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Bacterial Infections (bacterial + infections)
Kinds of Bacterial Infections Selected AbstractsSerious Bacterial Infections in Febrile Outpatient Pediatric Heart Transplant RecipientsACADEMIC EMERGENCY MEDICINE, Issue 10 2009Shan Yin MD Abstract Objectives:, The purpose of this study was to describe the incidence of serious bacterial infections (SBIs) in febrile outpatient pediatric heart transplant recipients and to assess the utility of using white blood cell (WBC) indices to identify patients at low risk for bacteremia. Methods:, A retrospective study was conducted on all heart transplant recipients followed at a single children's hospital. All outpatient visits from January 1, 1995, to June 1, 2007, in which fever was evaluated were reviewed. Patients with history of a primary immunodeficiency, receiving concurrent chemotherapy, or having had a stem cell or small bowel transplant were excluded. Demographic, historical, physical examination, laboratory, and radiographic data were then recorded. Results:, Sixty-nine patients had 238 individual episodes of fever evaluation; of these, 217 (91.2%) had blood cultures drawn with results available in their initial evaluation. There were six (2.8%) true-positive blood cultures and eight (3.7%) false-positive cultures. Chest radiography was done in 185 evaluations (77.8%), and 44 episodes of pneumonia (23.8%) were diagnosed. Of 112 urine cultures done, one (0.9%) was positive. Neither of two lumbar punctures performed were positive. In non,ill-appearing children without indwelling central lines or focal bacterial infections (pneumonia, cellulitis), the incidence of bacteremia was 1.2%. In children with a focal bacterial infection, the rate of bacteremia was 6.3%. WBC indices were not significantly different between bacteremic and nonbacteremic patients. A band-to-neutrophil ratio (BNR) of ,0.25 and a published guideline for identifying low-risk infants using WBC indices identified all bacteremic patients, each with a sensitivity of 100% (95% confidence interval [CI] = 48% to 100% and 54% to 100%, respectively). Conclusions:, The incidence of bacteremia was low in febrile, outpatient pediatric heart transplant patients, especially in those who were not ill-appearing and did not have a focus of serious infection. Two different low-risk criteria performed well in identifying the bacteremic patients, although given the low number of true-positive cultures, the CIs for the sensitivities of these tests were extremely wide, and neither test could be reliably used at present. A prospective multicenter study is required to confirm the low incidence of bacteremia and low-risk criteria in this population. [source] Serious Bacterial Infections in Febrile Infants in the Post,Pneumococcal Conjugate Vaccine EraACADEMIC EMERGENCY MEDICINE, Issue 7 2009Sherri L. Rudinsky MD Abstract Objectives:, The objective was to identify the epidemiology of serious bacterial infections (SBI) and the current utility of obtaining routine complete blood counts (CBC) and blood cultures to stratify infants at risk of SBI, in the study population of febrile infants in the post,heptavalent pneumococcal conjugate vaccine (PCV7) era. Methods:, A cohort study with nested case-controls was undertaken at a tertiary care military hospital emergency department (ED) from December 2002 through December 2003. Irrespective of clinical findings at the initial encounter, patients were included if they were under 3 months of age and had a home or ED temperature of ,100.4°F or if they were between 3 and 24 months of age with a temperature of ,102.3°F. Data abstracted included age, temperature, peripheral white blood cell (WBC) count, and discharge diagnosis. Culture (blood, urine, and cerebrospinal fluid [CSF]) and chest radiograph (CXR) results were obtained through review of the electronic hospital archives. SBI was defined as pneumonia, urinary tract infection (UTI), meningitis, or bacteremia. Results:, A total of 985 children aged 0 to 24 months were enrolled. Fifty-five percent were male, the median age was 12 months (interquartile range = 8,17 months), and 79% had received at least one PCV7. A total of 132 cases of SBI were identified in 129 infants (13.1%): 82 pneumonias, 45 UTI, five bacteremias, and no cases of bacterial meningitis. The frequency of bacteremia was 0.7%. No statistical difference was detected in the WBC count between the SBI and non-SBI groups (13.8 ± 5.8 and 11.7 ± 5.6, respectively; p = 0.055). No readily available WBC cutoff on the receiver operating characteristic (ROC) curve proved to be an accurate predictor of SBI. No statistical difference was detected in mean temperature between the SBI and non-SBI groups (103.3 ± 1.2 and 103.2 ± 1.2°F, respectively; p = 0.26), nor was there a difference noted when groups were broken down by age or height of fever. Conclusions:, The WBC count and height of fever were not found to be accurate predictors of SBI in infants age 3 to 24 months. UTI and pneumonias made up the vast majority of SBI in this population of infants. The overall bacteremia frequency was well below 1%. This calls into question the continued utility of obtaining routine complete cell counts and blood cultures in the febrile infant in the post-PCV7 era. [source] Staphylococcus aureus biofilm formation and tolerance to antibiotics in response to oscillatory shear stresses of physiological levelsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010Victoria Kostenko Abstract Bacterial infections in the blood system are usually associated with blood flow oscillation generated by some cardiovascular pathologies and insertion of indwelling devices. The influence of hydrodynamically induced shear stress fluctuations on the Staphylococcus aureus biofilm morphology and tolerance to antibiotics was investigated. Fluctuating shear stresses of physiologically relevant levels were generated in wells of a six-well microdish agitated by an orbital shaker. Numerical simulations were performed to determine the spatial distribution and local fluctuation levels of the shear stress field on the well bottom. It is found that the local biofilm deposition and morphology correlate strongly with shear stress fluctuations and maximum magnitude levels. Tolerance to killing by antibiotics correlates with morphotype and is generally higher in high shear regions. [source] Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C,HEPATOLOGY, Issue 4 2010Robert Roomer Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment. In this single-center cohort study, 2,876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions, and potential risk factors for infection during HCV treatment. The baseline mean absolute neutrophil count (ANC) was 3,420 cells/,L, and 16 patients had a baseline ANC of <1,500 cells/,L. During treatment, neutropenia, which was defined as ANC <750 cells/,L, was observed in 95 patients (29.7%) and ANC <375/,L was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. Multivariate logistic regression analysis revealed that age >55 years (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.19-3.56, P = 0.01) and baseline hyperglycemia (OR 2.17, 95% CI 1.15-4.10, P = 0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease were not risk factors for infection. Conclusion: Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment. (HEPATOLOGY 2010) [source] Incidence, spectrum and antibiotic sensitivity pattern of bacterial infections among patients with acute pancreatitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2001Pramod Kumar Garg Abstract Background and Aim: Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, and their antibiotic sensitivity pattern in patients with acute pancreatitis. Methods: All consecutive patients with acute pancreatitis were studied prospectively. Detailed investigations were carried out to identify bacterial infections and their antibiotic sensitivities in patients with suspected infection. These investigations included cultures of various body fluids, throat swabs, indwelling cannula and catheter tips. Pancreatic tissue was obtained by using needle aspiration or at surgery for Gram's stain, culture and sensitivity. All cultures were repeated until the presence of infection was confirmed or excluded. Results: A total of 169 patients with acute pancreatitis were studied during the period between January 1997 and June 2000 (mean age 41.3 years; 116 males and 53 females). Of the 169 patients, 63 had infections at various sites. A total of 80 cultures were positive, and 12 different bacterial isolates were cultured from samples taken from these 63 patients. Polymicrobial infection was seen in 32% of patients. Twenty-four patients had a confirmed pancreatic infection. Blood cultures had a growth of organisms in 19 patients, with evidence of ongoing or worsening pancreatitis, thus raising a strong suspicion of infected necrosis in them. The commonest organisms were Escherichia coli from 20 cultures and Pseudomonas aeruginosa from 18 cultures. The antibiotic sensitivity pattern showed that most bacteria were sensitive to third generation cephalosporins and quinolones; notably among them were cefotaxime, ceftazidime, and ciprofloxacin. Conclusion: Bacterial infections were seen in 37% of patients with acute pancreatitis. The commonest organisms were Pseudomonas aeruginosa and Escherichia coli. Most bacterial isolates were sensitive to third generation cephalosporins and quinolones. [source] ,-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysisLIVER INTERNATIONAL, Issue 8 2009Marco Senzolo Abstract Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and ,-blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of ,-blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non-RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using ,-blockers were evaluated. We performed a meta-analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Results: Three RCT and three retrospective studies in which ,-blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non-responders. Conclusions: This analysis suggests a role of ,-blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding. [source] Bacterial infections in cirrhosisLIVER INTERNATIONAL, Issue 4 2004Miguel Navasa Abstract: Spontaneous bacterial peritonitis, urinary tract infections, respiratory infections and bacteremia are the most frequent infective complications in cirrhosis. These infections are due to the concomitant presence of different facilitating mechanisms including changes in the intestinal flora and in the intestinal barrier, depression of activity of the reticuloendothelial system, decreased opsonic activity of the ascitic fluid, neutrophil leukocyte dysfunction and iatrogenic factors among others. The fact, that the probability of having a microorganism responsible for the infection quinolone resistant is higher than 30% should be taken into account when treating any infection in a cirrhotic patient receiving selective intestinal decontamination with quinolones, and therefore, quinolones as empiric treatment are not indicated. [source] Incidence Rate and Outcome of Gram-Negative Bloodstream Infection in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009M. N. Al-Hasan Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram-negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram-negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram-negative BSI was observed within the first month following SOT (210.3/1000 person-years [95% confidence interval (CI): 159.3,268.3]), with a sharp decline to 25.7 (95% CI: 20.1,32.1) and 8.2 (95% CI: 6.7,10.0) per 1000 person-years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram-negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9,13.1] vs. 5.2 [95% CI: 3.1,7.8] per 1000 person-years). The overall unadjusted 28-day all-cause mortality of Gram-negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy. [source] Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemiaACTA PAEDIATRICA, Issue 2 2001S Shang Aim: The clinical diagnosis of sepsis is difficult, particularly in neonates. It is necessary to develop a rapid and reliable method for detecting bacteria in blood and cerebrospinal fluid (CSF) Polymerase chain reaction (PCR) and reverse hybridization of the 16S rRNA gene would permit fast and sensitive determination of the presence of bacteria and differentiate gram-positive bacteria from gram-negative ones in clinical specimens. Methods: We developed a pair of primers according to the gene encoding 16SrRNA found in all bacteria. DNA fragments from different bacterial species and from clinical samples were detected with PCR, and with reverse hybridization using a universal bacterial probe, a gram-positive probe and a gram-negative probe. Results: A 371 bp DNA fragment was amplified from 20 different bacterial species. No signal was observed when human DNA and viruses were used as templates. The sensitivity could be improved to 10T -12 g. All 26 culture-positive clinical samples (22 blood samples and 4 CSF samples) were positive with PCR. The gram-negative and gram-positive probes hybridized to clinical samples and to known bacterial controls, as predicted by Gram's stain characteristics. Conclusions: Our results suggest that the method of PCR and reverse hybridization is rapid, sensitive and specific in detecting bacterial infections. This finding may be significant in the clinical diagnosis of sepsis in neonates. [source] Safety and efficacy of vaccinesDERMATOLOGIC THERAPY, Issue 2 2009Brenda L. Bartlett ABSTRACT For the past two centuries, vaccines have provided a safe and effective means of preventing a number of infectious diseases. Although the safety of some vaccines has been questioned in recent years, the currently available vaccines are more than a millionfold safer than the diseases they are designed to prevent. Vaccines, however, should always be used in conjunction with other public health interventions. One important intervention is education because the general public can be led to believe that vaccines are unsafe and not needed by misinformation readily available electronically and in print. Not only are some vaccines available via injection but other vaccines are also given orally or intranasally. New vaccines are being studied for topical and intravaginal use. In addition, new systems are being developed for more efficient production of vaccines, especially for influenza. Vaccines are currently available for only a limited number of viral and bacterial diseases. In the future, it is anticipated that safe and effective vaccines will be developed against a number of other viral and bacterial infections as well as fungal and protozoan diseases. [source] Overview of the use of antimicrobials for the treatment of bacterial infections in horsesEQUINE VETERINARY EDUCATION, Issue 8 2008E. F. Haggett Summary Use of antimicrobial drugs is central to the treatment of primary and secondary bacterial infection in horses. When selecting an antimicrobial to treat confirmed or suspected bacterial infection multiple factors should be considered, including: the likely infectious agent; distribution and dosage of selected drugs; mechanisms of action; and potential side effects. Many of these issues will be covered in subsequent articles in this series. The aim of this paper is to aid the clinician in the rational selection of antimicrobials by reviewing the mode of action, spectrum of activity, pharmacokinetics, pharmacodynamics, indications and potential side effects of the main classes of antimicrobial drugs. Extralabel use of drugs is common in veterinary medicine due to a lack of licensed products. This increases the importance of a thorough understanding of antimicrobials and their possible adverse effects. [source] An immunodeficiency in Fell ponies: a preliminary study into cellular responsesEQUINE VETERINARY JOURNAL, Issue 7 2001S. C. BELL Summary A putative immunodeficiency, causing mortality in UK Fell pony foals (Fell pony syndrome), was studied in affected foals and compared with healthy, age-matched foals. Differential cell counts of peripheral blood indicated that the syndrome foals were lymphopenic (P<0.05). Flow cytometric analysis of circulating leucocytes showed a reduced MHC II expression (P<0.01) on lymphocytes but not on polymorphonuclear cells in affected foals. There were no changes in the percentages of CD4+ or CD8+ T cells. There was an increased (P<0.05) expression of CD11a/18 by the lymphocytes of the syndrome foals, compared to the control foals, which is probably a response to systemic bacterial infections. The syndrome foals' lymphocytes responded to mitogens (PHA, ConA, PWM) at normal levels. The data do not conform to any known immunodeficiencies identified in any other species. Further analyses will be required, particularly on bone marrow function. [source] Partial splenic embolization in children with hereditary spherocytosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2008Barbara Pratl Abstract Objectives:, Although total splenectomy is able to reduce clinical symptoms in patients with hereditary spherocytosis (HS), splenectomized patients are at risk to develop overwhelming bacterial infections and, to a lesser extent, thromboembolic complications. In contrast, partial splenectomy or partial splenic embolization (PSE) may also decrease the rate of hemolytic complications while maintaining residual splenic function. The aim of this study was to investigate the benefit of PSE in children with moderate to severe HS. Patients and methods:, We performed PSE via retrograde transfemoral access in eight children (four female, four male) with moderate to severe HS at a median age of 8 yr. HS-related complications before PSE included gallstones in six and aplastic crises in four children. One patient was transfusion-dependent. Results:, No acute side effects were seen during or after PSE. Median hemoglobin increased significantly from levels between 7.5 g/dL and 11.65 g/dL before PSE to levels between 8.4 g/dL and 13.35 g/dL after PSE (P = 0.012). Median splenic sizes before PSE ranged from 9.7 cm/m2 to 19.0 cm/m2 and significantly decreased to values between 4.4 cm/m2 and 15.65 cm/m2 during follow-up (P = 0.012). Conclusions:, PSE appears to be a safe, effective and feasible treatment option for the management of children with moderate to severe HS. [source] IgG2 containing IgM,IgG immune complexes predominate in normal human plasma, but not in plasma of patients with warm autoimmune haemolytic anaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Dorothea Stahl Abstract:, The different physicochemical and sterical properties of IgG subclasses may favour a selective enrichment of defined IgG subclasses in IgM,IgG immune complexes (IC) of human plasma under physiological conditions. Such enrichment of IgG subclasses in IgM,IgG IC of plasma may differ from the normal IgG subclass distribution in plasma itself, and contribute to the physiological functions of IgM,IgG IC. Systematic studies on the IgG subclass distribution in IgM,IgG IC in humans are lacking. Using specific analytical techniques to characterise IgM,IgG IC in human plasma (i.e. fast protein liquid chromatography, enzyme-linked immunosorbent assay, affinity biosensor technology), and taking warm autoimmune haemolytic anaemia (WAIHA) of humans as a disease model, we here demonstrate that: (i) IgG2 is the predominant IgG subclass in IgM,IgG IC under physiological conditions, (ii) the predominance of IgG2 within IgM,IgG IC may get lost in polyclonal IgG-mediated autoimmune disease and (iii) the IgG subclass distribution in IgM,IgG IC influences the interaction between IC and blood cells involved in antigen presentation. The data presented here therefore extend the physiological function of IgG2, which is the protective immune response towards carbohydrate antigens in bacterial infections, and suggest IgG2-dependent regulation of immune responses to self-immunoglobulin in humans. The disturbed IgG subclass distribution in IgM,IgG IC of patients with WAIHA might influence activity of self-reactive B cells involved in the pathophysiology of the disease. [source] IL-6: Regulator of Treg/Th17 balanceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2010Akihiro Kimura Abstract IL-6 is a pleiotropic cytokine involved in the physiology of virtually every organ system. Recent studies have demonstrated that IL-6 has a very important role in regulating the balance between IL-17-producing Th17 cells and regulatory T cells (Treg). The two T-cell subsets play prominent roles in immune functions: Th17 cell is a key player in the pathogenesis of autoimmune diseases and protection against bacterial infections, while Treg functions to restrain excessive effector T-cell responses. IL-6 induces the development of Th17 cells from naïve T cells together with TGF-,; in contrast, IL-6 inhibits TGF-,-induced Treg differentiation. Dysregulation or overproduction of IL-6 leads to autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA), in which Th17 cells are considered to be the primary cause of pathology. Given the critical role of IL-6 in altering the balance between Treg and Th17 cells, controlling IL-6 activities is potentially an effective approach in the treatment of various autoimmune and inflammatory diseases. Here, we review the role of IL-6 in regulating Th17/Treg balance and describe the critical functions of IL-6 and Th17 in immunity and immune-pathology. [source] Effector T-cell differentiation during viral and bacterial infections: Role of direct IL-12 signals for cell fate decision of CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Selina J. Keppler Abstract To study the role of IL-12 as a third signal for T-cell activation and differentiation in vivo, direct IL-12 signaling to CD8+ T cells was analyzed in bacterial and viral infections using the P14 T-cell adoptive transfer model with CD8+ T cells that lack the IL-12 receptor. Results indicate that CD8+ T cells deficient in IL-12 signaling were impaired in clonal expansion after Listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or vesicular stomatitis virus. Although limited in clonal expansion after Listeria infection, CD8+ T cells deficient in IL-12 signaling exhibited normal degranulation activity, cytolytic functions, and secretion of IFN-, and TNF-,. However, CD8+ T cells lacking IL-12 signaling failed to up-regulate KLRG1 and to down-regulate CD127 in the context of Listeria but not viral infections. Thus, direct IL-12 signaling to CD8+ T cells determines the cell fate decision between short-lived effector cells and memory precursor effector cells, which is dependent on pathogen-induced local cytokine milieu. [source] Nod1 and Nod2 induce CCL5/RANTES through the NF-,B pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Catherine Werts Abstract The Nod-like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall. Recent evidence has demonstrated that Nod1 stimulates the release of chemokines that attract neutrophils at the site of infection, such as CXCL8/IL-8 in humans, and CXCL1/keratinocyte-derived chemokine and CXCL2/MIP-2 in mice. We aimed to determine whether Nod proteins could trigger the release of CCL5/RANTES, a chemokine known to attract a number of immune cells, but not neutrophils. Our results demonstrate that activation of both Nod1 and Nod2 results in substantial secretion of CCL5 by murine macrophages. Moreover, in vivo, the intraperitoneal injection of murine Nod1 or Nod2 agonists resulted in a rapid secretion of CCL5 into the bloodstream. We also observed that Nod-dependent secretion of CCL5 did not correlate with the induction of the interferon-, pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF-,B pathway in Nod-dependent stimulation of the CCL5 promoter. Together, these results identify a novel target downstream of Nod1 and Nod2, which is likely to play a key role in orchestrating the global Nod-dependent immune defense during bacterial infections. [source] Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodiesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2005Tania Abstract Secretory IgA (SIgA) is widely held to be responsible for the defense of the mucosae against pathogenics and other potentially harmful agents. In this study, polymeric Ig receptor (pIgR) knockout mice, which lack secretory antibodies (SAb), were used to investigate the role of vaccine-elicited SAb in protection against gastrointestinal bacterial infections. An essential role for specific SAb in protection against Vibrio cholerae was evident from experiments showing that vaccinated pIgR,/, mice, but not vaccinated C57BL/6 mice, were susceptible to cholera toxin challenge. Vaccination of C57BL/6 mice with Salmonella typhimurium elicited strong antigen-specific, mucosal responses, which blocked in vitro invasion of epithelia. However, vaccinated C57BL/6 and pIgR,/, mice were equally resistant to challenge infection with virulent S. typhimurium. Finally, we investigated the importance of SIgA in protection against recurrent infections with Citrobacter rodentium. Although higher numbers of bacteria were detected early after challenge infection in feces of vaccinated pIgR,/, mice compared with vaccinated C57BL/6 mice, both mouse strains showed complete clearance after 9,days. These results suggested that, in immune animals, SIgA is crucial for the protection of gastrointestinal surfaces against secreted bacterial toxins, may inhibit early colonization by C. rodentium, but is not essential for protection against re-infection with S. typhimurium or C. rodentium. [source] Interferon-, differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophagesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Karl Georg Häusler Abstract During bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto- and chemokines. In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern. Here, we analyzed the capacity of interferon-, (IFN,) to serve as such a leucocyte-to-microglia signal. Production of cyto- and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram-negative Escherichia coli or cell walls from Gram-positive Streptococcus pneumoniae (PCW). IFN, presence during the stimulation (0.1,100 ng/mL) modulated the patterns of LPS- and PCW-induced cyto- and chemokine release in a dose-dependent, potent and complex manner. While amounts of TNF, and IL-6 remained nearly unchanged, IFN, enhanced the production of IL-12, MCP-1 and RANTES, but attenuated that of KC, MIP-1, and MIP-2. Release modulation was obtained with IFN, preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation. Together the changes observed for the microglial chemokine release under IFN, would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations , as actually seen during the course of bacterial meningitis. The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte-derived IFN, could potentially regulate the microglial chemokine release pattern. [source] Exploring the mast cell enigma: a personal reflection of what remains to be doneEXPERIMENTAL DERMATOLOGY, Issue 2 2008Beate M. Henz Abstract: Mast cells are traditionally viewed as effector cells of allergic reactions and parasitic diseases, but their importance in host defense against bacteria, in tissue remodelling, their bone marrow and stem cell origin and a central role of the stem cell factor (SCF) as mast cell growth and chemotactic factor has been worked out only in recent years. Despite this, major aspects about the nature of the cells and their role in disease remain unclear. This holds in particular for the identification of mast cell precursors and the role of growth factors that stimulate specific mast cell commitment from stem cells, such as nerve growth factor, neutrotrophin-3 and certain interleukins, alone and during interaction with SCF. Early data suggesting also an involvement of specific transcription factors need to be expanded in this process. Furthermore, although mast cell proliferative disease (mastocytosis) has been shown to be often associated with SCF receptor c-kit mutations, reasons for the development of this disease remain unclear. This holds also for mast cell release mechanisms in many types of mast cell-dependent urticaria. Exciting new insights are emerging regarding the role of mast cells in bacterial infections, in defense against tumors, in wound healing and in the interplay with the nervous system, with hormones, and in the neurohormonal network. The aim of this reflection is to delineate the many known and unknown aspects of mast cells, with a special focus on their development, and to discuss in detail two mast cell-related diseases, namely mastocytosis and urticaria. [source] Contact-Killing Polyelectrolyte Microcapsules Based on Chitosan DerivativesADVANCED FUNCTIONAL MATERIALS, Issue 19 2010Di Cui Abstract Polyelectrolyte-multilayer microcapsules are made by layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes onto sacrificial colloidal particles, followed by core removal. In this paper, contact-killing polyelectrolyte microcapsules are prepared based solely on polysaccharides. To this end, water-soluble quaternized chitosan (QCHI) with varying degrees of substitution (DS) and hyaluronic acid (HA) are assembled into thin films. The quaternary ammonium groups are selectively grafted on the primary amine group of chitosan by exploiting its reaction with glycidyltrimethylammonium chloride (GTMAC) under homogeneous aqueous acidic conditions. The morphology of the capsules is closely dependent on the DS of the quaternized chitosan derivatives, which suggests differences in their complexation with HA. The DS is also a key parameter to control the antibacterial activity of QCHI against Escherichia Coli (E. coli). Thus, capsules containing the QCHI derivative with the highest DS are shown to be the most efficient to kill E. coli while retaining their biocompatibility toward myoblast cells, which suggests their potential as drug carriers able to combat bacterial infections. [source] Tooth Loss and Helicobacter pylori Seropositivity: the Newcastle Thousand Families Cohort Study at Age 49,51 YearsHELICOBACTER, Issue 1 2005Mark S. Pearce ABSTRACT Background.,Helicobacter pylori, one of the commonest chronic bacterial infections of humankind, is an important risk factor for gastric carcinoma. It has also been suggested to be present in dental plaque. This study investigated the potential link between the number of teeth lost and H. pylori seropositivity at age 50 years. Methods.,H. pylori seropositivity at age 50 years was investigated among 334 individuals born in Newcastle upon Tyne, United Kingdom, in May and June 1947 and related to the number of teeth lost, after adjusting for socioeconomic status. Results., The unadjusted risk of being seropositive for H. pylori increased with increasing number of teeth lost (odds ratio per tooth 1.03, 95% confidence interval 1.01,1.06, p = .019). However, after adjustment for socioeconomic status at birth and at age 50 years, the relationship was no longer significant (p = .36). Conclusions., Our results, obtained using prospectively collected data, suggest that any relationship between poor oral health and seropositivity to H. pylori may be due to both tooth loss and H. pylori colonization being associated with socioeconomic status and related factors. [source] Renal failure and bacterial infections in patients with cirrhosis: Epidemiology and clinical features,HEPATOLOGY, Issue 1 2007Silvano Fasolato The aim of the study was to investigate the prevalence and clinical course of renal failure that was induced by the various types of bacterial infections in patients with cirrhosis and ascites. Three hundred and nine patients, who were consecutively admitted to the 3 major hospitals of Padova, Italy, during the first 6 months of 2005, were studied prospectively. Of these, 233 patients (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal failure was observed in 35 of 104 patients (33.6%). The prevalence of renal failure was higher in biliary or gastrointestinal tract infections and in spontaneous bacterial peritonitis (SBP) and in than in other types of infections. In addition, the progressive form of renal failure was only precipitated by biliary or gastrointestinal tract infections, SBP, and urinary tract infections (UTI). In a multivariate analysis only MELD score (P = 0.001), the peak count of neutrophil leukocyte in blood (P = 0.04), and the lack of resolution of infection (P = 0.03) had an independent predictive value on the occurrence of renal failure. Conclusion: The results of the study show that the development of bacterial-induced renal failure in patients with cirrhosis and ascites is related to the MELD score, and to both the severity and the lack of resolution of the infection. A progressive form of renal failure occurs only as a consequence of biliary or gastrointestinal tract infections, SBP, and UTI. (HEPATOLOGY 2007;45:223,229.) [source] Protein array technology to investigate cytokine production by monocytes from patients with advanced alcoholic cirrhosis: An ex vivo pilot studyHEPATOLOGY RESEARCH, Issue 7 2009Khalid A. Tazi Aim:, In patients with advanced cirrhosis, little is known about the ability of peripheral blood monocytes to spontaneously produce signaling proteins such as cytokines. The aim of this ex vivo study was to evaluate cytokine production under baseline conditions and after stimulation by lipopolysaccharide (LPS), a toll-like receptor (TLR) agonist. Methods:, Peripheral blood monocytes were isolated from patients with advanced alcoholic cirrhosis (without ongoing bacterial infections) and normal subjects. Cells were left unstimulated or were stimulated with LPS. The abundance of 24 cytokines was measured using a filter-based, arrayed sandwich enzyme-linked immunosorbent assay (ELISA) in the supernatant of cultured monocytes. Results:, Cirrhotic monocytes spontaneously produced six proteins (TNF-,, IL-6, IL-8, MCP-1, RANTES and Gro), whereas normal monocytes produced only small amounts of IL-8 and RANTES. Analyses with the online gene set analysis toolkit WebGestalt (http://bioinfo.vanderbilt.edu/webgestalt) found enrichment for the six proteins in the human gene ontology subcategory (http://www.geneontology.org), Kyoto Encyclopedia of Genes and Genome pathways (http://www.genome.ad.jp/kegg/) and BioCarta pathways (http://www.biocarta.com/genes/index.asp) consistent with a proinflammatory phenotype of cirrhotic monocytes resulting from activated TLR signaling. Interestingly, LPS-elicited TLR engagement further increased the production of the six proteins and did not induce the secretion of any others, in particular the anti-inflammatory cytokine IL-10. LPS-stimulated normal monocytes produced TNF-,, IL-6, IL-8, MCP-1, RANTES, Gro and IL-10. Conclusion:, In patients with advanced cirrhosis, peripheral blood monocytes spontaneously produce proinflammatory cytokines, presumably in response to unrestricted TLR signaling. [source] Trends and determinants of severe morbidity in HIV-infected patients: the ANRS CO3 Aquitaine Cohort, 2000,2004,HIV MEDICINE, Issue 8 2007F Bonnet Objective The aim of the study was to characterize the causes, trends and determinants of severe morbidity in a large cohort of HIV-infected patients between 2000 and 2004. Method Severe morbid events were defined as medical events associated with hospitalization or death. Epidemiological and biological data were recorded at the time of the morbid event. Trends were estimated using Poisson regression. Results Among 3863 individuals followed between 2000 and 2004, 1186 experienced one or more severe events, resulting in 1854 hospitalizations or deaths. The severe events recorded included bacterial infections (21%), AIDS events (20%), psychiatric events (10%), cardiovascular events (9%), digestive events including cirrhosis (7%), viral infections (6%) and non-AIDS cancers (5%). Between 2000 and 2004, the incidence rate of AIDS events decreased from 60 to 20 per 1000 person-years, that of bacterial infections decreased from 45 to 24 per 1000 person-years, and that of psychiatric events decreased from 26 to 14 per 1000 person-years (all P<0.01), whereas the incidences of cardiovascular events and of non-AIDS cancers remained stable at 14 and 10 per 1000 person-years, on average, respectively. Conclusion Severe morbidity has shifted from AIDS-related to non-AIDS-related events during the course of HIV infection in developed countries. Limiting endpoints to AIDS events and death is insufficient to describe HIV disease progression in the era of combination antiretroviral therapy. [source] Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy, Bordeaux, France, 1998,1999HIV MEDICINE, Issue 3 2002F Bonnet Objectives To describe the causes of death in HIV-infected patients in the era of highly active antiretroviral therapy (HAART). Method A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death. Results Sixty-six deaths occurred in 1998, and 41 in 1999. Sixty-seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25,71), median CD4 was 162 cells/µL (0,957); 28% of patients had a CD4 count > 200 cells/µL and 7% plasma viral load < 500 HIV-RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non-Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV-related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS-defining events (48%), non AIDS HIV-related infection (3%), hepatitis B- or C-associated cirrhosis (14%), non HIV-related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment-related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS-related events were more often female, had a lower CD4 count, a higher level of HIV-RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes. Conclusions AIDS-related events are no longer the major causes of death of HIV-infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV-infected patients. [source] Inherited disorders of human Toll-like receptor signaling: immunological implicationsIMMUNOLOGICAL REVIEWS, Issue 1 2005Cheng-Lung Ku Summary:,In vitro nine of 10 known human Toll-like receptors (TLRs) are engaged by well-defined chemical agonists that mimic microbial compounds, raising the possibility that human TLRs play a critical role in protective immunity in vivo. We thus review here the recently described human primary immunodeficiencies caused by germline mutations in genes encoding molecules involved in cell signaling downstream from TLRs. Subjects with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) carry either X-linked recessive hypomorphic mutations in NEMO or autosomal dominant hypermorphic mutations in IKBA. Their cells show a broad defect in nuclear factor-,B (NF-,B) activation, with an impaired, but not abolished response to a large variety of stimuli including TLR agonists. EDA-ID patients show developmental anomalies of skin appendages and a broad spectrum of infectious diseases. Patients with autosomal recessive amorphic mutations in IRAK4 present a purely immunological syndrome and more restricted defects, with specific impairment of the Toll and interleukin-1 receptor (TIR),interleukin-1 receptor-associated kinase (IRAK) signaling pathway. In these subjects, the NF-,B- and mitogen-activated protein kinase-mediated induction of inflammatory cytokines in response to TIR agonists is impaired. The patients present a narrow range of pyogenic bacterial infections that become increasingly rare with age. Altogether, these data suggest that human TLRs play a critical role in host defense. However, they do not provide compelling evidence, as even the infectious phenotype of patients with mutations in IRAK4 may result from impaired signaling via receptors other than TLRs. Paradoxically, these experiments of nature raise the possibility that the entire set of human TLRs is largely redundant in protective immunity in vivo. [source] The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responsesIMMUNOLOGICAL REVIEWS, Issue 1 2000Shuhji Seki Summary: The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL-18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-g and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease. [source] Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximabINFLAMMATORY BOWEL DISEASES, Issue 5 2008Antonio Di Sabatino MD Abstract Background: Under experimental chronic inflammation, tumor necrosis factor (TNF)-, plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-, is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. Methods: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. Results: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients. Conclusions: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation. (Inflamm Bowel Dis 2008) [source] Current epidemiology of atopic dermatitis in south-eastern NigeriaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2004Edith N. Nnoruka MB Background, Atopic dermatitis (AD) is a common pruritic, eczematous skin disorder that runs a chronic and relapsing course. In Nigeria, it is currently on the increase, particularly amongst infants, and has created cost burdens for families. It occurs in association with a personal or family history of asthma, allergic rhinitis and conjunctivitis. Major and minor criteria exist as guidelines for arriving at a diagnosis of AD, and surveys from Western countries have shown that these features, in particular the minor features, vary with ethnicity and genetic background and can be used to aid diagnosis. African dermatologists have also voiced concern that the much used Hanifin criteria for diagnosis of AD may need some adaptation for use in Africa. Objective, To document the features and disease outcomes of AD seen amongst dermatology hospital patients in Enugu, south-eastern Nigeria, with a view to reflecting current features amongst Nigerian Blacks. Methods, A prospective study of AD patients seen over a 2-year period at a tertiary referral dermatology clinic (University of Nigeria Teaching Hospital, Enugu, Nigeria) was carried out. A total of 1019 patients aged between 4 weeks and 57 years were included in the study. Results, The prevalence of AD was 8.5%, which is much higher than the prevalence of AD reported in various parts of Nigeria 15 years ago. AD occurred before the age of 10 years in 523 (51.3%) patients, whilst 250 (24.5%) had onset after 21 years. The earliest age of onset in infants was in the first 6 weeks of life, and this was found in 129 patients (12.7%). Education and occupation of household heads were the most significant (P < 0.001) factors associated with seeking proper health care for the child's AD. Four hundred and forty-one (43.3%) patients presented with subacute atopic eczema and 326 (32%) patients with severe impeteginized eczema. Four hundred and twenty-five patients (41.7%) had at least one first-degree family member with AD (16.7%), allergic rhinitis (10.3%), asthma (14.6%) and allergic conjunctivitis (2.1%), while 55 (13.3%) of controls had a positive family history (P < 0.01) of allergy. A personal history of AD only, without concomitant respiratory allergies, was seen in 486 (47.7%) patients. The face was affected in 431 (42.3%) patients. Inverse distribution of a flexural rash was observed over the extensor aspect of the joints: the elbow in 502 patients (49.3%), the wrist joint in 183 patients (17.9%) and the knee joints in 354 patients (34.7). The commonly observed minor features included xerosis in 719 patients (71%), papular lichenoid lesions in 547 patients (54.1%), infraorbital folds in 498 patients (49.2%), palmar hyper linearity in 524 patients (51.8%) and raised peripheral blood eosinophils in 519 patients (51%), particularly for those with severe AD. Fissured heels, forehead lichenification, orbital darkening, nail pitting, sand paper-like skin lesions on the elbows/knees/lateral malleolli, knuckle dermatitis of the hands, palmar erythema and pitted keratolysis occurred more uncommonly as minor features. Infective complications were very common and included bacterial infections (folliculitis, impetiginized dermatitis and pyodermas) in 425 (41.7%) patients, fungal infections in 377 (37%) patients, parasitic infections (scabies) in 90 (8.8%) patients and viral infection (herpes simplex and molluscum contagiosum) in 29 (2.9%) patients. Thirteen of these atopics were also HIV positive. Aggravating factors most commonly reported included heat intolerance, excessive sweating, humidity, grass intolerance, thick woollen clothing and drug reactions. Only three patients had food intolerance. Three hundred and ten patients (30.4%) recalled their AD being worse in the hot humid periods and 383 (37.6%) could not recall any periods of relief or remission. Conclusions, The prevalence of AD amongst south-eastern Nigerian Blacks is on the increase, as in other areas, although it is still lower here than in other parts of the world. Many conventional minor features were found, but some occurred less frequently than in other countries, which may be attributed to ethnicity. Further studies will be required to confirm the ethnic differences in these features of AD amongst Nigerians and other Africans, to clarify the features of AD that are peculiar to Africans. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||