gram-negative and 59 Gram-positive anaerobic clinical isolates from various body sites were consecutively collected from January to December 2013. Antimicrobial susceptibility testing was performed using standardized methods and interpreted using EUCAST criteria. Patient's clinical and demographic data were recorded by clinical microbiologist. Among 35 isolates of Bacteroides spp., 97.1% were resistant to penicillin (PCN), 5.7% to amoxicillin/clavulanic acid (AMC), 8.6% to piperacillin/tazobactam (TZP), 29.0% to clindamycin (CLI) and 2.9% to metronidazole (MZ). Percentages of susceptible strains to imipenem (IPM), meropenem (MEM) and ertapenem (ETP) were 94.3. Resistance of other Gram-negative bacilli was 76.0% to PCN, 8.0% to AMC, 12.0% to TZP, 28.0% to CLI and 8% to MZ. All other Gram-negative strains were fully susceptible to MEM and ETP, while 96.0% were susceptible to IPM. Clostridium spp. isolates were 100% susceptible to all tested antibiotics except to CLI (two of four tested isolates were resistant). Propionibacterium spp. showed resistance to CLI in 4.3%, while 100% were resistant to MZ. Among other Gram-positive bacilli, 18.2% were resistant to PCN, 9.1% to CLI and 54.5% to MZ, while 81.8% of isolates were susceptible to carbapenems. Gram-positive cocci were 100% susceptible to all tested antimicrobials except to MZ, where 28.6% of resistant strains were recorded. Abdomen was the most common source of isolates (82.5%). The most prevalent types of infection were abscess (22.1%), sepsis (14.8%), appendicitis (13.9%) and peritonitis (6.6%). Twenty four patients (19.7%) received empiric antimicrobial therapy. One hundred and one patients (82.8%) had polymicrobial aerobic/anaerobic isolates cultivated from the same specimens. Almost all aerobic bacteria were of endogenous origin and showed fully susceptible antimicrobial profile; only 8.7% (9/104) were multiresistant and considered as hospital acquired. Based on our findings, β-lactam/β-lactamase inhibitor combinations and metronidazole remain useful antimicrobials for empiric treatment of anaerobic infections, while carbapenems should be reserved for situations were multidrug resistant, aerobic or facultative Gram-negative bacteria are expected. However, a certain percentage of resistant isolates were observed for each of these agents. Therefore, periodic resistance surveillance in anaerobes is highly recommended in order to guide empirical therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

ClinicalTrials.gov

2014-05-06

Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Case report. Candida lusitaniae peritonitis in a patient on continuous ambulatory peritoneal dialysis.

PubMed

Cinar, S; Nedret Koç, A; Taşkapan, H; Dogukan, A; Tokgöz, B; Utaş, C

2002-04-01

We report a case of Candida lusitania peritonitis in continuous ambulatory peritoneal dialysis. Since fluconazole therapy was not successful in this patient, the peritoneal catheter was removed and antifungal therapy continued, and the patient was then converted to haemodialysis. This treatment protocol was successful. We suggest that early peritoneal catheter removal should be considered in such cases.

[Design of Complex Cavity Structure in Air Route System of Automated Peritoneal Dialysis Machine].

PubMed

Quan, Xiaoliang

2017-07-30

This paper introduced problems about Automated Peritoneal Dialysis machine(APD) that the lack of technical issues such as the structural design of the complex cavities. To study the flow characteristics of this special structure, the application of ANSYS CFX software is used with k-ε turbulence model as the theoretical basis of fluid mechanics. The numerical simulation of flow field simulation result in the internal model can be gotten after the complex structure model is imported into ANSYS CFX module. Then, it will present the distribution of complex cavities inside the flow field and the flow characteristics parameter, which will provide an important reference design for APD design.

Peritonitis related to percutaneous endoscopic gastrostomy using the direct method for cancer patients.

PubMed

Osera, Shozo; Yano, Tomonori; Odagaki, Tomoyuki; Oono, Yasuhiro; Ikematsu, Hiroaki; Ohtsu, Atsushi; Kaneko, Kazuhiro

2015-10-01

Percutaneous endoscopic gastrostomy (PEG) using the direct method is generally indicated for cancer patients. However, there are little available data about peritonitis related to this method. The aim of this retrospective analysis was to assess peritonitis related to PEG using the direct method in patients with cancer. We assessed the prevalence of peritonitis and the relationship between peritonitis and patients' backgrounds, as well as the clinical course after peritonitis. Between December 2008 and December 2011, peritonitis was found in 9 (2.1 %) of 421 patients. Of the 9 patients with peritonitis, 4 had received PEG prior to chemoradiotherapy. Emergency surgical drainage was required in 1 patient, and the remaining 8 recovered with conservative treatment. Peritonitis occurred within 8 days of PEG for 8 of the 9 patients and occurred within 2 days of suture removal for 4 of the 9 patients. Peritonitis related to PEG using the direct method was less frequent for cancer patients. Peritonitis tended to occur within a few days after removal of securing suture and in patients with palliative stage.

Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model.

PubMed

Santos, Andressa Cristina Antunes; Correia, Carolina Argondizo; de Oliveira, Dalila Cunha; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

2016-12-01

Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

PubMed

Cakmak, Bulent; Cavusoglu, Turker; Ates, Utku; Meral, Ayfer; Nacar, Mehmet Can; Erbaş, Oytun

2015-04-01

Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti-inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated. Peritoneal endometriosis was surgically induced in 16 mature female Sprague-Dawley rats. The peritoneal endometriotic implant was confirmed after 28 days, and the animals were divided randomly into two groups. The control group (n = 8) was given 4 mL/day tap water by oral gavage, and the losartan group (n = 8) was given 20 mg/kg per day losartan p.o. We compared endometriotic implant size, extent and severity of adhesion, as well as plasma and peritoneal lavage fluid cytokine levels including vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, plasma inflammatory factor pentraxin-3 (PTX-3) and C-reactive protein (CRP) between the treatment groups. Mean surface endometriotic area, histological score of implants, adhesion formation, plasma VEGF, TNF, PTX-3 and CRP levels were significantly lower in the losartan group compared with control (P < 0.05). Furthermore, the peritoneal VEGF level was lower in the losartan group than in the control group (P < 0.001), but peritoneal TNF-α was similar in both groups (P > 0.05). Losartan suppressed the implant surface area of experimental endometriosis in rats and reduced the levels of plasma VEGF, TNF-α, PTX-3 and CRP. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Hyperbranched polyglycerol is an efficacious and biocompatible novel osmotic agent in a rodent model of peritoneal dialysis.

PubMed

Mendelson, Asher A; Guan, Qiunong; Chafeeva, Irina; da Roza, Gerald A; Kizhakkedathu, Jayachandran N; Du, Caigan

2013-01-01

To enhance the effectiveness of peritoneal dialysis (PD), new biocompatible PD solutions may be needed. The present study was designed to test the efficacy and biocompatibility of hyperbranched polyglycerol (HPG)-a nontoxic, nonimmunogenic water-soluble polyether polymer-in PD. Adult Sprague-Dawley rats were instilled with 30 mL HPG solution (molecular weight 3 kDa; 2.5% - 15%) or control glucose PD solution (2.5% Dianeal: Baxter Healthcare Corporation, Deerfield, IL, USA), and intraperitoneal fluid was recovered after 4 hours. Peritoneal injury and cellular infiltration were determined by histologic and flow cytometric analysis. Human peritoneal mesothelial cells were assessed for viability in vitro after 3 hours of PD fluid exposure. The 15% HPG solution achieved a 4-hour dose-related ultrafiltration up to 43.33 ± 5.24 mL and a dose-related urea clearance up to 39.17 ± 5.21 mL, results that were superior to those with control PD solution (p < 0.05). The dialysate-to-plasma (D/P) ratios of urea with 7.5% and 15% HPG solution were not statistically different from those with control PD solution. Compared with fluid recovered from the control group, fluid recovered from the HPG group contained proportionally fewer neutrophils (3.63% ± 0.87% vs 9.31% ± 2.89%, p < 0.0001). Detachment of mesothelial cells positive for human bone marrow endothelial protein 1 did not increase in the HPG group compared with the stain control (p = 0.1832), but it was elevated in the control PD solution group (1.62% ± 0.68% vs 0.41% ± 0.31%, p = 0.0031). Peritoneal biopsies from animals in the HPG PD group, compared with those from control PD animals, demonstrated less neutrophilic infiltration and reduced thickness. Human peritoneal mesothelial cell survival after HPG exposure was superior in vitro (p < 0.0001, 7.5% HPG vs control; p < 0.01, 15% HPG vs control). Exposure to glucose PD solution induced cytoplasmic vacuolation and caspase 3-independent necrotic cell death that was not seen with HPG solution. Our novel HPG PD solution demonstrated effective ultrafiltration and waste removal with reduced peritoneal injury in a rodent model of PD.

Hyperbranched Polyglycerol Is an Efficacious and Biocompatible Novel Osmotic Agent in a Rodent Model of Peritoneal Dialysis

PubMed Central

Mendelson, Asher A.; Guan, Qiunong; Chafeeva, Irina; da Roza, Gerald A.; Kizhakkedathu, Jayachandran N.; Du, Caigan

2013-01-01

♦ Objectives: To enhance the effectiveness of peritoneal dialysis (PD), new biocompatible PD solutions may be needed. The present study was designed to test the efficacy and biocompatibility of hyperbranched polyglycerol (HPG)—a nontoxic, nonimmunogenic water-soluble polyether polymer—in PD. ♦ Methods: Adult Sprague-Dawley rats were instilled with 30 mL HPG solution (molecular weight 3 kDa; 2.5% - 15%) or control glucose PD solution (2.5% Dianeal: Baxter Healthcare Corporation, Deerfield, IL, USA), and intraperitoneal fluid was recovered after 4 hours. Peritoneal injury and cellular infiltration were determined by histologic and flow cytometric analysis. Human peritoneal mesothelial cells were assessed for viability in vitro after 3 hours of PD fluid exposure. ♦ Results: The 15% HPG solution achieved a 4-hour dose-related ultrafiltration up to 43.33 ± 5.24 mL and a dose-related urea clearance up to 39.17 ± 5.21 mL, results that were superior to those with control PD solution (p < 0.05). The dialysate-to-plasma (D/P) ratios of urea with 7.5% and 15% HPG solution were not statistically different from those with control PD solution. Compared with fluid recovered from the control group, fluid recovered from the HPG group contained proportionally fewer neutrophils (3.63% ± 0.87% vs 9.31% ± 2.89%, p < 0.0001). Detachment of mesothelial cells positive for human bone marrow endothelial protein 1 did not increase in the HPG group compared with the stain control (p = 0.1832), but it was elevated in the control PD solution group (1.62% ± 0.68% vs 0.41% ± 0.31%, p = 0.0031). Peritoneal biopsies from animals in the HPG PD group, compared with those from control PD animals, demonstrated less neutrophilic infiltration and reduced thickness. Human peritoneal mesothelial cell survival after HPG exposure was superior in vitro (p < 0.0001, 7.5% HPG vs control; p < 0.01, 15% HPG vs control). Exposure to glucose PD solution induced cytoplasmic vacuolation and caspase 3-independent necrotic cell death that was not seen with HPG solution. ♦ Conclusions: Our novel HPG PD solution demonstrated effective ultrafiltration and waste removal with reduced peritoneal injury in a rodent model of PD. PMID:23349194

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

PubMed Central

Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

2008-01-01

Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

PubMed

Nakao, Masatsugu; Yamamoto, Izumi; Maruyama, Yukio; Nakashima, Akio; Matsuo, Nanae; Tanno, Yudo; Ohkido, Ichiro; Ikeda, Masato; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

2016-02-01

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

[Peritonitis in pediatric patients receiving peritoneal dialysis].

PubMed

Jellouli, Manel; Ferjani, Meriem; Abidi, Kamel; Hammi, Yosra; Boutiba, Ilhem; Naija, Ouns; Zarrouk, Chokri; Ben Abdallah, Taieb; Gargah, Tahar

2015-12-01

Peritonitis on catheter of dialysis represents the most frequent complication of the peritoneal dialysis (PD) in the pediatric population. It remains a significant cause of morbidity and mortality. In this study, we investigated the risk factors for peritonitis in children. In this study, we retrospectively collected the records of 85 patients who were treated with PD within the past ten years in the service of pediatrics of the University Hospital Charles-Nicolle of Tunis. Peritonitis rate was 0.75 episode per patient-year. Notably, peritonitis caused by Gram-positive organisms were more common. Analysis of infection risk revealed three significant independent factors: the poor weight (P=0.0045), the non-automated PD (P=0.02) and the short delay from catheter insertion to starting PD (P=0.02). The early onset peritonitis was significantly associated with frequent peritonitis episodes (P=0.0008). The mean duration between the first and second episode of peritonitis was significantly shorter than between PD commencement and the first episode of peritonitis. We revealed a significant association between Gram-negative peritonitis and the presence of ureterostomy (0.018) and between Gram-positive peritonitis and the presence of exit-site and tunnel infections (0.02). Transition to permanent hemodialysis was needed in many children but no death occurred in patients with peritonitis. Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention. Nutritional care must be provided to children to avoid poor weight. The automated dialysis has to be the modality of choice. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Adherence to peritoneal dialysis training schedule.

PubMed

Chow, Kai Ming; Szeto, Cheuk Chun; Leung, Chi Bon; Law, Man Ching; Kwan, Bonnie Ching-Ha; Li, Philip Kam-Tao

2007-02-01

Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients. This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions. Of the 159 incident peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late < or =20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P = 0.04). These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-28

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Degenrative Fibroid and Sclerosing Peritonitis

PubMed Central

Critchley, Michael; Bagley, John; Iqbal, Pervis

2012-01-01

Sclerosing peritonitis is a rare condition characterised by ascites, peritoneal and bowel wall thickening. Causes reported in the literature include luteal ovarian the comas, peritoneal dialysis, peritoneal chemotherapy and liver cirrhosis. We report an interesting case of a woman presenting with diarrhoea, abdominal distension, ascites and pleural effusion. She was subsequently diagnosed with Sclerosing Peritonitis caused by a degenerating fibroid which was successfully treated by Total Abdominal Hysterectomy and Bilateral Salpingoophrectomy. PMID:22928130

Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis.

PubMed

Yokoi, Hideki; Kasahara, Masato; Mori, Kiyoshi; Ogawa, Yoshihisa; Kuwabara, Takashige; Imamaki, Hirotaka; Kawanishi, Tomoko; Koga, Kenichi; Ishii, Akira; Kato, Yukiko; Mori, Keita P; Toda, Naohiro; Ohno, Shoko; Muramatsu, Hisako; Muramatsu, Takashi; Sugawara, Akira; Mukoyama, Masashi; Nakao, Kazuwa

2012-01-01

Long-term peritoneal dialysis induces peritoneal fibrosis with submesothelial fibrotic tissue. Although angiogenesis and inflammatory mediators are involved in peritoneal fibrosis, precise molecular mechanisms are undefined. To study this, we used microarray analysis and compared gene expression profiles of the peritoneum in control and chlorhexidine gluconate (CG)-induced peritoneal fibrosis mice. One of the 43 highly upregulated genes was pleiotrophin, a midkine family member, the expression of which was also upregulated by the solution used to treat mice by peritoneal dialysis. This growth factor was found in fibroblasts and mesothelial cells within the underlying submesothelial compact zones of mice, and in human peritoneal biopsy samples and peritoneal dialysate effluent. Recombinant pleiotrophin stimulated mitogenesis and migration of mouse mesothelial cells in culture. We found that in wild-type mice, CG treatment increased peritoneal permeability (measured by equilibration), increased mRNA expression of TGF-β1, connective tissue growth factor and fibronectin, TNF-α and IL-1β expression, and resulted in infiltration of CD3-positive T cells, and caused a high number of Ki-67-positive proliferating cells. All of these parameters were decreased in peritoneal tissues of CG-treated pleiotrophin-knockout mice. Thus, an upregulation of pleiotrophin appears to play a role in fibrosis and inflammation during peritoneal injury.

Accelerated recovery from Candida peritonitis of enteric origin by early surgical drainage in a peritoneal dialysis patient.

PubMed

Kazama, Itsuro; Muto, Shigeaki; Inoue, Makoto; Fukui, Taro; Kotoda, Atsushi; Takemura, Katsumi; Kimura, Takaaki; Ishikawa, Nobuo; Yagisawa, Takashi; Yumura, Wako; Kusano, Eiji

2011-12-01

A 62-year-old man on continuous ambulatory peritoneal dialysis was transferred to our hospital with recurrent abdominal pain and a cloudy peritoneal effluent. Three weeks before the transfer, his symptoms were successfully treated with broad-spectrum antibiotics. However, their effectiveness was lost for his recurrent symptoms. Fungal peritonitis was diagnosed because of an increased white blood cell count in the peritoneal fluid on admission and isolation of Candida albicans from a peritoneal fluid culture. Intravenous fos-fluconazole was immediately started, although it was ineffective for his deteriorating symptoms. The concomitant isolation of Candida albicans in a stool culture suggested that fungal peritonitis had an enteric origin. An emergency laparotomy revealed multiple diverticulosis and sigmoid colon diverticulitis. A surgical drainage was performed in addition to peritoneal catheter removal. Postoperatively, the patient's symptoms improved rapidly and there were no signs of recurrence with continuous administration of fos-fluconazole. Surgical drainage accelerated the recovery from fungal peritonitis. This patient is the first case showing the usefulness of stool culture in the diagnosis of fungal peritonitis secondary to prior bacterial peritonitis. This case also demonstrated the importance of laparotomy to confirm the enteric origin of the fungus, and the efficacy of early surgical drainage for the treatment.

Peritoneal Macrophage-Specific TNF-α Gene Silencing in LPS-Induced Acute Inflammation Model Using CD44 Targeting Hyaluronic Acid Nanoparticles.

PubMed

Kosovrasti, Verbena Y; Nechev, Lubomir V; Amiji, Mansoor M

2016-10-03

The main goal of this study was to evaluate tumor necrosis factor-alpha (TNF-α) gene silencing in peritoneal macrophages upon activation with lipopolysaccharide (LPS), using CD44-targeting hyaluronic acid (HA)-based nanoparticles encapsulating TNF-α-specific small interfering RNA (siTNF-α). HA nanoparticles were formulated by blending hyaluronic acid-poly(ethylene imine) (HA-PEI), hyaluronic acid-hexyl fatty acid (HA-C6), and hyaluronic acid-poly(ethylene glycol) (HA-PEG) in 3:2:1 weight ratio, and encapsulating siTNF-α to form spherical particles of 78-90 nm diameter. Following intraperitoneal (IP) administration in LPS-treated C57BL/6 mice, the nanoparticles were actively taken up by macrophages and led to a significant downregulation of peritoneal TNF-α level. Downregulation of peritoneal macrophage-specific TNF-α also had a significant impact on other pro-inflammatory cytokine and chemokine levels in the serum. The C57BL/6 group of mice challenged with 5 mg/kg LPS had a significantly higher survival rate when they were treated with 3 mg/kg siTNF-α, either prior or simultaneously with the LPS administration, as compared to the LPS-challenged mice, which were treated with controls including the scrambled siRNA formulation. Overall, the results of this study demonstrate that CD44 targeting HA nanoparticles can selectively deliver siTNF-α to peritoneal macrophages leading to downregulation of pro-inflammatory cytokines in the peritoneal fluid and in the serum. This RNAi strategy could potentially provide an important therapeutic modality for acute inflammatory diseases, such as septic shock.

Comparison of peritonitis rates and patient survival in automated and continuous ambulatory peritoneal dialysis: a 10-year single center experience.

PubMed

El-Reshaid, Wael; Al-Disawy, Hanan; Nassef, Hossameldeen; Alhelaly, Usama

2016-09-01

Peritonitis is a common complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). In this retrospective study, peritonitis rates and patient survival of 180 patients on CAPD and 128 patients on APD were compared in the period from January 2005 to December 2014 at Al-Nafisi Center in Kuwait. All patients had prophylactic topical mupirocin at catheter exit site. Patients on CAPD had twin bag system with Y transfer set. The peritonitis rates were 1 in 29 months in CAPD and 1 in 38 months in APD (p < 0.05). Percentage of peritonitis free patients over 10-year period in CAPD and APD were 49 and 60%, respectively (p < 0.05). Time to develop peritonitis was 10.25 ± 3.1 months in CAPD compared to 16.1 ± 4 months in APD (p < 0.001). Relapse and recurrence rates were similar in both groups. Median patient survival in CAPD and APD groups with peritonitis was 13.1 ± 1 and 14 ± 1.4 months respectively (p = 0.3) whereas in peritonitis free patients it was 15 ± 1.4 months in CAPD and 23 ± 3.1 months in APD (p = 0.025). APD had lower incidence rate of peritonitis than CAPD. Patient survival was better in APD than CAPD in peritonitis free patients but was similar in patients who had peritonitis.

The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.

PubMed

Wang, Qin; Hu, Ke-Jie; Ren, Ye-Ping; Dong, Jie; Han, Qing-Feng; Zhu, Tong-Ying; Chen, Jiang-Hua; Zhao, Hui-Ping; Chen, Meng-Hua; Xu, Rong; Wang, Yue; Hao, Chuan-Ming; Zhang, Xiao-Hui; Wang, Mei; Tian, Na; Wang, Hai-Yan

2016-01-01

♦ Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis. Copyright © 2016 International Society for Peritoneal Dialysis.

A retrospective assessment of risk factors for peritonitis among an urban CAPD population.

PubMed

Korbet, S M; Vonesh, E F; Firanek, C A

1993-01-01

Peritonitis is a major reason why patients transfer from peritoneal dialysis (PD) to hemodialysis. We evaluated the peritonitis infection rates in 146 peritoneal dialysis patients who underwent dialysis at our facility between 1 January 1981 and 31 December 1989. Peritonitis was the primary cause for changing treatment, with 24 (16.4%) of the patients transferring because of this complication. This represented 54.5% of all patients discontinuing CAPD due to method failure. A gamma-Poisson regression analysis was performed in an attempt to identify potential risk factors associated with an increased incidence of peritonitis. The results indicated that race, education level, and PD system used were significantly associated with the rate at which peritonitis occurred in our patient population. There was an almost twofold increase in the rate of peritonitis among blacks as compared to whites (2.2 vs 1.2 episodes/patient year). The level of education completed at the start of dialysis had a negative correlation with peritonitis rates. Patients with < or = 8, 9-12, and > or = 13 years of education had peritonitis rates of 2.4, 1.8, and 1.2 episodes/patient year, respectively. Finally, the system used had a significant effect with our patients on CCPD having lower peritonitis rates as compared to patients on either a connect or disconnect system (0.6 vs 2.5 vs 1.8 episodes/patient year, respectively). Recognizing potential risk factors for peritonitis will help us better understand and address this significant problem in our PD programs. Reducing peritonitis rates should facilitate a decrease in patient transfer due to method failure.

ANTI HISTAMINIC ACTIVITY OF CISSUS QUADRAGULARIS

PubMed Central

Begum, V. Hazeena; Sadique, J.

1999-01-01

Anti histaminic activity of cissus quadrangularis stem powder was carried out determining the histamine activity and histamine content in carrageenin induced rat paw swelling model and formalin induced peritonitis respectively. The crude powder at the dose of 100mg/1QQ00 gm exerted reduction to the maximum of 44% in the early hisamine phase swelling. Further it significantly reduced the histamine content in the peritoneal fluid. For comparison standard steroidal drug hydrocortisone and avil were used. PMID:22556903

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bookman, M.A.; Bast, R.C. Jr.

Small volume residual peritoneal disease in patients undergoing therapy for ovarian carcinoma remains an attractive, but elusive, target for immunobiological therapy. Hypothetical advantages and disadvantages of regional peritoneal therapy are being better defined through increased clinical experience and more sophisticated animal models. Developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology continue to provide an exciting, and nearly overwhelming, array of reagents for clinical evaluation. Ongoing and anticipated investigational trials should provide intriguing data in years to follow.198 references.

Effects of Citral on Lipopolysaccharide-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

PubMed

Song, Yan; Zhao, Hongfeng; Liu, Jinyang; Fang, Chao; Miao, Renying

2016-04-01

Citral is an active compound of lemongrass oil which has been reported to have anti-inflammatory effects. In this study, we investigated the effects of citral on lipopolysaccharide (LPS)-induced inflammatory response in a rat model of peritonitis and human umbilical vein endothelial cells (HUVECs). LPS was intraperitoneally injected into rats to establish a peritonitis model. The HUVECs were treated with citral for 12 h before exposure to LPS. The levels of TNF-α and IL-8 were measured using ELISA. Western blotting was used to detect the expression of VCAM-1, ICAM-1, NF-κB, and PPAR-γ. The results showed that citral had a protective effect against LPS-induced peritonitis. Citral decreased the levels of WBCs and inflammatory cytokines TNF-α and IL-6. Citral also inhibited LPS-induced myeloperoxidase (MPO) activity in the peritoneal tissue. Treatment of HUVECs with citral significantly inhibited TNF-α and IL-8 expression induced by LPS. LPS-induced VCAM-1 and ICAM-1 expression were also suppressed by citral. Meanwhile, we found that citral inhibited LPS-induced NF-κB activation in HUVECs. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, citral inhibits LPS-induced inflammatory response via activating PPAR-γ which attenuates NF-κB activation and inflammatory mediator production.

Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

PubMed

Waniewski, Jacek

2013-11-01

Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

CT, MRI and PET imaging in peritoneal malignancy

PubMed Central

Sahdev, Anju; Reznek, Rodney H.

2011-01-01

Abstract Imaging plays a vital role in the evaluation of patients with suspected or proven peritoneal malignancy. Nevertheless, despite significant advances in imaging technology and protocols, assessment of peritoneal pathology remains challenging. The combination of complex peritoneal anatomy, an extensive surface area that may host tumour deposits and the considerable overlap of imaging appearances of various peritoneal diseases often makes interpretation difficult. Contrast-enhanced multidetector computed tomography (MDCT) remains the most versatile tool in the imaging of peritoneal malignancy. However, conventional and emerging magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT techniques offer significant advantages over MDCT in detection and surveillance. This article reviews established and new techniques in CT, MRI and PET imaging in both primary and secondary peritoneal malignancies and provides an overview of peritoneal anatomy, function and modes of disease dissemination with illustration of common sites and imaging features of peritoneal malignancy. PMID:21865109

Non Candida albicans fungal peritonitis in continuous ambulatory peritoneal dialysis patients.

PubMed

Kleinpeter, M A; Butt, A A

2001-01-01

We report four episodes of non Candida albicans peritonitis (NCAP) in 3 patients on continuous ambulatory peritoneal dialysis (CAPD). Risk factors for NCAP included diabetes mellitus and prior antibiotic use in half of the cases. The antibiotic treatment was prescribed for exit-site infection (ESI) or peritonitis in the patient. Treatment for NCAP included antifungal therapy with oral fluconazole or intravenous amphotericin B. The NCAP resulted in catheter loss in 100% of the patients over time. Initial catheter salvage in one patient was followed 6 months later by catheter loss following treatment of a bacterial peritonitis that was complicated by the development of Candida (Torulopsis) glabrata peritonitis unresponsive to treatment with intravenous amphotericin B. Although the literature suggests that Candida peritonitis responds to oral fluconazole with and without catheter removal, this series suggests that the treatment of NCAP includes removal of the peritoneal dialysis catheter with appropriate antifungal agents.

Risk of Peritoneal Dialysis-Related Peritonitis in a Multi-Racial Asian Population.

PubMed

Ong, Loke Meng; Ch'ng, Chin Chin; Wee, Hong Chin; Supramaniam, Premaa; Zainal, Hadzlinda; Goh, Bak Leong; Bavanandan, Sunita; Mushahar, Lily; Hooi, Lai Seong; Ahmad, Ghazali

♦ BACKGROUND: Peritonitis is one of the most common complications of peritoneal dialysis (PD). Understanding the risk factors of peritonitis in a multi-racial Asian population may help to improve outcomes on PD. ♦ METHODS: We conducted a prospective observational study to identify risk factors for PD-related peritonitis over a 1-year period in 15 adult PD centers. All peritonitis episodes were independently adjudicated. ♦ RESULTS: A total of 1,603 participants with a mean age of 51.6 years comprising 52.7% females, 62.6% ethnic Malays, 27.0% Chinese, and 8.1% Indians were recruited. The overall peritonitis rate was 1 episode per 44.0 patient-months with 354 episodes recorded in 282 (17.6%) patients over 15,588 patient-months. Significant risk factors of peritonitis were severe obesity (incidence-rate ratio [IRR] 3.32, 95% confidence interval [CI]: 1.30, 8.45), hypoalbuminemia (IRR 1.61, 95% CI: 1.06, 2.46), Staphylococcus aureus nasal carriage (IRR 2.26, 95% CI: 1.46, 3.50), and use of Fresenius system (Fresenius Medical Care North America, Waltham, MA, USA) (IRR 2.49, 95% CI: 1.27, 4.89). The risk of peritonitis was lower in those on automated PD compared with standard PD (IRR 0.43, 95% CI: 0.25, 0.74), and in centers with a patient-staff ratio of 15 to 29.9 (IRR 0.67, 95% CI: 0.49, 0.90) and ≥ 30 (IRR 0.52, 95% CI: 0.34, 0.80). Prevalent patients and exit-site care with topical antibiotics were also protective against peritonitis. Peritonitis rates varied between racial groups. The IRRs of overall peritonitis and gram-positive peritonitis in Chinese versus other racial groups were 0.65 (95% CI: 0.46, 0.90) and 0.47 (95% CI: 0.24, 0.91), respectively. ♦ CONCLUSIONS: Multiple patient, center, and PD-system factors influence the risk of peritonitis. In the Asian population, there are racial differences in the risk of peritonitis. Copyright © 2017 International Society for Peritoneal Dialysis.

[Peritonitis in diverticulitis: the Bern concept].

PubMed

Seiler, C A; Brügger, L; Maurer, C A; Renzulli, P; Büchler, M W

1998-01-01

The colon is the most frequent origine for a diffuse peritonitis and diverticular perforation is again the most common source of a spontaneous secondary peritonitis. This paper first focuses on the treatment of peritonitis and secondly on the strategies of source control in peritonitis with special emphasis on the tactics (primary anastomosis vs. Hartmann procedure with colostomy) for surgical source control. Prospective analysis of 404 patients suffering from peritonitis (11/93-2/98), treated with an uniform treatment concept including early operation, source control and extensive intraoperative lavage (20 to 30 liters) as a standard procedure. Other treatment measures were added in special indications "on demand" only. Peritonitis was graded with the Mannheim Peritonitis Index (MPI). Tactics of source control in peritonitis due to diverticulitis were performed according to "general condition" respectively the MPI of the patient. The 404 patients averaged a MPI of 19 (0-35) in "local" peritonitis and a MPI of 26 (11-43) in "diffuse" peritonitis. The colon as a source of peritonitis resulted in MPI of 16 (0-33) in the case of "local" respectively 27 (11-43) in "diffuse" peritonitis. From 181 patients suffering from diverticulitis 144 needed an operation and in 78 (54%) peritonitis was present. Fourty-six percent (36) of the patients suffered from "local", 54% (42) from "diffuse" peritonitis. Resection with primary anastomosis was performed in 26% (20/78) whereas in 74% (58/78) of the patients a Hartmann procedure with colostomy was performed. The correlating MPI was 16 (0-28) vs. 23 (16-27) respectively. The analysis of complications and mortality based on the MPI showed a decent discrimination potential for primary anastomosis vs Hartmann procedure: morbidity 35% vs. 41%; reoperation 5% vs. 5%; mortality 0% vs. 14%. In case of peritonitis due to diverticulitis the treatment of peritonitis comes first. Thanks to advances in intensive care and improved anti-inflammatory care, a more conservative surgical concept nowadays is accepted. In the case of diverticulitis the MPI is helpful to choose between primary anastomosis vs. Hartmann procedure with colostomy as source control. The MPI includes the "general condition" of the patient into the tactical decision how to attain source control.

22-Oxacalcitriol Prevents Progression of Peritoneal Fibrosis in a Mouse Model

PubMed Central

Hirose, Misaki; Nishino, Tomoya; Obata, Yoko; Nakazawa, Masayuki; Nakazawa, Yuka; Furusu, Akira; Abe, Katsushige; Miyazaki, Masanobu; Koji, Takehiko; Kohno, Shigeru

2013-01-01

♦ Objective: Vitamin D plays an important role in calcium homeostasis and is used to treat secondary hyperparathyroidism among dialysis patients. The biologic activity of vitamin D and its analogs is mediated by vitamin D receptor (VDR), which is distributed widely throughout the body. Recent papers have revealed that low vitamin D levels are correlated with severe fibrosis in chronic diseases, including cystic fibrosis and hepatitis. The aim of the present study was to evaluate the protective effects of vitamin D against the progression of peritoneal fibrosis. ♦ Methods: Peritoneal fibrosis was induced by injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. An analog of vitamin D, 22-oxacalcitriol (OCT), was administered subcutaneously daily from initiation of the CG injections. The peritoneal tissue was excised at 3 weeks. Changes in morphology were assessed by hematoxylin and eosin staining. Expression of VDR, alpha smooth muscle actin (as a marker of myofibroblasts), type III collagen, transforming growth factor β(TGF-β), phosphorylated Smad2/3, F4/80 (as a marker of macrophages), and monocyte chemoattractant protein-1 (MCP-1) was examined by immunohistochemistry. Southwestern histochemistry was used to detect activated nuclear factor κB (NF-κB). ♦ Results: In the CG-injected mice, immunohistochemical analysis revealed expression of VDR in mesothelial cells, myofibroblasts, and macrophages in the thickened submesothelial zone. Treatment with OCT significantly prevented peritoneal fibrosis and reduced the accumulation of type III collagen in CG-treated mice. Among the markers of fibrosis, the numbers of myofibroblasts, cells positive for TGF-β, and cells positive for phosphorylated Smad2/3 were significantly decreased in the OCT-treated group compared with the vehicle-treated group. Furthermore, OCT suppressed inflammatory mediators of fibrosis, as shown by the reduced numbers of activated NF-κB cells, macrophages, and MCP-1-expressing cells. ♦ Conclusions: Our results indicate that OCT attenuates peritoneal fibrosis, an effect accompanied by reduced numbers of myofibroblasts, infiltrating macrophages, and TGF-β-positive cells, suggesting that vitamin D has potential as a novel therapeutic agent for preventing peritoneal sclerosis. PMID:23032084

Increased Incidence of Urolithiasis and Bacteremia During Proteus mirabilis and Providencia stuartii Coinfection Due to Synergistic Induction of Urease Activity

PubMed Central

Armbruster, Chelsie E.; Smith, Sara N.; Yep, Alejandra; Mobley, Harry L. T.

2014-01-01

Background. Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. Methods. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Results. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. Conclusions. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI. PMID:24280366

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients.

PubMed

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B Paul; Ito, Yasuhiko

2017-01-01

We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

Effects of Climatic Region on Peritonitis Risk, Microbiology, Treatment, and Outcomes: a Multicenter Registry Study

PubMed Central

Cho, Yeoungjee; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen P.; Brown, Fiona G.; Boudville, Neil; Wiggins, Kathryn J.; Bannister, Kym M.; Clayton, Philip; Johnson, David W.

2013-01-01

♦ Background: The impact of climatic variations on peritoneal dialysis (PD)-related peritonitis has not been studied in detail. The aim of the current study was to determine whether various climatic zones influenced the probability of occurrence or the clinical outcomes of peritonitis. ♦ Methods: Using ANZDATA registry data, the study in cluded all Australian patients receiving PD between 1 October 2003 and 31 December 2008. Climatic regions were defined according to the Köppen classification. ♦ Results: The overall peritonitis rate was 0.59 episodes per patient-year. Most of the patients lived in Temperate regions (65%), with others residing in Subtropical (26%), Tropical (6%), and Other climatic regions (Desert, 0.6%; Grassland, 2.3%). Compared with patients in Temperate regions, those in Tropical regions demonstrated significantly higher overall peritonitis rates and a shorter time to a first peritonitis episode [adjusted hazard ratio: 1.15; 95% confidence interval (CI): 1.01 to 1.31]. Culture-negative peritonitis was significantly less likely in Tropical regions [adjusted odds ratio (OR): 0.42; 95% CI: 0.25 to 0.73]; its occurrence in Subtropical and Other regions was comparable to that in Temperate regions. Fungal peritonitis was independently associated with Tropical regions (OR: 2.18; 95% CI: 1.22 to 3.90) and Other regions (OR: 3.46; 95% CI: 1.73 to 6.91), where rates of antifungal prophylaxis were also lower. Outcomes after first peritonitis episodes were comparable in all groups. ♦ Conclusions: Tropical regions were associated with a higher overall peritonitis rate (including fungal peritonitis) and a shorter time to a first peritonitis episode. Augmented peritonitis prophylactic measures such as antifungal therapy and exit-site care should be considered in PD patients residing in Tropical climates. PMID:22942270

Effect of the Dialysis Fluid Buffer on Peritoneal Membrane Function in Children

PubMed Central

Nau, Barbara; Gemulla, Gita; Bonzel, Klaus E.; Hölttä, Tuula; Testa, Sara; Fischbach, Michel; John, Ulrike; Kemper, Markus J.; Sander, Anja; Arbeiter, Klaus; Schaefer, Franz

2013-01-01

Summary Background and objectives Double-chamber peritoneal dialysis fluids exert less toxicity by their neutral pH and reduced glucose degradation product content. The role of the buffer compound (lactate and bicarbonate) has not been defined in humans. Design, setting, participants, & measurements A multicenter randomized controlled trial in 37 children on automated peritoneal dialysis was performed. After a 2-month run-in period with conventional peritoneal dialysis fluids, patients were randomized to neutral-pH, low-glucose degradation product peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content. Clinical and biochemical monitoring was performed monthly, and peritoneal equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and 10 months. Results No statistically significant difference in capillary blood pH, serum bicarbonate, or oral buffer supplementation emerged during the study. At baseline, peritoneal solute equilibration and clearance rates were similar. During the study, 4-hour dialysis to plasma ratio of creatinine tended to increase, and 24-hour dialytic creatinine and phosphate clearance increased with lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis fluid. Daily net ultrafiltration, which was similar at baseline (lactate fluid=5.4±2.6 ml/g glucose exposure, bicarbonate fluid=4.9±1.9 ml/g glucose exposure), decreased to 4.6±1.0 ml/g glucose exposure in the lactate peritoneal dialysis fluid group, whereas it increased to 5.1±1.7 ml/g glucose exposure in the bicarbonate content peritoneal dialysis fluid group (P=0.006 for interaction). Conclusions When using biocompatible peritoneal dialysis fluids, equally good acidosis control is achieved with lactate and bicarbonate buffers. Improved long-term preservation of peritoneal membrane function may, however, be achieved with bicarbonate-based peritoneal dialysis fluids. PMID:23124784

[Peritoneal dialysis at a regional hospital in Norway].

PubMed

Paulsen, Dag; Solbakken, Kjell; Valset, Torstein

2011-08-23

In 2006, an expert group appointed by the Norwegian Social and Health Directory recommended that the proportion of patients on peritoneal dialysis should increase from 15 % to about 30 %. We wanted to investigate if treatment in our hospital was in compliance with that recommendation. The patient material consisted of the total number of patients on dialysis and anonymised data collected for patients treated with peritoneal dialysis at Innlandet Hospital Trust, Lillehammer in the period 1.01.2004-31.12.2008. For patients in peritoneal dialysis we assessed patient dynamics, length of hospital stay, incidence of peritonitis, need for assistance and organisation of peritoneal dialysis activity. Dialysis treatment was given to 176 patients, 62 (35 %) of whom were treated by peritoneal dialysis for at least 30 days (mean treatment time 16.2 months). 17 patients were switched from hemodialysis to peritoneal dialysis and nine patients from peritoneal dialysis to hemodialysis. Patients older than 70 years stayed in hospital 6 days longer than those younger than 70 years. 27 (44 %) of the patients acquired peritonitis in the study period and 18 (29 %) patients needed help to exchange the dialysis bag. The proportion of patients treated with peritoneal dialysis in our hospital has reached the recommended level. The reason may be that all eligible patients are offered peritoneal dialysis and that the treatment chain is well organised.

Peritonitis as the First Presentation of Disseminated Listeriosis in a Patient on Peritoneal Dialysis-a Case Report.

PubMed

Beckerleg, Weiwei; Keskar, Vaibhav; Karpinski, Jolanta

2017-01-01

Infections with Listeria monocytogenes are uncommon but serious, with mortality rate approaching 30% in cases of systemic involvement despite first-line therapy. They are usually caused by ingestion of contaminated foods, but spontaneous infections have also been described. Listeria monocytogenes is a rare cause of peritonitis, and most of the published cases are in patients with cirrhosis and ascites. There are a few reported cases of Listeria peritonitis associated with peritoneal dialysis (PD), primarily isolated peritonitis.If detected early, Listeria peritonitis can be successfully treated with ampicillin, alone or in combination with gentamicin. Vancomycin has been listed as a second-line agent. However, it has been associated with treatment failure.In this case report, we present a patient who developed disseminated listeriosis, with peritonitis as the first manifestation of disseminated infection. This case illustrates the importance of having a high index of suspicion for L. monocytogenes if patients deteriorate despite empiric therapy for PD-associated peritonitis and serves as a further example demonstrating the inadequate coverage of vancomycin for L. monocytogenes . Copyright © 2017 International Society for Peritoneal Dialysis.

Combination therapy of 15-epi-lipoxin A4 with antibiotics protects mice from Escherichia coli-induced sepsis*.

PubMed

Ueda, Tomomi; Fukunaga, Koichi; Seki, Hiroyuki; Miyata, Jun; Arita, Makoto; Miyasho, Taku; Obata, Toru; Asano, Koichiro; Betsuyaku, Tomoko; Takeda, Junzo

2014-04-01

Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Prospective experimental study. University research laboratory. Male C57BL/6 mice. Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli. 15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

Improved biocompatibility of bicarbonate/lactate-buffered PDF is not related to pH.

PubMed

Zareie, Mohammad; Keuning, Eelco D; ter Wee, Piet M; Schalkwijk, Casper G; Beelen, Robert H J; van den Born, Jacob

2006-01-01

Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo. Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n=7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n=8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n=5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n=7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n=8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed. Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters P<0.05), accompanied by increased glucose absorption and reduced ultrafiltration capacity. Daily exposure to standard or acidified bicarbonate/lactate-buffered PDF improved the performance of the peritoneal membrane, evidenced by reduced new vessel formation in omentum (P<0.02) and parietal peritoneum (P<0.008), reduced fibrosis (P<0.02) and improved ultrafiltration capacity. No significant differences were found between standard and acidified bicarbonate/lactate-buffered PDF. During PET, acidic PDF was neutralized within 15 to 20 min. The bicarbonate/lactate-buffered PDF, acidity per se did not contribute substantially to peritoneal worsening in our in vivo model for PD, which might be explained by the buffering capacity of the peritoneum.

Peritoneal Dialysis

MedlinePlus

... include: Infections. An infection of the abdominal lining (peritonitis) is a common complication of peritoneal dialysis. An ... day. You might have a lower risk of peritonitis because you connect and disconnect to the dialysis ...

Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

PubMed

Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

2017-02-01

Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4^th hour of PET as slow transporter (< 0.47), slow-average transporter (0.47 - 0.56), fast-average transporter (0.57 - 0.67), and fast transporter (> 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p < 0.001) and therefore higher peritoneal phosphorus clearance (61.7 ± 15.1 L/week/1.73 m² vs. 48.4 ± 14.0 L/week/1.73 m², p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
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Prophylactic Antibiotics for Endoscopy-Associated Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Wu, Hsin-Hsu; Li, I-Jung; Weng, Cheng-Hao; Lee, Cheng-Chia; Chen, Yung-Chang; Chang, Ming-Yang; Fang, Ji-Tseng; Hung, Cheng-Chieh; Yang, Chih-Wei; Tian, Ya-Chung

2013-01-01

Introduction Continuous ambulatory peritoneal dialysis (CAPD) peritonitis may develop after endoscopic procedures, and the benefit of prophylactic antibiotics is unclear. In the present study, we investigated whether prophylactic antibiotics reduce the incidence of peritonitis in these patients. Patients and methods We retrospectively reviewed all endoscopic procedures, including esophagogastroduodenoscopy (EGD), colonoscopy, sigmoidoscopy, cystoscopy, hysteroscopy, and hysteroscopy-assisted intrauterine device (IUD) implantation/removal, performed in CAPD patients at Chang Gung Memorial Hospital, Taiwan, between February 2001 and February 2012. Results Four hundred and thirty-three patients were enrolled, and 125 endoscopies were performed in 45 patients. Eight (6.4%) peritonitis episodes developed after the examination. Antibiotics were used in 26 procedures, and none of the patients had peritonitis (0% vs. 8.1% without antibiotic use; p = 0.20). The peritonitis rate was significantly higher in the non-EGD group than in the EGD group (15.9% [7/44] vs. 1.2% [1/81]; p<0.005). Antibiotic use prior to non-EGD examinations significantly reduced the endoscopy-associated peritonitis rate compared to that without antibiotic use (0% [0/16] vs. 25% [7/28]; p<0.05). Peritonitis only occurred if invasive procedures were performed, such as biopsy, polypectomy, or IUD implantation, (noninvasive procedures, 0% [0/20] vs. invasive procedures, 30.4% [7/23]; p<0.05). No peritonitis was noted if antibiotics were used prior to examination with invasive procedures (0% [0/10] vs. 53.8% [7/13] without antibiotic use; p<0.05). Although not statistically significant, antibiotics may play a role in preventing gynecologic procedure-related peritonitis (antibiotics, 0% [0/4] vs. no antibiotics, 55.6% [5/9]; p = 0.10). Conclusion Antibiotic prophylaxis significantly reduced endoscopy-associated PD peritonitis in the non-EGD group. Endoscopically assisted invasive procedures, such as biopsy, polypectomy, IUD implantation/removal, and dilatation and curettage (D&C), pose a high risk for peritonitis. Prophylactic antibiotics for peritonitis prevention may be required in colonoscopic procedures and gynecologic procedures. PMID:23936514

Indication for peritoneal biopsy in tuberculous peritonitis.

PubMed

Chow, Kai Ming; Chow, Viola Chi-Ying; Szeto, Cheuk Chun

2003-06-01

With the introduction of effective antituberculous chemotherapy, the clinical outcome of tuberculous peritonitis depends much on the diagnostic accuracy of this disease entity. This review summarizes the current state-of-the-art thinking regarding the protean manifestation and diagnostic modalities of this major infectious disease. This review was compiled after an extensive search of the current and historical literature, comprising 1,070 cases of tuberculous peritonitis. A number of important areas were highlighted, with emphasis on the diagnostic value and clinical impact of peritoneal biopsy. We believe an aggressive diagnostic approach, particularly with peritoneal biopsy, is warranted for the diagnosis and timely treatment of tuberculous peritonitis.

Correlation of plasma and peritoneal diasylate clomipramine concentration with hemodynamic recovery after intralipid infusion in rabbits.

PubMed

Harvey, Martyn; Cave, Grant; Hoggett, Kerry

2009-02-01

Drug sequestration to an expanded plasma lipid phase has been proposed as a potential mechanism of action for lipid emulsions in lipophilic cardiotoxin overdose. The authors set out to document plasma and peritoneal diasylate clomipramine concentration after resuscitation with lipid emulsion in a rabbit model of clomipramine-induced hypotension. Twenty sedated mechanically ventilated New Zealand White rabbits were allocated to receive either 12 mL/kg 20% Intralipid or 12 mL/kg saline solution, following clomipramine infusion to 50% baseline mean arterial pressure (MAP). Hemodynamic parameters and serum clomipramine concentration were determined to 59 minutes. Peritoneal dialysis with 20% Intralipid or saline solution was evaluated for clomipramine concentration. Mean arterial pressure was greater in lipid-treated animals as assessed by repeated-measures analysis of variance (F[1,14] = 6.84; p = 0.020). Lipid infusion was associated with elevated plasma clomipramine concentration and reduced initial volume of distribution (Vd; 5.7 [+/-1.6] L/kg lipid vs. 15.9 [+/-7.2] L/kg saline; p = 0.0001). Peritoneal diasylate clomipramine concentration was greater in lipid-treated animals (366.2 [+/-186.2] microg/L lipid vs. 37.7 [+/-13.8] microg/L saline; p = 0.002). Amelioration of clomipramine-induced hypotension with lipid infusion is associated with reduced initial Vd and elevated plasma clomipramine concentration consistent with intravascular drug-lipid sequestration. Concomitant peritoneal dialysis with lipid emulsion enhances clomipramine extraction.

Fimbrial phase variation and systemic E. coli infection studied in the mouse peritonitis model.

PubMed

Nowicki, B; Vuopio-Varkila, J; Viljanen, P; Korhonen, T K; Mäkelä, P H

1986-08-01

Mouse peritonitis induced by intraperitoneal injection of a virulent (LD50 4 x 10(5) E. coli 018:K1:H7 strain isolated from neonatal meningitis was studied. These bacteria are capable of producing both type 1 and S fimbriae, binding to mannose or sialic acid containing glycoconjugates, respectively; the production of both fimbrial types is subject to phase variation. A broth culture of the bacteria was fractionated into subpopulations containing either type 1 or S fimbriae or neither (nonfimbriated cells), and each fraction, grown in broth to logarithmic growth phase, was used to infect groups of mice. The type 1 fraction was associated with decreased virulence as the fraction was eliminated rapidly without causing a progressive infection even at 10(6) bacteria/mouse, whereas both S and nonfimbriated cells started rapid multiplication in the peritoneal cavity and spread to the blood. In nonfibriated cells, however, S fimbriae production was induced at the same time so that at 1 h after injection, 60-70% of the bacteria in the peritoneal cavity and in the blood of the mice had S fimbriae. The injected S-fimbriated fraction remained completely S-fimbriated. Rapid induction of S fimbriae also took place in vitro when the nonfimbriated bacteria were grown in mouse serum or peritoneal fluid. Anti-S serum protected the mice from a lethal dose of S-fimbriated bacteria.

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis.

PubMed

Ito, Fumiya; Nishiyama, Takahiro; Shi, Lei; Mori, Masahiko; Hirayama, Tasuku; Nagasawa, Hideko; Yasui, Hiroyuki; Toyokuni, Shinya

2016-08-05

Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing ∼40-80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does. Copyright © 2016 Elsevier Inc. All rights reserved.

Rates of Intentional and Unintentional Nonadherence to Peritoneal Dialysis Regimes and Associated Factors.

PubMed

Yu, Zhen Li; Lee, Vanessa Yin Woan; Kang, Augustine Wee Cheng; Chan, Sally; Foo, Marjorie; Chan, Choong Meng; Griva, Konstadina

2016-01-01

With increasing emphasis on expanding home-based dialysis, there is a need to understand adherence outcomes. This study set out to examine the prevalence and predictors of nonadherence among patients undergoing peritoneal dialysis. A cross sectional sample of 201 peritoneal dialysis patients recruited between 2010-2011 from Singapore General Hospital completed measures of quality of life, medication beliefs, self-efficacy and emotional distress. Nonadherence rates were high; 18% for dialysis, 46% for medication and 78% for diet. Intentional nonadherence was more common for dialysis (p = .03), whereas unintentional nonadherence was more common for medication (p = .002). Multivariate models indicated significant associations for higher education (intermediate vs low OR = 3.18, high vs low OR = 4.70), lower environment quality of life (OR = 0.79), dialysis self-efficacy (OR = 0.80) with dialysis nonadherence; higher education (OR = 2.22), self-care peritoneal dialysis (OR = 3.10), perceived necessity vs concerns over medication (OR = 0.90), self-efficacy (OR = 0.76) with nonadherence to medication. The odds for nonadherence to diet were higher among patients who were younger (OR = 0.96), of Chinese ethnicity (OR = 2.99) and those reporting better physical health (OR = 1.30) and lower self-efficacy (OR = 0.49). Nonadherence is common in peritoneal dialysis. Self-efficacy and beliefs about medication are promising targets for interventions designed to improve adherence.

The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease

PubMed Central

Schwarzberg, Karen; Le, Rosalin; Bharti, Balambal; Lindsay, Suzanne; Casaburi, Giorgio; Salvatore, Francesco; Saber, Mohamed H.; Alonaizan, Faisal; Slots, Jørgen; Gottlieb, Roberta A.; Caporaso, J. Gregory; Kelley, Scott T.

2014-01-01

Periodontitis is a progressive disease of the periodontium with a complex, polymicrobial etiology. Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased periodontal sites. In this study, we used NGS approaches to characterize changes in periodontal pocket bacterial diversity after standard periodontal treatment. Despite consistent changes in the abundance of certain taxa in individuals whose condition improved with treatment, post-treatment samples retained the highest similarity to pre-treatment samples from the same individual. Deeper phylogenetic analysis of periodontal pathogen-containing genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response among species. Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance. PMID:24489772

Noisy neighbourhoods: quorum sensing in fungal–polymicrobial infections

PubMed Central

Dixon, Emily F.

2015-01-01

Summary Quorum sensing was once considered a way in which a species was able to sense its cell density and regulate gene expression accordingly. However, it is now becoming apparent that multiple microbes can sense particular quorum‐sensing molecules, enabling them to sense and respond to other microbes in their neighbourhood. Such interactions are significant within the context of polymicrobial disease, in which the competition or cooperation of microbes can alter disease progression. Fungi comprise a small but important component of the human microbiome and are in constant contact with bacteria and viruses. The discovery of quorum‐sensing pathways in fungi has led to the characterization of a number of interkingdom quorum‐sensing interactions. Here, we review the recent developments in quorum sensing in medically important fungi, and the implications these interactions have on the host's innate immune response. PMID:26243526

Combining ANOVA-PCA with POCHEMON to analyse micro-organism development in a polymicrobial environment.

PubMed

Geurts, Brigitte P; Neerincx, Anne H; Bertrand, Samuel; Leemans, Manja A A P; Postma, Geert J; Wolfender, Jean-Luc; Cristescu, Simona M; Buydens, Lutgarde M C; Jansen, Jeroen J

2017-04-22

Revealing the biochemistry associated to micro-organismal interspecies interactions is highly relevant for many purposes. Each pathogen has a characteristic metabolic fingerprint that allows identification based on their unique multivariate biochemistry. When pathogen species come into mutual contact, their co-culture will display a chemistry that may be attributed both to mixing of the characteristic chemistries of the mono-cultures and to competition between the pathogens. Therefore, investigating pathogen development in a polymicrobial environment requires dedicated chemometric methods to untangle and focus upon these sources of variation. The multivariate data analysis method Projected Orthogonalised Chemical Encounter Monitoring (POCHEMON) is dedicated to highlight metabolites characteristic for the interaction of two micro-organisms in co-culture. However, this approach is currently limited to a single time-point, while development of polymicrobial interactions may be highly dynamic. A well-known multivariate implementation of Analysis of Variance (ANOVA) uses Principal Component Analysis (ANOVA-PCA). This allows the overall dynamics to be separated from the pathogen-specific chemistry to analyse the contributions of both aspects separately. For this reason, we propose to integrate ANOVA-PCA with the POCHEMON approach to disentangle the pathogen dynamics and the specific biochemistry in interspecies interactions. Two complementary case studies show great potential for both liquid and gas chromatography - mass spectrometry to reveal novel information on chemistry specific to interspecies interaction during pathogen development. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Macrophage genetic reprogramming during chronic peritonitis is augmented by LPS pretreatment.

PubMed

Kanaan, Ziad; Gardner, Sarah; Carruba, Christopher; Mattingly, Jameson; Druen, Devin; Cheadle, William G

2012-06-15

Persistent and tertiary chronic peritonitis is a clinically challenging problem especially in those who are critically ill. This could be attributed to a state of immune-paralysis, known as microbial tolerance. Microbial tolerance is the diminished pro-inflammatory protein response following repeated stimulation by numerous pathogen-associated molecular patterns (PAMPs) of varying origins, which we have shown in this novel model of chronic peritonitis. We aimed in this study to investigate the molecular mechanisms behind microbial tolerance and the early innate immune response resolution in this model. C57BL/6 mice were pretreated intra-peritoneally (IP) with saline or endotoxin LPS 10 mg/kg (LPS 10). Following pretreatment, peritonitis was induced 24 h later injecting 10(3)Klebsiella pneumonia CFU IP. Gentamicin was administered 4 h prior to infection and BID thereafter. Peritoneal exudate cells (PEC) were obtained through peritoneal lavage and RNA was isolated (n = 3) at 4, 24, and 48 h following infection. SA Biosciences© RT2-Profiler PCR array mouse Toll-like receptor signaling pathway (PAMM_018A) data were further analyzed by Ingenuity Pathway Inc. analysis (IPA). Of the 89 genes studied, 26 were significantly up-regulated (fold change > 1.2 and P value < 0.05) in the saline pretreated group at 4, 24, and 48 h after infection. There were no down-regulated genes. In the LPS-pretreated group, 35 genes were significantly up-regulated; of these genes, 13 were not increased in the saline pretreated infected mice. This left 22 up-regulated genes in both infected groups. At 4 h, 6 of these 22 genes (CHUK, HMGB1, HSPD1, IRAK2, LY96, and TLR4) were further 2-fold increased in the LPS pretreatment group compared with the saline pretreatment group. Only IRAK2 was 2-fold increased at 24 h. By 48 h, no LPS effect was seen. When applying IPA analysis, six main canonical pathways were constantly dysregulated in the same significance order in both the saline and LPS group at 4, 24, and 48 h. These were: Toll-like receptor and NF-κB signaling, hepatic cholestasis, interleukin-6, and LPS-mediated MAPK signaling pathways, and pattern recognition receptors of bacterial pathway. Peritonitis increased PEC gene expression associated with sepsis and a pro-inflammatory response, which was further augmented by LPS pretreatment over 24 h only. Prior exposure to LPS did not induce PEC gene tolerance to subsequent infection with Klebsiella at the mRNA level. Post-transcriptional modification as microRNA down-regulation of inflammatory cytokines could possibly explain such phenomena. Published by Elsevier Inc.

Neutral Solution Low in Glucose Degradation Products Is Associated with Less Peritoneal Fibrosis and Vascular Sclerosis in Patients Receiving Peritoneal Dialysis

PubMed Central

Kawanishi, Kunio; Honda, Kazuho; Tsukada, Misao; Oda, Hideaki; Nitta, Kosaku

2013-01-01

♦ Background: The effects of novel biocompatible peritoneal dialysis (PD) solutions on human peritoneal membrane pathology have yet to be determined. Quantitative evaluation of human peritoneal biopsy specimens may reveal the effects of the new solutions on peritoneal membrane pathology. ♦ Methods: Peritoneal specimens from 24 PD patients being treated with either acidic solution containing high-glucose degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12) were investigated at the end of PD. As controls, pre-PD peritoneal specimens, obtained from 13 patients at PD catheter insertion, were also investigated. The extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end-product (AGE) accumulation were evaluated by quantitative or semi-quantitative methods. The average densities of CD31-positive vessels and podoplanin-positive lymphatic vessels were also determined. ♦ Results: Peritoneal membrane fibrosis, vascular sclerosis, and AGE accumulation were significantly suppressed in the neutral group compared with the acidic group. The neutral group also showed lower peritoneal equilibration test scores and preserved ultrafiltration volume. The density of blood capillaries, but not of lymphatic capillaries, was significantly increased in the neutral group compared with the acidic and pre-PD groups. ♦ Conclusions: Neutral solutions with low GDPs are associated with less peritoneal membrane fibrosis and vascular sclerosis through suppression of AGE accumulation. However, contrary to expectation, blood capillary density was increased in the neutral group. The altered contents of the new PD solutions modified peritoneal membrane morphology and function in patients undergoing PD. PMID:23123670

Non-compliance to the continuous ambulatory peritoneal dialysis procedure increases the risk of peritonitis.

PubMed

Mawar, Shashi; Gupta, Sanjay; Mahajan, Sandeep

2012-08-01

Peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) is the leading cause of technique failure. Information on the impact of non-compliance in performing CAPD exchange on peritonitis is limited. We aimed to find the prevalence of non-compliance to the CAPD procedure and its influence on the incidence of peritonitis. This observational study included 30 adult patients undergoing CAPD. The CAPD exchange procedure was observed at home and assessed as per the structured checklist and categorized into poor, average and good compliance. The compliance was correlated with the episodes of peritonitis in previous 1 year. The patients' mean age was 52 ± 13 years and the mean duration of CAPD was 2.1 ± 0.9 years. Only 16.5% of patients were good performers, while 67% were average performers, and 16.5% were poor performers. The technique skill was similar across all the steps of the procedure. The most common improperly performed steps were: not putting on a face mask in 68%, not flushing the tubing system in 60%, and not washing hands in 24%. Poor adherence to procedure was independent of age, gender, education and duration of dialysis. Ten episodes of peritonitis occurred in 5 patients over 1-year period. Peritonitis occurred in 60% of poor performers, whereas fully compliant patients had no peritonitis. Also 40% of the poorly compliant patients had multiple episodes of peritonitis. Poor compliance in performing the CAPD procedure is a modifiable risk factor for peritonitis. Adherence to recommended aseptic technique is the cornerstone of peritonitis prevention.

IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-05-01

Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2015-01-15

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.

PubMed

Abrahams, Alferso C; Habib, Sayed M; Dendooven, Amélie; Riser, Bruce L; van der Veer, Jan Willem; Toorop, Raechel J; Betjes, Michiel G H; Verhaar, Marianne C; Watson, Christopher J E; Nguyen, Tri Q; Boer, Walther H

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFβ1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

PubMed Central

Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

2014-01-01

Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study. PMID:25384022

Benefit of an operating vehicle preventing peritonitis in peritoneal dialysis patients: a retrospective, case-controlled study.

PubMed

Fang, Pan; Lu, Jia; Liu, Ying-Hong; Deng, Hong-Mei; Zhang, Lei; Zhang, Hong-Qing

2018-06-01

Peritonitis, which is one of the leading complications of peritoneal dialysis (PD) worldwide, severely affected morbidity and mortality of the PD patients. Although many efforts have been made to prevent PD-related peritonitis, it seems impossible to prevent it completely. Many causes have been reported to lead to peritonitis, and contamination during bag exchange is one of the important risk factors for peritonitis. Here, we introduce an operating vehicle, which we invented to provide a sterile and safe space for bag exchange. A single-center, retrospective, case-control study was undertaken to determine whether this operating vehicle has a protective role in preventing peritonitis. In total, 462 continuous ambulatory peritoneal dialysis patients were included in this study from October 2014 to March 2017. According to their personal will, these patients chose to use operating vehicle or traditional method during their bag exchange. The demographic, clinical and laboratory data of these patients in the two groups were collected, analyzed and compared. Of 462 patients with home dialysis, operating vehicle group consisted of 61 patients, and control group consisted of 401 patients. In the control group, over 677 patient-years, peritonitis occurred in 69 of 401 patients (17.2%), while in the operating vehicle group, over 60 patient-years, only 4 of 61 patients (6.6%) had episodes of peritonitis. The number of patients suffered from peritonitis was significantly decreased in the operating vehicle group (P = 0.034). Besides, there were a total of 99 episodes of peritonitis, and the rate was 1 episode every 7.2 patient-years in control group and 1 episode every 12 patient-years in the operating vehicle group. There was significant difference between the two groups (0.013). Positive dialysate cultures were obtained in majority of the peritonitis episodes (60.6%). Operating vehicle might help to reduce PD-related peritonitis by preventing contamination during bag exchange. Further studies are still needed to demonstrate the protective role of the operating vehicle in preventing peritonitis.

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambertucci, Flavia

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial rolemore » of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.« less

A case of bacterial peritonitis caused by Roseomonas mucosa in a patient undergoing continuous ambulatory peritoneal dialysis.

PubMed

Matsukuma, Yuta; Sugawara, Koji; Shimano, Shota; Yamada, Shunsuke; Tsuruya, Kazuhiko; Kitazono, Takanari; Higashi, Harumichi

2014-11-01

Bacterial peritonitis remains a life-threatening complication of peritoneal dialysis (PD). Roseomonas is a bacterial genus of pink-pigmented, oxidized, gram-negative coccobacilli that was first named in 1993. Importantly, Roseomonas mucosa exhibits antibiotic resistance, with significant resistance to cephalosporin, which is often selected as an empirical antibiotic regimen for peritonitis in PD patients. We herein report the case of a PD patient with bacterial peritonitis caused by Roseomonas mucosa that was fortunately identified using 16S rRNA gene sequencing and successfully treated with ciprofloxacin. Given that Roseomonas demonstrates resistance to a variety of antibiotics. The administration of empiric antibiotic therapy based on the recommendation of the International Society of Peritoneal Dialysis guidelines occasionally fails, leading to the aggravation of bacterial peritonitis. Hence, nephrologists should consider Roseomonas as one of the potential causative organisms of peritonitis, especially when gram-negative bacilli are resistant to cephalosporin and cannot be identified using standard laboratory methods.

Platelets Induce Apoptosis during Sepsis in a Contact-Dependent Manner That Is Inhibited by GPIIb/IIIa Blockade

PubMed Central

Sharron, Matthew; Hoptay, Claire E.; Wiles, Andrew A.; Garvin, Lindsay M.; Geha, Mayya; Benton, Angela S.; Nagaraju, Kanneboyina; Freishtat, Robert J.

2012-01-01

Purpose End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. Methods End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. Measurements and Main Results There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. Conclusions In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis. PMID:22844498

beta-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes.

PubMed

Basher, Fahmin; Fan, Hongkuan; Zingarelli, Basilia; Borg, Keith T; Luttrell, Lou M; Tempel, George E; Halushka, Perry V; Cook, James A

2008-01-01

Heterotrimeric Gi proteins have been previously implicated in signaling leading to inflammatory mediator production induced by bacterial lipopolysaccharide (LPS). beta-arrestins are ubiquitously expressed proteins that alter G-protein-coupled receptors signaling. beta-arrestin 2 plays a multifaceted role as a scaffold protein in regulating cellular inflammatory responses. Polymorphonuclear leukocytes (PMNs) activated by LPS induce inflammatory responses resulting in organ injury during sepsis. We hypothesized that beta-arrestin 2 is a critical modulator of inflammatory responses in PMNs. To examine the potential role of beta-arrestin 2 in LPS-induced cellular activation, we studied homozygous beta-arrestin 2 (-/-), heterozygous (+/-), and wildtype (+/+) mice. PMNs were stimulated with LPS for 16h. There was increased basal TNFalpha and IL-6 production in the beta-arrestin 2 (-/-) compared to both beta-arrestin 2 (+/-) and (+/+) cells. LPS failed to stimulate TNFalpha production in the beta-arrestin 2 (-/-) PMNs. However, LPS stimulated IL-6 production was increased in the beta-arrestin 2 (-/-) cells compared to (+/+) cells. In subsequent studies, peritoneal PMN recruitment was increased 81% in the beta-arrestin 2 (-/-) mice compared to (+/+) mice (p<0.05). beta-arrestin 2 deficiency resulted in an augmented expression of CD18 and CD62L (p<0.05). In subsequent studies, beta-arrestin 2 (-/-) and (+/+) mice were subjected to cecal ligation and puncture (CLP) and lung was collected and analyzed for myeloperoxidase activity (MPO) as index of PMNs infiltrate. CLP-induced MPO activity was significantly increased (p<0.05) in the beta-arrestin 2 (-/-) compared to (+/+) mice. These studies demonstrate that beta-arrestin 2 is a negative regulator of PMN activation and pulmomary leukosequestration in response to polymicrobial sepsis.

β-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes

PubMed Central

Basher, Fahmin; Fan, Hongkuan; Zingarelli, Basilia; Borg, Keith T.; Luttrell, Lou M.; Tempel, George E.; Halushka, Perry V.; Cook, James A.

2008-01-01

Heterotrimeric Gi proteins have been previously implicated in signaling leading to inflammatory mediator production induced by bacterial lipopolysaccharide (LPS). β-arrestins are ubiquitously expressed proteins that alter G-protein-coupled receptors signaling. β-arrestin 2 plays a multifaceted role as a scaffold protein in regulating cellular inflammatory responses. Polymorphonuclear leukocytes (PMNs) activated by LPS induce inflammatory responses resulting in organ injury during sepsis. We hypothesized that β-arrestin 2 is a critical modulator of inflammatory responses in PMNs. To examine the potential role of β-arrestin 2 in LPS-induced cellular activation, we studied homozygous β-arrestin 2 (-/-), heterozygous (+/-), and wildtype (+/+) mice. PMNs were stimulated with LPS for 16h. There was increased basal TNFα and IL-6 production in the β-arrestin 2 (-/-) compared to both β-arrestin 2 (+/-) and (+/+) cells. LPS failed to stimulate TNFα production in the β-arrestin 2 (-/-) PMNs. However, LPS stimulated IL-6 production was increased in the β-arrestin 2 (-/-) cells compared to (+/+) cells. In subsequent studies, peritoneal PMN recruitment was increased 81% in the β-arrestin 2 (-/-) mice compared to (+/+) mice (p<0.05). β-arrestin 2 deficiency resulted in an augmented expression of CD18 and CD62L (p<0.05). In subsequent studies, β-arrestin 2 (-/-) and (+/+) mice were subjected to cecal ligation and puncture (CLP) and lung was collected and analyzed for myeloperoxidase activity (MPO) as index of PMNs infiltrate. CLP-induced MPO activity was significantly increased (p<0.05) in the β-arrestin 2 (-/-) compared to (+/+) mice. These studies demonstrate that β-arrestin 2 is a negative regulator of PMN activation and pulmomary leukosequestration in response to polymicrobial sepsis. PMID:19079685

Effects of ω-3 Polyunsaturated Fatty Acids on the Homeostasis of CD4+ T Cells and Lung Injury in Mice With Polymicrobial Sepsis.

PubMed

Chang, Yu-Fan; Hou, Yu-Chen; Pai, Man-Hui; Yeh, Sung-Ling; Liu, Jun-Jen

2017-07-01

Sepsis is a common cause of death in critically ill patients. An overwhelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. ω-3 Polyunsaturated fatty acids (PUFAs) were found to have anti-inflammatory and immunomodulatory properties. This study investigated the effects of ω-3 PUFAs on the balance of Th subsets, Treg cells, and the inflammatory response in septic mice. Mice were randomly assigned to soybean oil (SO) and fish oil (FO) groups. The 2 groups received an identical nutrient distribution except for the sources of the fat. The SO group was fed soybean oil, while part of the soybean oil was replaced by fish oil in the FO group. The FO group had an ω-6/ω-3 PUFA ratio of 2:1. After feeding the diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed on days 0, 1, and 3. Compared with the SO group, the FO group had lower inflammatory mediator levels in the plasma and peritoneal lavage fluid after CLP. Also, the FO group had lower Th1, Th2, and Th17 percentages and a higher Th1/Th2 ratio in blood. In lung tissues, neutrophil infiltration was reduced, whereas peroxisome proliferator-activated receptor γ expression was upregulated. A fish oil diet with an ω-6/ω-3 PUFA ratio of 2:1 may elicit more balanced Th polarization, alleviate inflammatory responses, and attenuate lung injury in CLP-induced sepsis.

Peritonitis

MedlinePlus

Peritonitis Overview Peritonitis is inflammation of the peritoneum — a silk-like membrane that lines your inner abdominal wall and covers the ... usually due to a bacterial or fungal infection. Peritonitis can result from any rupture (perforation) in your ...

Fungal Peritonitis Due to Fusarium solani Species Complex Sequential Isolates Identified with DNA Sequencing in a Kidney Transplant Recipient in Brazil.

PubMed

da Silva-Rocha, Walicyranison Plinio; Zuza-Alves, Diana Luzia; Melo, Analy Salles de Azevedo; Chaves, Guilherme Maranhão

2015-12-01

Fungal peritonitis is a rare serious complication most commonly observed in immunocompromised patients under peritoneal dialysis. Nevertheless, this clinical condition is more difficult to treat than bacterial peritonitis. Bacterial peritonitis followed by the use of antibiotics is the main risk factor for developing fungal peritonitis. Candida spp. are more frequently isolated, and the isolation of filamentous fungi is only occasional. Here we describe a case of Fusarium solani species complex peritonitis associated with bacterial peritonitis in a female kidney transplant recipient with previous history of nephrotic syndrome. The patient has had Enterobacter sp. endocarditis and was hypertensive and diabetic. Two sequential isolates of F. solani were recovered from cultures and identified with different molecular techniques. She was successfully treated with 50 mg daily amphotericin B for 4 weeks.

Gastric cancer-derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier.

PubMed

Deng, Guang; Qu, Jinglei; Zhang, Ye; Che, Xiaofang; Cheng, Yu; Fan, Yibo; Zhang, Simeng; Na, Di; Liu, Yunpeng; Qu, Xiujuan

2017-07-01

An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer-derived exosomes is through concurrent apoptosis and mesothelial-to-mesenchymal transition (MMT). Additionally, upregulation of p-ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma. © 2017 Federation of European Biochemical Societies.

32 Years’ Experience of Peritoneal Dialysis-Related Peritonitis in a University Hospital

PubMed Central

van Esch, Sadie; Krediet, Raymond T.; Struijk, Dirk G.

2014-01-01

♦ Background: Peritonitis in peritoneal dialysis (PD) patients can lead to technique failure and contributes to infection-related mortality. Peritonitis prevention and optimization of treatment are therefore important in the care for PD patients. In the present study, we analyzed the incidence of peritonitis, causative pathogens, clinical outcomes, and trends in relation to three major treatment changes that occurred from 1979 onward: use of a disconnect system since 1988, daily mupirocin at the exit-site since 2001, and exclusive use of biocompatible dialysis solutions since 2004. ♦ Methods: In this analysis of prospectively collected data, we included peritonitis episodes from the start of PD at our center in August 1979 to July 2010. Incident PD patients were allocated to one of four groups: Group 1 - 182 patients experiencing 148 first peritonitis episodes between 1979 and 1987, before the introduction of the disconnect system; Group 2 - 352 patients experiencing 239 first episodes of peritonitis between 1988 and 2000, before implementation of daily mupirocin application at the catheter exit-site; Group 3 - 79 patients experiencing 50 first peritonitis episodes between 2001 and 2003, before the switch to biocompatible solutions; and Group 4-118 patients experiencing 91 first peritonitis episodes after 2004. Cephradine was used as initial antibiotic treatment. ♦ Results: In 32 years, 731 adult patients started PD, and 2234 episodes of peritonitis in total were diagnosed and treated. Of those episodes, 88% were cured with medical treatment only, and 10% resulted in catheter removal. In 3% of the episodes, the patient died during peritonitis. Median time to a first peritonitis episode increased from 40 days for group 1 to 150 for group 2, 269 for group 3, and 274 for group 4. The overall peritonitis rate and the gram-positive and gram-negative peritonitis rates showed a time-trend of decline. However, the duration of antibiotic treatment increased over time, with groups 3 and 4 having the longest duration of treatment, accompanied by a higher percentage of antibiotic switch. Increased resistance to cephradine was found for coagulase-negative Staphylococcus. ♦ Conclusions: Peritonitis rates declined significantly over the years because of several changes in PD treatment. However, the need to change the initial antibiotic increased because of diminished antibiotic susceptibility rates over time. Nevertheless, the cure rate was high and remained stable during the entire period analyzed, and the death rate remained low. Consequently, peritonitis is a manageable complication of PD that cannot be considered a contraindication to this mode of renal replacement therapy. PMID:24584620

Association of Modality with Mortality among Canadian Aboriginals

PubMed Central

Hemmelgarn, Brenda; Rigatto, Claudio; Komenda, Paul; Yeates, Karen; Promislow, Steven; Mojica, Julie; Tangri, Navdeep

2012-01-01

Summary Background and objectives Previous studies have shown that Aboriginals and Caucasians experience similar outcome on dialysis in Canada. Using the Canadian Organ Replacement Registry, this study examined whether dialysis modality (peritoneal or hemodialysis) impacted mortality in Aboriginal patients. Design, setting, participants, & measurements This study identified 31,576 adult patients (hemodialysis: Aboriginal=1839, Caucasian=21,430; peritoneal dialysis: Aboriginal=554, Caucasian=6769) who initiated dialysis between January of 2000 and December of 2009. Aboriginal status was identified by self-report. Dialysis modality was determined 90 days after dialysis initiation. Multivariate Cox proportional hazards and competing risk models were constructed to determine the association between race and mortality by dialysis modality. Results During the study period, 939 (51.1%) Aboriginals and 12,798 (53.3%) Caucasians initiating hemodialysis died, whereas 166 (30.0%) and 2037 (30.1%), respectively, initiating peritoneal dialysis died. Compared with Caucasians, Aboriginals on hemodialysis had a comparable risk of mortality (adjusted hazards ratio=1.04, 95% confidence interval=0.96–1.11, P=0.37). However, on peritoneal dialysis, Aboriginals experienced a higher risk of mortality (adjusted hazards ratio=1.36, 95% confidence interval=1.13–1.62, P=0.001) and technique failure (adjusted hazards ratio=1.29, 95% confidence interval=1.03–1.60, P=0.03) than Caucasians. The risk of technique failure varied by patient age, with younger Aboriginals (<50 years old) more likely to develop technique failure than Caucasians (adjusted hazards ratio=1.76, 95% confidence interval=1.23–2.52, P=0.002). Conclusions Aboriginals on peritoneal dialysis experience higher mortality and technique failure relative to Caucasians. Reasons for this race disparity in peritoneal dialysis outcomes are unclear. PMID:22997343

Impact of Pre-Dialysis Care on Clinical Outcomes in Peritoneal Dialysis Patients.

PubMed

Spigolon, Dandara N; de Moraes, Thyago P; Figueiredo, Ana E; Modesto, Ana Paula; Barretti, Pasqual; Bastos, Marcus Gomes; Barreto, Daniela V; Pecoits-Filho, Roberto

2016-01-01

Structured pre-dialysis care is associated with an increase in peritoneal dialysis (PD) utilization, but not with peritonitis risk, technical and patient survival. This study aimed at analyzing the impact of pre-dialysis care on these outcomes. All incident patients starting PD between 2004 and 2011 in a Brazilian prospective cohort were included in this analysis. Patients were divided into 2 groups: early pre-dialysis care (90 days of follow-up by a nephrology team); and late pre-dialysis care (absent or less than 90 days follow-up). The socio-demographic, clinical and biochemical characteristics between the 2 groups were compared. Risk factors for the time to the first peritonitis episode, technique failure and mortality based on Cox proportional hazards models. Four thousand one hundred seven patients were included. Patients with early pre-dialysis care presented differences in gender (female - 47.0 vs. 51.1%, p = 0.01); race (white - 63.8 vs. 71.7%, p < 0.01); education (<4 years - 61.9 vs. 71.0%, p < 0.01), respectively, compared to late care. Patients with early pre-dialysis care presented a higher prevalence of comorbidities, lower levels of creatinine, phosphorus, and glucose with a significantly better control of hemoglobin and potassium serum levels. There was no impact of pre-dialysis care on peritonitis rates (hazard ratio (HR) 0.88; 95% CI 0.77-1.01) and technique survival (HR 1.12; 95% CI 0.92-1.36). Patient survival (HR 1.20; 95% CI 1.03-1.41) was better in the early pre-dialysis care group. Earlier pre-dialysis care was associated with improved patient survival, but did not influence time to the first peritonitis nor technique survival in this national PD cohort. © 2016 S. Karger AG, Basel.

Predictors of Residual Renal Function Decline in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

PubMed Central

Szeto, Cheuk-Chun; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Chung, Sebastian; Yu, Vincent; Cheng, Phyllis Mei-Shan; Leung, Chi-Bon; Law, Man-Ching; Li, Philip Kam-Tao

2015-01-01

♦ Background: Residual renal function (RRF) is an important prognostic indicator in continuous ambulatory peritoneal dialysis (CAPD) patients. We determined the predictors of RRF loss in a cohort of incident CAPD patients. ♦ Methods: We reviewed the record of 645 incident CAPD patients. RRF loss is represented by the slope of decline of residual glomerular filtration rate (GFR) as well as the time to anuria. ♦ Results: The average rate of residual GFR decline was -0.083 ± 0.094 mL/min/month. The rate of residual GFR decline was faster with a higher proteinuria (r = -0.506, p < 0.0001) and baseline residual GFR (r = -0.560, p < 0.0001). Multivariate analysis showed that proteinuria, baseline residual GFR, and the use of diuretics were independent predictors of residual GFR decline. Cox proportional hazard model showed that proteinuria, glucose exposure, and the number of peritonitis episodes were independent predictors of progression to anuria, while a higher baseline GFR was protective. Each 1 g/day of proteinuria is associated with a 13.2% increase in the risk of progressing to anuria, each 10 g/day higher glucose exposure is associated with a 2.5% increase in risk, while each peritonitis episode confers a 3.8% increase in risk. ♦ Conclusions: Our study shows that factors predicting the loss of residual solute clearance and urine output are different. Proteinuria, baseline residual GFR, and the use of diuretics are independently related to the rate of RRF decline in CAPD patients, while proteinuria, glucose exposure, and the number of peritonitis episodes are independent predictors for the development of anuria. The role of anti-proteinuric therapy and measures to prevent peritonitis episodes in the preservation of RRF should be tested in future studies. PMID:24497594

Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival.

PubMed

Craciun, Florin L; Schuller, Elizabeth R; Remick, Daniel G

2010-12-01

Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.

[A classical but unknown cause of peritoneal effusion disclosed by echography. Typhoid fever].

PubMed

Judet, O; Rouveix, E; Verderi, D; Bismuth, V

1989-01-01

Two cases of peritoneal effusion discovered by sonography in patients with typhoid fever are reported. These peritoneal effusions have no pejorative value; only clinical findings can differentiate these simple effusions from a perforative thyphoid peritonitis, which is exceptional nowadays. Typhoid fever, among other febrile diseases should be considered when ultrasounds shows an isolated peritoneal effusion.

The expediency of peritoneal lavage for blunt trauma in children.

PubMed

Drew, R; Perry, J F; Fischer, R P

1977-12-01

Two hundred and thirty children, ten years of age or younger, suspected of having blunt abdominal injuries underwent diagnostic peritoneal lavage. Peritoneal lavage was 99.1 per cent accurate in determining the presence or absence of abdominal injuries. One patient had a false-positive peritoneal lavage. Sixty-nine of the 70 patients with blunt abdominal injuries, who underwent peritoneal lavage, had a positive peritoneal lavage; one patient had a false-negative peritoneal levage. Ninety-one per cent of the positive peritoneal lavages were grossly positive for hemoperitoneum. All 11 children with extraperitoneal abdominal injuries had positive peritoneal lavages from associated intraperitoneal injeries. The mortality for children with blunt abdominal injuries was 19.4 per cent. Intra-abdominal injuries were solely responsible for 29 per cent of the deaths and were a major contributing factor in an additional 21 per cent of the deaths. The routine use of diagnostic peritoneal lavage during the initial evaluation of blunt abdominal trauma was, in large part, responsible for the rapid, definitive treatment which -he children with abdominal injuries received. Sixty-five per cent of the children underwent exploratory laparotomy within one hour of admission to the hospital.

[Problems of peritoneal dialysis--history and research perspectives].

PubMed

Czyzewska, Krystyna; Grzelak, Teresa; Szary, Beata

2009-01-01

This paper specifies the peritoneal dialysis problems as a method of renal replacement therapy in a historical perspective. It pointed out to the dynamic development of peritoneal dialysis in the nineties and distinct slump of the presented treatment form at the turn of XXth and XXIst century, despite substantial progress in the dialysis techniques, effectiveness and biocompatibility of the therapy as well as a detailed evaluation of peritoneal function in vivo and in vitro. It showed descriptions and outline of the peritoneal cavity dating from ancient times, 19th-century animal experiments determining essential laws of peritoneal absorption and removal molecules, as well as the first peritoneal dialysis of a man which took place at the beginning of the 20th-century. The technical problems and peritonitis were the fundamental limitations of this therapy employment in this phase of dialysis development. The application of Tenckhoffs catheter and the technique specified as continuous ambulatory peritoneal dialysis was the invention and at the same time, the turning point which decided about the considerable progress of the described method of dialysis in the nineties. In this period, the analyses concerning failures of the peritoneal transport functions and protection of peritoneum during its long-term use as a dialysis membrane dominated. These studies referred to not absolutely biocompatibility factors of the environment of the peritoneal cavity during peritoneal dialysis. Thence, proposed future directions of analyses include researches concerning components of dialysis solution to assure long-term preservation of peritoneal transport functions and its secretory properties. It is not excluded that experiments of applying the newest achievements of regenerative medicine, in the scope of genetic modification and implantation of mesothelial cells will be continued.

Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation.

PubMed

Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Koga, Kenichi; Ishii, Akira; Mori, Keita P; Osaki, Keisuke; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki

2018-06-01

Connective tissue growth factor (CTGF/CCN2) regulates the signalling of other growth factors and promotes fibrosis. CTGF is increased in mice and humans with peritoneal fibrosis. Inhibition of CTGF has not been examined as a potential therapeutic target for peritoneal fibrosis because systemic CTGF knockout mice die at the perinatal stage. To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice by crossing CTGF floxed mice with RosaCreERT2 mice. We administered tamoxifen to Rosa-CTGF cKO mice to delete the CTGF gene throughout the body. We induced peritoneal fibrosis by intraperitoneal injection of chlorhexidine gluconate (CG) in wild-type and Rosa-CTGF cKO mice. Induction of peritoneal fibrosis in wild-type mice increased CTGF expression and produced severe thickening of the peritoneum. In contrast, CG-treated Rosa-CTGF cKO mice exhibited reduced thickening of the peritoneum. Peritoneal equilibration test revealed that the excessive peritoneal small-solute transport in CG-treated wild-type mice was normalized by CTGF deletion. CG-treated Rosa-CTGF cKO mice exhibited a reduced number of αSMA-, Ki67-, CD31- and MAC-2-positive cells in the peritoneum. Analyses of peritoneal mRNA showed that CG-treated Rosa-CTGF cKO mice exhibited reduced expression of Cd68, Acta2 (αSMA), Pecam1 (CD31) and Vegfa. These results indicate that a deficiency of CTGF can reduce peritoneal thickening and help to maintain peritoneal function by reducing angiogenesis and inflammation in peritoneal fibrosis. These results suggest that CTGF plays an important role in the progression of peritoneal fibrosis.

Experimental Escherichia coli peritonitis in immunosuppressed mice: the role of specific and non-specific immunity.

PubMed

Vuopio-Varkila, J

1988-01-01

An experimental Escherichia coli septicaemia-peritonitis model was adapted to immunosuppressed mice. The mice were made neutropenic by a sublethal dose of cyclophosphamide, which resulted in a 100-fold increase in their susceptibility to intraperitoneal injection of E. coli O18:K1. A lethal infection could be prevented by passive immunisation with anti-K1 capsular or anti-O18 LPS antibodies but not with anti-J5 bacterial antibodies. The anti-K1 and anti-O18 antisera were able to increase the LD50 of the E. coli challenge by factors of 50 and 5, respectively. The role of non-specific, lipopolysaccharide (LPS)-mediated resistance to infection was also investigated in this model, in which only long-living phagocytic cells such as macrophages are believed to be functional. Pretreatment of mice with LPS was shown to prevent growth of the bacterial challenge in the peritoneal cavity and blood and to result in a five-fold increase in the LD50 of the challenge strain. These findings suggest an important role for macrophages as effector cells in defence against E. coli infection.

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B. Paul; Ito, Yasuhiko

2017-01-01

Background We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. Methods We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. Results When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Conclusion Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis. PMID:28046064

Novel Predictors of Peritonitis-Related Outcomes in the BRAZPD Cohort

PubMed Central

de Moraes, Thyago Proença; Olandoski, Marcia; Caramori, Jaqueline C.T.; Martin, Luis C.; Fernandes, Natália; Divino-Filho, José Carolino; Pecoits-Filho, Roberto; Barretti, Pasqual

2014-01-01

♦ Introduction: Peritonitis remains the main cause of peritoneal dialysis (PD) technique failure worldwide, despite significant reductions in infection rates observed over the past decades. Several studies have described risk factors for peritonitis, technique failure and mortality. However, there are scarce data regarding predictors of complications during and after a peritonitis episode. The aim of our study was to analyze predictors of peritonitis-related outcome in the Brazilian Peritoneal Dialysis study (BRAZPD) cohort. ♦ Methods: All adult incident patients recruited in the BRAZPD Study between December 2004 and October 2007, who remained at least 90 days on PD and presented their first peritonitis episode (n = 474 patients) were included in the study. The endpoints analyzed were non-resolution, death due to a peritonitis episode and long-term technique survival after a peritonitis episode. ♦ Results: In the multivariable regression, non-resolution was independently associated with older age (odds ratio (OR) 1.02; p < 0.01), collagenosis as the primary renal disease (OR 4.6; p < 0.05) and Pseudomonas spp as etiological agent (OR 2.9; p < 0.05). Patients who were transferred from APD to CAPD during peritonitis therapy presented a higher risk of non-response (OR 2.5; p < 0.05). The only factor associated with death during a peritonitis episode was older age (OR 1.04; p < 0.05). Exposure to vancomycin and male gender were the independent predictors of long-term technique failure (OR 2.2; p < 0.01). ♦ Conclusion: Apart from confirming previous observations of the negative impact of older age and Pseudomonas spp peritonitis on outcomes, we observed that collagenosis may negatively impact response to treatment and exposure to vancomycin may possibly reduce long-term technique survival. It is important to emphasize that the association of vancomycin with technique failure does not prove causality. These findings shed light on new factors predicting outcome when peritonitis is diagnosed. PMID:24385333

Retrospective evaluation of recurrent secondary septic peritonitis in dogs (2000-2011): 41 cases.

PubMed

Barfield, Dominic M; Tivers, Michael S; Holahan, Matthew; Welch, Kristin; House, Arthur; Adamantos, Sophie E

2016-01-01

To describe the clinical characteristics of recurrent septic peritonitis in dogs. Multicenter retrospective observational study. Client-owned dogs with recurrent septic peritonitis. Three university emergency and referral hospitals. None. Medical records from 3 veterinary university teaching hospitals were reviewed and data were collected using a standardized data collection sheet for all cases of septic peritonitis during the study period (2000-2011). Forty one dogs met the inclusion criteria for recurrent peritonitis. All dogs underwent relaparotomy. The original cause of septic peritonitis in these cases included previous surgery for gastrointestinal foreign body removal (n = 26), gastrointestinal neoplasia (n = 3), gastric or duodenal ulceration (n = 3), biliary tract leakage (n = 2), and single instance for each of the following: penetrating foreign body, hernia strangulation, intussusception, mesenteric volvulus, infection of the laparotomy incision, prostatic abscess, and trauma. Eighteen animals survived to discharge. There was no difference detected between survivors and nonsurvivors with recurrent peritonitis in terms of inciting cause, serum albumin concentration, surgical management, or provision of appropriate initial antimicrobials. The survival rate for dogs having recurrent peritonitis was 43.9% (18/41 dogs). This retrospective study did not identify any significant prognostic indicators for dogs with recurrent peritonitis and that the mortality rate for dogs having more than one surgery for septic peritonitis is similar to that reported for a single surgery for septic peritonitis. ©Veterinary Emergency and Critical Care Society 2015.

Collection and analysis of peritoneal fluid from healthy llamas and alpacas.

PubMed

Cebra, Christopher K; Tornquist, Susan J; Reed, Shannon K

2008-05-01

To describe a technique for abdominocentesis in camelids and report peritoneal fluid biochemical and cytologic findings from healthy llamas and alpacas. Prospective study. Animals-17 adult llamas and 5 adult alpacas. Right paracostal abdominocentesis was performed. Peritoneal fluid was collected by gravity flow into tubes containing potassium-EDTA for cell count and cytologic evaluation and lithium heparin for biochemical analysis. Blood samples were collected via jugular venipuncture into heparinized tubes at the same time. Cytologic components were quantified. Fluid pH and concentrations of total carbon dioxide, sodium, potassium, chloride, lactate, and glucose were compared between peritoneal fluid and venous blood. All but 3 camelids had peritoneal fluid cell counts of < 3,000 nucleated cells/microL, with < 2,000 neutrophils/microL and < 1,040 large mononuclear cells/microL. All but 1 had peritoneal fluid protein concentrations of > or = 2.5 g/dL. Peritoneal fluid of camelids generally contained slightly less glucose, lactate, and sodium and roughly equal concentrations of potassium and chloride as venous blood. Peritoneal fluid was collected safely from healthy camelids. Compared with blood, peritoneal fluid usually had a low cell count and protein concentration, but some individuals had higher values. Electrolyte concentrations resembled those found in blood. High cell counts and protein concentrations found in peritoneal fluid of some healthy camelids may overlap with values found in diseased camelids, complicating interpretation of peritoneal fluid values.

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis.

PubMed Central

Shalit, I; Greenwood, R B; Marks, M I; Pederson, J A; Frederick, D L

1986-01-01

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed. These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD. In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients. PMID:2944477

Peritoneal fluid culture

MedlinePlus

Culture - peritoneal fluid ... sent to the laboratory for Gram stain and culture. The sample is checked to see if bacteria ... The peritoneal fluid culture may be negative, even if you have ... diagnosis of peritonitis is based on other factors, in addition ...

Aliskiren Prevents the Toxic Effects of Peritoneal Dialysis Fluids during Chronic Dialysis in Rats

PubMed Central

Pérez-Martínez, Juan; Pérez-Martínez, Francisco C.; Carrión, Blanca; Masiá, Jesús; Ortega, Agustín; Simarro, Esther; Nam-Cha, Syong H.; Ceña, Valentín

2012-01-01

The benefits of long-term peritoneal dialysis (PD) in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS) in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs) increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs. PMID:22558414

Clinical Characteristics and Outcomes of “Silent” and “Non-Silent” Peritonitis in Patients on Peritoneal Dialysis

PubMed Central

Dong, Jie; Luo, Suping; Xu, Rong; Chen, Yuan; Xu, Ying

2013-01-01

♦ Objectives: We compared the clinical characteristics and outcomes of “silent” peritonitis (meaning episodes without fever and abdominal pain) and “non-silent” peritonitis in patients on peritoneal dialysis (PD). ♦ Methods: Our cohort study collected data about all peritonitis episodes occurring between January 2008 and April 2010. Disease severity score, demographics, and biochemistry and nutrition data were recorded at baseline. Effluent cell counts were examined at regular intervals, and the organisms cultured were examined. Treatment failure was defined as peritonitis-associated death or transfer to hemodialysis. ♦ Results: Of 248 episodes of peritonitis occurring in 161 PD patients, 20.9% led to treatment failure. Of the 248 episodes, 51 (20.6%) were not accompanied by fever and abdominal pain. Patients with these silent peritonitis episodes tended to be older (p = 0.003). The baseline values for body mass index, triglycerides, and daily energy intake were significantly lower before silent peritonitis episodes than before non-silent episodes (p = 0.01, 0.003, and 0.001 respectively). Although silent peritonitis episodes were more often culture-negative and less often caused by gram-negative organisms, and although they presented with low effluent white cell counts on days 1 and 3, the risk for treatment failure in those episodes was not lower (adjusted odds ratio: 1.33; 95% confidence interval: 0.75 to 2.36; p = 0.33). ♦ Conclusions: Silent peritonitis is not a rare phenomenon, especially in older patients on PD. Although these episodes were more often culture-negative, silent presentation was not associated with a better outcome. PMID:22855888

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

PubMed Central

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements. PMID:23484081

Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.

PubMed

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases

PubMed Central

2010-01-01

Background Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium. Methods We have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR. Results As expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells) in the endometriotic lesions, showing a positive correlation with VEGF. Conclusion The present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity. PMID:20085636

Micrococcus species-related peritonitis in patients receiving peritoneal dialysis.

PubMed

Kao, Chih-Chin; Chiang, Chih-Kang; Huang, Jenq-Wen

2014-01-01

Peritonitis is a major complication of peritoneal dialysis (PD) and remains the most common cause of PD failure. Micrococci are catalase-positive, coagulase-negative, and gram-positive cocci that are spherical, often found in tetrad, and belong to the family Micrococcaceae. Micrococcus species are commonly found in the environment, and it is now recognized that Micrococcus species can be opportunistic pathogens in immunocompromised patients. The only consistent predisposing factor for Micrococcus infection is an immunocompromised state. We report three cases of Micrococcus PD peritonitis. Improper practice of PD may have been the causative factor. Although Micrococcus species are low-virulence pathogens, infection could result in refractory peritonitis and subsequent PD failure. Intraperitoneal administration of vancomycin for at least 2 weeks is recommended for Micrococcus peritonitis.

[News in peritoneal dialysis].

PubMed

Ryckelynck, Jean-Philippe; Lobbedez, Thierry; Ficheux, Maxence; Bonnamy, Cécile; El Haggan, Waël; Henri, Patrick; Chatelet, Valérie; Levaltier, Béatrice; Hurault de Ligny, Bruno

2007-12-01

Peritoneal dialysis, like hemodialysis, is a first-line therapy for patients with end-stage renal disease. Progress in medical devices and materials has reduced infectious complications such as peritonitis and catheter exit-site infections and thus decreased morbidity. Peritoneal dialysis fluids are increasingly biocompatible, result in fewer glucose degradation products, protect the peritoneal membrane better and thus improve tolerance. The maintenance of residual renal function, together with better comfort and no pain, help control the fluid and sodium balance. Automated peritoneal dialysis can be performed each night, either autonomously or assisted by a visiting nurse twice a day (to prepare, connect, and disconnect the machine). This treatment can thus be provided to most patients, regardless of their age. Peritoneal dialysis is indicated principally for young people waiting for a kidney transplantation (to preserve their vascular network), elderly patients who wish to remain either at home or in an institution, and patients with cardiac insufficiency, because of the better hemodynamic tolerance. Numerous obstacles, mainly nonmedical, still impede the development of peritoneal dialysis. Patients seen in emergencies start hemodialysis without necessarily receiving any information about peritoneal dialysis. Indeed, neither physicians nor patients receive adequate information.

Peritoneal manifestations of fascioliasis on CT images: a new observation.

PubMed

Song, Kyoung Doo; Lim, Jae Hoon; Kim, Mi Jeong; Jang, Yun Jin; Kim, Jae Woon; Cho, Seung Hyun; Kwon, Jung Hyeok

2013-08-01

To describe peritoneal manifestations of fascioliasis on CT. We reviewed CT images in 31 patients with fascioliasis confirmed by enzyme-linked immunosorbent assay (ELISA) (n = 24) or surgery (n = 7). Image analyses were performed to identify hepatic, biliary, and peritoneal abnormalities. Hepatic abnormalities were seen in 28 (90.3 %) of the 31 patients. The most common finding was caves sign, which was present in 25 (80.1 %) patients. Three patients (9.7 %) presented with biliary abnormalities exhibiting dilatation and enhancing wall thickening of the bile duct, wall thickening of the gallbladder, and elongated structures in the bile duct or gallbladder. Peritoneal abnormalities were seen in 14 (45.2 %) of the 31 patients. The most common peritoneal abnormality was mesenteric or omental infiltration, which was seen in 9 (29.0 %) patients. Other peritoneal findings included lymph node enlargement (n = 7), ascites (n = 7), thickening of ligamentum teres (n = 2), and peritoneal mass (n = 2). Peritoneal manifestations of fascioliasis are relatively common, and CT findings include mesenteric or omental infiltration, lymph node enlargement, ascites, thickening of the ligamentum teres, and peritoneal masses.

Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003.

PubMed

Davenport, Andrew

2009-01-01

Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.

Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows similarities to human bacterial vaginosis: implications for use as an animal model for HIV vaginal infection.

PubMed

Spear, Gregory T; Gilbert, Douglas; Sikaroodi, Masoumeh; Doyle, Lara; Green, Linda; Gillevet, Patrick M; Landay, Alan L; Veazey, Ronald S

2010-02-01

The composition of the lower genital tract microbiota in women is believed to affect the risk of sexually acquiring HIV. Since macaque genital microbiota could similarly impact vaginal infection with SIV we identified microbiota in 11 rhesus macaques using multitag pyrosequencing of the 16S rRNA gene. The microbiota was polymicrobial with a median of nine distinct bacterial taxa per macaque (range 3-16 taxa, each constituting 1% or more of the sequences). Taxa frequently found included Peptoniphilus, Sneathia, Porphyromonas, Mobiluncus, Atopobacter, Dialister, Thioreductor, Prevotella, and Streptococcus, many of which are also frequently found in women with bacterial vaginosis. Lactobacillus sequences (mostly L. johnsonii) were found in only four macaques but were not predominant in any (median of 0% of sequences, range 0-39%). All macaques were resampled 6 months after the first time point to determine the stability of the microbiota. The microbiota remained polymicrobial with a median of 10 taxa (range 6-18). Microbial patterns remained similar for six of the macaques, changed substantially in two, and had a mixed pattern in three. Significant sialidase enzyme activity, a marker of bacteria vaginosis in women, was detected in genital fluid from 9/11 and 8/11 macaques from the first and second time points, respectively. These results show that the macaque lower genital microbiota resembled a bacteria vaginosis-type microbiota in women and suggest that the microbiota of macaques in captivity promote rather than protect against vaginal infection with SIV. These results also suggest macaques could be used as an animal model to study some aspects of bacterial vaginosis.

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

ClinicalTrials.gov

2016-02-15

Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Animal models of polymicrobial pneumonia

PubMed Central

Hraiech, Sami; Papazian, Laurent; Rolain, Jean-Marc; Bregeon, Fabienne

2015-01-01

Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although “two hits” animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information. PMID:26170617

Peritoneal dialysis--experiences.

PubMed

Mirković, Tatjana Durdević

2010-01-01

Peritoneal dialysis is the method of treatment of terminal-stage chronic kidney failure. Nowadays, this method is complementary to haemodialysis. It is based on the principles of the diffusion of solutes and ultrafiltration of fluids across the peritoneal membrane, which acts as a filter. The dialysate is introduced into the peritoneum via the previously positioned peritoneal catheter. The peritoneal dialysis is carried out on daily basis, at home by the patient, and the "exchange" is repeated 4-5 times during the 24 hours. The first steps in peritoneal dialysis at the Department for Haemodialysis of the Clinical Centre of Vojvodina date back to 1973. Until 1992, the patients were subjected to this program only sporadically. Since 1998 the peritoneal dialysis method has been performed at the Clinic for Nephrology and Clinical Immunology. In the period 1998-2008 ninety nine peritoneal catheters were placed. Chronic glomerulonephritis, nephroangiosclerosis and diabetes were identified as the most common causes of chronic renal failure. Two methods of catheter placement were applied: the standard open surgery method (majority of patients) and laparoscopy. Most of the patients were subjected to continuous ambulatory peritoneal dialysis, whereas four patients received automatic dialysis. Transplantation was performed in 10 patients, i.e. cadaveric transplantation and living-related donor transplantation, each in 5 patients. Peritoneal dialysis was available as a service outside our institution as well. A ten-year experience in peritoneal dialysis gained at our Centre has proved the advantages and qualities of this method, strongly supporting its wider application in the treatment of terminal-stage chronic kidney failure.

Peritonitis and exit-site infection in pediatric automated peritoneal dialysis.

PubMed

Chiu, Man-Chun; Tong, Pak-Chiu; Lai, Wai-Ming; Lau, Shing-Chi

2008-06-01

We reviewed 30 patients in an automated peritoneal dialysis (APD) program from 2002 to 2006 for peritonitis. Patients were 11.6 +/- 5.5 years old at initiation of peritoneal dialysis (PD) and had a total of 976 PD months. The overall peritonitis rate was 1 episode in 54.2 patient-months, for a rate of 0.22 episode annually. The rate was considered low, which other than being an APD program, may be attributed to adherence to guidelines and in-charge nurse policy. A total of 17 episodes of peritonitis were identified in 9 patients, and the distribution of patient-specific peritonitis incidence appeared bimodal: 87% patients had no or only 1 episode of peritonitis, and 4 patients accounted for 12 episodes, with an average peritonitis rate of 1.0 annually. Causative organisms included Staphylococcus aureus, coagulase-negative Staphylococcus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, enterococci, alpha-hemolytic Streptococcus. Five episodes had concurrent exit-site infection with the same organism. During the same period in these 30 patients, 40 episodes of exit-site infection (ESI) were recorded in 23 patients. The overall ESI rate was 1 episode in 24.4 PD months. S. aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 70% of the infections. Nasal carriage of MRSA was found in 4 patients, and MRSA ESIs in 2. The ESI rate was not low as that observed in peritonitis, which may be attributed to the humid climate.

Profiling of Candida albicans Gene Expression During Intra-abdominal Candidiasis Identifies Biologic Processes Involved in Pathogenesis

PubMed Central

Cheng, Shaoji; Clancy, Cornelius J.; Xu, Wenjie; Schneider, Frank; Hao, Binghua; Mitchell, Aaron P.; Nguyen, M. Hong

2013-01-01

Background. The pathogenesis of intra-abdominal candidiasis is poorly understood. Methods. Mice were intraperitoneally infected with Candida albicans (1 × 106 colony-forming units) and sterile stool. nanoString assays were used to quantitate messenger RNA for 145 C. albicans genes within the peritoneal cavity at 48 hours. Results. Within 6 hours after infection, mice developed peritonitis, characterized by high yeast burdens, neutrophil influx, and a pH of 7.9 within peritoneal fluid. Organ invasion by hyphae and early abscess formation were evident 6 and 24 hours after infection, respectively; abscesses resolved by day 14. nanoString assays revealed adhesion and responses to alkaline pH, osmolarity, and stress as biologic processes activated in the peritoneal cavity. Disruption of the highly-expressed gene RIM101, which encodes an alkaline-regulated transcription factor, did not impact cellular morphology but reduced both C. albicans burden during early peritonitis and C. albicans persistence within abscesses. RIM101 influenced expression of 49 genes during intra-abdominal candidiasis, including previously unidentified Rim101 targets. Overexpression of the RIM101-dependent gene SAP5, which encodes a secreted protease, restored the ability of a rim101 mutant to persist within abscesses. Conclusions. A mouse model of intra-abdominal candidiasis is valuable for studying pathogenesis and C. albicans gene expression. RIM101 contributes to persistence within intra-abdominal abscesses, at least in part through activation of SAP5. PMID:24006479

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis.

PubMed

Jiang, Li; Chew, Shan-Hwu; Nakamura, Kosuke; Ohara, Yuuki; Akatsuka, Shinya; Toyokuni, Shinya

2016-07-01

Asbestos-induced mesothelial carcinogenesis is currently a profound social issue due to its extremely long incubation period and high mortality rate. Therefore, procedures to prevent malignant mesothelioma in people already exposed to asbestos are important. In previous experiments, we established an asbestos-induced rat peritoneal mesothelioma model, which revealed that local iron overload is a major cause of pathogenesis and that the induced genetic alterations are similar to human counterparts. Furthermore, we showed that oral administration of deferasirox modified the histology from sarcomatoid to the more favorable epithelioid subtype. Here, we used i.p. administration of desferal to evaluate its effects on asbestos-induced peritoneal inflammation and iron deposition, as well as oxidative stress. Nitrilotriacetate was used to promote an iron-catalyzed Fenton reaction as a positive control. Desferal significantly decreased peritoneal fibrosis, iron deposition, and nuclear 8-hydroxy-2'-deoxyguanosine levels in mesothelial cells, whereas nitrilotriacetate significantly increased all of them. Desferal was more effective in rat peritoneal mesothelial cells to counteract asbestos-induced cytotoxicity than in murine macrophages (RAW264.7). Furthermore, rat sarcomatoid mesothelioma cells were more dependent on iron for proliferation than rat peritoneal mesothelial cells. Because inflammogenicity of a fiber is proportionally associated with subsequent mesothelial carcinogenesis, iron elimination from the mesothelial environment can confer dual merits for preventing asbestos-induced mesothelial carcinogenesis by suppressing inflammation and mesothelial proliferation simultaneously. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Development of Peritoneal Tumor-Targeting Vector by In Vivo Screening with a Random Peptide-Displaying Adenovirus Library

PubMed Central

Yoshida, Kimiko; Goto, Naoko; Ohnami, Shumpei; Aoki, Kazunori

2012-01-01

The targeting of gene transfer at the cell-entry level is one of the most attractive challenges in vector development. However, attempts to redirect adenovirus vectors to alternative receptors by engineering the capsid-coding region have shown limited success, because the proper targeting ligands on the cells of interest are generally unknown. To overcome this limitation, we have constructed a random peptide library displayed on the adenoviral fiber knob, and have successfully selected targeted vectors by screening the library on cancer cell lines in vitro. The infection of targeted vectors was considered to be mediated by specific receptors on target cells. However, the expression levels and kinds of cell surface receptors may be substantially different between in vitro culture and in vivo tumor tissue. Here, we screened the peptide display-adenovirus library in the peritoneal dissemination model of AsPC-1 pancreatic cancer cells. The vector displaying a selected peptide (PFWSGAV) showed higher infectivity in the AsPC-1 peritoneal tumors but not in organs and other peritoneal tumors as compared with a non-targeted vector. Furthermore, the infectivity of the PFWSGAV-displaying vector for AsPC-1 peritoneal tumors was significantly higher than that of a vector displaying a peptide selected by in vitro screening, indicating the usefulness of in vivo screening in exploring the targeting vectors. This vector-screening system can facilitate the development of targeted adenovirus vectors for a variety of applications in medicine. PMID:23029088

Expression of the Homeobox Gene HOXA9 in Ovarian Cancer Induces Peritoneal Macrophages to Acquire an M2 Tumor-Promoting Phenotype

PubMed Central

Ko, Song Yi; Ladanyi, Andras; Lengyel, Ernst; Naora, Honami

2015-01-01

Tumor-associated macrophages (TAMs) exhibit an M2 macrophage phenotype that suppresses anti-tumor immune responses and often correlates with poor outcomes in patients with cancer. Patients with ovarian cancer frequently present with peritoneal carcinomatosis, but the mechanisms that induce naïve peritoneal macrophages into TAMs are poorly understood. In this study, we found an increased abundance of TAMs in mouse i.p. xenograft models of ovarian cancer that expressed HOXA9, a homeobox gene that is associated with poor prognosis in patients with ovarian cancer. HOXA9 expression in ovarian cancer cells stimulated chemotaxis of peritoneal macrophages and induced macrophages to acquire TAM-like features. These features included induction of the M2 markers, CD163 and CD206, and the immunosuppressive cytokines, IL-10 and chemokine ligand 17, and down-regulation of the immunostimulatory cytokine, IL-12. HOXA9-mediated induction of TAMs was primarily due to the combinatorial effects of HOXA9-induced, tumor-derived transforming growth factor-β2 and chemokine ligand 2 levels. High HOXA9 expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of TAMs and intratumoral T-regulatory cells and decreased abundance of CD8+ tumor-infiltrating lymphocytes. Levels of immunosuppressive cytokines were also elevated in ascites fluid of patients with tumors that highly expressed HOXA9. HOXA9 may, therefore, stimulate ovarian cancer progression by promoting an immunosuppressive microenvironment via paracrine effects on peritoneal macrophages. PMID:24332016

MicroRNAs Associated with Epithelial-Mesenchymal Transition Can Be Targeted to Inhibit Peritoneal Dissemination of Human Scirrhous Gastric Cancers.

PubMed

Takei, Yoshifumi; Shen, Guodong; Morita-Kondo, Ayami; Hara, Toshifumi; Mihara, Keichiro; Yanagihara, Kazuyoshi

2018-05-30

Scirrhous gastric cancers grow rapidly, and frequently invade the peritoneum. Such peritoneal dissemination properties markedly reduce patient survival. Thus, an effective means for inhibiting peritoneal dissemination is urgently required. We previously established a cell line, HSC-58, from a scirrhous gastric cancer patient, and further successfully isolated a metastatic line, 58As9, in nude mice upon orthotopic inoculation. Using the lines, we examined the mechanism underlying peritoneal dissemination from the viewpoint of microRNA (miRNA) expression. miRNA array and qRT-PCR analysis showed that the expressions of epithelial-mesenchymal transition (EMT)-associated miRNAs such as miR-200c and miR-141 were significantly low in 58As9. Using 58As9 with stably overexpressing miR-200c, miR-141, or both, together with a luciferase reporter assay, we found that miR-200c targeted zinc finger E-box-binding homeobox 1 (ZEB1) and miR-141 targeted ZEB2. The overexpressed lines reversed the EMT status from mesenchymal to epithelial in 58As9, and significantly reduced the invasion activity and peritoneal dissemination for a significant prolongation of survival in the orthotopic tumor models in nude mice. EMT-associated miRNAs such as miR-200c and miR-141 and their target genes ZEB1/ZEB2 have good potential for antiperitoneal dissemination therapy in patients with scirrhous gastric cancers. © 2018 S. Karger AG, Basel.

Rapamycin inhibits epithelial-to-mesenchymal transition of peritoneal mesothelium cells through regulation of Rho GTPases.

PubMed

Xiang, Shilong; Li, Meng; Xie, Xishao; Xie, Zhoutao; Zhou, Qin; Tian, Yuanshi; Lin, Weiqiang; Zhang, Xiaohui; Jiang, Hong; Shou, Zhangfei; Chen, Jianghua

2016-06-01

Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Rapamycin has been previously shown to inhibit EMT of PMCs and prevent peritoneal fibrosis. In this study, we investigated the undefined molecular mechanisms by which rapamycin inhibits EMT of PMCs. To define the protective effect of rapamycin, we initially used a rat PD model which was daily infused with 20 mL of 4.25% high glucose (HG) dialysis solution for 6 weeks to induce fibrosis. The HG rats showed decreased ultrafiltration volume and obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1. Rapamycin significantly ameliorated those pathological changes. Next, we treated rat PMCs with HG to induce EMT and/or rapamycin for indicated time. Rapamycin significantly inhibited HG-induced EMT, which manifests as increased expression of α-SMA, fibronectin, and collagen I, decreased expression of E-cadherin, and increased mobility. HG increased the phosphorylation of PI3K, Akt, and mTOR. Importantly, rapamycin inhibits the RhoA, Rac1, and Cdc42 activated by HG. Moreover, rapamycin repaired the pattern of F-actin distribution induced by HG, reducing the formation of stress fiber, focal adhesion, lamellipodia, and filopodia. Thus, rapamycin shows an obvious protective effect on HG-induced EMT, by inhibiting the activation of Rho GTPases (RhoA, Rac1, and Cdc42). © 2016 Federation of European Biochemical Societies.

Effect of oxiplex* films (PEO/CMC) on adhesion formation and reformation in rabbit models and on peritoneal infection in a rat model.

PubMed

Rodgers, K E; Schwartz, H E; Roda, N; Thornton, M; Kobak, W; diZerega, G S

2000-04-01

To assess the efficacy of Oxiplex (FzioMed, Inc., San Luis Obispo, CA) barriers. Film of polyethylene oxide and carboxymethylcellulose (Oxiplex) were tested for strength and tissue adherence. Films were selected for evaluation in models for biocompatability and adherence. Three films were selected for evaluation in efficacy studies, and one was evaluated for effects on bacterial peritonitis. Handling characteristics of Oxiplex film were evaluated via laparoscopy. University laboratory. Rabbits, rats, pigs. Placement of Oxiplex prototypes at the site of injury. Mechanical properties, biocompatibility, tissue adherence, adhesion development, infection potentiation, and device handling. Mechanical tests indicated that tensile strength and elongation were inversely correlated. All films tested had excellent tissue adherence properties. Selected films, based on residence time and biocompatibility, prevented adhesion formation in all animals and were highly efficacious in preventing adhesion reformation. The optimal Oxiplex prototype prevented adhesion reformation in 91% of the animals. This Oxiplex film, dyed to allow visualization, prevented adhesion reformation and did not affect bacterial peritonitis. In a laparoscopic model, the Oxiplex film, delivered in FilmSert forceps, via a 5.0-mm trocar, rapidly unfurled and could be easily applied to tissue with strong adherence. These data show development of an adhesion prevention material that is tissue adherent, can be placed via laparoscopy, and does not affect host resistance.

Citrobacter Peritoneal Dialysis Peritonitis: Rare Occurrence with Poor Outcomes

PubMed Central

Chao, Chia-Ter; Lee, Szu-Ying; Yang, Wei-Shun; Chen, Huei-Wen; Fang, Cheng-Chung; Yen, Chung-Jen; Chiang, Chih-Kang; Hung, Kuan-Yu; Huang, Jenq-Wen

2013-01-01

Introduction: Non-Pseudomonas gram-negative bacteria are responsible for an increasing proportion of cases of peritoneal dialysis (PD)-related peritonitis. The role of Citrobacter species in the etiology of PD-related peritonitis is often underestimated. In the present study, we aimed to describe the clinical features, laboratory findings, and short- and long-term outcomes in PD-related peritonitis caused by Citrobacter. Methods: A retrospective review of all episodes of PD-related peritonitis caused by Citrobacter from a single center between 1990 and 2010 was performed. Clinical features, microbiological data, and outcomes of these episodes were analyzed. Results: Citrobacter species was responsible for 11 PD-related episodes (1.8% of all peritonitis episodes) in 8 patients. Citrobacter freundii was the most common etiologic species (73%), and mixed growth was found in the other 3 episodes (27%). Approximately half (46%) of the episodes were associated with constipation and/or diarrhea. Of the Citrobacter isolates from all episodes, 54% were resistant to cefazolin, and only 18% were susceptible to cefmetazole. All isolates were susceptible to ceftazidime, cefepime, carbapenem, and aminoglycosides. More than half of the patients (54%) were hospitalized for index peritonitis, and 27% of the episodes involved a change in antibiotic medication. One patient had relapsing peritonitis caused by C. koseri (9%). The mortality rate of PD-related peritonitis caused by Citrobacter was 18%, and 89% of surviving patients developed technique failure requiring a modality switch after an average of 12 months of follow-up (range 1.2-31.2 months). Conclusion: PD-related peritonitis caused by Citrobacter is associated with poor outcomes, including high rates of antibiotic resistance, a high mortality rate, and a high rate of technique failure among survivors during the follow-up period. PMID:23869184

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

PubMed

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-12-01

♦ As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

The longitudinal effects of peritonitis on peritoneal membrane function
.

PubMed

Sia, Christopher S B; Paul, Eldho; Tregaskis, Peter; Walker, Rowan G; Wilson, Scott G

2017-12-01

The longitudinal effects of peritoneal dialysis (PD) peritonitis on small solute clearance and ultrafiltration are controversial. We identified 27 patients with PD peritonitis over a 4-year period at a tertiary hospital. Adequacy tests at an "early" (1 - 3 months), "intermediate" (6 ± 2 months), and a "late" (12 ± 2 months) time period after the episode were compared with a pre-peritonitis baseline. The effect of time on serum albumin, weekly creatinine clearance, Kt/V, and net fluid volume removal was assessed. At 12 months, 16/27 (59.3%) patients were no longer on PD. Ten were transferred to hemodialysis, predominantly due to peritonitis (60%). Five patients died, and 1 received a renal allograft. Total daily fluid volume removal significantly decreased over time with an aggregated mean reduction of 523 mL/day between the baseline and 12-month test (1,624 ± 139 mL vs. 1,101 ± 160 mL; p = 0.02). This was due to an equivalent loss of both ultrafiltration and residual urine output, although the separate decline in these individual parameters was not statistically significant. There was no significant change in Kt/V, creatinine clearance, or serum albumin indicating preserved solute transport in those patients with sustained technique survival post peritonitis. Peritonitis is a common cause for transfer to hemodialysis. Fluid volume removal is the most significantly affected parameter at 12 months post peritonitis, driven by the combination of both ultrafiltration reduction and loss of residual diuresis. Clinicians should be aware that peritonitis identifies patients at high risk for technique failure. These findings should prompt clinicians to closely surveil volume status and consider backup dialytic strategies as early as 12 months post peritonitis.
.

Age-Related Differences of Organism-Specific Peritonitis Rates: A Single-Center Experience.

PubMed

Kotera, Nagaaki; Tanaka, Mototsugu; Aoe, Mari; Chikamori, Masatomo; Honda, Tomoko; Ikenouchi, Ayako; Miura, Rika; Sugahara, Mai; Furuse, Satoshi; Saito, Katsunori; Mise, Naobumi

2016-12-01

Peritonitis remains an important cause of morbidity and mortality in peritoneal dialysis (PD) patients, but its incidence and the distribution of causative organisms vary widely between institutions and age groups. This study was performed to investigate the recent status and risk factors of PD-related peritonitis and to clarify differences between age groups. We retrospectively reviewed the medical records of 119 PD patients treated at our department between January 2002 and January 2013. We calculated both overall and organism-specific peritonitis rates and also analyzed risk factors. Sixty-three episodes of peritonitis occurred during 261.5 patient-years for an incident rate of 0.24 episodes/patient-year. Multivariate analysis showed that older age (≥65 years) and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (≥65 years old), the rate of peritonitis due to Gram-positive and Gram-negative bacteria was 0.17 and 0.08 episodes/patient-year, respectively, and Gram-positive peritonitis was markedly more frequent than in younger patients (<65 years old). In particular, there was a high frequency of Staphylococcus aureus peritonitis in elderly patients (0.09 episodes/patient-year) and it had a poor outcome. At our department, the risk of peritonitis was increased in older patients and patients with hypoalbuminemia. The distribution of causative organisms was markedly different between age groups and analysis of organism-specific peritonitis rates helped to identify current problems with our PD program. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients.

PubMed

Nakamoto, Hirotaka; Hamada, Chieko; Shimaoka, Tetsutaro; Sekiguchi, Yoshimi; Io, Hiroaki; Kaneko, Kayo; Horikoshi, Satoshi; Tomino, Yasuhiko

2014-03-01

Characteristics of pathological alterations in long-term peritoneal dialysis (PD) are thickening of submesothelial compact (SMC) zone, small-vessel vasculopathy, and loss of mesothelial cells. Bioincompatible PD fluid plays crucial roles in peritoneal injury. Encapsulating peritoneal sclerosis (EPS), a rare and serious complication, occurred in patients on long-term PD or frequent peritonitis episodes, and ~50 % of EPS developed after PD cessation. We hypothesized that PD-related peritoneal injury factors induced by bioincompatible PD fluid accumulated in the peritoneum and might induce EPS. We therefore examined the accumulation of advanced glycation end products (AGE) and beta 2-microglobulin (β2M) in peritoneum and evaluated the relationship between their accumulation, clinical parameters, and outcome after PD cessation. Forty-five parietal peritoneal specimens were obtained from 28 PD patients, 14 uremic patients, and three patients with normal kidney function. The peritoneal equilibration test was used for peritoneal function. AGE- and β2M-expressing areas were found in vascular walls, perivascular areas, and the deep layer of the SMC in short-term PD patients and extended over the entire SMC in long-term patients. Peritonitis and prolonged PD treatment aggravated peritoneal thickening and the proportion of AGE-expressing areas. The proportion of β2M-expressing areas was increased in long-term PD patients. Thickening of the SMC and the proportions of AGE- and β2M-expressing areas were not related to ascites or EPS after PD withdrawal. It appears that the increased proportion of AGE and β2M deposition induced by long-term exposure of PD fluid may be a marker of peritoneal injury.

A porcine model of sepsis resulting from the combined insults of hemorrhage and peritonitis.

PubMed

Parker, S J; Hill, P F; Brown, D; Kenward, C E; Watkins, P E

2000-01-01

The physiological responses to either hemorrhage or sepsis have been well documented, however, their simultaneous delivery, as often seen in penetrating trauma, has not been extensively studied. A terminally-anesthetized porcine model of fixed-volume hemorrhage combined with intraperitoneal sepsis was developed. Large White pigs (45-60 kg) were bled 40% of blood volume and peritonitis was induced using an E. coil (O18:K1:H7) culture. Three groups of animals were sequentially studied. Group A (n = 8) received 10(8) bacteria, and Groups B (n = 4) and C (n = 5) received 10(10) organisms. All animals were maintained on a 2.5 mL/kg/h infusion of 0.9% saline. Group C was autotransfused at 1 h. Animals were monitored for up to 24 h. Cardiovascular features of hypovolemia were recorded in all animals. Animals in Group A improved clinically with little microbiological evidence of systemic sepsis. Group B showed rapid cardiovascular collapse, early E. coil-positive blood cultures, and an early rise in serum TNF-alpha levels. Autotransfusion of Group C significantly improved cardiopulmonary parameters, acid-base status, and survival. A reproducible model of hemorrhage and peritonitis, appropriate for abdominal trauma, which allows investigation of resuscitative and pharmacological interventions has been characterized.

Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Patients with High-Grade, High-Volume Disseminated Mucinous Appendiceal Neoplasms.

PubMed

Polanco, Patricio M; Ding, Ying; Knox, Jordan M; Ramalingam, Lekshmi; Jones, Heather; Hogg, Melissa E; Zureikat, Amer H; Holtzman, Matthew P; Pingpank, James; Ahrendt, Steven; Zeh, Herbert J; Bartlett, David L; Choudry, Haroon A

2016-02-01

High-grade (HG) mucinous appendiceal neoplasms (MAN) have a worse prognosis than low-grade histology. Our objective was to assess the safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) in patients with high-grade, high-volume (HG-HV) peritoneal metastases in whom the utility of this aggressive approach is controversial. Prospectively collected perioperative data were compared between patients with peritoneal metastases from HG-HV MAN, defined as simplified peritoneal cancer index (SPCI) ≥12, and those with high-grade, low-volume (HG-LV; SPCI <12) disease. Kaplan-Meier curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. Overall, 54 patients with HG-HV and 43 with HG-LV peritoneal metastases underwent CRS/HIPEC. The HG-HV group had longer operative time, increased blood loss/transfusion, and increased intensive care unit length of stay (p < 0.05). Incomplete macroscopic cytoreduction (CC-1/2/3) was higher in the HG-HV group compared with the HG-LV group (68.5 vs. 32.6 %; p = 0.005). Patients with HG-HV disease demonstrated worse survival than those with HG-LV disease (overall survival [OS] 17 vs. 42 m, p = 0.009; time to progression (TTP) 10 vs. 14 m, p = 0.024). However, when complete macroscopic resection (CC-0) was achieved, the OS and progression-free survival of patients with HG-HV disease were comparable with HG-LV disease (OS 56 vs. 52 m, p = 0.728; TTP 20 vs. 19 m, p = 0.393). In a multivariate Cox proportional hazard regression model, CC-0 resection was the only significant predictor of improved survival for patients with HG-HV disease. Although patients with HG-HV peritoneal metastases from MAN have worse prognosis compared with patients with HG-LV disease, their survival is comparable when complete macroscopic cytoreduction is achieved.

[Clinical analysis for patients with continuous ambulatory peritoneal dialysis associated peritonitis].

PubMed

Liu, Jian; Huang, Xun; Liu, Yao; Xu, Hui; Gong, Rui'e; Li, Chunhui

2016-12-28

To analyze the clinical characteristics of continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis in the tertiary hospitals and to discuss the preventive and therapeutic strategy.
 Methods: The clinical characteristics, pathogens, resistance and outcomes of 126 CAPD associated peritonitis in 104 patients from Jan, 2013 to June, 2016, were retrospectively analyzed.
 Results: Among the patients, the incidence rates of abdominal pain, fever, diarrhea and emesis were 104 (82.54%), 56 (44.44%), 49 (38.89%), and 31 (23.60%), respectively. Among them, 88 patients suffered peritonitis once, other 16 patients suffered multiple peritonitis or recurrent peritonitis for 38 times. Among the 38 times, the numbers for recurrent, repeated or catheter-associated peritonitis were 2, 2, or 3, respectively. Peritoneal fluids from 103 cases were cultured, and 64 cases were positive in bacteria, with a rate of 62.14%. A total of 70 strains of bacteria were separated, including 42 strains of gram-positive bacteria, 21 strains of gram-negative bacteria, and 7 strains of fungus. The most common gram-positive pathogens were Staphylococcus epidermidis, Enterococcus faecalis and Staphylococcus haemolyticus, while Escherichia coli, Klebsiella pneumoniae and Klebsiella pneumoniae were the most common gram-negative bacteria. Candida albicans was the major fungal pathogens. Gram-positive cocci showed resistance to gentamycin, levofloxacin, moxifloxacin, vancomycin and linezolid, with a rate at 20.00%, 36.11%, 5%, 0%, and 0%, respectively. The gram-negative bacilli were resistent to cefoperazone/sulbactam, gentamycin, cephazolin, and ceftazidime, with a rate at 6.25%, 10.53%, 64.29%, and 15.38%, respectively. There were no imipenem, amikacin, piperacillin/tazobactam-resistant strains were found.
 Conclusion: The most common pathogen causing CAPD associated peritonitis is gram-positive bacteria. It is crucial to take the anti-infection therapy for CAPD associated peritonitis early. The positive rates for bacterial culture need to be enhanced through improvement of methods. At the same time, doctors could improve the outcome of CAPD associated peritonitis by adjusting the medication according to the drug sensitivity results.

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

PubMed

Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

2014-02-15

Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

Dissecting the Mechanisms of Linezolid Resistance in a Drosophila melanogaster Infection Model of Staphylococcus aureus

PubMed Central

Diaz, Lorena; Kontoyiannis, Dimitrios P.; Panesso, Diana; Albert, Nathaniel D.; Singh, Kavindra V.; Tran, Truc T.; Munita, Jose M.; Murray, Barbara E.; Arias, Cesar A.

2013-01-01

Background. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15–500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. Results. LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15–250 µg/mL failed to protect against NRS119 (survival, 1.6%–20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. Conclusions. The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis model. PMID:23547139

A Pilot Study of Peritoneal Perfusion with a Novel Hemoglobin Based Oxygen Carrier in Swine (Sus scrofa)

DTIC Science & Technology

2016-10-12

has a high rate of complications, obliges systemic anticoagulation, and requires a significant level of logistics support as well as expertise. In...the endotracheal tube was clamped, ceasing gas exchange in the lung. Arterial blood gases and time to death were then recorded. No differences were...observed between treatment and control animals in terms of C02, 02 and time to death . Peritoneal gas exchange did not improve oxygenation, ventilation or time to death in this severe model of lung injury.

Increased severity of Escherichia coli peritonitis in peritoneal dialysis patients independent of changes in in vitro antimicrobial susceptibility testing.

PubMed

Valdés-Sotomayor, Jorge; Cirugeda, Antonio; Bajo, María-Auxiliadora; del Peso, Gloria; Escudero, Elena; Sánchez-Tomero, José A; Selgas, Rafael

2003-01-01

Despite improvements in peritoneal dialysis (PD) technique, peritonitis continues to be one of the most frequent complications of PD. Nonresolving peritonitis remains a risk for severe anatomical peritoneal changes that may limit the viability of the membrane for dialysis purposes. We have observed remarkably poor outcome of peritonitis caused by Escherichia coli in the past 6 years. With its very low response rate to broad-spectrum antibiotics, the increased severity of E. coli peritonitis deteriorates peritoneal function and affects patient outcome. Retrospective study. Two large PD units in two university hospitals. The total number of patients reviewed was 456. The records of 49 E. coli peritonitis episodes were studied.The observation period started in 1980 and ended in March 2001. Sixteen males and 19 females were included. Severity was defined in terms of days of peritoneal inflammation, lack of response to a potentially useful antibiotic, requirement for catheter removal, and/or laparotomy. Study cases (study group) were those episodes appearing after 1996 (when the first severe cases appeared) and historic controls were episodes occurring before 1996. In the study group, 18 peritonitis episodes developed in 15 patients. In the control group, 31 peritonitis episodes developed in 20 patients. There were no significant differences in clinical presentation; however, the outcome was significantly poorer for the later period. A severe outcome occurred in 50% of study versus 10% of control patients. In fact, 68% of the episodes registered before 1996 were cured in 3 days or less. Concurring with this trend, the numbers of surgical interventions and catheter removals were also higher in the study group. Strikingly, E. coli did not show changes in in vitro susceptibility testing to antibiotics, although the in vivo response was much worse. We describe a change in the virulence of E. coli peritonitis episodes over the past 5 years leading to a high percentage of treatment failure, which does not depend on antibiotic sensitivity and seems to be dependent on changes in host response mechanisms.

Preferential Use of Central Metabolism In Vivo Reveals a Nutritional Basis for Polymicrobial Infection

PubMed Central

Alteri, Christopher J.; Himpsl, Stephanie D.; Mobley, Harry L. T.

2015-01-01

The human genitourinary tract is a common anatomical niche for polymicrobial infection and a leading site for the development of bacteremia and sepsis. Most uncomplicated, community-acquired urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more often associated with complicated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent requirements for specific central pathways in vivo despite colonizing and occupying the same host environment. Using mutants of specific central metabolism enzymes, we determined glycolysis mutants lacking pgi, tpiA, pfkA, or pykA all have fitness defects in vivo for P. mirabilis but do not affect colonization of E. coli during UTI. Similarly, the oxidative pentose phosphate pathway is required only for P. mirabilis in vivo. In contrast, gluconeogenesis is required only for E. coli fitness in vivo. The remarkable difference in central pathway utilization between E. coli and P. mirabilis during experimental UTI was also observed for TCA cycle mutants in sdhB, fumC, and frdA. The distinct in vivo requirements between these pathogens suggest E. coli and P. mirabilis are not direct competitors within host urinary tract nutritional niche. In support of this, we found that co-infection with E. coli and P. mirabilis wild-type strains enhanced bacterial colonization and persistence of both pathogens during UTI. Our results reveal that complementary utilization of central carbon metabolism facilitates polymicrobial disease and suggests microbial activity in vivo alters the host urinary tract nutritional niche. PMID:25568946

Phosphorylation of Extracellular Signal-Regulated Kinase (ERK)-1/2 Is Associated with the Downregulation of Peroxisome Proliferator–Activated Receptor (PPAR)-γ during Polymicrobial Sepsis

PubMed Central

Kaplan, Jennifer M; Hake, Paul W; Denenberg, Alvin; Nowell, Marchele; Piraino, Giovanna; Zingarelli, Basilia

2010-01-01

Peroxisome proliferator–activated receptor (PPAR)-γ is a ligand-activated transcription factor and regulates inflammation. Posttranslational modifications regulate the function of PPARγ, potentially affecting inflammation. PPARγ contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARγ. This study investigated the kinetics of PPARγ expression and activation in parenchymal and immune cells in sepsis using the MAPK/ERK kinase (MEK)-1 inhibitor, an upstream kinase of ERK1/2. Adult male Sprague Dawley rats were subjected to polymicrobial sepsis by cecal ligation and puncture. Rats received intraperitoneal injection of vehicle or the MEK1 inhibitor PD98059 (5 mg/kg) 30 min before cecal ligation and puncture. Rats were euthanized at 0, 1, 3, 6 and 18 h after cecal ligation and puncture. Control animals used were animals at time 0 h. Lung, plasma and peripheral blood mononuclear cells (PBMCs) were collected for biochemical assays. In vehicle-treated rats, polymicrobial sepsis resulted in significant lung injury. In the lung and PBMCs, nuclear levels of PPARγ were decreased and associated with an increase in phosphorylated PPARγ and phosphorylated ERK1/2 levels. Treatment with the MEK1 inhibitor increased the antiinflammatory plasma adipokine adiponectin, restored PPARγ expression in PBMCs and lung, and decreased lung injury. The inflammatory effects of sepsis cause changes in PPARγ expression and activation, in part, because of phosphorylation of PPARγ by ERK1/2. This phosphorylation can be reversed by ERK1/2 inhibition, thereby improving lung injury. PMID:20809049

Successful Treatment of PD Peritonitis Due to Morganella morganii Resistant to Third-Generation Cephalosporins - A Case Report.

PubMed

Keskar, Vaibhav; Biyani, Mohan; Amin, Syed Obaid; Knoll, Greg

2017-01-01

Morganella morganii is a rare cause of peritonitis in patients on peritoneal dialysis (PD). Most of the reported cases have resorted to a switch to hemodialysis. We herein report a case of peritonitis due to M. morganii resistant to third-generation cephalosporins, which was treated successfully with intraperitoneal (IP) tobramycin followed by oral ciprofloxacin. Early microbiologic diagnosis is essential in the treatment of peritonitis from rare microorganisms such as Morganella morganii , and appropriate antibiotic therapy is the key to avoiding catheter loss and subsequent switch to hemodialysis. Copyright © 2017 International Society for Peritoneal Dialysis.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-27

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Peritoneal Dialysis-Related Peritonitis: Atypical and Resistant Organisms.

PubMed

Cho, Yeoungjee; Struijk, Dirk Gijsbert

2017-01-01

Peritoneal dialysis (PD)-related peritonitis remains to be one of the most frequent and serious complications of PD. In this study, existing literature has been reviewed on PD peritonitis caused by atypical organisms and antibiotic resistant organisms and their impact on patient outcomes. Although uncommon, delay in recognition of PD peritonitis caused by atypical organisms can lead to poor patient outcomes if there is a delay in diagnosis and implementation of appropriate treatment. There is also a large difference in prevalence of antibiotic-resistant infections across the world with variable impact on reported patient-level outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Endoscopic Ultrasound (EUS) Guided Fine Needle Aspiration: A New Modality to Diagnose Peritoneal Tuberculosis in Presence of Decompensated Cirrhosis-A Case Series and Review of Literature.

PubMed

Daswani, Ravi; Kumar, Ashish; Singla, Vikas; Kaur, Gagandeep; Sharma, Praveen; Bansal, Naresh; Arora, Anil

2018-06-01

The gold-standard for diagnosis is growth of Mycobacterium tuberculosis on ascitic fluid or peritoneal culture. Due to the non-specific signs and symptoms of disease, its early diagnosis is difficult, especially in patients with decompensated cirrhosis. The reported sensitivity of ascitic fluid is low and to obtain tissue for peritoneal biopsy in patients with cirrhosis is difficult. Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) is a good alternative to obtain peritoneal tissue for establishing the diagnosis of peritoneal TB. To assess the role of EUS-FNA in the diagnosis of peritoneal tuberculosis in patients with decompensated cirrhosis. Consecutive patients with peritoneal thickening, ascites and decompensated cirrhosis underwent EUS-FNA from the thickened omentum. Presence of granuloma or demonstration of acid fast bacilli was diagnostic of peritoneal tuberculosis. A total of 5 patients with CLD underwent EUS-FNA from omentum. FNA cytology revealed granuloma with multinucleated cells in all patients (100%) and AFB stain was positive in 2 of them (40%). We hereby report the use of EUS guided fine needle aspiration (FNA) of peritoneum as a newer, safe and unexplored technique for diagnosis of peritoneal TB.

Influence of dialysis modality on plasma and tissue concentrations of pentosidine in patients with end-stage renal disease.

PubMed

Friedlander, M A; Wu, Y C; Schulak, J A; Monnier, V M; Hricik, D E

1995-03-01

Plasma and tissue concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the influence of dialysis modality and other clinical variables on the accumulation of pentosidine, we used high-performance liquid chromatography to measure this advanced glycation end-product in plasma, skin, and peritoneal samples obtained from 65 hemodialysis and 45 peritoneal dialysis patients. Plasma pentosidine levels were significantly lower in peritoneal dialysis patients. Concentrations of pentosidine in skin were similar in the two groups. In contrast, peritoneal concentrations of pentosidine were significantly higher in the patients maintained on peritoneal dialysis. Our results demonstrate that dialysis modality influences the plasma and tissue distribution of pentosidine. Compared with hemodialysis, peritoneal dialysis is associated with lower levels of this glycation end-product in plasma, but with higher levels in the peritoneum. The mechanisms accounting for lower circulating levels of pentosidine in peritoneal dialysis patients remain to be determined. Higher levels in peritoneal tissues may reflect chronic exposure to the high concentrations of glucose in peritoneal dialysate.

Effect of glucose concentration on peritoneal inflammatory cytokines in continuous ambulatory peritoneal dialysis patients.

PubMed Central

Sayarlioglu, Hayriye; Topal, Cevat; Sayarlioglu, Mehmet; Dulger, Haluk; Dogan, Ekrem; Erkoc, Reha

2004-01-01

OBJECTIVE: It is known that glucose concentrations of peritoneal dialysis solutions are detrimental to the peritoneal membrane. In order to determine the effect of glucose concentration on cytokine levels of peritoneal fluid of continuous ambulatory peritoneal dialysis (CAPD) patients, a cross-sectional study was performed. METHODS: Nine non-diabetic CAPD patients participated in two 8-h dwell sessions of overnight exchanges in consecutive days, with 1.36% and 3.86% glucose containing peritoneal dialysis solutions (Baxter-Eczacibas). Peritoneal dialysis fluid tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured. RESULTS: TNF-alpha levels after 1.36% and 3.86% glucose used dwells were 23+/-14 pg/ml and 28+/-4 pg/ml, respectively (p=0.78). The IL-6 levels were 106+/-57 pg/ml and 115+/-63 pg/ml (p=0.81), respectively. CONCLUSION: In our in vivo study we found that the glucose concentration of the conventional lactate-based CAPD solution has no effect on basal IL-6 and TNF-alpha levels of peritoneal fluid. Further in vivo studies with non-lactate-based CAPD solutions are needed in order to determine the effect of glucose concentration per se on cytokine release. PMID:15203553

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

PubMed

Campbell, Denise; Mudge, David W; Craig, Jonathan C; Johnson, David W; Tong, Allison; Strippoli, Giovanni Fm

2017-04-08

Peritoneal dialysis (PD) is an important therapy for patients with end-stage kidney disease and is used in more than 200,000 such patients globally. However, its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections. Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics, topical disinfectants to the exit site and antifungal agents. However, the effectiveness of these strategies has been variable and are based on a small number of randomised controlled trials (RCTs). The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear.This is an update of a Cochrane review first published in 2004. To evaluate the benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients. We searched the Cochrane Kidney and Transplant's Specialised Register to 4 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. RCTs or quasi-RCTs in patients receiving chronic PD, which evaluated any antimicrobial agents used systemically or locally to prevent peritonitis or exit-site/tunnel infection were included. Two authors independently assessed risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Thirty-nine studies, randomising 4435 patients, were included. Twenty additional studies have been included in this update. The risk of bias domains were often unclear or high; risk of bias was judged to be low in 19 (49%) studies for random sequence generation, 12 (31%) studies for allocation concealment, 22 (56%) studies for incomplete outcome reporting, and in 12 (31%) studies for selective outcome reporting. Blinding of participants and personnel was considered to be at low risk of bias in 8 (21%) and 10 studies (26%) for blinding of outcome assessors. It should be noted that blinding of participants and personnel was not possible in many of the studies because of the nature of the intervention or control treatment.The use of oral or topical antibiotic compared with placebo/no treatment, had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 191 patients, low quality evidence: RR 0.45, 95% CI 0.19 to 1.04) and the risk of peritonitis (5 studies, 395 patients, low quality evidence: RR 0.82, 95% CI 0.57 to 1.19).The use of nasal antibiotic compared with placebo/no treatment had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 338 patients, low quality evidence: RR 1.34, 95% CI 0.62 to 2.87) and the risk of peritonitis (3 studies, 338 patients, low quality evidence: RR 0.94, 95% CI 0.67 to 1.31).Pre/perioperative intravenous vancomycin compared with no treatment may reduce the risk of early peritonitis (1 study, 177 patients, low quality evidence: RR 0.08, 95% CI 0.01 to 0.61) but has an uncertain effect on the risk of exit-site/tunnel infection (1 study, 177 patients, low quality evidence: RR 0.36, 95% CI 0.10 to 1.32).The use of topical disinfectant compared with standard care or other active treatment (antibiotic or other disinfectant) had uncertain effects on the risk of exit-site/tunnel infection (8 studies, 973 patients, low quality evidence, RR 1.00, 95% CI 0.75 to 1.33) and the risk of peritonitis (6 studies, 853 patients, low quality evidence: RR 0.83, 95% CI 0.65 to 1.06).Antifungal prophylaxis with oral nystatin/fluconazole compared with placebo/no treatment may reduce the risk of fungal peritonitis occurring after a patient has had an antibiotic course (2 studies, 817 patients, low quality evidence: RR 0.28, 95% CI 0.12 to 0.63).No intervention reduced the risk of catheter removal or replacement. Most of the available studies were small and of suboptimal quality. Only six studies enrolled 200 or more patients. In this update, we identified limited data from RCTs and quasi-RCTs which evaluated strategies to prevent peritonitis and exit-site/tunnel infections. This review demonstrates that pre/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that antifungal prophylaxis with oral nystatin or fluconazole reduces the risk of fungal peritonitis following an antibiotic course. However, no other antimicrobial interventions have proven efficacy. In particular, the use of nasal antibiotic to eradicate Staphylococcus aureus, had an uncertain effect on the risk of peritonitis and raises questions about the usefulness of this approach. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered and high quality RCTs to inform decision making about strategies to prevent peritonitis is striking.

Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-01-05

Chemotherapeutic Agent Toxicity; Neuropathy; Neurotoxicity Syndrome; Pain; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Fungal peritonitis in patients undergoing continuous ambulatory peritoneal dialysis in Qatar.

PubMed

Khan, Fahmi Yousef; Elsayed, Mohammed; Anand, Deshmukh; Abu Khattab, Mohammed; Sanjay, Doiphode

2011-09-14

This study was conducted at Hamad General Hospital to determine the incidence of fungal peritonitis and to describe its clinical and microbiological findings in patients undergoing continuous ambulatory peritoneal dialysis in Qatar. The medical records of these patients between 1 January 2005 and 31 December 2008 were retrospectively reviewed and the collected data were analysed. During the study period, 141 episodes of peritonitis were observed among 294 patients. In 14 of these episodes (9.9%), fungal peritonitis was reported in 14 patients with a rate of 0.05 episodes per patient year, while the bacterial peritonitis rate was 0.63 per patient year. Thirteen (93%) patients had one or more previous episodes of bacterial peritonitis that was treated with multiple broad-spectrum antibiotics, 11 (85%) had received broad-spectrum antibiotics within the preceding month, 12 (92%) within three months, and 8 (62%) within six months. Candida species were the only fungal species isolated from the dialysate with predominance of non-albicans Candida species (especially Candida parapsilosis). Therapeutic approach was immediate catheter removal, followed by systemic antifungal therapy and temporary haemodialysis. Nine patients (64.3%) were continued on haemodialysis, whereas five patients (35.7%) died. Prior antibiotic use was an important risk factor predisposing patients to the development of fungal peritonitis. Early detection of fungal peritonitis would lead to early institution of appropriate therapy and prevention of complications.

Pancreatitis: an important cause of abdominal symptoms in patients on peritoneal dialysis.

PubMed

Caruana, R J; Wolfman, N T; Karstaedt, N; Wilson, D J

1986-02-01

In an eight-month period, four patients in our peritoneal dialysis program developed acute pancreatitis, an incidence significantly higher than that in our hemodialysis program. Diagnosis was difficult since the symptoms of pancreatitis were similar to those of peritoneal dialysis-associated peritonitis. Further difficulties in diagnosis were due to unreliability of serum amylase levels and "routine" ultrasound examinations in suggesting the presence of pancreatitis. Computerized tomography performed in three patients showed enlarged, edematous pancreata with large extrapancreatic fluid collections in all cases. Two patients died, one directly due to complications of pancreatitis. One patient was changed to hemodialysis and showed clinical and radiologic resolution of his pancreatitis. One patient remains on peritoneal dialysis but has now had four attacks of acute pancreatitis. No patient had classic risk factors for development of pancreatitis. Review of patient histories showed no common historical factors except for renal failure itself, peritoneal dialysis, peritonitis, catheter surgery, and hypoproteinemia. It is possible that metabolic abnormalities related to absorption of glucose and buffer from dialysate or absorption of a toxic substance present in dialysate, bags, or tubing can cause pancreatitis in patients on peritoneal dialysis. We feel that a diagnosis of pancreatitis should be considered when peritoneal dialysis patients present with abdominal pain, particularly if peritoneal fluid cultures are negative or if patients with positive cultures do not have prompt resolution of symptoms with appropriate antibiotic therapy.

[COMPARATIVE CHARACTERISTIC OF VARIOUS METHODS OF SIMULATION OF BILIARY PERITONITIS IN EXPERIMENT].

PubMed

Nichitaylo, M Yu; Furmanov, Yu O; Gutsulyak, A I; Savytska, I M; Zagriychuk, M S; Goman, A V

2016-02-01

In experiment on rabbits a comparative analysis of various methods of a biliary peritonitis simulation was conducted. In 6 animals a biliary peritonitis was simulated, using perforation of a gallbladder, local serous-fibrinous peritonitis have occurred in 50% of them. In 7 animals biliary peritonitis was simulated, applying intraabdominal injection of medical sterile bile in a 5-40 ml volume. Diffuse peritonitis with exudates and stratification of fibrin was absent. Most effective method have appeared that, when intraabdominal injection of bile was done together with E. coli culture in the rate of 0.33 microbal bodies McF (1.0 x 10(8) CFU/ml) on 1 kg of the animal body mass. Diffuse biliary peritonitis have occurred in all 23 animals, including serous-fibrinous one--in 17 (76%), and purulent-fibrinous--in 6 (24%).

Socio-Economic Status and Peritonitis in Australian Non-Indigenous Peritoneal Dialysis Patients

PubMed Central

Tang, Wen; Grace, Blair; McDonald, Stephen P.; Hawley, Carmel M.; Badve, Sunil V.; Boudville, Neil C.; Brown, Fiona G.; Clayton, Philip A.; Johnson, David W.

2015-01-01

♦ Background: The aim of the present study was to investigate the relationship between socio-economic status (SES) and peritoneal dialysis (PD)-related peritonitis. ♦ Methods: Associations between area SES and peritonitis risk and outcomes were examined in all non-indigenous patients who received PD in Australia between 1 October 2003 and 31 December 2010 (peritonitis outcomes). SES was assessed by deciles of postcode-based Australian Socio-Economic Indexes for Areas (SEIFA), including Index of Relative Socio-economic Disadvantage (IRSD), Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), Index of Economic Resources (IER) and Index of Education and Occupation (IEO). ♦ Results: 7,417 patients were included in the present study. Mixed-effects Poisson regression demonstrated that incident rate ratios for peritonitis were generally lower in the higher SEIFA-based deciles compared with the reference (decile 1), although the reductions were only statistically significant in some deciles (IRSAD deciles 2 and 4 – 9; IRSD deciles 4 – 6; IER deciles 4 and 6; IEO deciles 3 and 6). Mixed-effects logistic regression showed that lower probabilities of hospitalization were predicted by relatively higher SES, and lower probabilities of peritonitis-associated death were predicted by less SES disadvantage status and greater access to economic resources. No association was observed between SES and the risks of peritonitis cure, catheter removal and permanent hemodialysis (HD) transfer. ♦ Conclusions: In Australia, where there is universal free healthcare, higher SES was associated with lower risks of peritonitis-associated hospitalization and death, and a lower risk of peritonitis in some categories. PMID:24497587

Early Peritonitis in a Large Peritoneal Dialysis Provider System in Colombia.

PubMed

Vargas, Edgar; Blake, Peter G; Sanabria, Mauricio; Bunch, Alfonso; López, Patricia; Vesga, Jasmín; Buitrago, Alberto; Astudillo, Kindar; Devia, Martha; Sánchez, Ricardo

♦ BACKGROUND: Peritonitis is the most important complication of peritoneal dialysis (PD), and early peritonitis rate is predictive of the subsequent course on PD. Our aim was to calculate the early peritonitis rate and to identify characteristics and predisposing factors in a large nationwide PD provider network in Colombia. ♦ METHODS: This was a historical observational cohort study of all adult patients starting PD between January 1, 2012, and December 31, 2013, in 49 renal facilities in the Renal Therapy Services in Colombia. We studied the peritonitis rate in the first 90 days of treatment, its causative micro-organisms, its predictors and its variation with time on PD and between individual facilities. ♦ RESULTS: A total of 3,525 patients initiated PD, with 176 episodes of peritonitis during 752 patient-years of follow-up for a rate of 0.23 episodes per patient year equivalent to 1 every 52 months. In 41 of 49 units, the rate was better than 1 per 33 months, and in 45, it was better than 1 per 24 months. Peritonitis rates did not differ with age, ethnicity, socioeconomic status, or PD modality. We identified high incidence risk periods at 2 to 5 weeks after initiation of PD and again at 10 to 12 weeks. ♦ CONCLUSION: An excellent peritonitis rate was achieved across a large nationwide network. This occurred in the context of high nationwide PD utilization and despite high rates of socioeconomic deprivation. We propose that a key factor in achieving this was a standardized approach to management of patients. Copyright © 2017 International Society for Peritoneal Dialysis.

Association of Biocompatible Peritoneal Dialysis Solutions with Peritonitis Risk, Treatment, and Outcomes

PubMed Central

Cho, Yeoungjee; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen P.; Brown, Fiona G.; Boudville, Neil; Bannister, Kym M.; Clayton, Philip A.

2013-01-01

Summary Background and objectives The effect of biocompatible peritoneal dialysis (PD) solutions on PD-related peritonitis is unclear. This study sought to evaluate the relationship between use of biocompatible solutions and the probability of occurrence or clinical outcomes of peritonitis. Design, setting, participants, & measurements The study included all incident Australian patients receiving PD between January 1, 2007, and December 31, 2010, using Australia and New Zealand Dialysis and Transplant Registry data. All multicompartment PD solutions of neutral pH were categorized as biocompatible solutions. The independent predictors of peritonitis and the use of biocompatible solutions were determined by multivariable, multilevel mixed-effects Poisson and logistic regression analysis, respectively. Sensitivity analyses, including propensity score matching, were performed. Results Use of biocompatible solutions gradually declined (from 7.5% in 2007 to 4.2% in 2010), with preferential use among smaller units and among younger patients without diabetes mellitus. Treatment with biocompatible solution was associated with significantly greater overall rate of peritonitis (0.67 versus 0.47 episode per patient-year; incidence rate ratio, 1.49; 95% confidence interval [CI], 1.19 to 1.89) and with shorter time to first peritonitis (hazard ratio [HR], 1.48; 95% CI, 1.17 to 1.87), a finding replicated in propensity score–matched cohorts (HR, 1.36; 95% CI, 1.09 to 1.71). Conclusions In an observational registry study, use of biocompatible PD solutions was associated with higher overall peritonitis rates and shorter time to first peritonitis. Further randomized studies adequately powered for a primary peritonitis outcome are warranted. PMID:23949232

A Peritoneal Dialysis Regimen Low in Glucose and Glucose Degradation Products Results in Increased Cancer Antigen 125 and Peritoneal Activation

PubMed Central

le Poole, Caatje Y.; Welten, Angelique G.A.; ter Wee, Piet M.; Paauw, Nanne J.; Djorai, Amina N.; Valentijn, Rob M.; Beelen, Robert H.J.; van den Born, Jacob; van Ittersum, Frans J.

2012-01-01

♦ Background: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening. ♦ Methods: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated either with conventional lactate-buffered PDF (sPD regimen) or with a regimen low in glucose and GDPs: Nutrineal×1, Extraneal×1, and Physioneal×2 (NEPP regimen; all solutions: Baxter Healthcare, Utrecht, Netherlands). After 6 months, patients were switched to the alternative regimen for another 6 months. After 6 weeks of run-in, before the switch, and at the end of the study, 4-hour peritoneal equilibration tests were performed, and overnight effluents were analyzed for cells and biomarkers. Differences between the regimens were assessed by multivariate analysis corrected for time and regimen sequence. ♦ Results: The 45 patients who completed the study were equally distributed over both groups. During NEPP treatment, D4/D0 glucose was lower (p < 0.01) and D/P creatinine was higher (p = 0.04). In NEPP overnight effluent, mesothelial cells (p < 0.0001), cancer antigen 125 (p < 0.0001), hyaluronan (p < 0.0001), leukocytes (p < 0.001), interleukins 6 (p = 0.001) and 8 (p = 0.0001), and vascular endothelial growth factor (VEGF, p < 0.0001) were increased by a factor of 2 – 3 compared with levels in sPD effluent. The NEPP regimen was associated with higher transport parameters, but that association disappeared after the addition of VEGF to the model. The association between NEPP and higher effluent levels of VEGF could not be attributed to glucose and GDP loads. ♦ Conclusions: Study results indicate preservation of the mesothelium and increased peritoneal activation during NEPP treatment. Whether the increase in VEGF reflects an increase in mesothelial cell mass or whether it points to another, undesirable mechanism cannot be determined from the present study. Longitudinal studies are needed to finally evaluate the usefulness of the NEPP regimen for further clinical use. PMID:22045100

Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of Sepsis-Induced Immunosuppression

PubMed Central

Smirnov, Anna; Pohlmann, Stephanie; Nehring, Melanie; Ali, Shafaqat; Mann-Nüttel, Ritu; Scheu, Stefanie; Antoni, Anne-Charlotte; Hansen, Wiebke; Büettner, Manuela; Gardiasch, Miriam J.; Westendorf, Astrid M.; Wirsdörfer, Florian; Pastille, Eva; Dudda, Marcel; Flohé, Stefanie B.

2017-01-01

Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow cells (BMC) were isolated after sham or CLP operation, the cellular composition was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From 24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10. In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC in vitro reversed the increased IL-10 secretion of subsequently differentiating BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow after CLP required the function of sphingosine 1-phosphate receptors and C-C chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype according to their increased expression of MHC class II and CD86. A redistribution of CD4+ pDCs from MHC class II− to MHC class II+ cells concomitant with enhanced expression of CD11c finally led to the rise in the number of CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+ pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial sepsis, CD4+ pDCs are activated in the bone marrow and induce functional reprogramming of differentiating BMDC toward an immunosuppressive phenotype. PMID:29218051

In vitro Multi-Species Biofilms of Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa and Their Host Interaction during In vivo Colonization of an Otitis Media Rat Model

PubMed Central

Yadav, Mukesh K.; Chae, Sung-Won; Go, Yoon Young; Im, Gi Jung; Song, Jae-Jun

2017-01-01

Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are known to cause biofilm-related infections. MRSA and PA have been frequently isolated from chronically infected wounds, cystic fibrosis, chronic suppurative otitis media (CSOM), and from indwelling medical devices, and these bacteria co-exist; however, their interaction with each-other or with the host is not well known. In this study, we investigated MRSA and PA multi-species biofilm communities in vitro and their interaction with the host during in vivo colonization using an OM rat-model. In-vitro biofilm formation and in-vivo colonization were studied using CV-microtiter plate assay and OM rat-model respectively. The biofilms were viewed under scanning electron microscope and bacteria were enumerated using cfu counts. The differential gene expressions of rat mucosa colonized with single or multi-species of MRSA or PA were studied using RNA-sequencing of total transcriptome. In multi-species in-vitro biofilms PA partially inhibited SA growth. However, no significant inhibition of MRSA was detected during in-vivo colonization of multi-species in rat bullae. A total of 1,797 genes were significantly (p < 0.05) differentially expressed in MRSA or PA or MRSA + PA colonized rat middle ear mucosa with respect to the control. The poly-microbial colonization of MRSA and PA induced the differential expression of a significant number of genes that are involved in immune response, inflammation, signaling, development, and defense; these were not expressed with single species colonization by either MRSA or PA. Genes involved in defense, immune response, inflammatory response, and developmental process were exclusively up-regulated, and genes that are involved in nervous system signaling, development and transmission, regulation of cell growth and development, anatomical and system development, and cell differentiation were down-regulated after multi-species inoculation. These results indicate that poly-microbial colonization induces a host response that is different from that induced by single species infection. PMID:28459043

Abdominal Sarcoidosis Mimicking Peritoneal Carcinomatosis.

PubMed

Roh, Won Seok; Lee, Seungho; Park, Ji Hyun; Kang, Jeonghyun

2018-04-01

We present a patient diagnosed with skin sarcoidosis, breast cancer, pulmonary tuberculosis, and peritoneal sarcoidosis with a past history of colorectal cancer. During stage work up for breast cancer, suspicious lesions on peritoneum were observed in imaging studies. Considering our patient's history and imaging findings, we initially suspected peritoneal carcinomatosis. However, the peritoneal lesion was diagnosed as sarcoidosis in laparoscopic biopsy. This case demonstrates that abdominal sarcoidosis might be considered as a differential diagnosis when there is a lesion suspected of being peritoneal carcinomatosis with nontypical clinical presentations.

Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

ClinicalTrials.gov

2018-04-26

Recurrent Uterine Corpus Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Cancer; Recurrent Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Recurrent Actinobacillus peritonitis in an otherwise healthy thoroughbred horse.

PubMed

Watts, A E; Johnson, A L; Felippe, M J; Divers, T J

2011-04-01

A Thoroughbred gelding in North America was evaluated for Actinobacillus peritonitis on three different occasions over a 4-year period. At each presentation, peritoneal fluid had an elevated nucleated cell count (220,000-550,000 cells/µL) characterised by non-degenerate neutrophils, no visible bacteria, an elevated total protein (4.6-5.5 g/dL) and bacterial culture yielding Actinobacillus spp. Actinobacillus peritonitis appears to be a regional disease occurring in Australia and less commonly in New Zealand and North America. Recurrence, other than incomplete resolution, has not been previously reported. This case highlights the classical presentation, response to therapy and excellent prognosis despite the alarmingly abnormal peritoneal fluid characteristic of Actinobacillus peritonitis and questions the role of parasite migration in the pathogenesis. Finally, this case is remarkable because Actinobacillus peritonitis was recurrent over several years in an otherwise normal horse. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Paecilomyces variotii peritonitis in a patient on continuous ambulatory peritoneal dialysis.

PubMed

Uzunoglu, E; Sahin, A M

2017-06-01

Paecilomyces variotii (P. variotii) is an extremely rare cause of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. When diagnosed, it usually portends poor prognosis. Patient's survival depends on early laboratory diagnosis and proper treatment. We herein report a P. variotii peritonitis in a patient on CAPD which is a quite rare clinical entity. Laboratory diagnosis was confirmed via both morphological analysis and DNA sequencing. Antifungal susceptibility tests were performed and interpreted according to the Clinical Laboratory Standards Institute M38-A2 guidelines. After laboratory diagnosis, the patient was treated succesfully with liposomal amphotericin B and itraconazole combination and the peritoneal catheter was removed. This case is worthy of reporting since P. variotii is an uncommon cause of peritonitis and leads to dilemmas in both laboratory diagnosis and treatment strategies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator.

PubMed

Reymond, M A; Hu, B; Garcia, A; Reck, T; Köckerling, F; Hess, J; Morel, P

2000-01-01

Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum." A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions.

Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

PubMed

Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

2016-11-15

Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

Tuberculous peritonitis: CT appearance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, R.D.; Hunter, T.B.

1985-05-01

Rare, sporadic cases of tuberculous peritonitis do occur in the United States and other advanced countries. Because there are few descriptions of the CT appearance of the peritoneal forms of tuberculous (TB), this report illustrates a case of tuberculous peritonitis with prominent CT findings and discusses the differentiation of this entity from other, more common diseases.

Two Cases of Peritonitis Caused by Kocuria marina in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis▿

PubMed Central

Lee, Ja Young; Kim, Si Hyun; Jeong, Haeng Soon; Oh, Seung Hwan; Kim, Hye Ran; Kim, Yeong Hoon; Lee, Jeong Nyeo; Kook, Joong-Ki; Kho, Weon-Gyu; Bae, Il Kwon; Shin, Jeong Hwan

2009-01-01

Kocuria spp. are members of the Micrococcaceae family that are frequently found in the environment and on human skin. Few human infections have been reported. We describe what appear to be the first two cases of Kocuria marina peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. PMID:19692561

Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway.

PubMed

Niu, Xiaofeng; Wang, Yu; Li, Weifeng; Zhang, Hailin; Wang, Xiumei; Mu, Qingli; He, Zehong; Yao, Huan

2015-12-01

Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of protection by two endotoxin-neutralizing IgM monoclonal antibodies in different peritonitis models.

PubMed

Hustinx, W N; Benaissa-Trouw, B J; Harmsen, T; Klein, S; Verhoef, J; Hoepelman, A I; Kraaijeveld, K

1997-10-01

Two anti-core glycolipid (CGL) IgM monoclonal antibodies (mAbs 8-2 and 26-20), previously shown to display cross-reactivity with heterologous lipopolysaccharide (LPS) in vitro and to provide cross-protectivity against endotoxin challenge in vivo, were evaluated for their potential to protect mice against death from peritonitis caused by heterologous bacterial challenge. Without concurrent antibiotic treatment neither antibody was protective. Compared with a control mAb, prophylactic treatment with mAb 8-2 significantly increased the survival of gentamicin-treated mice challenged with the rough strain Salmonella minnesota Re595. Both mAb 8-2 and a control mAb, in combination with a suboptimal dose of ceftazidime, increased survival following challenge with the clinical isolate Escherichia coli O7:K1. In a model of mucin-enhanced peritonitis, neither mAb was protective against challenge with inocula of E. coli O7:K1, ranging from 10(2) to 10(4) bacteria. We conclude that protection of mice by anti-CGL mAb 8-2 against heterologous challenge is vitally dependent on concurrent treatment with antibiotics and that protection may not be attributable to the anti-CGL specificity of these antibodies.

Is the systemic microvascular endothelial glycocalyx in peritoneal dialysis patients related to peritoneal transport?

PubMed

Vlahu, Carmen A; Lopes Barreto, Deirisa; Struijk, Dirk G; Vink, Hans; Krediet, Raymond T

2014-01-01

The capillary wall coated by the endothelial glycocalyx is the main transport barrier during peritoneal dialysis (PD). Here, we investigated the relationships between measurements of the systemic endothelial glycocalyx and peritoneal transport in PD patients. We performed sidestream darkfield (SDF) imaging of the sublingual microvasculature in 15 patients, measured the perfused boundary region (PBR), which includes the permeable part of the glycocalyx, and calculated the estimated blood vessel density (EBVD). All patients underwent a peritoneal permeability analysis. No relationships were present between the imaging and peritoneal transport parameters, neither in the group as a whole nor in fast transporters. In patients with nonfast peritoneal transport status, PBR had a negative relationship with EBVD and small solute transport, and a positive one with net ultrafiltration (NUF). The EBVD showed a positive correlation with glucose absorption and a negative one with NUF. We found no relationships with the peritoneal transport of albumin. No relationships are present between the systemic endothelial glycocalyx, which was assessed by SDF, and peritoneal transport. In nonfast transporters, a reduction in blood vessel density caused by endothelial glycocalyx alterations or a thicker permeable phase of the glycocalyx delaying the access of small solutes to the small pores may be important. . © 2014 S. Karger AG, Basel

[Post-operative peritoneal washing cytology in cases of stage IIIa endometrial carcinoma with positive peritoneal cytology].

PubMed

Kato, T; Hirai, Y; Hasumi, K

1995-07-01

According to the new FIGO staging of corpus cancer, the cases with positive peritoneal cytology alone belong in stage IIIa. The authors previously reported, however, good prognosis of IIIa cases with only positive peritoneal cytology. In order to assess the potential of malignant cells in the peritoneal cavity to metastasize, post-operative peritoneal washing cytology was undertaken. This study was conducted on a total of 115 consecutive patients with endometrial carcinoma who underwent primary surgical therapy at the Cancer Institute Hospital during the 25-month period from December, 1991 to December, 1993. Fifteen cases were included in stage IIIa with positive intraoperative peritoneal cytology alone. In 12 cases with endometrioid adenocarcinoma, a Silascon tube was indwelt in the abdominal cavity before closure of the abdomen. The peritoneal cavity was washed with 500 ml of physiological saline through the indwelt tube 14 days after the operation. The cytology of recovered washings was negative in all cases. Only two cases received postoperative chemotherapy owing to other prognostic factors. These 12 cases are alive with no evidence of disease after 12 to 36 months. The present study demonstrated that malignant cells in the peritoneal cavity appear to have a very low potential for implantation into the peritoneum.

Peritoneal dialysis-related peritonitis caused by Pseudomonas species: Insight from a post-millennial case series.

PubMed

Lu, Wanhong; Kwan, Bonnie Ching-Ha; Chow, Kai Ming; Pang, Wing-Fai; Leung, Chi Bon; Li, Philip Kam-To; Szeto, Cheuk Chun

2018-01-01

Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear. We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015. Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure. Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy.

Acute dialysis-associated peritonitis in children with D+ hemolytic uremic syndrome.

PubMed

Adragna, Marta; Balestracci, Alejandro; García Chervo, Laura; Steinbrun, Silvina; Delgado, Norma; Briones, Liliana

2012-04-01

Acute peritoneal dialysis (PD) is the preferred therapy for renal replacement in children with post-diarrheal hemolytic uremic syndrome (D+ HUS), but peritonitis remains a frequent complication of this procedure. We reviewed data from 149 patients with D+ HUS who had undergone acute PD with the aim of determining the prevalence and risk factors for the development of peritonitis. A total of 36 patients (24.2%) presented peritonitis. The median onset of peritonitis manifestations was 6 (range 2-18) days after the initiation of dialysis treatment, and Gram-positive microorganisms were the predominant bacterial type isolated (15/36 patients). The patients were divided into two groups: with or without peritonitis, respectively. Univariate analysis revealed that a longer duration of the oligoanuric period, more days of dialysis, catheter replacement, stay in the intensive care unit, and hypoalbuminemia were significantly associated to the development of peritonitis. The multivariate analysis, controlled by duration of PD, identified the following independent risk factors for peritonitis: catheter replacement [p = 0.037, odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02-1.73], stay in intensive care unit (p = 0.0001, OR 2.62, 95% CI 1.65-4.19), and hypoalbuminemia (p = 0.0076, OR 1.45, 95% CI 1.10-1.91). Based on these findings, we conclude that the optimization of the aseptic technique during catheter manipulation and early nutritional support are targets for the prevention of peritonitis, especially in critically ill patients.

Epidemiology and Clinical Characteristics of Acinetobacter Peritoneal Dialysis-Related Peritonitis in Hong Kong-With a Perspective on Multi-Drug and Carbapenem Resistance.

PubMed

Li, Philip Hei; Cheng, Vincent C C; Yip, Terence; Yap, Desmond Y H; Lui, Sing-Leung; Lo, Wai-Kei

2017-01-01

♦ BACKGROUND: Acinetobacter spp. is an important cause of peritoneal dialysis (PD)-related peritonitis, but studies on Acinetobacter peritonitis have been scarce. In view of the rising concern of carbapenem-resistant Acinetobacter (CRA) and multidrug-resistant Acinetobacter (MDRA) infections, we conducted this study on the incidence of Acinetobacter peritonitis and the impact of CRA and MDRA on its outcome. ♦ METHODS: We retrospectively evaluated the clinical characteristics, prevalence, antibiotic sensitivity patterns, outcomes, and factors associated with treatment failure over the past 16 years in our patients with Acinetobacter PD-related peritonitis. ♦ RESULTS: Out of 2,389 episodes of peritonitis, there were 66 episodes (3%) of Acinetobacter peritonitis occurring in 59 patients. Twelve episodes were caused by MDRA (18%), of which 5 were CRA (8%). There was a progressive increase in the incidence of MDRA and CRA infections over the study period. Most isolates were sensitive to sulbactam combinations (ampicillin-sulbactam [95.4%] and cefoperazone-sulbactam [93.9%]), aminoglycosides (amikacin [92.4%], tobramycin [90.9%], and gentamicin [89.4%]), and carbapenems (imipenem [92.2%]). There was 1 case of relapse. Fifteen episodes resulted in catheter removal (23%), and 7 patients died (11%). Hypoalbuminemia (odds ratio [OR] = 0.85, p = 0.006) and carbapenem resistance (OR = 18.2, p = 0.049) were significantly associated with higher rates of treatment failure. ♦ CONCLUSION: Both carbapenem resistance and hypoalbuminemia were significantly associated with treatment failure. Up to 80% of peritonitis episodes by CRA resulted in catheter loss or mortality. Sulbactam combinations and/or aminoglycosides remained effective for the majority of Acinetobacter isolates. There seemed to be an increasing relative incidence of MDRA and CRA infections over the past 16 years. Copyright © 2017 International Society for Peritoneal Dialysis.

Relationship between bioimpedance-determined body composition and peritoneal transport in peritoneal dialysis.

PubMed

da Costa, Bernardo M; Del Peso, Gloria; Bajo, Maria Auxiliadora; Carreño, Gilda; Ferreira, Marta; Ferreira, Carina; Selgas, Rafael

2017-05-29

In peritoneal dialysis (PD) patients, body fluid homeostasis is dependent on peritoneal elimination of water and solutes. Patients with less favorable peritoneal transport parameters should be more overhydrated. Despite this, the association between faster transport and overhydration (OH) is weak, and the factors that influence hydration status are still poorly characterized. Modified peritoneal equilibration tests (PET) offer us new parameters that might correlate better with hydration status, like free water transport (FWT). The aim of this study was thus to establish the relationships between new peritoneal transport parameters and body composition parameters estimated by bioimpedance spectroscopy (BIS). Prospective observational study on incident PD patients with a baseline and 1-year follow-up evaluation. 61 patients were included in the baseline evaluation, 19 of whom had a 1-year follow-up evaluation; 67.2% were fluid overloaded. There was a negative correlation between D/P creatinine and FWT (r = -0.598, p = 0.000). The fraction of FWT was negatively correlated with OH (r = -0.302, p = 0.018). Peritoneal protein losses (PPL) were also correlated with OH (r = 0.287, p = 0.028). There were no significant differences in OH according to small-solute transport status or fluid output parameters. After 1 year, we observed a significant worsening of renal function and an improvement in 24-hour ultrafiltration (UF) and hydration status, but we detected no differences in peritoneal transport of water or solutes that could explain these changes. There is a poor relationship between kidney/peritoneal function parameters and body composition parameters. The fraction of FWT and PPL may be underestimated markers of peritoneal health and of its contribution to the hydration status.

Advanced nursing experience is beneficial for lowering the peritonitis rate in patients on peritoneal dialysis.

PubMed

Yang, Zhikai; Xu, Rong; Zhuo, Min; Dong, Jie

2012-01-01

We explored the relationship between the experience level of nurses and the peritonitis risk in peritoneal dialysis (PD) patients. Our observational cohort study followed 305 incident PD patients until a first episode of peritonitis, death, or censoring. Patients were divided into 3 groups according to the work experience in general medicine of their nurses-that is, least experience (<10 years), moderate experience (10 to <15 years), and advanced experience (≥ 15 years). Demographic characteristics, baseline biochemistry, and residual renal function were also recorded. Multivariate Cox regression was used to analyze the association of risks for all-cause and gram-positive peritonitis with patient training provided by nurses at different experience levels. Of the 305 patients, 91 were trained at the initiation of PD by nurses with advanced experience, 100 by nurses with moderate experience, and 114 by nurses with the least experience. Demographic and clinical variables did not vary significantly between the groups. During 13 582 patient-months of follow-up, 129 first episodes of peritonitis were observed, with 48 episodes being attributed to gram-positive organisms. Kaplan-Meier analysis showed that training by nurses with advanced experience predicted the longest period free of first-episode gram-positive peritonitis. After adjustment for some recognized confounders, the advanced experience group was still associated with the lowest risk for first-episode gram-positive peritonitis. The level of nursing experience was not significantly correlated with all-cause peritonitis risk. The experience in general medicine of nurses might help to lower the risk of gram-positive peritonitis among PD patients. These data are the first to indicate that nursing experience in areas other than PD practice can be vital in the training of PD patients.

Advanced Nursing Experience Is Beneficial for Lowering the Peritonitis Rate in Patients on Peritoneal Dialysis

PubMed Central

Yang, Zhikai; Xu, Rong; Zhuo, Min; Dong, Jie

2012-01-01

♦ Objectives: We explored the relationship between the experience level of nurses and the peritonitis risk in peritoneal dialysis (PD) patients. ♦ Methods: Our observational cohort study followed 305 incident PD patients until a first episode of peritonitis, death, or censoring. Patients were divided into 3 groups according to the work experience in general medicine of their nurses—that is, least experience (<10 years), moderate experience (10 to <15 years), and advanced experience (≥15 years). Demographic characteristics, baseline biochemistry, and residual renal function were also recorded. Multivariate Cox regression was used to analyze the association of risks for all-cause and gram-positive peritonitis with patient training provided by nurses at different experience levels. ♦ Results: Of the 305 patients, 91 were trained at the initiation of PD by nurses with advanced experience, 100 by nurses with moderate experience, and 114 by nurses with the least experience. Demographic and clinical variables did not vary significantly between the groups. During 13 582 patient–months of follow-up, 129 first episodes of peritonitis were observed, with 48 episodes being attributed to gram-positive organisms. Kaplan–Meier analysis showed that training by nurses with advanced experience predicted the longest period free of first-episode gram-positive peritonitis. After adjustment for some recognized confounders, the advanced experience group was still associated with the lowest risk for first-episode gram-positive peritonitis. The level of nursing experience was not significantly correlated with all-cause peritonitis risk. ♦ Conclusions: The experience in general medicine of nurses might help to lower the risk of gram-positive peritonitis among PD patients. These data are the first to indicate that nursing experience in areas other than PD practice can be vital in the training of PD patients. PMID:21719682

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis

PubMed Central

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-01-01

♦ Background: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ Methods: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ Results: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 – 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 – 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 – 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 – 0.94) and 0.39 (95% CI 0.20 – 0.75), respectively. ♦ Conclusions: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. PMID:26224791

Patient and family perspectives on peritoneal dialysis at home: findings from an ethnographic study.

PubMed

Baillie, Jessica; Lankshear, Annette

2015-01-01

To discuss findings from an ethnographic study, considering the experiences of patients and families, using peritoneal dialysis at home in the United Kingdom. Peritoneal dialysis is a daily, life-preserving treatment for end-stage renal disease, undertaken in the patient's home. With ever-growing numbers of patients requiring treatment for this condition, the increased use of peritoneal dialysis is being promoted. While it is known that quality of life is reduced when using dialysis, few studies have sought to explore experiences of peritoneal dialysis specifically. No previous studies were identified that adopted an ethnographic approach. A qualitative design was employed, utilising ethnographic methodology. Ethical and governance approvals were gained in November 2010 and data were generated in 2011. Patients (n = 16) and their relatives (n = 9) were interviewed and observed using peritoneal dialysis in their homes. Thematic analysis was undertaken using Wolcott's (1994) three stage process: Description, Analysis and Interpretation. This article describes four themes: initiating peritoneal dialysis; the constraints of peritoneal dialysis due to medicalisation of the home environment and the imposition of rigid timetables; the uncertainty of managing crises and inevitable deterioration; and seeking freedom through creativity and hope of a kidney transplant. This study highlights the culture of patients and their families living with peritoneal dialysis. Despite the challenges posed by the treatment, participants were grateful they were able to self-manage at home. Furthermore, ethnographic methods offer an appropriate and meaningful way of considering how patients live with home technologies. Participants reported confusion about kidney transplantation and also how to identify peritonitis, and ongoing education from nurses and other healthcare professionals is thus vital. Opportunities for sharing experiences of peritoneal dialysis were valued by participants and further peer-support services should thus be considered. © 2014 John Wiley & Sons Ltd.

Peritonitis following percutaneous gastrostomy tube insertions in children.

PubMed

Dookhoo, Leema; Mahant, Sanjay; Parra, Dimitri A; John, Philip R; Amaral, Joao G; Connolly, Bairbre L

2016-09-01

Percutaneous retrograde gastrostomy has a high success rate, low morbidity, and can be performed under different levels of sedation or local anesthesia in children. Despite its favourable safety profile, major complications can occur. Few studies have examined peritonitis following percutaneous retrograde gastrostomy in children. To identify potential risk factors and variables influencing the development and early diagnosis of peritonitis following percutaneous retrograde gastrostomy. We conducted a retrospective case-control study of children who developed peritonitis within 7 days of percutaneous retrograde gastrostomy between 2003 and 2012. From the 1,504 patients who underwent percutaneous retrograde gastrostomy, patients who developed peritonitis (group 1) were matched by closest date of procedure to those without peritonitis (group 2). Peritonitis was defined according to recognized clinical criteria. Demographic, clinical, procedural, management and outcomes data were collected. Thirty-eight of 1,504 children (2.5%; 95% confidence interval, 1.8-3.5) who underwent percutaneous retrograde gastrostomy developed peritonitis ≤7 days post procedure (group 1). Fever (89%), irritability (63%) and abdominal pain (55%) occurred on presentation of peritonitis. Group 1 patients were all treated with antibiotics; 41% underwent additional interventions: tube readjustments (8%), aspiration of pneumoperitoneum (23%), laparotomy (10%) and intensive care unit admission (10%). In group 1, enteral feeds started on average 3 days later and patients were discharged 5 days later than patients in group 2. There were two deaths not directly related to peritonitis. Neither age, gender, weight, underlying diagnoses nor operator was identified as a risk factor. Peritonitis following percutaneous retrograde gastrostomy in children occurs in approximately 2.5% of cases. No risk factors for its development were identified. Medical management is usually sufficient for a good outcome. Patients with peritonitis are delayed starting feeds and have a hospital stay that is an average of 5 days longer than those without.

The effects of living distantly from peritoneal dialysis units on peritonitis risk, microbiology, treatment and outcomes: a multi-centre registry study

PubMed Central

2012-01-01

Background The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes. Methods The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data. Results 365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived <100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p = 0.001), whilst overall peritonitis rates were higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p < 0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable between the two groups. Conclusions Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients. PMID:22702659

Effects of a Statewide Protocol for the Management of Peritoneal Dialysis-Related Peritonitis on Microbial Profiles and Antimicrobial Susceptibilities: A Retrospective Five-Year Review.

PubMed

McGuire, Amanda L; Carson, Christine F; Inglis, Timothy J J; Chakera, Aron

2015-12-01

♦ Peritonitis is a major complication of peritoneal dialysis (PD) and is associated with significant morbidity and mortality. Early empirical antibiotic therapy is recommended, with the choice of agents guided by local resistance patterns. As routine use of specific antimicrobial agents can drive resistance, regular assessment of causative organisms and their susceptibility to empirical therapy is essential. ♦ We conducted a retrospective review of all PD peritonitis cases and positive PD fluid cultures obtained over a 5-year period in Western Australia following the introduction of a statewide protocol for the initial management of PD peritonitis with intraperitoneal vancomycin and gentamicin. ♦ The incidence of PD peritonitis decreased from 1 in 16 patient months (0.75/year at risk) to 1 in 29 patient months (0.41/year at risk) over the 5 years. There were 1,319 culture-positive samples and 1,069 unique isolates identified. Gram-positive bacteria accounted for 69.9% of positive cultures, with vancomycin resistance averaging 2% over the study period. Gram-negative bacteria accounted for 25.4% of positive cultures, with gentamicin resistance identified in an average of 8% of organisms. No increase in antimicrobial resistance to vancomycin or gentamicin occurred over the 5 years and there was no change in the proportion of gram-positive (69.9%), gram-negative (25.4%) or fungal (4.4%) organisms causing PD peritonitis. ♦ Over time, the peritonitis rates have dramatically improved although the profile of causative organisms remains similar. Empirical treatment of PD peritonitis with intraperitoneal vancomycin and gentamicin remains efficacious, with high levels of susceptibility and no evidence that the introduction of this statewide empirical PD peritonitis treatment protocol is driving resistance to these agents. Copyright © 2015 International Society for Peritoneal Dialysis.

Peritoneal Dialysis-Related Peritonitis Due to Melioidosis: A Potentially Devastating Condition.

PubMed

Kanjanabuch, Talerngsak; Lumlertgul, Nuttha; Pearson, Lachlan J; Chatsuwan, Tanittha; Pongpirul, Krit; Leelahavanichkul, Asada; Thongbor, Nisa; Nuntawong, Gunticha; Praderm, Laksamon; Wechagama, Pantiwa; Narenpitak, Surapong; Wechpradit, Apinya; Punya, Worauma; Halue, Guttiga; Naka, Phetpailin; Jeenapongsa, Somboon; Eiam-Ong, Somchai

2017-01-01

♦ BACKGROUND: Melioidosis, an infectious disease caused by Burkholderia pseudomallei , is endemic in Southeast Asia and Northern Australia. Although a wide range of clinical manifestations from this organism are known, peritonitis associated with peritoneal dialysis (PD) has rarely been reported. ♦ PATIENTS AND METHODS: Peritoneal dialysis patients from all regions in Thailand were eligible for the study if they had peritonitis and either peritoneal fluid or effluent culture positive for B. pseudomallei . Patient data obtained included baseline characteristics, laboratory investigations, treatments, and clinical outcomes. When possible, PD fluid and removed Tenckhoff (TK) catheters were submitted for analyses of minimal inhibitory concentration (MIC) and microbial biofilm, respectively. ♦ RESULTS: Twenty-six patients were identified who were positive for peritoneal B. pseudomallei infection. The recorded mean age was 50 ± 15 (24 - 75) years, and the majority (58%) were female. Most of the cases were farmers living in Northeastern and Northern Thailand. Almost half of the cases had diabetes. Infections were reported commonly during the monsoon season and winter. The clinical presentations of peritonitis were similar to the manifestations from other microorganisms. Nine patients (41%) died (7 from sepsis), 6 fully recovered, and 7 switched to permanent hemodialysis. The mortality was potentially associated with sepsis ( p = 0.007), infection during the monsoon season ( p = 0.017), high initial dialysate neutrophils ( p = 0.045), and high hematocrit ( p = 0.045). Although no antibiotic resistance to ceftazidime and carbapenems was detected, approximately 50% of patients died with this treatment. Microbial biofilms were identified on the luminal surface of 4 out of 5 TK catheters, but the removal of the catheter did not alter the outcomes. ♦ CONCLUSION: Peritoneal dialysis-related peritonitis due to melioidosis is uncommon but highly fatal. Increased awareness, early diagnosis, and optimal management are mandatory. Copyright © 2017 International Society for Peritoneal Dialysis.

Using a Multidisciplinary Training Program to Reduce Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Gadola, Liliana; Poggi, Carla; Poggio, María; Sáez, Lucía; Ferrari, Alejandra; Romero, Jorge; Fumero, Soledad; Ghelfi, Gianella; Chifflet, Liliana; Borges, Patricia Larre

2013-01-01

♦ Objectives: The present study evaluated the tool used to assess patients’ skills and the impact on peritonitis rates of a new multidisciplinary peritoneal dialysis (PD) education program (PDEP). ♦ Methods: After the University Hospital Ethics Committee approved the study, the educational and clinical records of PD patients were retrospectively analyzed in two phases. In phase I, an Objective Structured Assessment (OSA) was used during August 2008 to evaluate the practical skills of 25 patients with adequate Kt/V and no mental disabilities who had been on PD for more than 1 month. Test results were correlated with the prior year’s peritonitis rate. In phase II, the new PDEP, consisting of individual lessons, a retraining schedule, and group meetings, was introduced starting 1 September 2008. Age, sex, years of education, time on PD, number of training sessions, and peritonitis episodes were recorded. Statistical analyses used t-tests, chi-square tests, and Poisson distributions; a p value of less than 0.05 was considered significant. ♦ Results: In phase I, 25 patients [16 men, 9 women; mean age: 54 ± 15 years (range: 22 - 84 years); mean time on PD: 35 ± 30 months (range: 1 - 107 months)] were studied. The OSA results correlated with peritonitis rates: patients who passed the test had experienced significantly lower peritonitis rates during the prior year (p < 0.05). In phase II, after the new PDEP was introduced, overall peritonitis rates significantly declined (to 0.28 episodes/patient-year from 0.55 episodes/patient-year, p < 0.05); the Staphylococcus peritonitis rate also declined (to 0.09 episodes/patient-year from 0.24 episodes/patient-year, p < 0.05). ♦ Conclusions: The OSA is a reliable tool for assessing patients’ skills, and it correlates with peritonitis rates. The multidisciplinary PDEP significantly improved outcomes by further lowering peritonitis rates. PMID:22753455

Weekend Compared with Weekday Presentations of Peritoneal Dialysis-Associated Peritonitis

PubMed Central

Johnson, David W.; Clayton, Philip; Cho, Yeoungjee; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen; Boudville, Neil; Wiggins, Kathryn J.; Bannister, Kym; Brown, Fiona

2012-01-01

♦ Objective: Management of peritoneal dialysis (PD)-associated peritonitis requires timely intervention by experienced staff, which may not be uniformly available throughout the week. The aim of the present study was to examine the effects of weekend compared with weekday presentation on peritonitis outcomes. ♦ Methods: The study, which used data from the Australia and New Zealand Dialysis and Transplant Registry, included all Australian patients receiving PD between 1 October 2003 and 31 December 2008. The independent predictors of weekend presentation and subsequent peritonitis outcomes were assessed by multivariate logistic regression. ♦ Results: Peritonitis presentation rates were significantly lower on Saturdays [0.46 episodes per year; 95% confidence interval (CI): 0.42 to 0.49 episodes per year] and on Sundays (0.43 episodes per year; 95% CI: 0.40 to 0.47 episodes per year) than all other weekdays; they peaked on Mondays (0.76 episodes per year; 95% CI: 0.72 to 0.81 episodes per year). Weekend presentation with a first episode of peritonitis was independently associated with lower body mass index and residence less than 100 km away from the nearest PD unit. Patients presenting with peritonitis on the weekend were significantly more likely to be hospitalized [adjusted odds ratio (OR): 2.32; 95% CI: 1.85 to 2.90], although microbial profiles and empiric antimicrobial treatments were comparable between the weekend and weekday groups. Antimicrobial cure rates were also comparable (79% vs 79%, p = 0.9), with the exception of cure rates for culture-negative peritonitis, which were lower on the weekend (80% vs 88%, p = 0.047). Antifungal prophylaxis was less likely to be co-prescribed for first peritonitis episodes presenting on weekdays (OR: 0.68; 95% CI: 0.05 to 0.89). ♦ Conclusions: Patients on PD are less likely to present with peritonitis on the weekend. Nevertheless, the microbiology, treatment, and outcomes of weekend and weekday PD peritonitis presentations are remarkably similar. Exceptions include the associations of weekend presentation with a higher hospitalization rate and a lower cure rate in culture-negative infection. PMID:22302768

Safety and effectiveness evaluation of a domestic peritoneal dialysis fluid packed in non-PVC bags: study protocol for a randomized controlled trial.

PubMed

Zhou, Jianhui; Cao, Xueying; Lin, Hongli; Ni, Zhaohui; He, Yani; Chen, Menghua; Zheng, Hongguang; Chen, Xiangmei

2015-12-29

Peritoneal dialysis is an important type of renal replacement therapy for uremic patients. In peritoneal dialysis, fluids fill in and flow out of the abdominal cavity three to five times per day. Usually, the fluid is packed in a polyvinyl chloride (PVC) bag. Safety concerns have arisen over di-(2-ethylhexyl) phthalate, which is essential in the formation of PVC materials. In 2011, the National Development and Reform Commission of China released a catalog of industrial structural adjustments, mandating the elimination of PVC bags for intravenous infusion and food containers. Although bags for peritoneal dialysis fluid were not included in the elimination list, several manufacturers began to develop new materials for fluid bags. HUAREN peritoneal dialysis fluid consists of the same electrolytes and buffer agent as in Baxter fluid, but is packed in bags that do not contain PVC. This multicenter randomized controlled trial was designed to compare peritoneal dialysis fluid packed in non-PVC-containing and PVC-containing bags. Further, the study sought to determine the proper dose of peritoneal dialysis fluid and the actual survival rates of Chinese patients undergoing peritoneal dialysis. The study participants are adults undergoing continuous ambulatory peritoneal dialysis for 30 days to 6 months. All eligible patients are randomized (1:1) to peritoneal dialysis with Baxter and HUAREN dialysis fluids (initial dose, 6 l/day), with dosages adjusted according to a unified protocol. The primary outcomes are the 1-, 2-, 3-, 4-, and 5-year overall survival rates. Secondary outcome measures include technique survival rates, reductions in estimated glomerular filtration rate, nutritional status, quality of life, cardiovascular events, medical costs and drop-out rates. Safety outcome measures include adverse events, changes in vital signs and laboratory parameters, peritonitis, allergies, and quality of products. This study is the first to evaluate the long-term safety and effectiveness of a non-PVC packed peritoneal dialysis fluid. The effects of plasticizer on patient long-term survival will be determined. The characteristics of Chinese patients undergoing peritoneal dialysis will be determined, including proper dose, technique survival rates, patient survival rates, and medical costs. Clinicaltrials.gov NCT01779557 .

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial

PubMed Central

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

Background The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. Methods Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. Results Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference −0.004 per month, 95% confidence interval (95% CI) −0.005 to −0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9–39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. Conclusions Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted. PMID:22859794

Peritoneal Morphology After Long-Term Peritoneal Dialysis with Biocompatible Fluid: Recent Clinical Practice in Japan

PubMed Central

Ayuzawa, Nobuhiro; Ishibashi, Yoshitaka; Takazawa, Yutaka; Kume, Haruki; Fujita, Toshiro

2012-01-01

♦ Background: Morphology changes of the peritoneal membrane after long-term peritoneal dialysis (PD) consist of denudation of peritoneal mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those changes are considered to be the result of uremia and bioincompatible effects of conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In the last decade, biocompatible dialysate with neutral pH and low GDPs has become widely used. Clinical practice has been modified in Japan, especially for anuric patients, and now includes the use of hybrid therapy. The impact on peritoneal morphology has not been well reported. ♦ Objective: The aim of the present study was to investigate the long-term effect on peritoneal morphology and function of biocompatible fluid use and current clinical practice in Japan, including hybrid dialysis therapy. ♦ Methods: We evaluated peritoneal biopsy specimens from patients who had undergone PD for more than 3 years. We used the average peritoneal thickness (APT) of the submesothelial compact zone as a marker of interstitial sclerosis and the lumen/vessel diameter ratio (L/V ratio) at postcapillary venules as a marker of hyalinizing vasculopathy. Demography and other data for the patients, including dialysate-to-plasma (D/P) ratio of creatinine, were obtained at baseline and every 6 months by peritoneal equilibration test. ♦ Results: Between 2002 and 2009, 110 patients started PD therapy with biocompatible dialysate at Tokyo University Hospital. Among them, 11 patients (8 men, 3 women; age: 54.2 ± 11.8 years; 1 with diabetes mellitus) were enrolled into this morphology study. The mean duration of PD in this group was 61 ± 11.3 months, and the mean time to peritoneal biopsy was 58 ± 15.1 months. The median APT was 180 μm (96 – 1424 μm), and the median L/V ratio was 0.66 (0.46 – 0.74). No obvious correlations between APT, L/V ratio, and PD duration were detected. The D/P creatinine of the 11 patients was maintained at a favorably low value, comparable with that of the other 99 patients. ♦ Conclusions: Peritoneal dialysis therapy using biocompatible dialysate in conjunction with modification of clinical practice may minimize the progression of peritoneal interstitial sclerosis and hyalinizing vasculopathy, preserving favorable peritoneal function for more than 3 years. PMID:21804136

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

PubMed

Melcarne, Luigi; Sopeña, Julia; Martínez-Cerezo, Francisco José; Vergara, Mercedes; Miquel, Mireia; Sánchez-Delgado, Jordi; Dalmau, Blai; Machlab, Salvador; Portilla, Dustin; González-Padrón, Yonaisy; Real Álvarez, Mónica; Carpintero, Chantal; Casas, Meritxell

2018-02-01

Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat.

PubMed

Stanojević, Stanislava; Kovačević-Jovanović, Vesna; Dimitrijević, Mirjana; Vujić, Vesna; Ćuruvija, Ivana; Blagojević, Veljko; Leposavić, Gordana

2015-11-01

The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied. Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro. Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1β) and peritoneal (TNF-α, IL-1β, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-β by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-α and more IL-10, whereas peritoneal macrophages produced less IL-1β and TGF-β than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages. Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro-inflammatory/anti-inflammatory cytokine secretory balance. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transabdominal preperitoneal herniorrhaphy using laser-assisted tissue soldering in a porcine model.

PubMed

Lanzafame, Raymond J; Soltz, Barbara A; Stadler, Istvan; Soltz, Robert

2009-01-01

Collagen solder is capable of fixation of surgical meshes during laparoscopic herniorrhaphy without compromising tissue integration, increasing adhesions or inflammation. This pilot study describes development of instrumentation and techniques for transabdominal preperitoneal (TAPP) herniorrhaphy using laser-assisted soldering technology. Anesthetized 20-kg to 25-kg female Yorkshire pigs underwent laparoscopy performed using a 3-trocar technique. Peritoneal incisions were made and pockets created in the preperitoneal space for mesh placement. Parietex TEC mesh segments embedded in 60% collagen-solder were soldered to the muscle surface by using a prototype laser (1.45micro, 4.5W CW, 5mm spot, and 55 degrees C set temperature) and custom laparoscopic handpiece. Parietex TEC mesh segments (Control) were affixed to the muscle with fibrin sealant (Tisseel). Peritoneal closure was with staples (Control) or by soldering collagen embedded Vicryl mesh segments over the peritoneal incision (Mesh/TAPP). Segments were inserted using a specially designed introducer. Animals were recovered and underwent second-look laparoscopy at 6 weeks postimplantation. Mesh sites were harvested after animals were euthanized. The mesh-solder constructs were easily inserted and affixed in the TAPP approach. Tisseel tended to drip during application, particularly in vertical and ventral locations. Postoperative healing was similar to Control segments in all cases. Mesh/TAPP closures healed without scarring or adhesion formation. Collagen-based tissue soldering permits normal wound healing and may mitigate or reduce use of staples for laparoscopic mesh fixation and peritoneal closure. Laser-assisted mesh fixation and peritoneal closure is a promising alternative for laparoscopic herniorrhaphy. Further development of this strategy is warranted.

PET Imaging of Ovarian Carcinoma With 18F-FSPG

ClinicalTrials.gov

2018-06-04

Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Pneumatosis cystoides intestinalis associated with massive free air mimicking perforated diffuse peritonitis.

PubMed

Sakurai, Yoichi; Hikichi, Masahiro; Isogaki, Jun; Furuta, Shinpei; Sunagawa, Risaburo; Inaba, Kazuki; Komori, Yoshiyuki; Uyama, Ichiro

2008-11-21

While pneumatosis cystoides intestinalis (PCI) is a rare disease entity associated with a wide variety of gastrointestinal and non-gastrointestinal disorders, PCI associated with massive intra- and retroperitoneal free air is extremely uncommon, and is difficult to diagnose differentially from perforated peritonitis. We present two cases of PCI associated with massive peritoneal free air and/or retroperitoneal air that mimicked perforated peritonitis. These cases highlight the clinical importance of PCI that mimics perforated peritonitis, which requires emergency surgery. Preoperative imaging modalities and diagnostic laparoscopy are useful to make an accurate diagnosis.

[Characteristics of postoperative peritonitis].

PubMed

Lock, J F; Eckmann, C; Germer, C-T

2016-01-01

Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

Peritonitis in peritoneal dialysis patients in Uruguay.

PubMed

Gadola, Liliana; Orihuela, Lucía; Pérez, Daniel; Gómez, Teresa; Solá, Laura; Chifflet, Liliana; Mautone, Mariela; Torres, Eugenia; Rodriguez, Grisel

2008-01-01

Uruguay is a South American country (3241003 inhabitants) where renal replacement treatment is universally available. The aim of this study was to analyze the incidence and outcome of peritonitis, and the causative organisms and their sensitivity, in order to recommend an empiric initial antibiotic treatment. A retrospective descriptive study of all peritonitis during the period 2004-2005 was performed (144 peritonitis, 44% due to gram-positive bacteria). We conclude that the high prevalence of methicillin-resistant coagulase-negative staphylococci justifies the use of vancomycin in the national empiric initial antibiotic protocols.

Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study.

PubMed

Rutter, Joni L; Wacholder, Sholom; Chetrit, Angela; Lubin, Flora; Menczer, Joseph; Ebbers, Sarah; Tucker, Margaret A; Struewing, Jeffery P; Hartge, Patricia

2003-07-16

In the general population, the risk of developing ovarian cancer is reduced in women who have undergone tubal ligation, hysterectomy, or oophorectomy, although peritoneal cancer can arise after bilateral oophorectomy. In studies from genetic screening clinics, women with mutations in the breast and ovarian susceptibility genes BRCA1 and BRCA2 have been found to have a low risk of peritoneal carcinoma in the first years after bilateral oophorectomy. We assessed the level and persistence of reduction of ovarian (including peritoneal) cancer risk after gynecologic surgeries for women who carry BRCA1/2 mutations but were not selected from high-risk clinics. We identified 1124 Israeli women with incident ovarian cancer or primary peritoneal cancer and tested 847 of them for the three Ashkenazi founder mutations. We compared gynecologic surgery history among all case patients, BRCA1 (n = 187) and BRCA2 (n = 64) carrier case patients, and the non-carrier case patients (n = 598) with that in control subjects drawn from a population registry (n = 2396). We estimated ovarian cancer risk (odds ratios [ORs] with 95% confidence intervals [CIs]) after gynecologic surgery in mutation carriers and non-carriers with logistic regression models. Eight women with primary peritoneal cancer and 128 control subjects reported a previous bilateral oophorectomy (OR = 0.12, 95% CI = 0.06 to 0.24). Other gynecologic surgeries were associated with a 30%-50% reduced risk of ovarian cancer, depending on the type of surgery, with surgery to remove some ovarian tissue associated with the most risk reduction (OR = 0.34, 95% CI = 0.16 to 0.74). Reduced risks were seen in BRCA1/2 carriers and non-carriers. Age at surgery and years since surgery did not affect risk reductions. Both BRCA1/2 mutation carriers and non-carriers have reduced risk of ovarian or peritoneal cancer after gynecologic surgery. The magnitude of the reduction depends upon the type and extent of surgery.

Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

PubMed Central

Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

2011-01-01

Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms. PMID:21912714

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

PubMed

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Influence of dichloromethylene bisphosphonate on the in vitro phagocytosis of hydroxyapatite particles by rat peritoneal exudate cells: an electron microscopic and chemiluminescence study.

PubMed Central

Hyvönen, P M; Kowolik, M J

1992-01-01

Transmission electron microscopy and standard chemiluminescence assays were used to investigate the in vivo effect of dichloromethylene bisphosphonate (clodronate) on the phagocytosis of pure hydroxyapatite particles by rat peritoneal macrophages and the production of chemiluminescence by the peritoneal exudate cells. Hydroxyapatite (control) and a hydroxyapatite/clodronate suspension (28 mumol clodronate per gram of hydroxyapatite, experimental) were injected into the peritoneum of rats, the clodronate dose being 10 micrograms/kg. Macrophages were harvested at 12, 24, 48, and 96 hours after injection and the particle phagocytosis was assessed by transmission electron microscopy. Hydroxyapatite alone was completely phagocytosed by 24 hours and hydroxyapatite reacted with clodronate was completely phagocytosed by 48 hours. From 48 hours onwards hydroxyapatite particle dissolution was observed in the phagosomes of cells in the two groups. At 48 hours the chemiluminescence produced by the peritoneal exudate cells was also measured. Clodronate and clodronate/hydroxyapatite enhanced cell activity on subsequent challenge with phorbol myristate acetate or zymosan. Clodronate seemed to exhibit an inhibitory effect on the phagocytic activity and an enhancement of the chemiluminescence production by the cells in this model, indicating that it was modifying the inflammatory cell response. Images PMID:1532298

Anti-granuloma activity of Coriandrum sativum in experimental models

PubMed Central

Nair, Vinod; Singh, Surender; Gupta, Yogendra Kumar

2013-01-01

Background: Coriandrum sativum has been used in the traditional systems of medicine for management of arthritis and other inflammatory disorders. Objectives: In this study, we have evaluated the anti-inflammatory and anti-granuloma activities of Coriandrum sativum hydroalcoholic extract (CSHE) in experimental models. Materials and Methods: The anti-inflammatory activity of CSHE was evaluated using carrageenan-induced paw edema model and the anti-granuloma activity of CSHE was evaluated using the subcutaneous cotton pellet implantation-induced granuloma formation and stimulation of peritoneal macrophages with complete Freund's adjuvant. Serum tumor necrosis factor-α (TNF-α), IL-6, IL-1 β levels, and peritoneal macrophage expression of TNF-R1 were evaluated as markers of global inflammation. Results: CSHE at the highest dose tested (32 mg/kg) produced a significant reduction (P < 0.05) in paw edema after carrageenan administration. CSHE treatment also reduced dry granuloma weight in all treated animals. Serum IL-6 and IL-1 β levels were significantly (P < 0.05) lower in the CSHE (32 mg/kg)-treated group as compared to control. Although there was an increase in serum TNF-α level in the CSHE-treated group as compared to control, TNF-R1 expression on peritoneal macrophages was found to be reduced. Conclusion: Thus, the result of this study demonstrates the anti-inflammatory and anti-granuloma activities of CSHE in experimental models, and validates its traditional use for the management of arthritis and other inflammatory disorders. PMID:23741156

Acinetobacter Peritoneal Dialysis Peritonitis: A Changing Landscape over Time

PubMed Central

Chao, Chia-Ter; Lee, Szu-Ying; Yang, Wei-Shun; Chen, Huei-Wen; Fang, Cheng-Chung; Yen, Chung-Jen; Chiang, Chih-Kang; Hung, Kuan-Yu; Huang, Jenq-Wen

2014-01-01

Background Acinetobacter species are assuming an increasingly important role in modern medicine, with their persistent presence in health-care settings and antibiotic resistance. However, clinical reports addressing this issue in patients with peritoneal dialysis (PD) peritonitis are rare. Methods All PD peritonitis episodes caused by Acinetobacter that occurred between 1985 and 2012 at a single centre were retrospectively reviewed. Clinical features, microbiological data, and outcomes were analysed, with stratifications based upon temporal periods (before and after 2000). Results Acinetobacter species were responsible for 26 PD peritonitis episodes (3.5% of all episodes) in 25 patients. A. baumannii was the most common pathogen (54%), followed by A. iwoffii (35%), with the former being predominant after 2000. Significantly more episodes resulted from breaks in exchange sterility after 2000, while those from exit site infections decreased (P = 0.01). The interval between the last and current peritonitis episodes lengthened significantly after 2000 (5 vs. 13.6 months; P = 0.05). All the isolates were susceptible to cefepime, fluoroquinolone, and aminoglycosides, with a low ceftazidime resistance rate (16%). Nearly half of the patients (46%) required hospitalisation for their Acinetobacter PD-associated peritonitis, and 27% required an antibiotic switch. The overall outcome was fair, with no mortality and a 12% technique failure rate, without obvious interval differences. Conclusions The temporal change in the microbiology and origin of Acinetobacter PD-associated peritonitis in our cohort suggested an important evolutional trend. Appropriate measures, including technique re-education and sterility maintenance, should be taken to decrease the Acinetobacter peritonitis incidence in PD patients. PMID:25314341

Peritonitis in children with automated peritoneal dialysis: a single-center study of a 10-year experience.

PubMed

Dotis, John; Myserlis, Pavlos; Printza, Nikoleta; Stabouli, Stella; Gkogka, Chrysa; Pavlaki, Antigoni; Papachristou, Fotios

2016-08-01

Peritoneal dialysis (PD) constitutes the preferred dialysis modality for children requiring renal replacement therapy with peritonitis being one of the most common complications of PD. This study was performed to evaluate the epidemiology, microbiology, and outcomes of PD-associated peritonitis in Greek children for a 10-year period. A total of 27 patients (16 males) with a mean age 121.8 ± 57.2 months were retrospective analyzed. Patients were on PD therapy for a mean duration of 45.2 ± 26.1 months. We found 23 episodes of PD-associated peritonitis occurred in 9 out of 27 patients (0.23 episodes/patient-year), with four patients experienced two or more peritonitis episodes. Gram-positive bacteria were responsible for 15 (65.2%) peritonitis episodes, with Staphylococcus aureus being the predominant specie isolated in 30.4% of cases. A total of seven episodes of exit-site infections (ESIs) were identified in five patients (0.069 episodes/patient-year) with the most common bacteria isolated being S. aureus (57.4%). Initial antibiotic treatment included intraperitoneal vancomycin plus ceftazidime in the majority of cases (82.6%). At the end of study, 12 (44.4%) patients remained on PD, 11 (41.8%) underwent renal transplantation, 2 (7.4%) shifted to hemodialysis and unfortunately, two patients (7.4%) died. Conclusively, our study revealed a noticeable low peritonitis and ESIs rate as compared to international data and represents the first evaluation of the characteristics and outcomes of peritonitis in the Greek pediatric PD population.

Intra-peritoneal chronic loculation in peritoneal dialysis patients - a new medical management approach.

PubMed

Mitoiu, Dan; David, Cristiana; Peride, Ileana; Niculae, Andrei; Mureşan, Alin; Ciocâlteu, Alexandru; Geavlete, Bogdan Florin; Checheriţă, Ionel Alexandru

2014-01-01

Peritoneal dialysis (PD) limitation as renal replacement therapy is mostly due to peritonitis and complications. Formation and persistence of intra-abdominal loculations is often under-diagnosed. Encapsulated peritoneal sclerosis (EPS) is a life-threatening complication, but malnutrition, recurrent peritonitis and early membrane failure are insidious enemies that need to be emphasized. It is important to highlight the persistence of intra-abdominal fluid collection after clinical resolution of peritonitis in PD patients and to indicate a new medical management approach for an early diagnosis. During five years, we selected PD peritonitis cases followed by a six months interval free of infections. Ninety-seven subjects were followed at six months and one year after the first peritonitis. Tomography had been performed to patients presenting a positive inflammatory state without a specific infectious cause. Subjects presenting documented localized fluid collection (31 cases) were divided into: drug-treated group and those undergoing laparoscopy by a new surgery technique (seven patients); a comparison regarding the clinical state and biohumoral parameters was assessed in both groups. The prevalence of intra-abdominal loculation following an apparent resolved peritonitis was high (31.9%). The cases undergoing laparoscopy presented a better evolution - improved clinical status (p=0.001), higher hemoglobin values (p=0.06), significant lower doses of erythropoietin requirement (p=0.03), improved dialysis adequacy (p=0.005) and inflammatory state. In cases with confirmed fluid encapsulated loculation, an active attitude (screening imaging protocol and laparoscopic exploration) appears to be mandatory, decreasing the risk of EPS, a serious complication which pathology and treatment are incompletely understood.

Colonoscopy in automated peritoneal dialysis patients: value of prophylactic antibiotics: a prospective study on a single antibiotic.

PubMed

Al-Hwiesh, Abdullah K; Abdul-Rahman, Ibrahiem S; Hussameldeen, Mohammad A; Al-Audah, Nadia; Abdelrahman, Abdalla; Moaigel, Hala M; El-Salamony, Tamer; Noor, Abdul-Salam; Al-Osail, Aisha; Al-Sayel, Dalal; Al-Dossari, Nourah

2017-10-13

To evaluate the need for prophylactic antibiotics in automated peritoneal dialysis (APD) patients undergoing flexible colonoscopy. A total of 93 patients on automated peritoneal dialysis (APD) undergoing diagnostic colonoscopy were enrolled in a prospective, randomized study. Patients were randomized into 2 age- and sex-matched groups; group A (46 patients) with intraperitoneal (IP) ceftazidime prior to colonoscopy and group B (47 patients) without prophylactic antibiotics. The relations between peritonitis and different parameters were analyzed. Of all colonoscopies, 60.2% showed normal findings, 17.2% with colonic polyps at different sites, 12.9% with angiodysplastic-like lesions, 5.4% with colonic ulcer(s), 3.2% with diverticulae without diverticulitis and 1.1% had transverse colon stricture. Post-colonoscopy peritonitis was documented in 3 (6.5%) and 4 (8.5%) patients in groups A and B, respectively (p = 0.2742); the causative organisms were mainly gram negative bacteria. Polypectomy was not associated with increased peritonitis episodes. By multiple logistic regression analysis, diabetes mellitus was the only independent variable that entered into the best predictive equation over the development of post-colonoscopy peritonitis but not antibiotic use. The relation between prophylactic antibiotic use prior to colonoscopy in APD patients and the risk of peritonitis was lacking. Only diabetes mellitus appears to be of significance. Polypectomy did not increase peritonitis episodes.

Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

PubMed

Bernardo, Ana Paula; Oliveira, Jose C; Santos, Olivia; Carvalho, Maria J; Cabrita, Antonio; Rodrigues, Anabela

2015-12-07

Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P<0.001, and 39.4 ± 10.1% versus 27.2 ± 11.5%, P=0.002, respectively), lower IGFBP-1 (8.2 ± 7.2 versus 21.0 ± 16.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P<0.001). Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance. Copyright © 2015 by the American Society of Nephrology.

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

PubMed Central

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-01-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate. PMID:27869192

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

NASA Astrophysics Data System (ADS)

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-11-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.

Peritoneal Super Scan on 18F - FDG PET-CT in a Patient of Burkitt's Lymphoma.

PubMed

Roy, Shambo Guha; Parida, Girish Kumar; Tripathy, Sarthak; Singhal, Abhinav; Shamim, Shamim Ahmed; Tripathi, Madhavi

2017-01-01

Peritoneal lymphomatosis is seen less frequently, but when seen, it is mostly associated with aggressive variants of malignancies. FDG uptake has been reported in peritoneal lymphomatosis both in DLBCL and Burkitt's lymphoma. We report a case of Burkitt's lymphoma with involvement of entire peritoneum, which looks like a "peritoneal super scan" on FDG PET-CT.

Peritonitis Due to Roseomonas fauriae in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis

PubMed Central

Bibashi, Evangelia; Sofianou, Danai; Kontopoulou, Konstantina; Mitsopoulos, Efstathios; Kokolina, Elisabeth

2000-01-01

Roseomonas is a newly described genus of pink-pigmented, nonfermentative, gram-negative bacteria that have been recognized as a cause of human infections. Roseomonas fauriae is a species rarely isolated from clinical specimens. We report the first known case of peritonitis caused by R. fauriae in a patient receiving continuous ambulatory peritoneal dialysis. PMID:10618142

Molecular mechanisms of peritoneal dissemination in gastric cancer.

PubMed

Kanda, Mitsuro; Kodera, Yasuhiro

2016-08-14

Peritoneal dissemination represents a devastating form of gastric cancer (GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Does the use of neutral pH, low glucose degradation product peritoneal dialysis fluids lead to better patient outcomes?

PubMed

Cho, Yeoungjee; Johnson, David W

2014-03-01

This review will examine the impact of neutral pH, low glucose degradation product (GDP) peritoneal dialysis fluid use on patient-level clinical outcomes in peritoneal dialysis patients. Recently published results from the balANZ trial and a meta-analysis suggest that the use of neutral pH, low GDP peritoneal dialysis fluids leads to better preservation of residual renal function, including residual diuresis, without added harmful effects. The impact of neutral pH, low GDP peritoneal dialysis fluids on other clinical outcomes (e.g. peritonitis) remains uncertain due to conflicting results from randomized controlled trials. A meta-analysis was unable to clarify this further due to generally suboptimal trial quality and insufficient statistical power. At present, based on the best available evidence, the use of neutral pH, low GDP peritoneal dialysis fluids is associated with some important clinical benefits without added harm. Further studies in the area are needed to establish the cost-effectiveness of this therapy and to clarify the effects of biocompatible fluids on patient-level outcomes, such as peritonitis, quality of life, technique survival and patient survival.

Clinical indices of in vivo biocompatibility: the role of ex vivo cell function studies and effluent markers in peritoneal dialysis patients.

PubMed

Mackenzie, Ruth; Holmes, Clifford J; Jones, Suzanne; Williams, John D; Topley, Nicholas

2003-12-01

Clinical indices of in vivo biocompatibility: The role of ex vivo cell function studies and effluent markers in peritoneal dialysis patients. Over the past 20 years, studies of the biocompatibility profile of peritoneal dialysis solutions (PDF) have evolved from initial in vitro studies assessing the impact of solutions on leukocyte function to evaluations of mesothelial cell behavior. More recent biocompatibility evaluations have involved assessments of the impact of PDF on membrane integrity and cell function in peritoneal dialysis (PD) patients. The development of ex vivo systems for the evaluation of in vivo cell function, and effluent markers of membrane integrity and inflammation in patients exposed both acutely and chronically to conventional and new PDF will be interpreted in the context of our current understanding of the biology of the dialyzed peritoneum. The available data indicate that exposure of the peritoneal environment to more biocompatible PDF is associated with improvements in peritoneal cell function, alterations in markers of membrane integrity, and reduced local inflammation. These data suggest that more biocompatible PDF will have a positive impact on host defense, peritoneal homeostasis, and the long-term preservation of peritoneal membrane function in PD patients.

Lack of motivation: a new modifiable risk factor for peritonitis in patients undergoing peritoneal dialysis?

PubMed

Paudel, Klara; Namagondlu, Girish; Samad, Nasreen; McKitty, Khadija; Fan, Stanley L

2015-03-01

Can we identify modifiable risk factors for peritonitis in patients undergoing peritoneal dialysis (PD)? We aimed to determine whether housing standard, PD exchange technique or patient motivation might be modifiable risks for peritonitis. We also explored the relationship between lack of motivation and depression. Nurse home visits assessed PD exchange technique, environment and patient motivation. Motivation scores were correlated separately with an Apathy Evaluation Score and a depression score using PHQ-9 questionnaires. Home hygiene, exchange technique and motivation were above average in 53%, 56% and 60%, respectively in 104 patients undergoing PD. After 15 months, 25.9% patients developed peritonitis but nurses' ratings of homes and exchange techniques were not predictive. Low patient motivation was predictive. Patients rated to have above or below median motivation had significantly different Apathy Scores (p = 0.0002). Unmotivated depressed patients were significantly more likely to develop peritonitis compared to motivated depressed patients. Lack of motivation predicted peritonitis particularly if associated with depression. Further studies are required focusing on specific motivation scoring schemes and the psychosocial support that might lead to better outcomes. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Morphological characteristics in peritoneum in patients with neutral peritoneal dialysis solution.

PubMed

Hamada, Chieko; Honda, Kazuho; Kawanishi, Kunio; Nakamoto, Hirotaka; Ito, Yasuhiko; Sakurada, Tsutomu; Tanno, Yudo; Mizumasa, Toru; Miyazaki, Masanobu; Moriishi, Misaki; Nakayama, Masaaki

2015-09-01

Peritoneal dialysis solution (PDS) plays a role in functional and morphological damage to the peritoneum. This study aimed to clarify the effect of neutral PDS in preventing morphological changes by assessing peritoneal damage and comparing morphological alterations between PD patients treated with neutral PDS and acidic PDS. Sixty-one patients participated from seven hospitals. All patients were treated with neutral PDS excluding icodextrin, during their entire PD treatment, and experienced no episode of peritonitis. The thickness of submesothelial compact (SMC) zone and the presence of vasculopathy in the anterior parietal abdominal peritoneum were assessed. The impact of icodextrin, hybrid therapy, and peritoneal rest and lavage in morphological alterations were determined. There was no significant difference in the average SMC thickness between neutral and acidic PDS. The vessel patency in patients using neutral PDS was significantly higher compared to that in acidic PDS at any time during PD. There were no significant suppressive effects from interventions or use of icodextrin with respect to peritoneal morphological injury. A monolayer of mesothelial cell was observed in approximately half the patients, especially in their receiving lavage patients. Neutral PDS, accompanied by other preventive approaches against peritoneal injury, might suppress the development of peritoneal morphological alterations.

Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

P-LUM-08: Endoscopic ultrasound-guided fine needle aspiration: A new modality to diagnose peritoneal tuberculosis in the presence of decompensated cirrhosis – a case series

PubMed Central

Daswani, Ravi; Singla, Vikas; Arora, Anil; Sharma, Praveen; Bansal, Naresh; Kumar, Ashish

2017-01-01

The gold standard for diagnosis of peritoneal tuberculosis is growth of Mycobacterium tuberculosis on ascitic fluid or peritoneal culture. Due to the nonspecific signs and symptoms of disease, its early diagnosis is difficult, especially in patients with decompensated cirrhosis. The reported sensitivity of ascitic fluid is low, and to obtain tissue for peritoneal biopsy in patients with cirrhosis is difficult. Thus, there is an urgent need to explore newer diagnostic modalities, especially those that can provide perioneal tissue by less invasive means. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is a good alternative to obtain peritoneal tissue for establishing the diagnosis of peritoneal tuberculosis (TB). We hereby report the use of EUS- FNA of the peritoneum in five patients with decompensated cirrhosis, in whom the diagnosis could not be confirmed by other means; thus, we propose EUS-FNA of the peritoneum as a new, safe, and unexplored technique for diagnosis of peritoneal TB.

Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections

PubMed Central

Shaikh, Faraz; Weintrob, Amy C.; Rodriguez, Carlos J.; Murray, Clinton K.; Lloyd, Bradley A.; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M. Leigh; Tribble, David R.

2015-01-01

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. PMID:25972413

Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections.

PubMed

Warkentien, Tyler E; Shaikh, Faraz; Weintrob, Amy C; Rodriguez, Carlos J; Murray, Clinton K; Lloyd, Bradley A; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M Leigh; Tribble, David R

2015-07-01

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease.

PubMed

Van Driessche, L; Valgaeren, B R; Gille, L; Boyen, F; Ducatelle, R; Haesebrouck, F; Deprez, P; Pardon, B

2017-05-01

Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of calves in a short period of time. The extent of commensal overgrowth and agreement of BAL with DNS culture results in preweaned calves are unknown. To compare commensal overgrowth and bacterial culture results between DNS and BAL samples. A total of 183 preweaned calves (144 with bovine respiratory disease and 39 healthy animals). Cross-sectional study. Deep nasopharyngeal swab and BAL samples were taken from each calf and cultured to detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between culture results of DNS and BAL samples were determined by kappa statistics and logistic regression. Bronchoalveolar lavage samples were less often polymicrobial, more frequently negative and yielded more pure cultures compared to DNS, leading to a clinically interpretable culture result in 79.2% of the cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in healthy animals, but not different between DNS and BAL samples. Only Histophilus somni was more likely to be isolated from BAL samples. In clinical cases, a polymicrobial DNS culture result did not increase the probability of a polymicrobial BAL result by ≥30%, nor did it influence the probability of a negative culture. A significant herd effect was noted for all observed relationships. Nonendoscopic BAL samples are far less overgrown by bacteria compared to DNS samples under the conditions of this study, facilitating clinical interpretation and resulting in a higher return on investment in bacteriologic culturing. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Comparison of Inoculation with the InoqulA and WASP Automated Systems with Manual Inoculation

PubMed Central

Croxatto, Antony; Dijkstra, Klaas; Prod'hom, Guy

2015-01-01

The quality of sample inoculation is critical for achieving an optimal yield of discrete colonies in both monomicrobial and polymicrobial samples to perform identification and antibiotic susceptibility testing. Consequently, we compared the performance between the InoqulA (BD Kiestra), the WASP (Copan), and manual inoculation methods. Defined mono- and polymicrobial samples of 4 bacterial species and cloudy urine specimens were inoculated on chromogenic agar by the InoqulA, the WASP, and manual methods. Images taken with ImagA (BD Kiestra) were analyzed with the VisionLab version 3.43 image analysis software to assess the quality of growth and to prevent subjective interpretation of the data. A 3- to 10-fold higher yield of discrete colonies was observed following automated inoculation with both the InoqulA and WASP systems than that with manual inoculation. The difference in performance between automated and manual inoculation was mainly observed at concentrations of >106 bacteria/ml. Inoculation with the InoqulA system allowed us to obtain significantly more discrete colonies than the WASP system at concentrations of >107 bacteria/ml. However, the level of difference observed was bacterial species dependent. Discrete colonies of bacteria present in 100- to 1,000-fold lower concentrations than the most concentrated populations in defined polymicrobial samples were not reproducibly recovered, even with the automated systems. The analysis of cloudy urine specimens showed that InoqulA inoculation provided a statistically significantly higher number of discrete colonies than that with WASP and manual inoculation. Consequently, the automated InoqulA inoculation greatly decreased the requirement for bacterial subculture and thus resulted in a significant reduction in the time to results, laboratory workload, and laboratory costs. PMID:25972424

Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis.

PubMed

Sossdorf, Maik; Fischer, Jacqueline; Meyer, Stefan; Dahlke, Katja; Wissuwa, Bianka; Seidel, Carolin; Schrepper, Andrea; Bockmeyer, Clemens L; Lupp, Amelie; Neugebauer, Sophie; Schmerler, Diana; Rödel, Jürgen; Claus, Ralf A; Otto, Gordon P

2013-10-01

High physical activity levels are associated with wide-ranging health benefits, disease prevention, and longevity. In the present study, we examined the impact of regular physical exercise on the severity of organ injury and survival probability, as well as characteristics of the systemic immune and metabolic response during severe polymicrobial sepsis. Animal study. University laboratory. Male C57BL/6N mice. Mice were trained for 6 weeks by treadmill and voluntary wheel running or housed normally. Polymicrobial sepsis in mice was induced by injection of fecal slurry. Subsequently, mice were randomized into the following groups: healthy controls, 6 hours postsepsis, and 24 hours postsepsis. Blood and organ samples were collected and investigated by measuring clinical chemistry variables, cytokines, plasma metabolites, and bacterial clearance. Organ morphology and damage were characterized by histological staining. Physical exercise improved survival and the ability of bacterial clearance in blood and organs. The release of pro- and anti-inflammatory cytokines, including interleukin-6 and interleukin-10, was diminished in trained compared to untrained mice during sepsis. The sepsis-associated acute kidney tubular damage was less pronounced in pretrained animals. By metabolic profiling and regression analysis, we detected lysophosphatidylcholine 14:0, tryptophan, as well as pimelylcarnitine linked with levels of neutrophil gelatinase-associated lipocalin representing acute tubular injury (corrected R=0.910; p<0.001). We identified plasma lysophosphatidylcholine 16:0, lysophosphatidylcholine 17:0, and lysophosphatidylcholine 18:0 as significant metabolites discriminating between trained and untrained mice during sepsis. Regular physical exercise reduces sepsis-associated acute kidney injury and death. As a specific mechanism of exercise-induced adaptation, we identified various lysophosphatidylcholines that might function as surrogate for improved outcome in sepsis.

Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-28

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-10-23

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage.

PubMed

Yokoyama, Minako; Oyama, Fumie; Ito, Asami; Yokota, Megumi; Matsukura, Daisuke; Tsutsumi, Shinji; Kasai, Tomonori; Nitobe, Yohshiro; Morikawa, Akiko; Ozaki, Takashi; Yokoyama, Yoshihito

2016-01-01

We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.

[Evaluation of the epidemiological, clinical and laboratory findings in continuous ambulatory peritoneal dialysis related peritonitis attacks].

PubMed

Bulut, Cemal; Oztürk, Reyhan; Yilmaz, Gül Ruhsar; Parpucu, Hülya; Irmak, Hasan; Kinikli, Sami; Duranay, Murat; Demiröz, Ali Pekcan

2008-04-01

The aims of this study were to assess epidemiological features, clinical outcomes, laboratory findings, causative organisms and treatment approach for continuous ambulatory peritoneal dialysis (CAPD) -related peritonitis cases. A total of 50 patients (35 male, 15 female; age range: 18-83 years, mean age: 49 +/-17 years) with CAPD related peritonitis treated in Infectious Diseases and Clinical Microbiology Department of Ankara Training and Research Hospital between February-July 2006 were enrolled into this study. Demographic characteristics, symptoms, physical examination findings and laboratory parameters of patients were recorded and evaluated at the baseline, 48 hours and at the end of treatment. Fifty six peritonitis episodes occurred during the study period, and overall incidence of peritonitis was calculated as 1.6 episodes/patient-year. The most common presenting symptoms were cloudiness of the peritoneal dialysis fluid (100%), abdominal pain (98%), nausea (74%) and vomiting (54%). Abdominal tenderness and rebaund (100%) were the most common physical examination findings. Increased levels of C-reactive protein, erythrocyte sedimentation rate and procalcitonin were detected in 88%, 94% and 42% of the patients, respectively. The mean white blood cell count of peritoneal dialysate fluids was 905/mm3 (170-17900/mm3) in 56 episodes. In direct microscopic examination of peritoneal fluid samples with Gram stain, positivity was detected in 10 (18%) of the attacks, in which eight yielded gram-positive cocci and two gram-negative bacilli. The rate of culture positivity was 74% in the peritonitis episodes, and no microorganism was isolated from the cultures of 26% of the episodes. The most frequently isolated microorganisms were coagulase-positive staphylococci, followed by Staphylococcus aureus (n:4) and E. coli (n:4) with the rates of 7% of each, Enterococcus spp. (n:3), Klebsiella spp. (n:3) and Pseudomonas spp. (n:3) with the rates of 5% of each, and Streptococcus spp. (n:1), diphtheroid bacillus (n:1) and Candida albicans (n:1) with the rates of 2% of each. Eightyfour percent of patients were successfully treated with intraperitoneal cefazolin and gentamicin empirically. Three of the patient's CAPD therapy was converted to hemodialysis, while two patients have died. As a result, since peritonitis is still the major complication of CAPD despite the technological developments, the informations about causative microorganisms and their antimicrobial susceptibilities would be helpful for the early and accurate treatment of peritonitis.

Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-06-11

Low Grade Ovarian Serous Adenocarcinoma; Micropapillary Serous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Peritoneal Super Scan on 18F - FDG PET-CT in a Patient of Burkitt's Lymphoma

PubMed Central

Roy, Shambo Guha; Parida, Girish Kumar; Tripathy, Sarthak; Singhal, Abhinav; Shamim, Shamim Ahmed; Tripathi, Madhavi

2017-01-01

Peritoneal lymphomatosis is seen less frequently, but when seen, it is mostly associated with aggressive variants of malignancies. FDG uptake has been reported in peritoneal lymphomatosis both in DLBCL and Burkitt's lymphoma. We report a case of Burkitt's lymphoma with involvement of entire peritoneum, which looks like a “peritoneal super scan” on FDG PET-CT. PMID:28533652

[Ascitic peritonitis due to Candida albicans].

PubMed

Suárez, A; Otero, L; Navascués, C A; Menéndez, M T; Román, F J; García, R; Saro, C; Rodríguez, A

1994-09-01

We report a case of spontaneous peritonitis due to Candida albicans, in a diabetic patient with alcoholic liver cirrhosis, ascites, gastrointestinal bleeding from esophageal varices, sepsis, renal failure and encephalopathy. These factors, added to prolonged antibiotic therapy and instrumental manipulations, could have resulted in the colonization by Candida, usually described in secondary peritonitis, but perhaps underdiagnosed in cirrhotic patients with spontaneous peritonitis and severe multiorgan failure.

Which cause of diffuse peritonitis is the deadliest in the tropics? A retrospective analysis of 305 cases from the South-West Region of Cameroon.

PubMed

Chichom-Mefire, Alain; Fon, Tabe Alain; Ngowe-Ngowe, Marcelin

2016-01-01

Acute diffuse peritonitis is a common surgical emergency worldwide and a major contributor to non-trauma related death toll. Its causes vary widely and are correlated with mortality. Community acquired peritonitis seems to play a major role and is frequently related to hollow viscus perforation. Data on the outcome of peritonitis in the tropics are scarce. The aim of this study is to analyze the impact of tropic latitude causes of diffuse peritonitis on morbidity and mortality. We retrospectively reviewed the records of 305 patients operated on for a diffuse peritonitis in two regional hospitals in the South-West Region of Cameroon over a 7 years period. The contributions of various causes of peritonitis to morbidity and mortality were analyzed. The diagnosis of diffuse peritonitis was suggested on clinical ground only in more than 93 % of cases. The most common causes of diffuse peritonitis included peptic ulcer perforation (n = 69), complications of acute appendicitis (n = 53) and spontaneous perforations of the terminal ileum (n = 43). A total of 142 complications were recorded in 96 patients (31.5 % complication rate). The most common complications included wound dehiscence, sepsis, prolonged paralytic ileus and multi-organ failure. Patients with typhoid perforation of the terminal ileum carried a significantly higher risk of developing a complication (p = 0.002). The overall mortality rate was 15.1 %. The most common cause of death was septic shock. Differential analysis of mortality of various causes of peritonitis indicated that the highest contributors to death toll were typhoid perforation of terminal ileum (34.7 % of deaths), post-operative peritonitis (19.5 %) and peptic ulcer perforation (15.2 %). The diagnosis of diffuse peritonitis can still rely on clinical assessment alone in the absence of sophisticated imaging tools. Peptic ulcer and typhoid perforations are still major contributors to death toll. Patients presenting with these conditions require specific attention and prevention policies must be reinforced.

Effluent CA 125 concentration in chronic peritoneal dialysis patients: influence of PD duration, peritoneal transport and PD regimen.

PubMed

Fusshöller, Andreas; Grabensee, Bernd; Plum, Jörg

2003-01-01

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 +/- 11.2 vs. 20.7 +/- 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 +/- 11.0 vs. 21.6 +/- 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid. Copyright 2003 S. Karger AG, Basel

Therapeutic Efficacy of Alpha-RIT Using a (213)Bi-Anti-hCD138 Antibody in a Mouse Model of Ovarian Peritoneal Carcinomatosis.

PubMed

Derrien, Aurélie; Gouard, Sébastien; Maurel, Catherine; Gaugler, Marie-Hélène; Bruchertseifer, Frank; Morgenstern, Alfred; Faivre-Chauvet, Alain; Classe, Jean-Marc; Chérel, Michel

2015-01-01

Ovarian peritoneal carcinomatosis is a pathology for which effective cures are currently lacking. New research protocols seek to eradicate residual micrometastases following cytoreductive surgery by using hyperthermic intraperitoneal chemotherapy (HIPEC) or radioimmunotherapy (RIT). This study aims to first develop alpha-RIT using an anti-CD138 mAb radiolabeled with an alpha-emitter, bismuth-213 ((213)Bi-B-B4) and HIPEC in a nude mouse model and second to compare and combine these techniques. A murine model of postoperative ovarian peritoneal carcinomatosis was established. A pilot group of six mice received an intraperitoneal injection of luciferase-tagged SHIN-3 cells and bioluminescence was measured every day. Cytoreductive surgery was performed at day 14 (n = 4) and 29 (n = 2). Because the residual bioluminescence signal measured after surgery was equivalent to that obtained 3 days after the graft, HIPEC or alpha-RIT treatments were applied 3 days after the graft. Ten mice were treated by HIPEC with cisplatine (37.5 mg/mL), 11 with 7.4 MBq of (213)Bi-B-B4, seven with 11.1 MBq of (213)Bi-B-B4, and 10 mice were treated with the combined therapy (HIPEC + 7.4 MBq of (213)Bi-B-B4). Eleven mice received no treatment. Bioluminescence imaging and survival were assessed. Alpha-RIT 7.4 MBq and 11.1 MBq significantly improved survival (p = 0.0303 and p = 0.0070, respectively), whereas HIPEC and HIPEC + alpha-RIT treatments did not significantly ameliorate survival as compared to the control group. Survival was significantly increased by alpha-RIT treatment in mice with peritoneal carcinomatosis of ovarian origin; however, HIPEC alone or in combination with alpha-RIT had no significant effect.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing

PubMed Central

Dinc, Soykan; Ozaslan, Cihangir; Kuru, Bekir; Karaca, Sefa; Ustun, Huseyin; Alagol, Haluk; Renda, Nurten; Oz, Murat

2006-01-01

Objectives Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway. PMID:17152569