Studies of transmission of mycobacterial infections in Chinook salmon

USGS Publications Warehouse

Ross, A.J.; Johnson, H.E.

1962-01-01

THE INCLUSION OF VISCERA AND CARCASSES OF TUBERCULOUS ADULT SALMON IN THE DIET OF JUVENILE SALMONIDS is considered to be the major source of mycobacterial infections in hatchery-reared fish (Wood and Ordal, 1958; Ross, Earp, and Wood, 1959). In considering additional modes of infection, we speculated about transovarian transmission or a mechanical process arising from contamination of the ova at the egg-taking stage with subsequent entry of the bacteria into the egg at the time of fertilization. This paper is a report on observations made during an experiment designed to test the latter theories.

[Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá].

PubMed

Beltrán-León, Magda; Pérez-Llanos, Francy; Sánchez, Liliana; Parra-López, Carlos; Navarrete, Myriam; Sánchez, Ricardo; Awad, Carlos; Granada, Ana María; Quintero, Edgardo; Briceño, Óscar; Cruz, Óscar; Murcia, Martha Isabel

2018-03-15

Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015. To determine the prevalence and risk factors associated to mycobacterial infections in HIVpositive patients in two public hospitals from Bogotá. A prospective and descriptive study was carried out by an active search for tuberculosis cases and non-tuberculous mycobacterial infections in HIV-positive patients. We considered demographic, social, clinical, and personal habits as variables. Statistical analyses were done using Stata 13™ software. Three hundred and fifty six patients were included, 81.2% were men and 18.8% were women; the mean age was 36.5 years. Tuberculosis infection had a frequency of 19.9% (95% CI: 15.9-24.5%) and non-tuberculous mycobacterial infection had a 3.9% frequency (95% CI: 2.16-6.5%). Bivariate analysis showed a statistically significant association between tuberculosis infection and CD4+ T cell counts (p=0.003), viral load (p=0.008), antiretroviral therapy (p=0.014), and body mass index (BMI) <18 kg/m2 (p=0.000). In non-tuberculous mycobacterial infections there was a statistically significantassociation with BMI (p=0.027) and CD4+ T cell counts (p=0.045). Factors associated with an impaired immune system caused by HIV infection are an important risk factor for developing tuberculosis. The lack of antiretroviral therapy and the BMI were also important risk factors for tuberculosis.

Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

PubMed Central

Ufimtseva, Elena

2016-01-01

The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells. PMID:27066505

Usefulness of Chinese Herbal Medicines as Host-Directed Therapeutics against Mycobacterial Infections: A Review.

PubMed

Tomioka, Haruaki

2017-01-01

The high incidence of tuberculosis (TB) in developing countries, the resurgence of TB in industrialized countries, and the worldwide increase in the prevalence of Mycobacterium avium complex infections have prompted the quest for new antimycobacterial drugs. However, the development of such chemotherapeutics is currently making very slow progress. It therefore appears that devising improved administration protocols for clinical treatment against intractable mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of novel antimycobacterial drugs. The modulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. Particularly, the mild and long-term up-regulation of host immune reactions against mycobacterial pathogens using Chinese herbal medicines (CHMs) may be beneficial for immunoadjunctive therapy. This review focuses on the current status and future prospects regarding the development of CHMs that can be useful for the clinical control of intractable mycobacterial infections.

Hematopoietic stem cell gene therapy for IFNγR1 deficiency protects mice from mycobacterial infections.

PubMed

Hetzel, Miriam; Mucci, Adele; Blank, Patrick; Nguyen, Ariane Hai Ha; Schiller, Jan; Halle, Olga; Kühnel, Mark-Philipp; Billig, Sandra; Meineke, Robert; Brand, Daniel; Herder, Vanessa; Baumgärtner, Wolfgang; Bange, Franz-Christoph; Goethe, Ralph; Jonigk, Danny; Förster, Reinhold; Gentner, Bernhard; Casanova, Jean-Laurent; Bustamante, Jacinta; Schambach, Axel; Kalinke, Ulrich; Lachmann, Nico

2018-02-01

Mendelian susceptibility to mycobacterial disease is a rare primary immunodeficiency characterized by severe infections caused by weakly virulent mycobacteria. Biallelic null mutations in genes encoding interferon gamma receptor 1 or 2 ( IFNGR1 or IFNGR2 ) result in a life-threatening disease phenotype in early childhood. Recombinant interferon γ (IFN-γ) therapy is inefficient, and hematopoietic stem cell transplantation has a poor prognosis. Thus, we developed a hematopoietic stem cell (HSC) gene therapy approach using lentiviral vectors that express Ifnγr1 either constitutively or myeloid specifically. Transduction of mouse Ifnγr1 -/- HSCs led to stable IFNγR1 expression on macrophages, which rescued their cellular responses to IFN-γ. As a consequence, genetically corrected HSC-derived macrophages were able to suppress T-cell activation and showed restored antimycobacterial activity against Mycobacterium avium and Mycobacterium bovis Bacille Calmette-Guérin (BCG) in vitro. Transplantation of genetically corrected HSCs into Ifnγr1 -/- mice before BCG infection prevented manifestations of severe BCG disease and maintained lung and spleen organ integrity, which was accompanied by a reduced mycobacterial burden in lung and spleen and a prolonged overall survival in animals that received a transplant. In summary, we demonstrate an HSC-based gene therapy approach for IFNγR1 deficiency, which protects mice from severe mycobacterial infections, thereby laying the foundation for a new therapeutic intervention in corresponding human patients. © 2018 by The American Society of Hematology.

Control of Mycobacterial Infections in Mice Expressing Human Tumor Necrosis Factor (TNF) but Not Mouse TNF.

PubMed

Olleros, Maria L; Chavez-Galan, Leslie; Segueni, Noria; Bourigault, Marie L; Vesin, Dominique; Kruglov, Andrey A; Drutskaya, Marina S; Bisig, Ruth; Ehlers, Stefan; Aly, Sahar; Walter, Kerstin; Kuprash, Dmitry V; Chouchkova, Miliana; Kozlov, Sergei V; Erard, François; Ryffel, Bernard; Quesniaux, Valérie F J; Nedospasov, Sergei A; Garcia, Irene

2015-09-01

Tumor necrosis factor (TNF) is an important cytokine for host defense against pathogens but is also associated with the development of human immunopathologies. TNF blockade effectively ameliorates many chronic inflammatory conditions but compromises host immunity to tuberculosis. The search for novel, more specific human TNF blockers requires the development of a reliable animal model. We used a novel mouse model with complete replacement of the mouse TNF gene by its human ortholog (human TNF [huTNF] knock-in [KI] mice) to determine resistance to Mycobacterium bovis BCG and M. tuberculosis infections and to investigate whether TNF inhibitors in clinical use reduce host immunity. Our results show that macrophages from huTNF KI mice responded to BCG and lipopolysaccharide similarly to wild-type macrophages by NF-κB activation and cytokine production. While TNF-deficient mice rapidly succumbed to mycobacterial infection, huTNF KI mice survived, controlling the bacterial burden and activating bactericidal mechanisms. Administration of TNF-neutralizing biologics disrupted the control of mycobacterial infection in huTNF KI mice, leading to an increased bacterial burden and hyperinflammation. Thus, our findings demonstrate that human TNF can functionally replace murine TNF in vivo, providing mycobacterial resistance that could be compromised by TNF neutralization. This new animal model will be helpful for the testing of specific biologics neutralizing human TNF. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Fighting mycobacterial infections by antibiotics, phytochemicals and vaccines.

PubMed

Bamberger, Denise; Jantzer, Nora; Leidner, Katharina; Arend, Joachim; Efferth, Thomas

2011-07-01

Buruli ulcer is a neglected disease caused by Mycobacterium ulcerans and represents the world's third most common mycobacterial infection. It produces the polyketide toxins, mycolactones A, B, C and D, which induce apoptosis and necrosis. Clinical symptoms are subcutaneous nodules, papules, plaques and ulcerating oedemae, which can enlarge and destroy nerves and blood vessels and even invade bones by lymphatic or haematogenous spread (osteomyelitis). Patients usually do not suffer from pain or systematic inflammation. Surgery is the treatment of choice, although recurrence is common and wide surgical excisions including healthy tissues result in significant morbidity. Antibiotic therapy with rifamycins, aminoglycosides, macrolides and quinolones also improves cure rates. Still less exploited treatment options are phytochemicals from medicinal plants used in affected countries. Vaccination against Buruli ulcer is still in its infancy. Copyright © 2010. Published by Elsevier SAS.

Mycobacterial blood culture as the only means of diagnosis of disseminated tuberculosis in advanced HIV infection.

PubMed

Mathuram, Alice Joan; Michael, Joy Sarojini; Turaka, Vijay Prakash; Jasmine, Sudha; Carey, Ronald; Ramya, I

2018-04-01

The diagnosis of disseminated tuberculosis (TB) in advanced HIV infection is often delayed because of difficulty in obtaining suitable specimens for culture. A total of 32 such patients from South India with positive mycobacterial blood cultures were studied over ten years. Almost all (90%) had a febrile illness and the majority (68.7%) had clinical lung involvement, but only 27.3% had positive sputum smears. Liver biopsy yielded a positive diagnosis in only 1/7. Cytopenia was almost universal (96.9%). Bone marrow cultures were, however, positive in 54.8%, of whom one-quarter grew atypical mycobacteria. Mycobacterial blood culture is therefore a useful adjunct test to diagnose TB in advanced HIV.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

PubMed

Conti, Francesca; Lugo-Reyes, Saul Oswaldo; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Güzide; Borges de Oliveira, Edgar; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G; Emiroglu, Melike; Öz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Pérez, Nestor; Regairaz, Lorena; Guidos Morales, Héctor Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Ortega, Maria Claudia; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret Bano; Vogt, Guillaume; Blanche, Stéphane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J; Kütükçüler, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, Jacinta

2016-07-01

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Our objective was to assess the effect of mycobacterial disease in patients with CGD. We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Efficacy of BACTEC TB in the rapid confirmatory diagnosis of mycobacterial infections. A Lebanese tertiary care center experience.

PubMed

Itani, Lina Y; Cherry, Mohamad A; Araj, George F

2005-01-01

Rapid detection of Mycobacterium tuberculosis (MTB), especially multidrug-resistant strains, is of importance for prompt clinical management and initiation of public health control measures. Culture remains the "gold" standard in the confirmatory laboratory diagnosis of mycobacterial infections. The reliability of the automated radiometric BACTEC 460 TB (BACTEC) system for the rapid detection of mycobacteria in clinical specimens was evaluated and compared to the conventional culture on Lowenstein-Jensen (LJ) medium. All clinical specimens submitted for mycobacterial culture were processed and simultaneously cultured on both BACTEC broth medium and LJ solid medium. Acid-fast bacilli (AFB) smears were also performed on the sediments. Differentiation of mycobacterial isolates as MTB or Mycobacterium sp. other than tuberculosis (MOTT) was based on the BACTEC NAP test. All positive culture findings recovered between January 1997 and December 2003 were analyzed in this study. A total of 3300 specimens were tested of which 355 (10.7%) yielded positive cultures consisting of 233 (65.6%) MTB and 122 (34.4%) MOTT. The percentages of AFB smear-positive were 45% and 49% in clinical specimens yielding MTB & MOTT, respectively. Though several types of specimens were cultured, most isolates (72% of MTB & 91% of MOTT) were recovered from respiratory specimens. Overall, the BACTEC showed significantly higher mycobacteria recovery rate (91%) than LJ (77%). In terms of times to detection, BACTEC showed significantly shorter detection time of isolates than LJ for the overall (mean 9.6 days for BACTEC vs. 22.8 days for LJ) and for each category of AFB smear finding. The detection time is shortened for BACTEC with the increasing grade of smear positivity. BACTEC is substantially more sensitive, efficient and rapid than LJ in the laboratory diagnosis of mycobacterial infections. This system also provides rapid differentiation of MTB from MOTT and susceptibility test results on MTB

Onchocerciasis modulates the immune response to mycobacterial antigens

PubMed Central

Stewart, G R; Boussinesq, M; Coulson, T; Elson, L; Nutman, T; Bradley, J E

1999-01-01

Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-γ) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth antigen and PPD increased with ascending children's age. IFN-γ and cellular proliferation to PPD were not related to age, but in response to helminth antigen were significantly higher in children of age 9–12 years than children of either the younger age group (5–8 years) or the older group (13–16 years). Thus, there was a MF density-related down-regulation of cellular responsiveness and age-related skewing toward type 2 which was paralleled in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies. PMID:10469056

Validation of a CD1b tetramer assay for studies of human mycobacterial infection or vaccination.

PubMed

Layton, Erik D; Yu, Krystle K Q; Smith, Malisa T; Scriba, Thomas J; De Rosa, Stephen C; Seshadri, Chetan

2018-07-01

CD1 tetramers loaded with lipid antigens facilitate the identification of rare lipid-antigen specific T cells present in human blood and tissue. Because CD1 proteins are structurally non-polymorphic, these tetramers can be applied to genetically diverse human populations, unlike MHC-I and MHC-II tetramers. However, there are no standardized assays to quantify and characterize lipid antigen-specific T cells present within clinical samples. We incorporated CD1b tetramers loaded with the mycobacterial lipid glucose monomycolate (GMM) into a multi-parameter flow cytometry assay. Using a GMM-specific T-cell line, we demonstrate that the assay is linear, reproducible, repeatable, precise, accurate, and has a limit of detection of approximately 0.007%. Having formally validated this assay, we performed a cross-sectional study of healthy U.S. controls and South African adolescents with and without latent tuberculosis infection (LTBI). We show that GMM-specific T cells are specifically detected in South African subjects with LTBI and not in U.S. healthy controls. This assay can be expanded to include additional tetramers or phenotypic markers to characterize GMM-specific T cells in studies of mycobacterial infection, disease, or vaccination. Copyright © 2018 Elsevier B.V. All rights reserved.

A spatial epidemiological analysis of nontuberculous mycobacterial infections in Queensland, Australia.

PubMed

Chou, Michael P; Clements, Archie C A; Thomson, Rachel M

2014-05-21

The epidemiology of infections with nontuberculous mycobacteria (NTM) has been changing and the incidence has been increasing in some settings. The main route of transmission to humans is considered to be from the environment. We aimed to describe spatial clusters of cases of NTM infections and to identify associated climatic, environmental and socio-economic variables. NTM data were obtained from the Queensland Mycobacterial Reference Laboratory for the period 2001-2011. A Bayesian spatial conditional autoregressive model was constructed at the postcode level, with covariates including soil variables, maximum, mean and minimum rainfall and temperature, income (proportion of population earning < $32,000 and < $52,000) and land use category. Significant clusters of NTM infection were identified in the central Queensland region overlying the Surat sub-division of the Great Artesian Basin, as well as in the lower North Queensland Local Government Area known as the Whitsunday region. Our models estimated an expected increase of 21% per percentage increase of population earning < $52,000 (95% CI 9-34%) and an expected decrease of 13% for every metre increase of average topsoil depth for risk of Mycobacterium intracellulare infection (95% CI -3 - -22%). There was an estimated increase of 79% per mg/m3 increase of soil bulk density (95% CI 26-156%) and 19% decrease for every percentage increase in population earning < $32,000 for risk of M. kansasii infection (95% CI -3 - -49%). There were distinct spatial clusters of M. kansasii, M. intracellulare and M. abscessus infections in Queensland, and a number of socio-ecological, economic and environmental factors were found to be associated with NTM infection risk.

Pulmonary Nontuberculous Mycobacterial Disease

PubMed Central

Kim, Richard D.; Greenberg, David E.; Ehrmantraut, Mary E.; Guide, Shireen V.; Ding, Li; Shea, Yvonne; Brown, Margaret R.; Chernick, Milica; Steagall, Wendy K.; Glasgow, Connie G.; Lin, JingPing; Jolley, Clara; Sorbara, Lynn; Raffeld, Mark; Hill, Suvimol; Avila, Nilo; Sachdev, Vandana; Barnhart, Lisa A.; Anderson, Victoria L.; Claypool, Reginald; Hilligoss, Dianne M.; Garofalo, Mary; Fitzgerald, Alan; Anaya-O'Brien, Sandra; Darnell, Dirk; DeCastro, Rosamma; Menning, Heather M.; Ricklefs, Stacy M.; Porcella, Stephen F.; Olivier, Kenneth N.; Moss, Joel; Holland, Steven M.

2008-01-01

Rationale: Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive. Objectives: To prospectively determine the morphotype, immunophenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM. Methods: We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001–2002 dataset. Measurements and Main Results: Patients were 59.9 (±9.8 yr [SD]) old, and 5.4 (±7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated nontuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-γ/IL-12 pathway. CD4+, CD8+, B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene. Conclusions: Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis

Reconstruction of infected abdominal wall defects using latissimus dorsi free flap.

PubMed

Kim, Sang Wha; Han, Sang Chul; Hwang, Kyu Tae; Ahn, Byung Kyu; Kim, Jeong Tae; Kim, Youn Hwan

2013-12-01

Infected abdominal defects are a challenge to surgeons. In this study, we describe 10 cases in which the latissimus dorsi myocutaneous flap was used for successful reconstruction of abdominal wall defects severely infected with methicillin-resistant Staphylococcus aureus (MRSA). Retrospective review of 10 patients with abdominal wall defects that were reconstructed using the latissimus dorsi myocutaneous flap between 2002 and 2010. All patients had abdominal defects with hernias, combined with MRSA infections. The sizes of the flaps ranged from 120 to 364 cm(2) . The deep inferior epigastric artery was the recipient vessel in nine patients and the internal mammary vessels were used for one patient. There were no complications relating to the flaps, although there were other minor complications including wound dehiscence, haematoma and fluid correction. After reconstruction, there were no signs of infection during follow-up periods, and the patients were satisfied with the final results. Reconstruction using the latissimus dorsi myocutaneous flap, including muscle fascia structures, is a potential treatment option for severely infected large abdominal wall defects. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

Application of a whole blood mycobacterial growth inhibition assay to study immunity against Mycobacterium tuberculosis in a high tuberculosis burden population

PubMed Central

Smit, Erica; Erasmus, Mzwandile; Day, Jonathan; Makhethe, Lebohang; de Kock, Marwou; Hughes, E. Jane; van Rooyen, Michele; Stone, Lynnett; Hanekom, Willem; Brennan, Michael J.; Wallis, Robert S.; Hatherill, Mark; Scriba, Thomas J.

2017-01-01

The determinants of immunological protection against Mycobacterium tuberculosis (M.tb) infection in humans are not known. Mycobacterial growth inhibition assays have potential utility as in vitro surrogates of in vivo immunological control of M.tb. We evaluated a whole blood growth inhibition assay in a setting with high burden of TB and aimed to identify immune responses that correlate with control of mycobacterial growth. We hypothesized that individuals with underlying M.tb infection will exhibit greater M.tb growth inhibition than uninfected individuals and that children aged 4 to 12 years, an age during which TB incidence is curiously low, will also exhibit greater M.tb growth inhibition than adolescents or adults. Neither M.tb infection status, age of the study participants, nor M.tb strain was associated with differential control of mycobacterial growth. Abundance and function of innate or T cell responses were also not associated with mycobacterial growth. Our data suggest that this assay does not provide a useful measure of age-associated differential host control of M.tb infection in a high TB burden setting. We propose that universally high levels of mycobacterial sensitization (through environmental non-tuberculous mycobacteria and/or universal BCG vaccination) in persons from high TB burden settings may impart broad inhibition of mycobacterial growth, irrespective of M.tb infection status. This sensitization may mask the augmentative effects of mycobacterial sensitization on M.tb growth inhibition that is typical in low burden settings. PMID:28886145

Helicobacter pylori infection, serum pepsinogens, and pediatric abdominal pain: a pilot study.

PubMed

Kassem, Eias; Naamna, Medhat; Mawassy, Kadri; Beer-Davidson, Gany; Muhsen, Khitam

2017-08-01

The significance of Helicobacter pylori (H. pylori) infection in pediatric abdominal pain remains poorly recognized. We examined associations of H. pylori infection and serum pepsinogens (PGs), as non-invasive markers of gastritis, with pediatric abdominal pain. A case-control study was conducted among 99 children aged 5-17 years admitted to one hospital for abdominal pain (cases) without an apparent organic reason. Using enzyme-linked immunosorbent assays, sera were tested and compared with 179 controls for anti-H. pylori immunoglobulin G (IgG) antibodies and PGI and PGII levels. Multivariable analysis was performed to adjust for potential confounders. H. pylori IgG sero-positivity was 34.3 and 36.3% in cases and controls, respectively, P = 0.7. H. pylori-infected children had higher median PGI and PGII levels and a lower PGI/PGII ratio than uninfected children. Cases infected with H. pylori had a higher median PGII level (P < 0.001) and lower PGI/PGII ratio (P = 0.036) than controls infected with H. pylori. The percentage of cases with PGII ≥7.5 μg/L, as indication for antral inflammation, was higher than in controls: 58.6 versus 44.7%, P = 0.027. Children with PGII levels ≥7.5 μg/L had increased risk for abdominal pain: adjusted prevalence ratio 1.73 [95% confidence intervals 1.02, 2.93], P = 0.039. Children with increased serum PGII levels, as an indication of gastritis, are more likely to have abdominal pain. Serum PGs can be a useful non-invasive marker for gastritis, in evaluating children with severe abdominal pain with no apparent organic reason. What is Known: • The significance of Helicobacter pylori infection in pediatric abdominal pain remains debated. • Serum pepsinogens (PGs), non-invasive markers of gastric inflammation, were rarely utilized in assessing the association between H. pylori in pediatric abdominal pain of unknown origin. What is New: • High serum PGII level, as an indication of gastritis, rather than H. pylori

Mycobacterial growth inhibition is associated with trained innate immunity.

PubMed

Joosten, Simone A; van Meijgaarden, Krista E; Arend, Sandra M; Prins, Corine; Oftung, Fredrik; Korsvold, Gro Ellen; Kik, Sandra V; Arts, Rob Jw; van Crevel, Reinout; Netea, Mihai G; Ottenhoff, Tom Hm

2018-05-01

The lack of defined correlates of protection hampers development of vaccines against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb) interaction. Here, we used a mycobacterial growth inhibition assay (MGIA) based on peripheral blood mononuclear cells to investigate the capacity to control outgrowth of bacille Calmette-Guérin (BCG). Interestingly, strong control of BCG outgrowth was observed almost exclusively in individuals with recent exposure to Mtb, but not in (long-term) latent TB infection, and only modestly in BCG vaccinees. Mechanistically, control of mycobacterial outgrowth strongly correlated with the presence of a CD14dim monocyte population, but also required the presence of T cells. The nonclassical monocytes produced CXCL10, and CXCR3 receptor blockade inhibited the capacity to control BCG outgrowth. Expression of CXCR3 splice variants was altered in recently Mtb-exposed individuals. Cytokines previously associated with trained immunity were detected in MGIA supernatants, and CXCL9, CXCL10, and CXCL11 represent new markers of trained immunity. These data indicate that CXCR3 ligands are associated with trained immunity and are critical factors in controlling mycobacterial outgrowth. In conclusion, control of mycobacterial outgrowth early after exposure to Mtb is the result of trained immunity mediated by a CXCL10-producing nonclassical CD14dim monocyte subset.

[Experience of the three-stage strategy for intestinal fistula complicated with complex abdominal infection].

PubMed

Zhao, Qingchuan; Li, Xuzhao; Li, Xiaohua; Wang, Juan

2017-03-25

Intestinal fistula, as a serious complication after abdominal surgery, not only leads to a series of pathophysiological changes such as fluid loss, malnutrition and organ dysfunction, but also causes the severe abdominal infection, which often threatens the life of patients. How to make the diagnosis and give the treatment of intestinal fistula is the key to save the lives of high-risk patients. In our hospital, during the past course of diagnosis and treatment for intestinal fistula complicated with severe abdominal infection, based on the combination of literatures at home and abroad with our clinical experiences for many years, an effective three-stage prevention and treatment strategy was formed gradually, which included early diagnosis, effective treatment of infection source, open drainage of abdominal infection and early enteral nutrition support. This strategy subverts the traditional concept of surgery alone, and becomes an effective means to save patients with severe abdominal infection.

Factors associated with pastoral community knowledge and occurrence of mycobacterial infections in Human-Animal Interface areas of Nakasongola and Mubende districts, Uganda

PubMed Central

2010-01-01

Background Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens whose role in human and animal disease is increasingly being recognized. Major concerns are their role as opportunistic pathogens in HIV/AIDS infections. The role of open natural water sources as source and livestock/wildlife as reservoirs of infections to man are well documented. This presents a health challenge to the pastoral systems in Africa that rely mostly on open natural water sources to meet livestock and human needs. Recent study in the pastoral areas of Uganda showed infections with same genotypes of NTM in pastoralists and their livestock. The aim of this study was to determine the environmental, animal husbandry and socio-demographic factors associated with occurrence and the pastoral community knowledge of mycobacterial infections at the human-environment-livestock/wildlife interface (HELI) areas in pastoral ecosystems of Uganda. Methods Two hundred and fifty three (253) individuals were subjected to a questionnaire survey across the study districts of Nakasongola and Mubende. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. Results Humans sharing of the water sources with wild animals from the forest compared to savannah ecosystem (OR = 3.3), the tribe of herding pastoral community (OR = 7.9), number of rooms present in household (3-5 vs. 1-2 rooms) (OR = 3.3) were the socio-demographic factors that influenced the level of knowledge on mycobacterial infections among the pastoral communities. Tribe (OR = 6.4), use of spring vs. stream water for domestic use (OR = 4.5), presence of sediments in household water receptacle (OR = 2.32), non separation of water containers for drinking and domestic use (OR = 2.46), sharing of drinking water sources with wild animals (OR = 2.1), duration of involvement of >5 yrs in cattle keeping (OR = 3.7) and distance of household to animal night shelters (>20 meters) (OR = 3.8) were significant

The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review.

PubMed

Brode, S K; Daley, C L; Marras, T K

2014-11-01

Tuberculosis (TB) rates are decreasing in many areas, while non-tuberculous mycobacteria (NTM) infection rates are increasing. The relationship between the epidemiology of TB and NTM infections is not well understood. To understand the epidemiologic relationship between TB and NTM disease worldwide. A systematic review of Medline (1946-2014) was conducted to identify studies that reported temporal trends in NTM disease incidence. TB rates for each geographic area included were then retrieved. Linear regression models were fitted to calculate slopes describing changes over time. There were 22 studies reporting trends in rates of NTM disease, representing 16 geographic areas over four continents: 75% of areas had climbing incidence rates, while 12.5% had stable rates and 12.5% had declining rates. Most studies (81%) showed declining TB incidence rates. The proportion of incident mycobacterial disease caused by NTM was shown to be rising in almost every geographic area (94%). We found an increase in the proportion of mycobacterial disease caused by NTM in many parts of the world due to a simultaneous reduction in TB and increase in NTM disease. Research into the interaction between mycobacterial infections may help explain this inverse relationship.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

PubMed

Cai, Ren-Tian; Yu, Feng-Xue; Tao, Zhen; Qian, Xue-Qin; Chen, Jun; Lu, Hong-Zhou

2017-11-02

It is difficult to quickly distinguish non-tuberculous mycobacterial (NTM) infection from tuberculosis (TB) infection in human immunodeficiency virus (HIV)-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries. A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and were compared between the HIV/TB and HIV/NTM groups. A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy (ART) before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count(5.60 × 10 9 /L) and the proportion of neutrophils in the leukocyte count (76.70%) in the HIV/TB group were significantly higher than those in the HIV/NTM group (4.40 × 10 9 /L [P = 0.0014] and 69.30% [P < 0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P < 0.001). The creatinine and urea levels were not significantly different between the two groups. The ESR (84.00 mm/h) and the concentration of CRP (59.60 mg/L) were significantly higher in the HIV/TB group than in the HIV/NTM group (52.00 mm/h and 19.60 mg/L, respectively) (P < 0.001). To distinguish TB infection from NTM infection, the best cut

Intestinal lymphangiectasia: an undescribed cause of malabsorption and incomplete immunological recovery in HIV-infected patients.

PubMed

Marco-Lattur, Maria D; Payeras, Antoni; Campins, Antoni A; Pons, Jaume; Cifuentes, Carmen; Riera, Melcior

2011-02-01

Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. To describe HIV patients who developed IL. Clinical Case series. 4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections

PubMed Central

Tobin, David M.; Roca, Francisco J.; Oh, Sungwhan F.; McFarland, Ross; Vickery, Thad W.; Ray, John P.; Ko, Dennis C.; Zou, Yuxia; Bang, Nguyen D.; Chau, Tran T. H.; Vary, Jay C.; Hawn, Thomas R.; Dunstan, Sarah J.; Farrar, Jeremy J.; Thwaites, Guy E.; King, Mary-Claire; Serhan, Charles N.; Ramakrishnan, Lalita

2012-01-01

Summary Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A4 hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B4. We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation. PMID:22304914

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.

PubMed

Amaral, Eduardo P; Conceição, Elisabete L; Costa, Diego L; Rocha, Michael S; Marinho, Jamocyr M; Cordeiro-Santos, Marcelo; D'Império-Lima, Maria Regina; Barbosa, Theolis; Sher, Alan; Andrade, Bruno B

2016-10-28

Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. NAC exhibits potent anti-mycobacterial effects and may limit M

Diffuse abdominal gallium-67 citrate uptake in salmonella infections

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

Garty, I.; Koren, A.

1987-11-01

Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate.

Surgical site infections in an abdominal surgical ward at Kosovo Teaching Hospital.

PubMed

Raka, Lul; Krasniqi, Avdyl; Hoxha, Faton; Musa, Ruustem; Mulliqi, Gjyle; Krasniqi, Selvete; Kurti, Arsim; Dervishaj, Antigona; Nuhiu, Beqir; Kelmendi, Baton; Limani, Dalip; Tolaj, Ilir

2007-12-01

Abdominal surgical site infections (SSI) cause substantial morbidity and mortality for patients undergoing operative procedures. We determined the incidence of and risk factors for SSI after abdominal surgery in the Department of Abdominal Surgery at the University Clinical Centre of Kosovo (UCCK). Prospective surveillance of patients undergoing abdominal surgery was performed between December 2005 and June 2006. CDC definitions were followed to detect SSI and study forms were based on Europe Link for Infection Control through Surveillance (HELICS) protocol. A total of 253 surgical interventions in 225 patients were evaluated. The median age of patients was 42 years and 55.1% of them were male. The overall incidence rate of SSI was 12%. Follow-up was achieved for 84.1% of the procedures. For patients with an SSI, the median duration of hospitalization was 9 days compared with 4 days for those without an SSI (p2, use of antibiotic prophylaxis and NNIS class of >2 were all significant at p < .001. The SSI rates for the NNIS System risk classes 0, 1 and 2-3 were 4.2%, 46.7% and 100%, respectively. SSI caused considerable morbidity among surgical patients in UCCK. Appropriate active surveillance and infection control measures should be introduced during preoperative, intra-operative, and postoperative care to reduce infection rates.

Mycobacterial Infections

MedlinePlus

... many different kinds. The most common one causes tuberculosis. Another one causes leprosy. Still others cause infections ... aren't "typical" because they don't cause tuberculosis. But they can still harm people, especially people ...

Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.

PubMed

Singpiel, Alena; Kramer, Julia; Maus, Regina; Stolper, Jennifer; Bittersohl, Lara Friederike; Gauldie, Jack; Kolb, Martin; Welte, Tobias; Sparwasser, Tim; Maus, Ulrich A

2018-03-01

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ pos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

Non-tuberculous Mycobacterial Infections in Thoracic Transplant Candidates and Recipients.

PubMed

Rao, Mana; Silveira, Fernanda P

2018-05-12

To review and discuss the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of non-tuberculous mycobacteria (NTM) in thoracic transplantation. Non-tuberculous mycobacteria are ubiquitous but are an uncommon cause of disease after solid organ transplantation. The incidence of infection is higher in thoracic transplant recipients than in abdominal transplant recipients, with most cases seen after lung transplantation. It is associated with increased morbidity and, occasionally, mortality. Infection in the pre-transplant setting can occur in lung transplant candidates, often posing a dilemma regarding transplant listing. Disease manifestations are diverse, and pulmonary disease is the most common. Diagnosis requires a high index of suspicion. Treatment requires a multiple-drug combination and is limited by drug-drug interactions and tolerability. Mycobacterium abscessus is a challenge in lung transplant recipients, due to its intrinsic resistance and propensity to relapse even after prolonged therapy. Mycobacterium chimaera is an emerging pathogen associated with contamination of heater-cooler units and is described to cause disease months after cardiothoracic surgery. NTM infections in thoracic organ transplant recipients are uncommon but are associated with substantial morbidity and mortality. Data from larger multicenter studies is needed to better define the epidemiology of NTM in thoracic transplantation, best treatment options, and the management of infected transplant candidates.

Surgical site infections in an abdominal surgical ward at Kosovo Teaching Hospital.

PubMed

Raka, Lul; Krasniqi, Avdyl; Hoxha, Faton; Musa, Ruustem; Mulliqi, Gjyle; Krasniqi, Selvete; Kurti, Arsim; Dervishaj, Antigona; Nuhiu, Beqir; Kelmendi, Baton; Limani, Dalip; Tolaj, Ilir

2008-01-01

Abdominal surgical site infections (SSI) cause substantial morbidity and mortality for patients undergoing operative procedures. We determined the incidence of and risk factors for SSI after abdominal surgery in the Department of Abdominal Surgery at the University Clinical Centre of Kosovo (UCCK). Prospective surveillance of patients undergoing abdominal surgery was performed between December 2005 and June 2006. CDC definitions were followed to detect SSI and study forms were based on Europe Link for Infection Control through Surveillance (HELICS) protocol. A total of 253 surgical interventions in 225 patients were evaluated. The median age of patients was 42 years and 55.1% of them were male. The overall incidence rate of SSI was 12%. Follow-up was achieved for 84.1% of the procedures. For patients with an SSI, the median duration of hospitalization was 9 days compared with 4 days for those without an SSI (p < 0.001). Surgical procedures were classified as emergent in 53.3% of cases. Superficial incisional SSI was most common (55%). Clinical infections were culture positive in 40.7% of cases. Duration of operation, duration of preoperative stay, wound class, ASA score > 2, use of antibiotic prophylaxis and NNIS class of > 2 were all significant at p < .001. The SSI rates for the NNIS System risk classes 0, 1 and 2-3 were 4.2%, 46.7% and 100%, respectively. SSI caused considerable morbidity among surgical patients in UCCK. Appropriate active surveillance and infection control measures should be introduced during preoperative, intra-operative, and postoperative care to reduce infection rates.

Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

PubMed

Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

2016-12-01

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Non-tuberculous mycobacterial infection of the musculoskeletal system: pattern of infection and efficacy of combined surgical/antimicrobial treatment.

PubMed

Park, J W; Kim, Y S; Yoon, J O; Kim, J S; Chang, J S; Kim, J M; Chun, J M; Jeon, I H

2014-11-01

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes. ©2014 The British Editorial Society of Bone & Joint Surgery.

Meropenem: an updated review of its use in the management of intra-abdominal infections.

PubMed

Lowe, M N; Lamb, H M

2000-09-01

Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin. Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

Abdominal tap

MedlinePlus

Peritoneal tap; Paracentesis; Ascites - abdominal tap; Cirrhosis - abdominal tap; Malignant ascites - abdominal tap ... abdominal cavity ( most often cancer of the ovaries ) Cirrhosis of the liver Damaged bowel Heart disease Infection ...

Recommendations for intra-abdominal infections consensus report

PubMed Central

Avkan-Oğuz, Vildan; Baykam, Nurcan; Sökmen, Selman; Güner, Rahmet; Agalar, Fatih; Alp, Emine; Doğrul, Ahmet; Turhan, Özge; Ağalar, Canan; Kurtaran, Behice; Geçim, İbrahim Ethem; Özaras, Reşat; Yılmaz, Gürdal; Akbulut, Ayhan; Koksal, İftihar

2016-01-01

Guidelines include the recommendations of experts from various specialties within a topic in consideration of data specific to each country. However, to date there has not been a guideline standardizing the nomenclature and offering recommendations for intra-abdominal infections (IAIs) in Turkey. This is mainly due to the paucity of laboratory studies regarding the clinical diagnosis and treatment of IAIs or the sensitivity of microorganisms isolated from patients with IAIs. However, due to the diversification of host characteristics and advancements in technological treatment methods, it has become imperative to ‘speak a common language’. For this purpose May 2015, a group of 15 experts in intra-abdominal infections, under the leadership of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey (EKMUD) and with representatives from the Turkish Surgical Association, Turkish Society of Colon and Rectal Surgery, Hernia Society, Turkish Society of Hepato-pancreato-biliary Surgery, and the Turkish Society of Hospital Infections and Control, was formed to analyze relevant studies in the literature. Ultimately, the suggestions for adults found in this consensus report were developed using available data from Turkey, referring predominantly to the 2010 guidelines for diagnosing and managing complicated IAIs in adults and children by the Infectious Diseases Society of America (IDSA) and the Surgical Infection Society. The recommendations are presented in two sections, from the initial diagnostic evaluation of patients to the treatment approach for IAI. This Consensus Report was presented at the EKMUD 2016 Congress in Antalya and was subsequently opened for suggestions on the official websites of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey and Turkish Surgical Association for one month. The manuscript was revised according to the feedback received. PMID:28149134

Sclerotiorin inhibits protein kinase G from Mycobacterium tuberculosis and impairs mycobacterial growth in macrophages.

PubMed

Chen, Dongni; Ma, Shuangshuang; He, Lei; Yuan, Peibo; She, Zhigang; Lu, Yongjun

2017-03-01

As a eukaryotic-like Ser/Thr protein kinase, Mycobacterium tuberculosis virulent effector protein kinase G (PknG) mediates mycobacterial survival by regulating bacterial cell metabolic processes and preventing phagosome-lysosome fusion in host macrophages. Targeting PknG is an effective strategy for development of anti-tuberculosis (TB) drugs. In the study, we found that sclerotiorin, derived from marine fungi from the South China Sea, exhibited moderately strong inhibitory effects on recombinant PknG, with an IC 50 value of 76.5 μM, and acted as a non-competitive inhibitor. The dissociation constant (K D ) of sclerotiorin determined by MST was 11.4 μM, demonstrating a moderate binding strength between them. Sclerotiorin could substantially impair the mycobacterial survival in infected macrophages while the macrophage viability remained unaffected, though it did not inhibit the mycobacterial growth in culture. When sclerotiorin was used in combination with rifampicin, intracellular mycobacterial growth decreased as sclerotiorin concentration increased. Docking analysis suggested a binding mechanism of inhibition with performing interactions with the P-loop and catalytic loop of PknG. In summary, we reported that sclerotiorin had moderately strong PknG inhibitory activity, but no cytotoxicity, and it could substantially decrease the mycobacterial growth inside macrophages, suggesting that sclerotiorin has potential to supplement antibiotic therapy for TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Pylephlebitis: a rare but possible complication of intra-abdominal infections].

PubMed

Pérez-Bru, Susana; Nofuentes-Riera, Carmen; García-Marín, Andrés; Luri-Prieto, Paloma; Morales-Calderón, Miguel; García-García, Salvador

2015-01-01

Pylephlebitis or septic thrombophlebitis of the portal venous system is a rare but serious complication of intra-abdominal infections which drain into the portal venous system. Its diagnosis is based on clinical suspicion and imaging tests, mainly a computed tomography scan, given the lack of specificity of the signs and symptoms. Spread of septic emboli is the major cause of morbidity and mortality. The aim of the study was to analyse patients diagnosed in our hospital. Retrospective descriptive study of patients diagnosed with pylephlebitis in our hospital. Four patients were included, 3 men and one woman. In 3 cases it was acute cholecystitis that led to the diagnosis of pylephlebitis at the same time as the intra-abdominal infection. Emergency surgery was performed in one case, whilst the other 2 were treated conservatively. Blood cultures were performed in all cases, and empirical antibiotic treatment was used. In the only case of acute appendicitis, diagnosis of pylephlebitis was achieved during the study of postoperative fever, with empirical antibiotic treatment also being started. The haematologist was requested to start the required anticoagulation therapy in all cases. Pylephlebitis is a rare complication of intra-abdominal infections that may make lead to a worse outcome. A high level of suspicion is required as well as imaging tests to make an early diagnosis and appropriate treatment. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Non-tuberculous mycobacterial infections.

PubMed

Petrini, Björn

2006-01-01

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms in contrast to those belonging to the M. tuberculosi complex (MTB). NTM infects and causes disease only in hosts with local or general predisposing factors. Lung infection following inhalation of NTM is the most common NTM disease but soft tissue infections may occur in connection with contaminated trauma or surgery. Microbiological diagnosis is obtained by microscopy for acid-fast bacteria (AFB) on secretions or biopsies, and by culture on special media. With the high specificity of MTB- polymerase chain reaction (PCR), a positive AFB smear combined with negative MTB-PCR denotes infection with NTM. Sophisticated species diagnosis of cultured NTM is attained by various molecular methods, where 16S rDNA-sequencing remains the gold standard. The panorama of infection with different rapidly growing (RGM) or slowly growing mycobacteria (SGM) in Sweden is described. Sensitivity testing in vitro to antimycobacterial drugs against NTM does not always preclude the in vivo efficacy. Standard antimycobacterial treatment regimens have been defined for infection with several NTM species. Sensitivity testing should be performed in selected cases only, as in case of relapse or suspected development of resistance of the NTM strain. The spectrum of disease caused by NTM species that display a very low pathogenic potential is likely to widen over time as severe immunosuppression will continue to be prevalent in several patient categories.

Abdominal strength in voiding cystometry: a risk factor for recurrent urinary tract infections in women.

PubMed

Salinas, Jesus; Virseda, Miguel; Méndez, Santiago; Menéndez, Pablo; Esteban, Manuel; Moreno, Jesus

2015-12-01

Recurrent urinary tract infections are a common condition in women. The aim of this study is the evaluation of lower urinary tract dysfunctions that are risk factors for recurrent urinary tract infections in women. We conducted a case-control study in 49 women with recurrent urinary tract infections (rUTIs) and 49 control women without rUTIs, comparing the urinary symptoms and urodynamic data of both groups. The main significant differences between these groups were age (the women were older in the control group) and the value of abdominal pressure during voiding cystometry (this was higher in the group with rUTIs). After controlling age as a confounding factor, it was confirmed that the value of maximum abdominal pressure during voiding was the only factor to facilitate the rUTIs and the ideal cut-off was 28 cm H(2)O. Abdominal strength in the voiding phase constitutes a risk factor for recurrent urinary tract infections in women.

Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish

PubMed Central

Hammarén, Milka Marjut; Luukinen, Bruno Vincent; Pesu, Marko; Rämet, Mika; Parikka, Mataleena

2014-01-01

Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease. PMID:24968056

Clinical and scientific importance of source control in abdominal infections: summary of a symposium

PubMed Central

Bohnen, John M.A.; Marshall, John C.; Fry, Donald E.; Johnson, Steven B.; Solomkin, Joseph S.

1999-01-01

In May 1997, a panel of surgeon-investigators met to discuss the clinical importance and research implications of controlling the source of abdominal infections. It was concluded that source control is critical to therapeutic success and that antimicrobial therapy and other adjunctive interventions will fail if the source of infection is not controlled by resection, exteriorization or other means. The panelists presented different definitions of source control, depending on the scientific purpose of the definition. All participants agreed that failure to consider the adequacy of source control of infection has limited the value of most clinical trials of therapeutic anti-infective agents. Besides recognizing source control as an essential goal of patient care, the panelists emphasized the need for further investigative work to define, record and stratify the adequacy of source control in clinical trials of therapeutic agents for abdominal infections. PMID:10223073

Detection and Characterization of Infections and Infection Susceptibility

ClinicalTrials.gov

2018-06-26

Immune Disorders; Chronic Granulomatous Disease; Genetic Immunological Deficiencies; Hyperimmunoglobulin-E Recurrent Infection Syndrome; Recurrent Infections; Unknown Immune Deficiency; GATA2 Deficiency (MonoMAC); Nontuberculous Mycobacterial Infections; Hyper IgE (Job s) Syndrome; Leukocyte Adhesion Deficiency; Susceptibility to Disseminated Infections; Primary Immune Deficiency Disease (PIDD)

Hand Infections

MedlinePlus

... drainage or pus should be sent for laboratory testing to determine the type of bacteria causing the infection and the appropriate antibiotic for treatment. CAUSES Atypical Mycobacterial Infections Rarely, a ...

1 Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes

PubMed Central

Smith, Victoria L.; Jackson, Liam; Schorey, Jeffrey S.

2015-01-01

Exosomes are extracellular vesicles of endocytic origin, which function in intercellular communication. Our previous studies indicate that exosomes released from M. tuberculosis infected macrophages contain soluble mycobacterial proteins. However, it was unclear how these secreted proteins were targeted to exosomes. In this study we determined that exosome production by the murine macrophage cell line RAW264.7 requires the endosomal sorting complexes required for transport (ESCRT) and that trafficking of mycobacterial proteins from phagocytosed bacilli to exosomes was dependent on protein ubiquitination. Moreover, soluble mycobacterial proteins when added exogenously to RAW264.7 or human HEK 293 cells were endocytosed, ubiquitinated and released via exosomes. This suggested that endocytosed proteins could be recycled from cells through exosomes. This hypothesis was supported using the tumor–associated protein He4 which when endocytosed by RAW264.7 or HEK 293 cells was transported to exosomes in an ubiquitin-dependent manner. Our data suggest that ubiquitination is a modification sufficient for trafficking soluble proteins within the phagocytic/endocytic network to exosomes. PMID:26246139

Replacement of the Thoracoabdominal Aorta after Endovascular Abdominal Aneurysm Repair for Ruptured Infected Aneurysm: A Case Report

PubMed Central

Kondo, Nobuo; Tamura, Kentaro; Sakaguchi, Taichi; Chikazawa, Genta; Yoshitaka, Hidenori

2017-01-01

A 73-year-old man underwent emergency endovascular abdominal aneurysm repair (EVAR) for a ruptured infected abdominal aortic aneurysm. Two years after EVAR, he was admitted with a spiking fever and left lower back pain. Computed tomography scan revealed not only recurrent graft infection with psoas abscess but also infection around the orifice of the superior mesenteric artery. Because conservative medical therapy with antibiotics could not control the infection, we performed complete removal of the infected stent graft, debridement of psoas abscess, and in situ replacement of the thoracoabdominal aorta using rifampicin-soaked prosthetic grafts, followed by the omental flap. He was discharged with no complications. PMID:29034025

Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

PubMed

Hawser, Stephen; Hoban, Daryl J; Badal, Robert E; Bouchillon, Samuel K; Biedenbach, Douglas; Hackel, Meredith; Morrissey, Ian

2015-02-01

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.

Risk Assessment of Abdominal Wall Thickness Measured on Pre-Operative Computerized Tomography for Incisional Surgical Site Infection after Abdominal Surgery.

PubMed

Tongyoo, Assanee; Chatthamrak, Putipan; Sriussadaporn, Ekkapak; Limpavitayaporn, Palin; Mingmalairak, Chatchai

2015-07-01

The surgical site infection (SSI) is a common complication of abdominal operation. It relates to increased hospital stay, increased healthcare cost, and decreased patient's quality of life. Obesity, usually defined by BMI, is known as one of the risks of SSI. However, the thickness of subcutaneous layers of abdominal wall might be an important local factor affecting the rate of SSI after the abdominal operations. The objective of this study is to assess the importance of the abdominal wall thickness on incisional SSI rate. The subjects of the present study were patients who had undergone major abdominal operations at Thammasat University Hospital between June 2013 and May 2014, and had been investigated with CT scans before their operations. The demographic data and clinical information of these patients were recorded. The thickness ofsubcutaneous fatty tissue from skin down to the most superficial layer of abdominal wall muscle at the surgical site was measured on CT images. The wound infectious complication was reviewed and categorized as superficial and deep incisional SSIfollowing the definition from Centersfor Disease Control and Prevention (CDC) guidelines. The significance ofeach potentialfactors on SSI rates was determined separately with student t-test for quantitative data and χ2-test for categorical data. Then all factors, which had p < 0.10, were included into the multivariate logistic regression analysis and were analyzed with significance at p < 0.05. One hundred and thirty-nine patients were included in this study. They all underwent major abdominal surgery and had had pre-operative CTscans. Post-operative SSI was 25.2% (35/139), superficial and deep types in 27 and 8 patients, respectively. The comparison of abdominal wall thickness between patients with and without infection was significantly different (20.0 ± 8.4 mm and 16.0 ± 7.2 mm, respectively). When the thickness at 20 mm was used as the cut-off value, 43 of 139 patients had abdominal wall

[Biologics and mycobacterial diseases].

PubMed

Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

PubMed

Sartelli, Massimo; Weber, Dieter G; Ruppé, Etienne; Bassetti, Matteo; Wright, Brian J; Ansaloni, Luca; Catena, Fausto; Coccolini, Federico; Abu-Zidan, Fikri M; Coimbra, Raul; Moore, Ernest E; Moore, Frederick A; Maier, Ronald V; De Waele, Jan J; Kirkpatrick, Andrew W; Griffiths, Ewen A; Eckmann, Christian; Brink, Adrian J; Mazuski, John E; May, Addison K; Sawyer, Rob G; Mertz, Dominik; Montravers, Philippe; Kumar, Anand; Roberts, Jason A; Vincent, Jean-Louis; Watkins, Richard R; Lowman, Warren; Spellberg, Brad; Abbott, Iain J; Adesunkanmi, Abdulrashid Kayode; Al-Dahir, Sara; Al-Hasan, Majdi N; Agresta, Ferdinando; Althani, Asma A; Ansari, Shamshul; Ansumana, Rashid; Augustin, Goran; Bala, Miklosh; Balogh, Zsolt J; Baraket, Oussama; Bhangu, Aneel; Beltrán, Marcelo A; Bernhard, Michael; Biffl, Walter L; Boermeester, Marja A; Brecher, Stephen M; Cherry-Bukowiec, Jill R; Buyne, Otmar R; Cainzos, Miguel A; Cairns, Kelly A; Camacho-Ortiz, Adrian; Chandy, Sujith J; Che Jusoh, Asri; Chichom-Mefire, Alain; Colijn, Caroline; Corcione, Francesco; Cui, Yunfeng; Curcio, Daniel; Delibegovic, Samir; Demetrashvili, Zaza; De Simone, Belinda; Dhingra, Sameer; Diaz, José J; Di Carlo, Isidoro; Dillip, Angel; Di Saverio, Salomone; Doyle, Michael P; Dorj, Gereltuya; Dogjani, Agron; Dupont, Hervé; Eachempati, Soumitra R; Enani, Mushira Abdulaziz; Egiev, Valery N; Elmangory, Mutasim M; Ferrada, Paula; Fitchett, Joseph R; Fraga, Gustavo P; Guessennd, Nathalie; Giamarellou, Helen; Ghnnam, Wagih; Gkiokas, George; Goldberg, Staphanie R; Gomes, Carlos Augusto; Gomi, Harumi; Guzmán-Blanco, Manuel; Haque, Mainul; Hansen, Sonja; Hecker, Andreas; Heizmann, Wolfgang R; Herzog, Torsten; Hodonou, Adrien Montcho; Hong, Suk-Kyung; Kafka-Ritsch, Reinhold; Kaplan, Lewis J; Kapoor, Garima; Karamarkovic, Aleksandar; Kees, Martin G; Kenig, Jakub; Kiguba, Ronald; Kim, Peter K; Kluger, Yoram; Khokha, Vladimir; Koike, Kaoru; Kok, Kenneth Y Y; Kong, Victory; Knox, Matthew C; Inaba, Kenji; Isik, Arda; Iskandar, Katia; Ivatury, Rao R; Labbate, Maurizio; Labricciosa, Francesco M; Laterre, Pierre-François; Latifi, Rifat; Lee, Jae Gil; Lee, Young Ran; Leone, Marc; Leppaniemi, Ari; Li, Yousheng; Liang, Stephen Y; Loho, Tonny; Maegele, Marc; Malama, Sydney; Marei, Hany E; Martin-Loeches, Ignacio; Marwah, Sanjay; Massele, Amos; McFarlane, Michael; Melo, Renato Bessa; Negoi, Ionut; Nicolau, David P; Nord, Carl Erik; Ofori-Asenso, Richard; Omari, AbdelKarim H; Ordonez, Carlos A; Ouadii, Mouaqit; Pereira Júnior, Gerson Alves; Piazza, Diego; Pupelis, Guntars; Rawson, Timothy Miles; Rems, Miran; Rizoli, Sandro; Rocha, Claudio; Sakakushev, Boris; Sanchez-Garcia, Miguel; Sato, Norio; Segovia Lohse, Helmut A; Sganga, Gabriele; Siribumrungwong, Boonying; Shelat, Vishal G; Soreide, Kjetil; Soto, Rodolfo; Talving, Peep; Tilsed, Jonathan V; Timsit, Jean-Francois; Trueba, Gabriel; Trung, Ngo Tat; Ulrych, Jan; van Goor, Harry; Vereczkei, Andras; Vohra, Ravinder S; Wani, Imtiaz; Uhl, Waldemar; Xiao, Yonghong; Yuan, Kuo-Ching; Zachariah, Sanoop K; Zahar, Jean-Ralph; Zakrison, Tanya L; Corcione, Antonio; Melotti, Rita M; Viscoli, Claudio; Viale, Perluigi

2016-01-01

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Comparison of prosthetic materials for abdominal wall reconstruction in the presence of contamination and infection.

PubMed Central

Brown, G L; Richardson, J D; Malangoni, M A; Tobin, G R; Ackerman, D; Polk, H C

1985-01-01

Abdominal wall defects resulting from trauma, invasive infection, or hernia present a difficult problem for the surgeon. In order to study the problems associated with the prosthetic materials used for abdominal wall reconstruction, an animal model was used to simulate abdominal wall defects in the presence of peritonitis and invasive infection. One hundred guinea pigs were repaired with either polytetrafluorethylene (PTFE) or polypropylene mesh (PPM). Our experiments included intra-operative contamination with Staphylococcus aureus. We found significantly fewer organisms (p less than 0.05) adherent to the PTFE than to the PPM when antibiotics were administered after surgery, as well as when no antibiotics were given. In the presence of peritonitis, we found no real difference in numbers of intraperitoneal bacteria present whether PTFE or PPM was used. In all instances, the PTFE patches produced fewer adhesions and were more easily removed. From these experiments, it appears that PTFE may be associated with fewer problems than PPM in the presence of contamination and infection. Images FIG. 1. PMID:3159353

Reconstruction of Abdominal Wall of a Chronically Infected Postoperative Wound with a Rectus Abdominis Myofascial Splitting Flap

PubMed Central

Bae, Sung Kyu; Kang, Seok Joo; Kim, Jin Woo; Kim, Young Hwan

2013-01-01

Background If a chronically infected abdominal wound develops, complications such as peritonitis and an abdominal wall defect could occur. This could prolong the patient's hospital stay and increase the possibility of re-operation or another infection as well. For this reason, a solution for infection control is necessary. In this study, surgery using a rectus abdominis muscle myofascial splitting flap was performed on an abdominal wall defect. Methods From 2009 to 2012, 5 patients who underwent surgery due to ovarian rupture, cesarean section, or uterine myoma were chosen. In each case, during the first week after operation, the wound showed signs of infection. Surgery was chosen because the wounds did not resolve with dressing. Debridement was performed along the previous operation wound and dissection of the skin was performed to separate the skin and subcutaneous tissue from the attenuated rectus muscle and Scarpa's fascial layers. Once the anterior rectus sheath and muscle were adequately mobilized, the fascia and muscle flap were advanced medially so that the skin defect could be covered for reconstruction. Results Upon 3-week follow-up after a rectus abdominis myofascial splitting flap operation, no major complication occurred. In addition, all of the patients showed satisfaction in terms of function and esthetics at 3 to 6 months post-surgery. Conclusions Using a rectus abdominis myofascial splitting flap has many esthetic and functional benefits over previous methods of abdominal defect treatment, and notably, it enabled infection control by reconstruction using muscle. PMID:23362477

Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents.

PubMed

Garg, Gaurav; Pande, Milind; Agrawal, Ambika; Li, Jie; Kumar, Rakesh

2016-04-15

In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Abdominal wall reconstruction following removal of a chronically infected mid-urethral tape.

PubMed

Walker, Helen; Brooker, Thomas; Gelman, Wolf

2009-10-01

We report a rare postoperative complication of a mid-urethral tape. The patient presented with a chronic infection resistant to treatment with several weeks of antibiotics, with eventual surgical removal, and the resulting complications of an infected incisional hernia and vesico-cutaneous fistula required reconstruction of the abdominal wall with Permacol and excision of the vesico-cutaneous fistula. We also look briefly at the impact of health tourism on the National Health Service.

The Child with Recurrent Mycobacterial Disease.

PubMed

Reed, Brian; Dolen, William K

2018-06-23

Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1. Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations. If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation.

Mycobacterial biomaterials and resources for researchers.

PubMed

Hazbón, Manzour Hernando; Rigouts, Leen; Schito, Marco; Ezewudo, Matthew; Kudo, Takuji; Itoh, Takashi; Ohkuma, Moriya; Kiss, Katalin; Wu, Linhuan; Ma, Juncai; Hamada, Moriyuki; Strong, Michael; Salfinger, Max; Daley, Charles L; Nick, Jerry A; Lee, Jung-Sook; Rastogi, Nalin; Couvin, David; Hurtado-Ortiz, Raquel; Bizet, Chantal; Suresh, Anita; Rodwell, Timothy; Albertini, Audrey; Lacourciere, Karen A; Deheer-Graham, Ana; Alexander, Sarah; Russell, Julie E; Bradford, Rebecca; Riojas, Marco A

2018-06-01

There are many resources available to mycobacterial researchers, including culture collections around the world that distribute biomaterials to the general scientific community, genomic and clinical databases, and powerful bioinformatics tools. However, many of these resources may be unknown to the research community. This review article aims to summarize and publicize many of these resources, thus strengthening the quality and reproducibility of mycobacterial research by providing the scientific community access to authenticated and quality-controlled biomaterials and a wealth of information, analytical tools and research opportunities.

Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research.

PubMed

Dedieu, L; Serveau-Avesque, C; Kremer, L; Canaan, S

2013-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide with a strong impact in developing countries. Mycobacterium tuberculosis, the etiological agent of TB, has a high capacity to evade the host immune system and establish a chronic, asymptomatic and latent infection. In a latent TB infection, persistent bacilli are present in a non-replicating dormant state within host granulomas. During reactivation, bacilli start replicating again leading to an active TB infection that can be highly contagious. Mycobacterial lipids and lipolytic enzymes are thought to play important physiological roles during dormancy and reactivation. The role of lipolytic enzymes in the physiology of M. tuberculosis and physiopathology of the disease will be discussed in this review, with an emphasis on the secreted or cell wall-associated, surface exposed lipolytic enzymes characterized to date. Studies on the localization, enzymatic activity and immunological properties of these enzymes highlighted their possible usefulness as new diagnostic markers in the fight against TB. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Abdominal Sepsis.

PubMed

De Waele, Jan J

2016-08-01

Abdominal infections are an important challenge for the intensive care physician. In an era of increasing antimicrobial resistance, selecting the appropriate regimen is important and, with new drugs coming to the market, correct use is important more than ever before and abdominal infections are an excellent target for antimicrobial stewardship programs. Biomarkers may be helpful, but their exact role in managing abdominal infections remains incompletely understood. Source control also remains an ongoing conundrum, and evidence is increasing that its importance supersedes the impact of antibiotic therapy. New strategies such as open abdomen management may offer added benefit in severely ill patients, but more data are needed to identify its exact role. The role of fungi and the need for antifungal coverage, on the other hand, have been investigated extensively in recent years, but at this point, it remains unclear who requires empirical as well as directed therapy.

Intra-abdominal infection combined with intra-abdominal hypertension aggravates the intestinal mucosal barrier dysfunction.

PubMed

Li, Yuan; Ren, Jianan; Wu, Xiuwen; Li, Jieshou

2018-02-28

Some patients with intra-abdominal infection (IAI) may develop intra-abdominal hypertension (IAH) during treatment. The present study investigated the impact of IAI combined with IAH on the intestinal mucosal barrier in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups: (i) IAI and IAH; (ii) IAI alone; (iii) IAH alone; and (iv) Control group. IAI model: cecal ligation and puncture for 48 h; IAH model: raised intra-abdominal pressure (IAP) of 20 mmHg for 4 h. Pathological changes in intestinal mucosa were confirmed by light and scanning electron microscopy. FITC-conjugated dextran (FITC-dextran) by gavage was used to measure intestinal mucosal permeability in plasma. Endotoxin, d-Lactate, and diamine oxidase (DAO) in plasma were measured to determine intestinal mucosal damage. Malonaldehyde (MDA), superoxide dismutase (SOD), and GSH in ileum tissues were measured to evaluate intestinal mucosal oxidation and reducing state. Histopathologic scores were significantly higher in the IAI and IAH group, followed by IAI alone, IAH alone, and the control group. FITC-dextran, d-Lactate, DAO, and endotoxin in plasma and MDA in ileum tissues had similar trends. GSH and SOD were significantly lowest the in IAI and IAH group. Occludin levels were lowest in the ileums of the IAI and IAH group. All differences were statistically significant ( P -values <0.001). IAI combined with IAH aggravates damage of the intestinal mucosal barrier in a rabbit model. The combined effects were significantly more severe compared with a single factor. IAI combined with IAH should be prevented and treated effectively. © 2018 The Author(s).

Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

PubMed

Reavill, Drury R; Schmidt, Robert E

2012-01-01

Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

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.

Distinguishing infected from noninfected abdominal fluid collections after surgery: an imaging, clinical, and laboratory-based scoring system.

PubMed

Gnannt, Ralph; Fischer, Michael A; Baechler, Thomas; Clavien, Pierre-Alain; Karlo, Christoph; Seifert, Burkhardt; Lesurtel, Mickael; Alkadhi, Hatem

2015-01-01

Mortality from abdominal abscesses ranges from 30% in treated cases up to 80% to 100% in patients with undrained or nonoperated abscesses. Various computed tomographic (CT) imaging features have been suggested to indicate infection of postoperative abdominal fluid collections; however, features are nonspecific and substantial overlap between infected and noninfected collections exists. The purpose of this study was to develop and validate a scoring system on the basis of CT imaging findings as well as laboratory and clinical parameters for distinguishing infected from noninfected abdominal fluid collections after surgery. The score developmental cohort included 100 consecutive patients (69 men, 31 women; mean age, 58 ± 17 years) who underwent portal-venous phase CT within 24 hours before CT-guided intervention of postoperative abdominal fluid collections. Imaging features included attenuation (Hounsfield unit [HU]), volume, wall enhancement and thickness, fat stranding, as well as entrapped gas of fluid collections. Laboratory and clinical parameters included diabetes, intake of immunosuppressive drugs, body temperature, C-reactive protein, and leukocyte blood cell count. The score was validated in a separate cohort of 30 consecutive patients (17 men, 13 women; mean age, 51 ± 15 years) with postoperative abdominal fluid collections. Microbiologic analysis from fluid samples served as the standard of reference. Diabetes, body temperature, C-reactive protein, attenuation of the fluid collection (in HUs), wall enhancement and thickness of the wall, adjacent fat stranding, as well as entrapped gas within the fluid collection were significantly different between infected and noninfected collections (P < 0.001). Multiple logistic regression analysis revealed diabetes, C-reactive protein, attenuation of the fluid collection (in HUs), as well as entrapped gas as significant independent predictors of infection (P < 0.001) and thus was selected for constructing a scoring

Susceptibility to mycobacterial disease due to mutations in IL-12Rβ1 in three Iranian patients.

PubMed

Alinejad Dizaj, Maryam; Mortaz, Esmaeil; Mahdaviani, Seyed Alireza; Mansouri, Davood; Mehrian, Payam; Verhard, Els M; Varahram, Mohammad; Babaie, Delara; Adcock, Ian M; Garssen, Johan; van de Vosse, Esther; Velayati, Aliakbar

2018-06-01

In the last decade, autosomal recessive interleukin-12 receptor β1 (IL-12Rβ1) deficiency, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), has been diagnosed in a few children and adults with severe tuberculosis in Iran. Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rβ1 but with different clinical manifestations. All three were homozygous for either an IL-12Rβ1 missense or nonsense mutation that caused the IL-12Rβ1 protein not to be expressed on the cell membrane and completely abolished the cellular response to recombinant IL-12. Our findings suggest that the presence of IL-12Rβ1 deficiency should be determined in children with mycobacterial infections at least in countries with a high prevalence of parental consanguinity and in areas endemic for TB like Iran.

The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States

PubMed Central

Strollo, Sara E.; Adjemian, Jennifer; Adjemian, Michael K.

2015-01-01

Rationale: State-specific case numbers and costs are critical for quantifying the burden of pulmonary nontuberculous mycobacterial disease in the United States. Objectives: To estimate and project national and state annual cases of nontuberculous mycobacterial disease and associated direct medical costs. Methods: Available direct cost estimates of nontuberculous mycobacterial disease medical encounters were applied to nontuberculous mycobacterial disease prevalence estimates derived from Medicare beneficiary data (2003–2007). Prevalence was adjusted for International Classification of Diseases, 9th Revision, undercoding and the inclusion of persons younger than 65 years of age. U.S. Census Bureau data identified 2010 and 2014 population counts and 2012 primary insurance-type distribution. Medical costs were reported in constant 2014 dollars. Projected 2014 estimates were adjusted for population growth and assumed a previously published 8% annual growth rate of nontuberculous mycobacterial disease prevalence. Measurements and Main Results: In 2010, we estimated 86,244 national cases, totaling to $815 million, of which 87% were inpatient related ($709 million) and 13% were outpatient related ($106 million). Annual state estimates varied from 48 to 12,544 cases ($503,000–$111 million), with a median of 1,208 cases ($11.5 million). Oceanic coastline states and Gulf States comprised 70% of nontuberculous mycobacterial disease cases but 60% of the U.S. population. Medical encounters among individuals aged 65 years and older ($562 million) were twofold higher than those younger than 65 years of age ($253 million). Of all costs incurred, medications comprised 76% of nontuberculous mycobacterial disease expenditures. Projected 2014 estimates resulted in 181,037 national annual cases ($1.7 billion). Conclusions: For a relatively rare disease, the financial cost of nontuberculous mycobacterial disease is substantial, particularly among older adults. Better data on disease

The assessment of changes to the nontuberculous mycobacterial metabolome in response to anti-TB drugs.

PubMed

Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

2018-06-26

Mycobacterium species can cause a range of nontuberculous infections of healthy and immunocompromised people as well as infect people during and after surgical procedures. The similarity of nontuberculous mycobacteria (NTM) to the tuberculosis bacilli (TB) could ultimately enable the use of anti-TB drugs for the genus. Hence, three NTM (M. smegmatis, M. phlei and M. avium) were cultured under different lab conditions, causing two mycobacterial phenotypes (active and dormant), and treated with isoniazid (INH) and ethambutol (EMB) independently or in combination. Metabolite profiling was applied to facilitate the investigation and characterisation of intracellular targets affected by the antibiotics. Aliquots of the cell culture were taken over the treatment period and the metabolite profile of the cells analysed by GC/MS. Comparative analysis of the metabolite levels to untreated mycobacteria confirmed the successful action of the antibiotics on the metabolism of all three species. Furthermore, single metabolites and metabolite pathways affected by the antibiotics could be identified and included, besides the known target sites for INH and EMB on mycobacterial cells, changes in e.g. nucleotide and saccharide levels. The combined treatment highlighted the property of EMB to enhance the effects of INH even under hypoxic culture conditions.

[Septic shock due to community-acquired complicated intra-abdominal infection treated with ertapenem: outcome in 25 cases].

PubMed

Maseda, E; Lillo, M; Fernández, L; Villagrán, M J; Gómez-Rice, A; Ramasco, F

2008-04-01

To assess the effectiveness of ertapenem in patients admitted to a surgical intensive care unit with septic shock due to community-acquired complicated intra-abdominal infection. Patients undergoing emergency surgery for community-acquired complicated intra-abdominal infection were enrolled prospectively. All patients were given intravenous ertapenem at a rate of 1 g/24 h and the guidelines of the Surviving Sepsis Campaign were applied. Outcome measures were duration of antibiotic therapy, mean length of stay in the surgical intensive care unit (ICU), antibiotic failure, and death while in the surgical ICU. Twenty-five patients with a mean (SD) age of 74 (14) years were enrolled. The origin of infection was the colon in 56% of the cases; most patients (76%) had generalized peritonitis. The mean stay in the surgical ICU was 10 (7) days. The mean duration of antibiotic therapy was 5.8 (1.26) days. Antibiotic failure occurred in 12%. Mortality in the surgical ICU was 28%. Our findings suggest that patients with community-acquired intra-abdominal infection and septic shock have a good chance of survival when treated according to the guidelines of the Surviving Sepsis Campaign. Ertapenem seems to give good results when used in this setting.

Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

PubMed

Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

2015-12-01

Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Over-Expression of the Mycobacterial Trehalose-Phosphate Phosphatase OtsB2 Results in a Defect in Macrophage Phagocytosis Associated with Increased Mycobacterial-Macrophage Adhesion

PubMed Central

Li, Hao; Wu, Mei; Shi, Yan; Javid, Babak

2016-01-01

Trehalose-6-phosphate phosphatase (OtsB2) is involved in the OtsAB trehalose synthesis pathway to produce free trehalose and is strictly essential for mycobacterial growth. We wished to determine the effects of OtsB2 expression on mycobacterial phenotypes such as growth, phagocytosis and survival in macrophages. Mycobacterium bovis-bacillus calmette-guerin (BCG) over-expressing OtsB2 were able to better survive in stationary phase. Over-expression of OtsB2 led to a decrease in phagocytosis but not survival in THP-1 macrophage-like cells, and this was not due to a decrease in general macrophage phagocytic activity. Surprisingly, when we investigated macrophage–mycobacterial interactions by flow cytometry and atomic force microscopy, we discovered that BCG over-expressing OtsB2 have stronger binding to THP-1 cells than wild-type BCG. These results suggest that altering OtsB2 expression has implications for mycobacterial host–pathogen interactions. Macrophage–mycobacteria phagocytic interactions are complex and merit further study. PMID:27867377

Animal Models of Mycobacteria Infection

PubMed Central

Ordway, Diane J.; Orme, Ian M.

2011-01-01

This unit describes the infection of mice and guinea pigs with mycobacteria via various routes, as well as necropsy methods for the determination of mycobacterial loads within target organs. Additionally, methods for cultivating mycobacteria and preparing stocks are described. The protocols outlined are primarily used for M. tuberculosis, but can also be used for the study of other non-tuberculosis mycobacterial species. PMID:18432756

Post-translational Acetylation of MbtA Modulates Mycobacterial Siderophore Biosynthesis*

PubMed Central

Vergnolle, Olivia; Xu, Hua; Tufariello, JoAnn M.; Favrot, Lorenza; Malek, Adel A.; Jacobs, William R.; Blanchard, John S.

2016-01-01

Iron is an essential element for life, but its soluble form is scarce in the environment and is rarer in the human body. Mtb (Mycobacterium tuberculosis) produces two aryl-capped siderophores, mycobactin (MBT) and carboxymycobactin (cMBT), to chelate intracellular iron. The adenylating enzyme MbtA catalyzes the first step of mycobactin biosynthesis in two half-reactions: activation of the salicylic acid as an acyl-adenylate and ligation onto the acyl carrier protein (ACP) domain of MbtB to form covalently salicylated MbtB-ACP. We report the first apo-MbtA structure from Mycobacterium smegmatis at 2.3 Å. We demonstrate here that MbtA activity can be reversibly, post-translationally regulated by acetylation. Indeed the mycobacterial Pat (protein lysine acetyltransferase), Rv0998, specifically acetylates MbtA on lysine 546, in a cAMP-dependent manner, leading to enzyme inhibition. MbtA acetylation can be reversed by the NAD+-dependent DAc (deacetyltransferase), Rv1151c. Deletion of Pat and DAc genes in Mtb revealed distinct phenotypes for strains lacking one or the other gene at low pH and limiting iron conditions. This study establishes a direct connection between the reversible acetylation system Pat/DAc and the ability of Mtb to adapt in limited iron conditions, which is critical for mycobacterial infection. PMID:27566542

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.

[Reccurent mycobacterial diseases in patients with impaired axis IL-12/INF-gamma].

PubMed

Strach, Magdalena; Nalepa, Piotr; Sulicka-Grodzicka, Joanna; Kierzkowska, Izabella; Siedlar, Maciej; Grodzicki, Tomasz

2013-01-01

Mycobacteria is a large group of pathogens that are common in environment, in soil and tap water. Although mycobacteria [non tuberculosis mycobacteria] can inhabit body surface without causing any disease in the circumstances of primary or secondary immunodeficiency can cause clinically significant organ or systemic damage. Defect of IL-12/INFgamma axis is an example of primary immunodeficiency that predispose to mycobacterial infections while protection against other microorganisms is not damaged. We present review of known defects of IL-12/IFNgamma axis and brief presentation of our own experience.

Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective

PubMed Central

Kurup, Asok; Liau, Kui-Hin; Ren, Jianan; Lu, Min-Chi; Navarro, Narciso S.; Farooka, Muhammad Waris; Usman, Nurhayat; Destura, Raul V.; Sirichindakul, Boonchoo; Tantawichien, Terapong; Lee, Christopher K.C.; Solomkin, Joseph S.

2014-01-01

Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs. PMID:25568794

Introducing the new BTS Guideline: Management of non-tuberculous mycobacterial pulmonary disease (NTM-PD).

PubMed

Haworth, Charles S; Floto, R Andres

2017-11-01

The new BTS Guidelines for the management of non-tuberculous mycobacterial pulmonary disease combine the best available evidence with expert consensus to generate a set of pragmatic Guidelines, published as a supplement to this issue of Thorax, to assist in the management of these challenging infections. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway

PubMed Central

Lee, Wook-Bin; Kang, Ji-Seon; Yan, Ji-Jing; Lee, Myeong Sup; Jeon, Bo-Young; Cho, Sang-Nae; Kim, Young-Joon

2012-01-01

Trehalose 6,6′-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle−/− mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti-mycobacterial

Extracellular Vesicles Released from Mycobacterium tuberculosis-Infected Neutrophils Promote Macrophage Autophagy and Decrease Intracellular Mycobacterial Survival

PubMed Central

Alvarez-Jiménez, Violeta D.; Leyva-Paredes, Kahiry; García-Martínez, Mariano; Vázquez-Flores, Luis; García-Paredes, Víctor Gabriel; Campillo-Navarro, Marcia; Romo-Cruz, Israel; Rosales-García, Víctor Hugo; Castañeda-Casimiro, Jessica; González-Pozos, Sirenia; Hernández, José Manuel; Wong-Baeza, Carlos; García-Pérez, Blanca Estela; Ortiz-Navarrete, Vianney; Estrada-Parra, Sergio; Serafín-López, Jeanet; Wong-Baeza, Isabel; Chacón-Salinas, Rommel; Estrada-García, Iris

2018-01-01

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100–1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication. We previously demonstrated that human neutrophils infected in vitro with Mtb H37Rv release EVs (EV-TB), but the effect of these EVs on other cells relevant for the control of Mtb infection, such as macrophages, has not been completely analyzed. In this study, we characterized the EVs produced by non-stimulated human neutrophils (EV-NS), and the EVs produced by neutrophils stimulated with an activator (PMA), a peptide derived from bacterial proteins (fMLF) or Mtb, and observed that the four EVs differed in their size. Ligands for toll-like receptor (TLR) 2/6 were detected in EV-TB, and these EVs favored a modest increase in the expression of the co-stimulatory molecules CD80, a higher expression of CD86, and the production of higher amounts of TNF-α and IL-6, and of lower amounts of TGF-β, in autologous human macrophages, compared with the other EVs. EV-TB reduced the amount of intracellular Mtb in macrophages, and increased superoxide anion production in these cells. TLR2/6 ligation and superoxide anion production are known inducers of autophagy; accordingly, we found that EV-TB induced higher expression of the autophagy-related marker LC3-II in macrophages, and the co-localization of LC3-II with Mtb inside infected macrophages. The intracellular mycobacterial load increased when autophagy was inhibited with

Extracellular Vesicles Released from Mycobacterium tuberculosis-Infected Neutrophils Promote Macrophage Autophagy and Decrease Intracellular Mycobacterial Survival.

PubMed

Alvarez-Jiménez, Violeta D; Leyva-Paredes, Kahiry; García-Martínez, Mariano; Vázquez-Flores, Luis; García-Paredes, Víctor Gabriel; Campillo-Navarro, Marcia; Romo-Cruz, Israel; Rosales-García, Víctor Hugo; Castañeda-Casimiro, Jessica; González-Pozos, Sirenia; Hernández, José Manuel; Wong-Baeza, Carlos; García-Pérez, Blanca Estela; Ortiz-Navarrete, Vianney; Estrada-Parra, Sergio; Serafín-López, Jeanet; Wong-Baeza, Isabel; Chacón-Salinas, Rommel; Estrada-García, Iris

2018-01-01

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication. We previously demonstrated that human neutrophils infected in vitro with Mtb H37Rv release EVs (EV-TB), but the effect of these EVs on other cells relevant for the control of Mtb infection, such as macrophages, has not been completely analyzed. In this study, we characterized the EVs produced by non-stimulated human neutrophils (EV-NS), and the EVs produced by neutrophils stimulated with an activator (PMA), a peptide derived from bacterial proteins (fMLF) or Mtb, and observed that the four EVs differed in their size. Ligands for toll-like receptor (TLR) 2/6 were detected in EV-TB, and these EVs favored a modest increase in the expression of the co-stimulatory molecules CD80, a higher expression of CD86, and the production of higher amounts of TNF-α and IL-6, and of lower amounts of TGF-β, in autologous human macrophages, compared with the other EVs. EV-TB reduced the amount of intracellular Mtb in macrophages, and increased superoxide anion production in these cells. TLR2/6 ligation and superoxide anion production are known inducers of autophagy; accordingly, we found that EV-TB induced higher expression of the autophagy-related marker LC3-II in macrophages, and the co-localization of LC3-II with Mtb inside infected macrophages. The intracellular mycobacterial load increased when autophagy was inhibited with wortmannin

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

Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

PubMed

Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

2015-05-01

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference.

PubMed

Sartelli, Massimo; Catena, Fausto; Abu-Zidan, Fikri M; Ansaloni, Luca; Biffl, Walter L; Boermeester, Marja A; Ceresoli, Marco; Chiara, Osvaldo; Coccolini, Federico; De Waele, Jan J; Di Saverio, Salomone; Eckmann, Christian; Fraga, Gustavo P; Giannella, Maddalena; Girardis, Massimo; Griffiths, Ewen A; Kashuk, Jeffry; Kirkpatrick, Andrew W; Khokha, Vladimir; Kluger, Yoram; Labricciosa, Francesco M; Leppaniemi, Ari; Maier, Ronald V; May, Addison K; Malangoni, Mark; Martin-Loeches, Ignacio; Mazuski, John; Montravers, Philippe; Peitzman, Andrew; Pereira, Bruno M; Reis, Tarcisio; Sakakushev, Boris; Sganga, Gabriele; Soreide, Kjetil; Sugrue, Michael; Ulrych, Jan; Vincent, Jean-Louis; Viale, Pierluigi; Moore, Ernest E

2017-01-01

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.

Post-translational Acetylation of MbtA Modulates Mycobacterial Siderophore Biosynthesis.

PubMed

Vergnolle, Olivia; Xu, Hua; Tufariello, JoAnn M; Favrot, Lorenza; Malek, Adel A; Jacobs, William R; Blanchard, John S

2016-10-14

Iron is an essential element for life, but its soluble form is scarce in the environment and is rarer in the human body. Mtb (Mycobacterium tuberculosis) produces two aryl-capped siderophores, mycobactin (MBT) and carboxymycobactin (cMBT), to chelate intracellular iron. The adenylating enzyme MbtA catalyzes the first step of mycobactin biosynthesis in two half-reactions: activation of the salicylic acid as an acyl-adenylate and ligation onto the acyl carrier protein (ACP) domain of MbtB to form covalently salicylated MbtB-ACP. We report the first apo-MbtA structure from Mycobacterium smegmatis at 2.3 Å. We demonstrate here that MbtA activity can be reversibly, post-translationally regulated by acetylation. Indeed the mycobacterial Pat (protein lysine acetyltransferase), Rv0998, specifically acetylates MbtA on lysine 546, in a cAMP-dependent manner, leading to enzyme inhibition. MbtA acetylation can be reversed by the NAD + -dependent DAc (deacetyltransferase), Rv1151c. Deletion of Pat and DAc genes in Mtb revealed distinct phenotypes for strains lacking one or the other gene at low pH and limiting iron conditions. This study establishes a direct connection between the reversible acetylation system Pat/DAc and the ability of Mtb to adapt in limited iron conditions, which is critical for mycobacterial infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of bovine gamma delta T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. Gamma delta T cells are known to participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector p...

Epidemiology of Nontuberculous Mycobacterial Lung Disease and Tuberculosis, Hawaii, USA.

PubMed

Adjemian, Jennifer; Frankland, Timothy B; Daida, Yihe G; Honda, Jennifer R; Olivier, Kenneth N; Zelazny, Adrian; Honda, Stacey; Prevots, D Rebecca

2017-03-01

Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005-2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2-3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility.

Anti-mycobacterial peptides: made to order with delivery included.

PubMed

Carroll, James; O' Mahony, Jim

2011-01-01

"TB is too often a death sentence. It does not have to be this way,"- Nelson Mandela. Despite the success of anti-mycobacterial drugs over the past 70 years, mycobacterial disease, particularly tuberculosis is still responsible for millions of annual deaths worldwide. Additionally, the emergence of Multidrug Resistant (MDR-TB) and Extensively Drug Resistant (XDR-TB) Tuberculosis has motivated calls by the World Health Organization (WHO) for novel drugs, vaccines and diagnostic tests. Consequently, the identification and evaluation of a range of anti-mycobacterial compounds against pathogenic mycobacterial species is of paramount importance. My colleagues and I at Cork Institute of Technology (CIT) and University College Cork (UCC) have tackled this issue through the initial optimization of the rapid, robust and inexpensive microtitre alamarBlue assay (MABA) and subsequent employment of this assay to facilitate the rapid assessment of a new wave of potential therapeutic compounds, namely bacteriocins, in particular type 1 bacteriocins known as lantibiotics. The gene encoded nature of these peptides facilitates their genetic manipulation and consequent activities as anti-microbial agents. In this regard, it may be possible to one day develop diverse populations of anti-mycobacterial bacteriocins with species specific activities. This may in turn provide more targeted therapies, resulting in less side effects, shorter treatment times and thus better patient compliance. Although current drug regimes are effective in the interim, previous lessons have taught us not to be complacent. In the words of the Intel founder Andrew Grove, 'Success breeds complacency. Complacency breeds failure. Only the paranoid survive'. Armed with knowledge of previous failures, it is the duty of the scientific community to anticipate future bacterial resistance and have an arsenal of compounds standing by in such an eventuality.

Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape

PubMed Central

Lapierre, Pascal; Mir, Mushtaq; Chase, Michael R.; Pyle, Margaret M.; Gawande, Richa; Ahmad, Rushdy; Sarracino, David A.; Ioerger, Thomas R.; Fortune, Sarah M.; Derbyshire, Keith M.; Wade, Joseph T.; Gray, Todd A.

2015-01-01

RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS) mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5’ untranslated region (UTR) and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5’ end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5’ ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5’ UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression. PMID:26536359

Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

PubMed

Shell, Scarlet S; Wang, Jing; Lapierre, Pascal; Mir, Mushtaq; Chase, Michael R; Pyle, Margaret M; Gawande, Richa; Ahmad, Rushdy; Sarracino, David A; Ioerger, Thomas R; Fortune, Sarah M; Derbyshire, Keith M; Wade, Joseph T; Gray, Todd A

2015-11-01

RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS) mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR) and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.

Abdominal Wall Endometriosis Mimicking Metastases.

PubMed

Nambiar, Rakul; Anoop, T M; Mony, Rari P

2018-06-01

Abdominal wall lesions can be broadly divided into nontumorous and tumorous conditions. Nontumorous lesions include congenital lesion, abdominal wall hernia, inflammation and infection, vascular lesions, and miscellaneous conditions like hematoma. Tumorous lesions include benign and malignant neoplasms. Here, we report an unusual case of abdominal wall endometriosis mimicking metastases in a patient with breast carcinoma.

Whole genome sequencing reveals mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients.

PubMed

Ssengooba, Willy; de Jong, Bouke C; Joloba, Moses L; Cobelens, Frank G; Meehan, Conor J

2016-08-05

In the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments. From a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis. Of the 25 concordant pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16-101)/mm(3) and ten (77 %) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution. Using a phylogenetic approach to identify the ancestral compartment, in two (15 %) patients the blood isolate was ancestral to the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs were identical. Among HIV-infected patients with poor cellular immunity, infection with multiple strains of M. tuberculosis was found in half of the patients. In those patients with identical strains, whole genome sequencing indicated that M. tuberculosis intra-patient microevolution does occur in a few patients, yet did not reveal a consistent direction of spread between sputum and blood. This suggests that these compartments are highly connected and potentially seed each other repeatedly.

Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

PubMed Central

Taus, Francesco; Santucci, Marilina B.; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

2015-01-01

A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

Inhibitors Selective for Mycobacterial Versus Human Proteasomes

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

Lin, G.; Li, D; Sorio de Carvalho, L

Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-onemore » compounds kill non-replicating M.?tuberculosis and act as selective suicide-substrate inhibitors of the M.?tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.« less

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

Recurrent mycobacterial osteomyelitis. Report of a case due to Mycobacterium avium-intracellulare-scrofulaceum complex and BCG vaccination.

PubMed

Solheim, L F; Kjelsberg, F

1982-01-01

A 28-year-old man suffering from recurrent mycobacterial osteomyelitis during several years is reported. Eight years old he had a Mycobacterium scrofulaceum infection in his right calcaneus. A serious infection with multiple foci of osteomyelitis occurred after BCG vaccination at the age of 14 years and 11 years later multifocal lesions of osteomyelitis due to Mycobacterium avium-intracellulare-scrofulaceum complex appeared. The special clinical problems due to the relative or complete resistence of these organisms to antituberculous drugs are emphasized. The mainstays of treatment are surgical revision and drainage with prolonged and intensive multiple drug therapy.

New Targets and Inhibitors of Mycobacterial Sulfur Metabolism§

PubMed Central

Paritala, Hanumantharao; Carroll, Kate S.

2015-01-01

The identification of new antibacterial targets is urgently needed to address multidrug resistant and latent tuberculosis infection. Sulfur metabolic pathways are essential for survival and the expression of virulence in many pathogenic bacteria, including Mycobacterium tuberculosis. In addition, microbial sulfur metabolic pathways are largely absent in humans and therefore, represent unique targets for therapeutic intervention. In this review, we summarize our current understanding of the enzymes associated with the production of sulfated and reduced sulfur-containing metabolites in Mycobacteria. Small molecule inhibitors of these catalysts represent valuable chemical tools that can be used to investigate the role of sulfur metabolism throughout the Mycobacterial lifecycle and may also represent new leads for drug development. In this light, we also summarize recent progress made in the development of inhibitors of sulfur metabolism enzymes. PMID:23808874

Effect of major abdominal surgery on the host immune response to infection.

PubMed

Buttenschoen, Klaus; Fathimani, Kamran; Buttenschoen, Daniela Carli

2010-06-01

The present review summarizes key studies on the effects of major abdominal surgery on the host response to infection published during the last 18 months. Surgical trauma causes stereotyped systemic proinflammatory and compensatory anti-inflammatory reactions. It is leukocyte reprogramming rather than general immune suppression. The list of recent findings is long. Preoperative infectious challenge was found to increase survival. Obesity is associated with increased production of interleukin-17A in peritonitis. Abdominal surgery alters expression of toll-like receptors (TLRs). The acute phase reaction down-regulates the transcription factor carbohydrate response element binding protein. Myosin light chain kinase activation is a final pathway of acute tight junction regulation of gut barrier and zonula occludens 1 protein is an essential effector. The brain is involved in regulating the immune and gut system. Elimination of lipopolysaccharide is challenging. Th1/Th2 ratio is lowered in patients with postoperative complications. Cholinergic anti-inflammatory pathways can inhibit tissue damage. The new substance PXL01 prevents adhesions. Postoperative infection causes incisional hernias. Hypothermia reduced human leukocyte antigen DR surface expression and delayed tumor necrosis factor clearance. Systems biology identified interferon regulatory factor 3 as the negative regulator of TLR signaling. Protective immunity could contribute defeating surgical infections. Systemic inflammation is the usual response to trauma. All organs seem to be involved and linked up in cybernetic systems aiming at reconstitution of homeostasis. Although knowledge is still fragmentary, it is already difficult to integrate known facts and new technologies are required for information processing. Defining criteria to develop therapeutic strategies requires much more insight into molecular mechanisms and cybernetics of organ systems.

Prophylactic antibiotics for penetrating abdominal trauma.

PubMed

Brand, Martin; Grieve, Andrew

2013-11-18

Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no

Acid-fast bacilli culture positivity and drug resistance in abdominal tuberculosis in Mumbai, India.

PubMed

Samant, Hrishikesh; Desai, Devendra; Abraham, Philip; Joshi, Anand; Gupta, Tarun; Rodrigues, Camilla; George, Siji

2014-09-01

Culture positivity for Mycobacterium tuberculosis complex (MTB) in abdominal tuberculosis (TB) using Lowenstein Jensen medium and Bactec system varies from 25 % to 36 %. Data on the prevalence of drug resistance in primary abdominal TB is scant. Our aim was to study the acid-fast bacilli (AFB) culture positivity rate in primary abdominal TB using Bactec Mycobacterial Growth Indicator Tubes (MGIT) system and the prevalence of drug resistance in these patients. Records of patients with abdominal TB (diagnosed on clinical features, endoscopy, histology, microbiology) seen during the period 2008 to 2013 were retrieved from the Gastroenterology and Microbiology departments. Patients with extra-abdominal TB (five pulmonary, two nodal), adnexal (one), and HIV (one) were excluded from analysis. Of 61 patients, 31 (50.8 %) had a positive AFB culture. In the 30 culture-negative patients, histology showed non-caseating granulomas in 25 patients. Drug sensitivity pattern was analyzed in 18 patients; resistance was detected in eight (14.3 % of all patients and 44.4 % of patients in whom drug sensitivity was done) including three (5.4 % of all subjects and 16.6 % in whom drug sensitivity was available) who were multidrug-resistant. The rate of AFB culture positivity in primary abdominal TB was 50.8 % using Bactec MGIT. Likelihood of drug resistance was seen in 14.3 %, of whom 5.4 % were multidrug-resistant.

Study of H. pylori infection in children with recurrent abdominal pain attending the pediatrics outpatient clinic of Zagazig University Hospitals.

PubMed

Badr, M A; El-Saadany, Hosam F; Ali, Adel S A; Abdelrahman, D

2012-12-01

This study assessed the prevalence of H. pylori infection in children with recurrent abdominal pain attending the Outpatient Pediatric Clinic of Zagazig University Hospitals. The study was conducted on 100 children suffering from different GIT symptoms mainly recurrent abdominal pain, they were categorized into 3 categories according to their ages. First category below 5 years, second category between 5 and 10 years and last category above 10 years. All subjects underwent full history taking, clinical examination and laboratory investigations. Protozoa infection was in 29% of patients, helminthes 10%, chronic constipation 4% and UTI 4%. The patients with apparent etiology were excluded. The data do not support the hypothesis that there is a direct role for H. pylori infection as a causative agent for Recurrent Abdominal Pain (RAP) in children. The mean +/- SD of age of patients were 5.7 +/- 3.7, with range of 1:18 years. Male to female ratio was 1:1.1. H. pylori serum IgG antibodies were in 26 patients (43.3%) and 24 controls (p = 0.71), and H. pylori stool Ag in stool of 22 cases and 20 controls (p = 0.7).

Mannose-Binding Lectin Deficiency Facilitates Abdominal Candida Infections in Patients with Secondary Peritonitis▿

PubMed Central

van Till, J. W. Olivier; Modderman, Piet W.; de Boer, Martin; Hart, Margreet H. L.; Beld, Marcel G. H. M.; Boermeester, Marja A.

2008-01-01

Mannose-binding lectin (MBL) deficiency due to variations in the MBL gene is associated with increased susceptibility to infections. In this study, the association between MBL deficiency and the occurrence of abdominal yeast infection (AYI) in peritonitis patients was examined. Eighty-eight patients with secondary peritonitis requiring emergency laparotomy were included. MBL genotype (wild type [WT] versus patients with variant genotypes), MBL plasma concentrations, and Candida risk factors were examined in patients with and those without AYI (positive abdominal yeast cultures during [re]laparotomy). A variant MBL genotype was found in 53% of patients with AYI and 38% of those without AYI (P = 0.18). A significantly higher proportion of variant patients had an AYI during early peritonitis (during first laparotomy) than WT patients (39% versus 16%, respectively; P = 0.012). Patients with AYI had lower MBL levels than did patients without AYI (0.16 μg/ml [0.0 to 0.65 μg/ml] versus 0.65 μg/ml (0.19 to 1.95 μg/ml); P = 0.007). Intensity of colonization (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0 to 1.1), MBL plasma concentrations of <0.5 μg/ml (OR, 4.5; 95% CI, 1.2 to 16.3), and numbers of relaparotomies (OR, 1.7; 95% CI, 1.0 to 2.8) were independently associated with AYI. In summary, deficient MBL plasma levels were independently associated with the development of AYI in patients with secondary peritonitis and seemed to facilitate early infection. PMID:17978009

Epidemiology of Nontuberculous Mycobacterial Lung Disease and Tuberculosis, Hawaii, USA

PubMed Central

Frankland, Timothy B.; Daida, Yihe G.; Honda, Jennifer R.; Olivier, Kenneth N.; Zelazny, Adrian; Honda, Stacey; Prevots, D. Rebecca

2017-01-01

Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005–2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2–3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility. PMID:28221128

Variable Case Detection and Many Unreported Cases of Surgical-Site Infection Following Colon Surgery and Abdominal Hysterectomy in a Statewide Validation.

PubMed

Calderwood, Michael S; Huang, Susan S; Keller, Vicki; Bruce, Christina B; Kazerouni, N Neely; Janssen, Lynn

2017-09-01

OBJECTIVE To assess hospital surgical-site infection (SSI) identification and reporting following colon surgery and abdominal hysterectomy via a statewide external validation METHODS Infection preventionists (IPs) from the California Department of Public Health (CDPH) performed on-site SSI validation for surgical procedures performed in hospitals that voluntarily participated. Validation involved chart review of SSI cases previously reported by hospitals plus review of patient records flagged for review by claims codes suggestive of SSI. We assessed the sensitivity of traditional surveillance and the added benefit of claims-based surveillance. We also evaluated the positive predictive value of claims-based surveillance (ie, workload efficiency). RESULTS Upon validation review, CDPH IPs identified 239 SSIs following colon surgery at 42 hospitals and 76 SSIs following abdominal hysterectomy at 34 hospitals. For colon surgery, traditional surveillance had a sensitivity of 50% (47% for deep incisional or organ/space [DI/OS] SSI), compared to 84% (88% for DI/OS SSI) for claims-based surveillance. For abdominal hysterectomy, traditional surveillance had a sensitivity of 68% (67% for DI/OS SSI) compared to 74% (78% for DI/OS SSI) for claims-based surveillance. Claims-based surveillance was also efficient, with 1 SSI identified for every 2 patients flagged for review who had undergone abdominal hysterectomy and for every 2.6 patients flagged for review who had undergone colon surgery. Overall, CDPH identified previously unreported SSIs in 74% of validation hospitals performing colon surgery and 35% of validation hospitals performing abdominal hysterectomy. CONCLUSIONS Claims-based surveillance is a standardized approach that hospitals can use to augment traditional surveillance methods and health departments can use for external validation. Infect Control Hosp Epidemiol 2017;38:1091-1097.

Use of negative pressure wound therapy in the management of infected abdominal wounds containing mesh: an analysis of outcomes.

PubMed

Baharestani, Mona Mylene; Gabriel, Allen

2011-04-01

The purpose of this study was to examine the clinical outcomes of negative pressure wound therapy (NPWT) using reticulated open-cell foam (ROCF) in the adjunctive management of abdominal wounds with exposed and known infected synthetic mesh. A non randomised, retrospective review of medical records for 21 consecutive patients with infected abdominal wounds treated with NPWT was conducted. All abdominal wounds contained exposed synthetic mesh [composite, polypropylene (PP), or knitted polyglactin 910 (PG) mesh]. Demographic and bacteriological data, wound history, pre-NPWT and comparative post-NPWT, operative procedures and complications, hospital length of stay (LOS) and wound healing outcomes were all analysed. Primary endpoints measured were (1) hospital LOS prior to initiation of NPWT, (2) total time on NPWT, (3) hospital LOS from NPWT initiation to discharge and (4) wound closure status at discharge. A total of 21 patients with abdominal wounds with exposed, infected mesh were treated with NPWT. Aetiology of the wounds was ventral hernia repair (n = 11) and acute abdominal wall defect (n = 10). Prior to NPWT initiation, the mean hospital LOS for the composite, PP and PG meshes were 76 days (range: 21-171 days), 51 days (range: 32-62 days) and 19 days (range: 12-39 days), respectively. The mean hospital LOS following initiation of NPWT for wounds with exposed composite, PP and PG mesh were 28, 31 and 32 days, respectively. Eighteen of the 21 wounds (86%) reached full closure after a mean time of 26 days of NPWT and a mean hospital LOS of 30 days postinitiation of NPWT. Three wounds, all with composite mesh left in situ, did not reach full closure, although all exhibited decreased wound dimensions, granulating beds and decreased surface area exposure of mesh. During NPWT/ROCF, one hypoalbuminemic patient with exposed PP mesh developed an enterocutaneous fistula over a prior enterotomy site. This patient subsequently underwent total mesh extraction, takedown of

Mycobacterium genavense infections in non-HIV immunocompromised hosts: a systematic review.

PubMed

Mahmood, Maryam; Ajmal, Saira; Abu Saleh, Omar M; Bryson, Alexandra; Marcelin, Jasmine R; Wilson, John W

2018-05-01

Mycobacterium genavense is a non-tuberculous mycobacterium which can rarely cause disease in non-HIV immunocompromised hosts. We describe our experience with this unusual infection and perform a systematic review of the literature to describe the features of M. genavense infection in non-HIV immunocompromised hosts. All cases of Mycobacterium genavense infection in non-HIV patients at our institution were reviewed. In addition, we conducted a systematic review of the literature to identify previously published cases of M. genavense infections in non-HIV hosts. Two cases of M. genavense were identified at our center; a 51-year-old renal transplant recipient with a prosthetic knee joint infection and a 66-year-old woman with idiopathic CD4 lymphocytopenia with gastrointestinal tract disease. The systematic review identified 44 cases of M. genavense infection in non-HIV hosts. The most common underlying conditions were solid organ transplantation (40%), sarcoidosis (14%) and hematopoietic stem cell transplantation (7%). Disease most commonly involved the gastrointestinal tract, spleen, liver or bone marrow. Diagnosis was challenging with PCR required for identification in nearly all cases. Over one-third of patients died, which may reflect the combination of infection and underlying comorbidities. Overall cure was achieved in 61% with a mean duration of antimycobacterial therapy of 15.5 months (range 10-24). M. genavense infection is a rare mycobacterial infection in non-HIV immunocompromised hosts. It should be suspected in immunocompromised patients presenting with disseminated mycobacterial infection, acid fast bacilli on smear or histopathologic examination, with poor or no growth in mycobacterial cultures.

Preincisional intraparietal Augmentin in abdominal operations.

PubMed Central

Pollock, A. V.; Evans, M.; Smith, G. M.

1989-01-01

A total of 624 consecutive eligible patients undergoing abdominal operations received a single preoperative dose of amoxycillin/clavulanic acid (1.2 g Augmentin) for the prophylaxis of surgical wound infection. They were randomised to have the antibiotic injected intravenously at induction of anaesthesia (n = 328) or infiltrated subcutaneously along the line of the proposed incision (n = 296). The incidence of wound infections was considerably lower in the group given the antibiotic into the abdominal wall (8.4% compared with 15.9%--chi 2 = 7.90, P = 0.005). No significant differences were found in the incidence of other major or minor infective or non-infective postoperative complications between the groups. It is concluded that preincisional intraparietal injection is more effective than intravenous injection of Augmentin for the prophylaxis of surgical wound infection. PMID:2523210

Multisite Infection with Mycobacterium abscessus after Replacement of Breast Implants and Gluteal Lipofilling

PubMed Central

Rüegg, Eva; Cheretakis, Alexandre; Modarressi, Ali; Harbarth, Stephan; Pittet-Cuénod, Brigitte

2015-01-01

Introduction. Medical tourism for aesthetic surgery is popular. Nontuberculous mycobacteria (NTM) occasionally cause surgical-site infections. As NTM grow in biofilms, implantations of foreign bodies are at risk. Due to late manifestation, infections occur when patients are back home, where they must be managed properly. Case Report. A 39-year-old healthy female was referred for acute infection of the right gluteal area. Five months before, she had breast implants replacement, abdominal liposuction, and gluteal lipofilling in Mexico. Three months postoperatively, implants were removed for NTM-infection in Switzerland. Adequate antibiotic treatment was stopped after seven days for drug-related hepatitis. At entrance, gluteal puncture for bacterial analysis was performed. MRI showed large subcutaneous collection. Debridement under general anaesthesia was followed by open wound management. Total antibiotic treatment was 20 weeks. Methods. Bacterial analysis of periprosthetic and gluteal liquids included Gram-stain plus acid-fast stain, and aerobic, anaerobic and mycobacterial cultures.  Results. In periprosthetic fluid, Mycobacterium abscessus, Propionibacterium, and Staphylococcus epidermidis were identified. The same M. abscessus strain was found gluteally. The gluteal wound healed within six weeks. At ten months' follow-up, gluteal asymmetry persists for deep scarring. Conclusion. This case presents major complications of multisite aesthetic surgery. Surgical-site infections in context of medical tourism need appropriate bacteriological investigations, considering potential NTM-infections. PMID:25893122

Intracerebral Mycobacterium bovis bacilli Calmette-Guerin infection-induced immune responses in the CNS 1

PubMed Central

Lee, JangEun; Ling, Changying; Kosmalski, Michelle M.; Hulseberg, Paul; Schreiber, Heidi A.; Sandor, Matyas; Fabry, Zsuzsanna

2010-01-01

To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette-Guerin. Granuloma and IFN-γ+CD4+ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4+ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4+ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3+CD4+ T cells and PD-L2+ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection. PMID:19535154

Abdominal Pain Syndrome

MedlinePlus

... blood clots to the lungs) Abdominal or chest wall pain: Shingles (herpes zoster infection) Costochondritis (inflammation of ... or tumors), fat (evidence of impaired digestion and absorption of food), and the presence of germs. X- ...

The cost-effectiveness of cefepime plus metronidazole versus imipenem/cilastatin in the treatment of complicated intra-abdominal infection.

PubMed

Barie, Philip S; Rotstein, Ori D; Dellinger, E Patchen; Grasela, Thaddeus H; Walawander, Cynthia A

2004-01-01

Our objective was to compare the economic benefits of cefepime plus metronidazole with those of imipenem/cilastatin in the treatment of complicated intra-abdominal infections. We used a retrospective analysis of clinical outcomes and health resource utilization data collected during a randomized, double-blind, multi-center clinical trial. Seventeen university-affiliated hospitals in the United States and Canada participated, as did 323 patients with complicated intra-abdominal infections. Decision analysis was conducted using a decision node of cefepime vs. imipenem, and chance nodes that included an Acute Physiology and Chronic Health Evaluation (APACHE) II score of #15 versus .15; a need for posttreatment surgical procedures; and clinical outcomes. Effectiveness of treatment was measured by differences in the length and cost of hospital stays, the number and cost of surgical procedures after treatment, cure rates, and the cost of antibiotics. Also evalulated were the incremental costs of cure (i.e., the costs of additional cures). Comparing cefepime plus metronidazole with imipenem/cilastatin, the expected cost of patient care was $8,218 versus $10,414, respectively, and the cost-effectiveness ratio per cure was $10,058 versus $13,685. For severely ill patients (APACHE II score .15), the expected cost was $12,962 versus $23,153, and the cost-effectiveness ratio per cure was $15,321 versus $64,313. Cefepime plus metronidazole was more cost-effective than imipenem/cilastatin in the treatment of complicated intra-abdominal infections, primarily because of fewer post-treatment surgical procedures and shorter hospital stays. The primary advantage accrued to severely ill patients who had an APACHE II score .15.

Recent developments in antibiotic agents for the treatment of complicated intra-abdominal infections.

PubMed

Lin, Shang-Yi; Huang, Chung-Hao; Ko, Wen-Chien; Chen, Yen-Hsu; Hsueh, Po-Ren

2016-01-01

Treatment of complicated intra-abdominal infections (cIAIs) is becoming increasingly difficult because of the widespread emergence of multidrug-resistant organisms. In this review, we discuss the effectiveness of several new antibiotics for the treatment of cIAIs, including new β-lactamase inhibitor combinations (BLICs) and tetracycline-class drugs, recently developed aminoglycosides and quinolones, and novel lipoglycopeptides and oxazolidinones. Of the new BLICs, ceftolozane/tazobactam is associated with adequate clinical cure rates in patients with cIAIs. Currently, two new β-lactamase inhibitors, namely avibactam and MK-7655, are under development for clinical use in the treatment of cIAIs. Eravacycline, a novel, fully synthetic tetracycline-class drug, has been shown in Phase II and III clinical trials to be more potent than tigecycline against a significant number of multidrug-resistant organisms causing cIAIs. Plazomicin, a next-generation aminoglycoside, is a promising agent for treatment of cIAIs due to multidrug-resistant pathogens. Of the recently developed quinolones, delafloxacin and finafloxacin have been shown to be effective against pathogens that survive and multiply in mildly acidic environments, although further clinical studies examining their clinical utility in the treatment of cIAIs are warranted. Oritavancin, a new semisynthetic lipoglycopeptide agent, has been demonstrated to be a potent antibiotic in the treatment of cIAIs due to drug-resistant Gram-positive organisms. Several other new antibiotics in development also show promise and will hopefully broaden the possibilities for treatment of complicated intra-abdominal infections due to MDR pathogens.

Traumatic abdominal hernia complicated by necrotizing fasciitis.

PubMed

Martínez-Pérez, Aleix; Garrigós-Ortega, Gonzalo; Gómez-Abril, Segundo Ángel; Martí-Martínez, Eva; Torres-Sánchez, Teresa

2014-11-01

Necrotizing fasciitis is a critical illness involving skin and soft tissues, which may develop after blunt abdominal trauma causing abdominal wall hernia and representing a great challenge for physicians. A 52-year-old man was brought to the emergency department after a road accident, presenting blunt abdominal trauma with a large non-reducible mass in the lower-right abdomen. A first, CT showed abdominal hernia without signs of complication. Three hours after ICU admission, he developed hemodynamic instability. Therefore, a new CT scan was requested, showing signs of hernia complication. He was moved to the operating room where a complete transversal section of an ileal loop was identified. Five hours after surgery, he presented a new episode of hemodynamic instability with signs of skin and soft tissue infection. Due to the high clinical suspicion of necrotizing fasciitis development, wide debridement was performed. Following traumatic abdominal wall hernia (TAWH), patients can present unsuspected injuries in abdominal organs. Helical CT can be falsely negative in the early moments, leading to misdiagnosis. Necrotizing fasciitis is a potentially fatal infection and, consequently, resuscitation measures, wide-spectrum antibiotics, and early surgical debridement are required. This type of fasciitis can develop after blunt abdominal trauma following wall hernia without skin disruption.

Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection.

PubMed

Kashan, David; Muthu, Nagarajan; Chaucer, Benjamin; Davalos, Fidencio; Bernstein, Michael; Chendrasekhar, Akella

2016-06-01

Background: Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens. Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens . (J GYNECOL SURG 32:182).

Jávea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients.

PubMed

Pemán, Javier; Aguilar, Gerardo; Valía, Juan Carlos; Salavert, Miguel; Navarro, David; Zaragoza, Rafael

Although the management of the invasive candidiasis has improved in the last decade, controversial issues yet remain, especially in the diagnostic and therapeutic approaches to Candida peritonitis and other forms of intra-abdominal fungal infections. We sought to identify core clinical knowledge about intra-abdominal fungal infections and to achieve high-agreement recommendations required to care for critically ill adult patients with Candida peritonitis and other forms of intra-abdominal fungal infection. A biregional Spanish survey, to elucidate the consensus about the already mentioned fungal infections by means of the Delphi technique, was conducted anonymously by e-mail with 29 multidisciplinary experts in invasive fungal infections from 14 hospitals in the Valencia and Murcia communities during 2014. Respondents included intensivists, anesthesiologists, microbiologists, pharmacologists, and infectious disease specialists, who answered 31 questions prepared by a coordination group after a strict review of the literature from the 5 previous years. The educational objectives spanned 6 categories: epidemiology, microbiological diagnosis, clinical diagnosis, antifungal treatment, de-escalation therapy, and special situations. The agreement required among the panelists for each item to be selected had to be higher than 70%. After extracting the recommendations from the selected items, a meeting at which the experts were asked to validate the previously selected recommendations in a second round of scoring took place. After the second round, 36 recommendations were validated according to the following distribution: epidemiology (5), microbiological diagnosis (4), clinical diagnosis (4), antifungal treatment (3), de-escalation therapy (4), and special situations (16). Treatment of Candida peritonitis and other forms of intra-abdominal fungal infections in ICU patients requires a broad range of knowledge application and skills that our recommendations address. Based

Trichuris trichiura Infection in North Korean Defector Resulted in Chronic Abdominal Pain and Growth Retardation.

PubMed

Kim, Jong Bin; Seo, Kwang Il; Moon, Won

2017-04-25

Trichuris trichiura infection is a common helminth infection, which is transmitted via soil, with worldwide distribution, especially in rural areas of developing countries. Occasionally, sporadic cases occur in non-endemic, developed areas due to the widespread of immigration. We experienced a case of Trichuris dysentery syndrome in a young North Korean defector, who had been suffering from chronic abdominal pain for 10 years. He is relatively short and thin compared with his older brother. Unexpectedly, the diagnosis, made by a colonoscopy, revealed numerous, small, white, and gently moving worms at the cecum and ascending colon. After 3 days of albendazole (400 mg once daily) administration, clinical symptoms subsided dramatically. On the follow-up colonoscopy, which was performed two months after the completion of his treatment, complete eradication was identified. Soil-transmitted helminths, including Trichuris trichiura , are disappearing becoming less prevalent in South Korea as a result of both national driving force and environmental improvement. However, these diseases should be considered when we meet foreign patients from developing countries, like North Korea, presenting chronic abdominal pain. Moreover, proper treatment of North Korean defectors and performing cohort studies of them would help to prepare for the possible unification era in the field of gastroenterology.

Impact of Percutaneous Drainage on Outcome of Intra-abdominal Infection Associated With Pediatric Perforated Appendicitis.

PubMed

Bonadio, William; Langer, Miriam; Cueva, Julie; Haaland, Astrid

2017-10-01

Perforated appendicitis can result in potentially serious complications requiring prolonged medical care. The optimal approach to successfully managing this condition is controversial. Review of 80 consecutive cases of pediatric acute perforated appendicitis with intra-abdominal infection (IAI) medically managed with parenteral antibiotics and percutaneous drainage (PD) during a 7-year period. All patients received broad spectrum parenteral antibiotic therapy. One-third were hospitalized for >2 weeks. IAI was identified on admission in 60% compared with developing during hospitalization in 40% of cases. Before performing PD, the mean duration of antibiotic therapy in those who developed IAI during hospitalization was 6 days. IAI cultures yielded 127 bacterial isolates; polymicrobial infection occurred in 65% of cases. Only 7% of aspirates were sterile. The most common pathogens were Escherichia coli (82%), of which 5 isolates exhibited extended-spectrum β-lactamase production, and streptococci (40%). At the time of PD, 60% were febrile (mean duration of in-hospital fever, 7.5 days); 67% defervesced within 24 hours after the procedure. Posthospitalization abdominal complications (recurrent IAI or appendicitis) occurred in one-third of patients. Children with perforated appendicitis and IAI often have a complicated and prolonged clinical course. Medical management consisting solely of parenteral antibiotic therapy is frequently ineffective in resolving IAI. Rapid clinical improvement commonly follows PD.

Genotyping and drug susceptibility testing of mycobacterial isolates from population-based tuberculosis prevalence survey in Ghana.

PubMed

Addo, Kennedy Kwasi; Addo, Samuel Ofori; Mensah, Gloria Ivy; Mosi, Lydia; Bonsu, Frank Adae

2017-12-02

Mycobacterium tuberculosis complex (MTBC) and Non-tuberculosis Mycobacterium (NTM) infections differ clinically, making rapid identification and drug susceptibility testing (DST) very critical for infection control and drug therapy. This study aims to use World Health Organization (WHO) approved line probe assay (LPA) to differentiate mycobacterial isolates obtained from tuberculosis (TB) prevalence survey in Ghana and to determine their drug resistance patterns. A retrospective study was conducted whereby a total of 361 mycobacterial isolates were differentiated and their drug resistance patterns determined using GenoType Mycobacterium Assays: MTBC and CM/AS for differentiating MTBC and NTM as well MTBDRplus and NTM-DR for DST of MTBC and NTM respectively. Out of 361 isolates, 165 (45.7%) MTBC and 120 (33.2%) NTM (made up of 14 different species) were identified to the species levels whiles 76 (21.1%) could not be completely identified. The MTBC comprised 161 (97.6%) Mycobacterium tuberculosis and 4 (2.4%) Mycobacterium africanum. Isoniazid and rifampicin monoresistant MTBC isolates were 18/165 (10.9%) and 2/165(1.2%) respectively whiles 11/165 (6.7%) were resistant to both drugs. Majority 42/120 (35%) of NTM were M. fortuitum. DST of 28 M. avium complex and 8 M. abscessus complex species revealed that all were susceptible to macrolides (clarithromycin, azithromycin) and aminoglycosides (kanamycin, amikacin, and gentamicin). Our research signifies an important contribution to TB control in terms of knowledge of the types of mycobacterium species circulating and their drug resistance patterns in Ghana.

Does disseminated nontuberculous mycobacterial disease cause false-positive Determine B-LAM lateral flow assay results? A retrospective review.

PubMed

Nel, Jeremy S; Lippincott, Christopher K; Berhanu, Rebecca; Spencer, David C; Sanne, Ian M; Ive, Prudence

2017-06-02

We retrospectively reviewed the Determine TB-LAM lateral flow assay (LF-LAM) results among HIV-infected patients with disseminated nontuberculous mycobacterial (NTM) disease. LF-LAM was positive in 19/21 patients without evidence of tuberculosis coinfection. Although tuberculosis-NTM coinfection may have been underdiagnosed, our results suggest that disseminated NTM disease may cause false-positive LF-LAM results. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Mycobacterial Hsp65 potentially cross-reacts with autoantibodies of diabetes sera and also induces (in vitro) cytokine responses relevant to diabetes mellitus.

PubMed

Rani, Pittu Sandhya; Babajan, Banaganapalli; Tulsian, Nikhil K; Begum, Mahabubunnisa; Kumar, Ashutosh; Ahmed, Niyaz

2013-11-01

Diabetes mellitus is a multifactorial disease and its incidence is increasing worldwide. Among the two types of diabetes, type-2 accounts for about 90% of all diabetic cases, whereas type-1 or juvenile diabetes is less prevalent and presents with humoral immune responses against some of the autoantigens. We attempted to test whether the sera of type-1 diabetes patients cross-react with mycobacterial heat shock protein 65 (Hsp65) due to postulated epitope homologies between mycobacterial Hsp65 and an important autoantigen of type-1 diabetes, glutamic acid decarboxylase-65 (GAD65). In our study, we used either recombinant mycobacterial Hsp65 protein or synthetic peptides corresponding to some of the potential epitopes of mycobacterial Hsp65 that are shared with GAD65 or human Hsp60, and a control peptide sourced from mycobacterial Hsp65 which is not shared with GAD65, Hsp60 and other autoantigens of type-1 diabetes. The indirect ELISA results indicated that both type-1 diabetes and type-2 diabetes sera cross-react with conserved mycobacterial Hsp65 peptides and recombinant mycobacterial Hsp65 protein but do not do so with the control peptide. Our results suggest that cross-reactivity of mycobacterial Hsp65 with autoantibodies of diabetes sera could be due to the presence of significantly conserved peptides between mycobacterial Hsp65 and human Hsp60 rather than between mycobacterial Hsp65 and GAD65. The treatment of human peripheral blood mononuclear cells (PBMCs) with recombinant mycobacterial Hsp65 protein or the synthetic peptides resulted in a significant increase in the secretion of cytokines such as IL-1β, IL-8, IL-6, TNF-α and IL-10. Taken together, these findings point towards a dual role for mycobacterial Hsp65: in inducing autoimmunity and in inflammation, the two cardinal features of diabetes mellitus.

Detection and differentiation of Mycobacterium tuberculosis and nontuberculous mycobacterial isolates by real-time PCR.

PubMed

Shrestha, Nabin K; Tuohy, Marion J; Hall, Gerri S; Reischl, Udo; Gordon, Steven M; Procop, Gary W

2003-11-01

Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35 degrees C (63.27 to 65.42 degrees C); M. kansasii, 59.20 degrees C (58.07 to 60.33 degrees C); M. avium, 57.82 degrees C (57.05 to 58.60 degrees C); M. intracellulare, 54.46 degrees C (53.69 to 55.23 degrees C); M. marinum, 58.91 degrees C (58.28 to 59.55 degrees C); rapidly growing mycobacteria, 53.09 degrees C (50.97 to 55.20 degrees C) or 43.19 degrees C (42.19 to 44.49 degrees C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M. tuberculosis is a true negative. The specific melting temperature also provides a suggestion of the identity of the NTM present, when the most commonly encountered mycobacterial species are considered. In a parallel comparison, both the LightCycler assay and the COBAS Amplicor M. tuberculosis assay correctly categorized 48 of 50 specimens that were proven by culture to contain M. tuberculosis, and the LightCycler assay correctly characterized 3 of 3 specimens that contained NTM.

Detection and Differentiation of Mycobacterium tuberculosis and Nontuberculous Mycobacterial Isolates by Real-Time PCR

PubMed Central

Shrestha, Nabin K.; Tuohy, Marion J.; Hall, Gerri S.; Reischl, Udo; Gordon, Steven M.; Procop, Gary W.

2003-01-01

Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35°C (63.27 to 65.42°C); M. kansasii, 59.20°C (58.07 to 60.33°C); M. avium, 57.82°C (57.05 to 58.60°C); M. intracellulare, 54.46°C (53.69 to 55.23°C); M. marinum, 58.91°C (58.28 to 59.55°C); rapidly growing mycobacteria, 53.09°C (50.97 to 55.20°C) or 43.19°C (42.19 to 44.49°C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M. tuberculosis is a true negative. The specific melting temperature also provides a suggestion of the identity of the NTM present, when the most commonly encountered mycobacterial species are considered. In a parallel comparison, both the LightCycler assay and the COBAS Amplicor M. tuberculosis assay correctly categorized 48 of 50 specimens that were proven by culture to contain M. tuberculosis, and the LightCycler assay correctly characterized 3 of 3 specimens that contained NTM. PMID:14605148

[Serological and cellular reactivity to mycobacterial proteins in Hansen's disease].

PubMed

Rada, Elsa; Aranzazu, Nacarid; Rodríguez, Vestalia; Borges, Rafael; Convit, Jacinto

2010-09-01

The study was designed for evaluating immunological reactivity to various mycobacterial protein preparations using serological and cell-mediated immunological tests in patients with clinical leprosy signs, predominantly, with the multibacillary forms. All patients were adults with ages between 20 and 30 years. Fifty eight (n = 81) percent corresponded to Lepromatous Leprosy (LL), 29% (n = 41) to Borderline Lepromatous Leprosy (BL) and 10% (n = 41) to Borderline Borderline Leprosy (BB); only 3% were Borderline Tuberculoid (BT) patients: 74% males and 26% females. The most frequent reactional phenomenon was of the Erythema Nodosum (ENL) type. The mycobacterial proteins tested were: total crude Mycobacterium leprae antigens (MISA); Mycobacterium bovis (MbSA and excretion MbSA); partially purified excretion protein antigen, with a 30 kDa relative movility (Ml30); and recombinant M. leprae proteins (Mt70, Mb 65, Ml 36, 28, 18 and 10 kDa). Two of the recombinant proteins (Ml10 and Ml 36 kDa) presented a statiscally significant higher serological reactivity, directly related with a larger bacillary load (p = 0.0051 and 0.050 respectively). The 30 kDa protein was predominantly recognized by antibodies from multibacillary patients. Results show that mean antibody values were higher in non reactional patients when tested against complete proteins (MbSA and ex MbSA) when compared with the group of patients who presented reactional phenomena (p = 0.000567 and 0.000061, respectively). Comparing reactional with non reactional patients, it was seen that mean antibody values against complete proteins (MbSA and ex MbSA) were higher in non reactional individuals (p = 0.000567 and 0.000061, respectively). This same behavior occurred towards individual mycobacterial proteins (30, 10 and 36 kDa). The T lymphocyte prolypherative response in reactional and non reactional patients towards mycobacterial proteins (MlSA, Ml 10 kDa, MbSA, ex MbSA) was negative.

Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease.

PubMed

Szymanski, Eva P; Leung, Janice M; Fowler, Cedar J; Haney, Carissa; Hsu, Amy P; Chen, Fei; Duggal, Priya; Oler, Andrew J; McCormack, Ryan; Podack, Eckhard; Drummond, Rebecca A; Lionakis, Michail S; Browne, Sarah K; Prevots, D Rebecca; Knowles, Michael; Cutting, Gary; Liu, Xinyue; Devine, Scott E; Fraser, Claire M; Tettelin, Hervé; Olivier, Kenneth N; Holland, Steven M

2015-09-01

The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not. To examine genetic variants in patients with PNTM, their unaffected family members, and a control group. Whole-exome sequencing was done on 69 white patients with PNTM and 18 of their white unaffected family members. We performed a candidate gene analysis using immune, cystic fibrosis transmembrance conductance regulator (CFTR), cilia, and connective tissue gene sets. The numbers of patients, family members, and control subjects with variants in each category were compared, as was the average number of variants per person. A significantly higher number of patients with PNTM than the other subjects had low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue categories (35, 26, 90, and 90%, respectively). Patients with PNTM also had significantly more cilia and connective tissue variants per person than did control subjects (2.47 and 2.55 compared with 1.38 and 1.40, respectively; P = 1.4 × 10(-6) and P = 2.7 × 10(-8), respectively). Patients with PNTM had an average of 5.26 variants across all categories (1.98 in control subjects; P = 2.8 × 10(-17)), and they were more likely than control subjects to have variants in multiple categories. We observed similar results for family members without PNTM infection, with the exception of the immune category. Patients with PNTM have more low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue genes than their unaffected family members and control subjects. We propose that PNTM infection is a multigenic disease in which combinations of variants across gene categories, plus environmental exposures, increase susceptibility to the infection.

Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials.

PubMed

Bassetti, Matteo; McGovern, Paul C; Wenisch, Christoph; Meyer, R Daniel; Yan, Jean Li; Wible, Michele; Rottinghaus, Scott T; Quintana, Alvaro

2015-09-01

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

ESAT-6 Targeting to DEC205+ Antigen Presenting Cells Induces Specific-T Cell Responses against ESAT-6 and Reduces Pulmonary Infection with Virulent Mycobacterium tuberculosis.

PubMed

Silva-Sánchez, Aarón; Meza-Pérez, Selene; Flores-Langarica, Adriana; Donis-Maturano, Luis; Estrada-García, Iris; Calderón-Amador, Juana; Hernández-Pando, Rogelio; Idoyaga, Juliana; Steinman, Ralph M; Flores-Romo, Leopoldo

2015-01-01

Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen's naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205+ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and pulmonary mycobacterial load). Treatment with α-DEC-ESAT alone induced ESAT-6-specific IFN-γ producing CD4+ T cells and prime-boost immunization prior to Mtb infection resulted in early influx (d14 post-infection) and increased IFN-γ+ production by specific T cells in the lungs, compared to scarce IFN-γ production in control mice. In vivo CTL killing was quantified in relevant tissues upon transferring target cells loaded with mycobacterial antigens. During infection, α-DEC-ESAT-treated mice showed increased target cell killing in the lungs, where histology revealed cellular infiltrate and considerably reduced bacterial burden. Targeting the mycobacterial antigen ESAT-6 to DEC205+ APCs before infection expands specific T cell clones responsible for early T cell responses (IFN-γ production and CTL activity) and substantially reduces lung bacterial burden. Delivering mycobacterial antigens directly to APCs provides a unique approach to study in vivo the role of APCs and specific T cell responses to assess their potential anti-mycobacterial functions.

ESAT-6 Targeting to DEC205+ Antigen Presenting Cells Induces Specific-T Cell Responses against ESAT-6 and Reduces Pulmonary Infection with Virulent Mycobacterium tuberculosis

PubMed Central

Silva-Sánchez, Aarón; Meza-Pérez, Selene; Flores-Langarica, Adriana; Donis-Maturano, Luis; Estrada-García, Iris; Calderón-Amador, Juana; Hernández-Pando, Rogelio; Idoyaga, Juliana; Flores-Romo, Leopoldo

2015-01-01

Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen’s naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205+ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and pulmonary mycobacterial load). Treatment with α-DEC-ESAT alone induced ESAT-6-specific IFN-γ producing CD4+ T cells and prime-boost immunization prior to Mtb infection resulted in early influx (d14 post-infection) and increased IFN-γ+ production by specific T cells in the lungs, compared to scarce IFN-γ production in control mice. In vivo CTL killing was quantified in relevant tissues upon transferring target cells loaded with mycobacterial antigens. During infection, α-DEC-ESAT-treated mice showed increased target cell killing in the lungs, where histology revealed cellular infiltrate and considerably reduced bacterial burden. Targeting the mycobacterial antigen ESAT-6 to DEC205+ APCs before infection expands specific T cell clones responsible for early T cell responses (IFN-γ production and CTL activity) and substantially reduces lung bacterial burden. Delivering mycobacterial antigens directly to APCs provides a unique approach to study in vivo the role of APCs and specific T cell responses to assess their potential anti-mycobacterial functions. PMID:25915045

Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial activity.

PubMed

Fomogne-Fodjo, M C Y; Ndinteh, D T; Olivier, D K; Kempgens, P; van Vuuren, S; Krause, R W M

2017-01-04

Tetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25µg/mL) and M. aurum (65µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne-Fodjo et al., 2014). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs. T. potatoria medium polar extract [MeOH/DCM (1:1, v/v)] was fractionated sequentially with petroleum ether to which EtOAC and MeOH were gradually added to increase the polarity. The examination of T. potatoria extract and its fractions was guided by bioassays for anti-mycobacterial activity against M. smegmatis (ATCC 23246) and M. aurum (NCTC 10437) using the minimum inhibitory concentration (MIC) method. All the isolated compounds were structurally elucidated using spectroscopic techniques and evaluated for their anti-mycobacterial activity. Two novel secondary metabolites (1, 2) named tetraceranoate and N-hydroxy imidate-tetracerane, together with five known compounds [β-stigmasterol (3), stigmast-5-en-3β-yl acetate (4), betulinic acid (5), betulin (6) and lupeol (7)] were isolated and identified. Tetraceranoate exhibited the best activity against M. smegmatis with a minimum inhibitory concentration (MIC) of 7.8µg/mL, while β-stigmasterol, betulinic acid and betulin showed appreciable anti-mycobacterial activity against both strains (MIC 15µg/mL). Seven compounds were isolated from the medium polar extract [MeOH/DCM (1:1, v/v)] of T. potatoria stem bark. Only tetraceranoate one of the isolated compounds showed antibacterial activity against

Pharmacoeconomics of ciprofloxacin plus metronidazole vs. piperacillin-tazobactam for complicated intra-abdominal infections.

PubMed

Paladino, Joseph A; Gilliland-Johnson, Kristin K; Adelman, Martin H; Cohn, Stephen M

2008-06-01

A series of 459 hospitalized adults with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter clinical trial. The present study was conducted to add a pharmacoeconomic analysis to the results. A cost-effectiveness analysis from the perspective of the hospital provider was carried out. Decision analysis was used to illustrate outcomes and to provide a basis on which to conduct a sensitivity analysis. Cost-effectiveness ratios, representing the cost per expected successfully treated patient, were calculated to determine the most cost-effective alternative. Among 244 economically evaluable patients, enrolled from 34 centers in the U.S. and Canada, 131 patients received ciprofloxacin-metronidazole (75% clinical success rate), and 113 received piperacillin-tazobactam (65% clinical success rate; p = 0.06). Switch to oral antibiotics was possible for 81 patients who received ciprofloxacin-metronidazole (85% clinical success rate) and 67 piperacillin-tazobactam patients (70% clinical success rate; p = 0.027). The mean hospital cost was US$10,662 +/- 7,793 for patients in the ciprofloxacin-metronidazole group and $10,009 +/- 7,023 for patients in the piperacillin-tazobactam group (p = 0.492). Significantly lower costs were documented for patients who could be switched to oral antibiotics than for those continued on intravenous antibiotic orders ($8,684 +/- 4,120 vs. $12,945 +/- 10,204, respectively; p < 0.001). Patients with appendicitis had lower mean hospital costs than those with other infections ($7,169 +/- 3,705 vs. $12,097 +/- 8,342, respectively; p < 0.001). The cost-effectiveness ratios were $14,216:1 for patients in the ciprofloxacin-metronidazole group and $15,398:1 for patients in the piperacillin-tazobactam group. The mean hospital costs associated with ciprofloxacin-metronidazole were similar to those of piperacillin-tazobactam for the treatment of adults with complicated intra-abdominal infections. Lower costs were

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

PubMed Central

Appelberg, Rui; Moreira, Diana; Barreira-Silva, Palmira; Borges, Margarida; Silva, Letícia; Dinis-Oliveira, Ricardo Jorge; Resende, Mariana; Correia-Neves, Margarida; Jordan, Michael B; Ferreira, Nuno C; Abrunhosa, Antero J; Silvestre, Ricardo

2015-01-01

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. PMID:25807843

Modeling tuberculosis pathogenesis through ex vivo lung tissue infection.

PubMed

Carranza-Rosales, Pilar; Carranza-Torres, Irma Edith; Guzmán-Delgado, Nancy Elena; Lozano-Garza, Gerardo; Villarreal-Treviño, Licet; Molina-Torres, Carmen; Villarreal, Javier Vargas; Vera-Cabrera, Lucio; Castro-Garza, Jorge

2017-12-01

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Several in vitro and in vivo experimental models have been used to study TB pathogenesis and induction of immune response during Mycobacterium tuberculosis infection. Precision cut lung tissue slices (PCLTS) is an experimental model, in which all the usual cell types of the organ are found, the tissue architecture and the interactions amongst the different cells are maintained. PCLTS in good physiological conditions, monitored by MTT assay and histology, were infected with either virulent Mycobacterium tuberculosis strain H37Rv or the TB vaccine strain Mycobacterium bovis BCG. Histological analysis showed that bacilli infecting lung tissue slices were observed in the alveolar septa, alveolar light spaces, near to type II pneumocytes, and inside macrophages. Mycobacterial infection of PCLTS induced TNF-α production, which is consistent with previous M. tuberculosis in vitro and in vivo studies. This is the first report of using PCLTS as a system to study M. tuberculosis infection. The PCLTS model provides a useful tool to evaluate the innate immune responses and other aspects during the early stages of mycobacterial infection. Copyright © 2017. Published by Elsevier Ltd.

Anti-mycobacterial natural products from the Canadian medicinal plant Juniperus communis.

PubMed

Carpenter, Caitlyn D; O'Neill, Taryn; Picot, Nadia; Johnson, John A; Robichaud, Gilles A; Webster, Duncan; Gray, Christopher A

2012-09-28

Common juniper, Juniperus communis, is amongst the plants most frequently used by the indigenous peoples of North America for medicinal purposes. The First Nations of the Canadian Maritimes use infusions of juniper primarily as a tonic and for the treatment of tuberculosis. Previous investigations of extracts derived from the aerial parts of J. communis have shown it to possess anti-mycobacterial activity. The aim of the study is to isolate and identify anti-mycobacterial constituents from the aerial parts of J. communis. Methanolic extracts of J. communis needles and branches were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The anti-mycobacterial constituents were identified by NMR, MS and polarimetry. The diterpenes isocupressic acid and communic acid and the aryltetralin lignan deoxypodophyllotoxin were isolated from the J. communis extract. Isocupressic acid and communic acid (isolated as an inseparable 3:2 mixture of cis and trans isomers) displayed MICs of 78 μM and 31 μM and IC(50)s of 46 μM and 15 μM against M. tuberculosis H37Ra respectively. Deoxypodophyllotoxin was less active, with a MIC of 1004 μM and an IC(50) of 287 μM. Isocupressic acid, communic acid and deoxypodophyllotoxin were identified as the principal constituents responsible for the anti-mycobacterial activity of the aerial parts of J. communis. Although further research will be required to evaluate the relative activities of the two communic acid isomers, this work validates an ethnopharmacological use of this plant by Canadian First Nations and Native American communities. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Measuring the Global Substrate Specificity of Mycobacterial Serine Hydrolases Using a Library of Fluorogenic Ester Substrates.

PubMed

Bassett, Braden; Waibel, Brent; White, Alex; Hansen, Heather; Stephens, Dominique; Koelper, Andrew; Larsen, Erik M; Kim, Charles; Glanzer, Adam; Lavis, Luke D; Hoops, Geoffrey C; Johnson, R Jeremy

2018-04-16

Among the proteins required for lipid metabolism in Mycobacterium tuberculosis are a significant number of uncharacterized serine hydrolases, especially lipases and esterases. Using a streamlined synthetic method, a library of immolative fluorogenic ester substrates was expanded to better represent the natural lipidomic diversity of Mycobacterium. This expanded fluorogenic library was then used to rapidly characterize the global structure activity relationship (SAR) of mycobacterial serine hydrolases in M. smegmatis under different growth conditions. Confirmation of fluorogenic substrate activation by mycobacterial serine hydrolases was performed using nonspecific serine hydrolase inhibitors and reinforced the biological significance of the SAR. The hydrolases responsible for the global SAR were then assigned using gel-resolved activity measurements, and these assignments were used to rapidly identify the relative substrate specificity of previously uncharacterized mycobacterial hydrolases. These measurements provide a global SAR of mycobacterial hydrolase activity, a picture of cycling hydrolase activity, and a detailed substrate specificity profile for previously uncharacterized hydrolases.

Nontuberculous mycobacterial infection of the musculoskeletal system in immunocompetent hosts.

PubMed

Gundavda, Manit K; Patil, Hitendra G; Agashe, Vikas M; Soman, Rajeev; Rodriques, Camilla; Deshpande, Ramesh B

2017-01-01

Nontuberculous mycobacteria (NTM) were considered saprophytic organisms for many years but now are recognized as human pathogens. Although humans are routinely exposed to NTM, the rate of clinical infection is low. Such infections usually occur in the elderly and in patients who are immunocompromised. However, there has been an increasing incidence in recent years of infections in immunocompetent hosts. NTM infections in immunocompetent individuals are secondary to direct inoculation either contamination from surgical procedures or penetrating injuries rather than hematogenous dissemination. Clinically and on histopathology, musculoskeletal infections caused by NTM resemble those caused by Mycobacterium tuberculosis but are mostly resistant to routine antituberculosis medicines. Six cases of NTM infection in immunocompetent hosts presenting to the department from 2004 to 2015 were included in study. Of which two cases (one patella and one humerus) of infection were following an open wound due to trauma while two cases (one hip and one shoulder) of infection were by inoculation following an intraarticular injection for arthrogram of the joint, one case was infection following arthroscopy of knee joint and one case (calcaneum) was infection following local injection for the treatment of plantar fasciitis. All patients underwent inaging and tissue diagnosis with samples being sent for culture, staining, and histopathology. Clinical suspicion of NTM inoculation led to the correct diagnosis (four cases with culture positive and two cases with histopathological diagnosis). There treatment protocol for extrapulmonary NTM infection was radical surgical debridement and medical management based on drug sensitivity testing in culture positive cases. At a mean follow up of 3 years (range1-9 years) all patients had total remission and excellent results. Whenever a case of chronic granulomatous infection is encountered that does not respond to standard anti-tuberculous treatment

Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh

PubMed Central

Biá Ventura, Thatiana Lopes; da Silva Machado, Fernanda Lacerda; de Araujo, Marlon Heggdorne; de Souza Gestinari, Lísia Mônica; Kaiser, Carlos Roland; de Assis Esteves, Francisco; Lasunskaia, Elena B.; Soares, Angélica Ribeiro; Muzitano, Michelle Frazão

2015-01-01

Background: Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis. Objective: In the present study, we evaluated the inhibition of nitric oxide (NO) and tumor necrosis factor-α production and the anti-mycobacterial activity of crude extracts from the red Alga Laurencia dendroidea (from the South-Eastern coast of Brazil). Halogenated sesquiterpenes elatol (1), obtusol (2) and cartilagineol (3), previously isolated from this Alga by our group, were also studied. Materials and Methods: The lipopolysaccharide-activated macrophage cells (RAW 264.7) were used as inflammation model. Cytotoxic effect was determined using a commercial lactate dehydrogenase (LDH) kit and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The growing Mycobacterium inhibition was verified against Mycobacterium bovis Bacillus Calmette–Guérin and M. tuberculosis H37 Rv strains. Results: The crude extract from Alga collected at Angra dos Reis, RJ, Brazil, was the most active inhibitor of both mycobacterial growth (half maximal inhibitory concentration [IC50] 8.7 ± 1.4 μg/mL) and NO production by activated macrophages (IC50 5.3 ± 1.3 μg/mL). The assays with isolated compounds revealed the anti-mycobacterial activity of obtusol (2), whereas (-)-elatol (1) inhibited the release of inflammatory mediators, especially NO. To our knowledge, this is the first report describing an anti-mycobacterial effect of L. dendroidea extract and demonstrating the association of this activity with obtusol (2). Conclusion: The described effects of active compounds from L. dendroidea are promising for the control of inflammation in infectious diseases and specifically, against mycobacterial infections

Treatment of Non-Tuberculous Mycobacterial Lung Disease.

PubMed

Philley, Julie V; DeGroote, Mary Ann; Honda, Jennifer R; Chan, Michael M; Kasperbauer, Shannon; Walter, Nicholas D; Chan, Edward D

2016-12-01

Treatment of non-tuberculous mycobacterial lung disease (NTM-LD) is challenging for several reasons including the relative resistance of NTM to currently available drugs and the difficulty in tolerating prolonged treatment with multiple drugs. Yet-to-be-done, large, multicenter, prospective randomized studies to establish the best regimens will also be arduous because multiple NTM species are known to cause human lung disease, differences in virulence and response to treatment between different species and strains within a species will make randomization more difficult, the need to distinguish relapse from a new infection, and the difficulty in adhering to the prescribed treatment due to intolerance, toxicity, and/or drug-drug interactions, often necessitating modification of therapeutic regimens. Furthermore, the out-of-state resident status of many patients seen at the relatively few centers that care for large number of NTM-LD patients pose logistical issues in monitoring response to treatment. Thus, current treatment regimens for NTM-LD is largely based on small case series, retrospective analyses, and guidelines based on expert opinions. It has been nearly 10 years since the publication of a consensus guideline for the treatment of NTM-LD. This review is a summary of the available evidence on the treatment of the major NTM-LD until more definitive studies and guidelines become available.

Specific detection of the cleavage activity of mycobacterial enzymes using a quantum dot based DNA nanosensor

NASA Astrophysics Data System (ADS)

Jepsen, Morten Leth; Harmsen, Charlotte; Godbole, Adwait Anand; Nagaraja, Valakunja; Knudsen, Birgitta R.; Ho, Yi-Ping

2015-12-01

We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes.We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes. Electronic supplementary information (ESI) available: Characterization of the QD-based DNA Nanosensor. See DOI: 10.1039/c5nr06326d

Children with moderate-high infection with Entamoeba coli have higher percentage of body and abdominal fat than non-infected children.

PubMed

Zavala, G A; García, O P; Campos-Ponce, M; Ronquillo, D; Caamaño, M C; Doak, C M; Rosado, J L

2016-12-01

Intestinal parasites, virus and bacterial infections are positively associated with obesity and adiposity in vitro and in animal models, but conclusive evidence of this relationship in humans is lacking. The aim of this cross-sectional study was to determine differences in adiposity between infected and non-infected children, with a high prevalence of intestinal parasitic infection and obesity. A total of 296 school-aged children (8.0 ± 1.5 years) from a rural area in Querétaro, Mexico, participated in this study. Anthropometry (weight, height and waist circumference) and body fat (DXA) were measured in all children. A fresh stool sample was collected from each child and analysed for parasites. Questionnaires related to socioeconomic status and clinical history were completed by caretakers. Approximately 11% of the children were obese, and 19% were overweight. The overall prevalence of infection was 61%. Ascaris lumbricoides was the most prevalent soil transmitted helminth (16%) followed by hookworm. Entamoeba coli was the predominant protozoa (20%) followed by Endolimax nana, Balantidium coli, Entamoeba histolytica/dispar, Iodamoeba bütschlii and Giardia lamblia. Children with moderate-heavy infection of E. coli had significantly higher waist circumference, waist-to-height ratio, body and abdominal fat than children not infected or with light-intensity infection (p < 0.05). These findings raise the possibility that a moderate or heavy infection with E. coli may contribute to fat deposition and thereby have long-term consequences on human health. Further studies are needed to better understand if E. coli contributes directly to fat deposition and possible mechanisms. © 2015 World Obesity Federation.

Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PubMed Central

López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

2016-01-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

Carbapenem-resistant Lactobacillus intra-abdominal infection in a renal transplant recipient with a history of probiotic consumption.

PubMed

Vanichanan, Jakapat; Chávez, Violeta; Wanger, Audrey; De Golovine, Aleksandra M; Vigil, Karen J

2016-12-01

Lactobacillus sp. is a low virulence bacterium, which rarely causes infection in immunocompetent individuals and usually is considered a contaminant. Normally this organism is susceptible to β-lactam antibiotics, yet resistant strains have been reported. Here, we report a case of a 60-year-old renal transplant recipient who developed an intra-abdominal abscess which grew a carbapenem-resistant Lactobacillus casei. This is significant since it is the first report of a clinical isolate of Lactobacillus sp. that demonstrated both microbiological and clinical resistance to carbapenem use. Moreover, the probiotic supplement that the patient had taken also grew a similar organism raising the concern of probiotic associated infection in immunocompromised individual.

[Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases].

PubMed

Monneuse, O; Gruner, L; Barth, X; Malick, P; Timsit, M; Gignoux, B; Tissot, E

2007-01-01

Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.

Cooling towers--a potential environmental source of slow-growing mycobacterial species.

PubMed

Black, Walter C; Berk, Sharon G

2003-01-01

Over the last decade a rise in the frequency of disease caused by nontuberculous mycobacteria (NTM) has occurred, especially among AIDS patients. The lack of evidence for person-to-person transmission indicates the environment is a source of infection. The ecology and environmental sources of NTMs are poorly understood, and many pathogenic strains have not been observed outside of clinical cases. Several species of NTMs have been reported from treated water distribution systems; however, one type of manmade environment that has not been examined for mycobacteria is that of cooling towers of air-conditioning systems. Such environments not only harbor a variety of microbial species, they also disseminate them in aerosols. The present investigation examined nine cooling towers from various locations in the United States. Cooling tower water was concentrated, treated with cetylpyridinium chloride, and plated onto Middlebrook 7H10 agar supplemented with OADC and cycloheximide. Colonies presumed to be mycobacterial species were isolated and acid-fast stained. Identification was made by amplifying and sequencing 1450 bp fragments of the 16S rRNA gene in both directions, and comparing resulting sequences with those in GenBank. Results showed that at least 75% of tower samples contained NTMs, and most of the isolates closely matched known mycobacterial pathogens. Isolates most closely matched the following GenBank sequences: Mycobacterium intracellulare, M. szulgai, M. bohemicum, M. gordonae, M. nonchromogenicum, and M. n. sp. "Fuerth 1999." This is the first report of specific NTMs in cooling tower water, and the first report of M. n. sp. "Fuerth 1999" from any environmental sample. Although cooling towers have a relatively high pH, they may favor the growth and dissemination of such potential pathogens, and future epidemiologic investigations should consider cooling towers as possible environmental sources of mycobacteria.

The use of light-emitting diode fluorescence to diagnose mycobacterial lymphadenitis in fine-needle aspirates from children

PubMed Central

van Wyk, A. C.; Marais, B. J.; Warren, R. M.; van Wyk, S. S.; Wright, C. A.

2011-01-01

SUMMARY BACKGROUND Fine-needle aspiration biopsy (FNAB) is a simple, safe and effective method for investigating suspected mycobacterial lymphadenitis in children. Fluorescence microscopy can provide rapid mycobacterial confirmation. Light-emitting diodes (LEDs) provide a cheap and robust excitation light source, making fluorescence microscopy feasible in resource-limited settings. OBJECTIVE To compare the diagnostic performance of LED fluorescence microscopy on Papanicolaou (PAP) stained smears with the conventional mercury vapour lamp (MVL). METHODS FNAB smears routinely collected from palpable lymph nodes in children with suspected mycobacterial disease were PAP-stained and evaluated by two independent microscopists using different excitatory light sources (MVL and LED). Mycobacterial culture results provided the reference standard. A manually rechargeable battery-powered LED power source was evaluated in a random subset. RESULTS We evaluated 182 FNAB smears from 121 children (median age 31 months, interquartile range 10–67). Mycobacterial cultures were positive in 84 of 121 (69%) children. The mean sensitivity with LED (mains-powered), LED (rechargeable battery-powered) and MVL was respectively 48.2%, 50.0% and 51.8% (specificity 78.4%, 86.7% and 78.4%). Inter-observer variation was similar for LED and MVL (κ = 0.5). CONCLUSION LED fluorescence microscopy provides a reliable alternative to conventional methods and has many favourable attributes that would facilitate improved, decentralised diagnostic services. PMID:21276297

Granulomatous encephalomyelitis and intestinal ganglionitis in a spectacled Amazon parrot (Amazona albifrons) infected with Mycobacterium genavense.

PubMed

Gomez, G; Saggese, M D; Weeks, B R; Hoppes, S M; Porter, B F

2011-01-01

An approximately 30-year-old male spectacled Amazon parrot (Amazona albifrons) was presented with a 2-week history of ataxia, head shaking, weight loss and seizures. Gross findings on necropsy examination included atrophy of the musculature, ruffled feathers and minimal epicardial and abdominal fat. Microscopically, there were perivascular cuffs of macrophages with fewer lymphocytes in the grey and white matter of the brain and spinal cord. These lesions were accompanied by gliosis and mild vacuolation of the white matter. In the small intestine, up to 70% of the intestinal ganglia were effaced by infiltrates of macrophages and fewer lymphocytes. The intestinal lamina propria contained multiple inflammatory aggregates of a similar nature. Ziehl-Neelsen staining revealed the presence of numerous bacilli within the cytoplasm of macrophages in the central nervous system (CNS) and enteric ganglia. Amplification of the DNAJ gene confirmed a mycobacterial infection and subsequent polymerase chain reaction (PCR) using a species-specific primer confirmed the aetiology as Mycobacterium genavense. Infection of the CNS with Mycobacterium spp. is uncommon and has not been previously reported in a parrot. This case is unusual in that the organism exhibited tropism for neural tissue. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mycobacterial species as case-study of comparative genome analysis.

PubMed

Zakham, F; Belayachi, L; Ussery, D; Akrim, M; Benjouad, A; El Aouad, R; Ennaji, M M

2011-02-08

The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species.

Original Mycobacterial Sin, a consequence of highly homologous antigens?

PubMed

Jenkins, A O; Michel, A; Rutten, V

2017-05-01

The role of antigens shared between Mycobacteria in in-vivo cross-reactive immune responses in host animals, have been reported to be responsible for reduced BCG vaccination efficacy as well reduced specificity of routine immunological diagnostic tests. This presents with significant disease control challenges in humans and animals. The present review highlights the results of previous studies on the effect of pre-sensitization to environmental mycobacteria on either pathogenic mycobacteria and/or M. bovis BCG, in experimental animals. It also takes an in-depth view into assessing the genetic similarities and relationships between atypical mycobacteria and Mycobacterium tuberculosis complex (MTBC) and how they might explain the immunological imprint of environmental mycobacteria in directing the hosts' immune response upon subsequent exposure to other classes of mycobacteria. The outcome of this review suggests that genetic closeness between particular atypical mycobacteria and MTBC usually indicate a higher level of homology for certain shared protective antigens. This ultimately results in a higher level of cross reactive immune responses as compared with other atypical mycobacteria that are further away genetically. This would explain the different effects of environmental mycobacteria on MTBC that have been reported in the different studies. In other words the direction of the host immune system in response to exposure to MTBC would depend on the type of environmental mycobacteria that was encountered in the initial exposure. We also explain these mycobacterial interactions in the context of the phenomenon of "Original Mycobacterial Sin". The effects of these inevitable mycobacterial interactions on field diagnosis and control by vaccination and how to circumvent them are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Addressing social influences reduces antibiotic duration in complicated abdominal infection: a mixed methods study.

PubMed

Broom, Jennifer; Tee, Chin Li; Broom, Alex; Kelly, Mark D; Scott, Tahira; Grieve, David A

2018-03-06

Antimicrobial therapy for intra-abdominal infections is often inappropriately prolonged. An intervention addressing factors influencing the duration of intravenous antibiotic use was undertaken. This study reports the antibiotic prescribing patterns before and after the intervention and a qualitative analysis of the experience of the intervention. Quantitative: A retrospective audit of patients with complicated intra-abdominal infection before and after a multifaceted persuasive intervention was performed. Qualitative: Semi-structured interviews were performed to evaluate which elements of the intervention were perceived to be effective. An intervention including collaborative inter-specialty and inter-professional educational meetings, and education of all professional streams was undertaken. Quantitative: Twenty-three patients before and 22 patients after the intervention were included. The total duration of antibiotics decreased significantly following the intervention (9.2 versus 6.6 days P = 0.02). The duration of intravenous antibiotics did not change significantly (5.4 versus 4.5 days, P = 0.06). Qualitative: Eighteen health-care professionals participated. Thematic analysis indicated that a collaborative approach between senior surgical and infectious disease specialists in the pre-intervention stage led to perceived ownership and leadership of the intervention by the surgical team, which was thought critical to the success of the intervention. Conversely, the ability of nurses and pharmacists to influence antibiotic practice was considered limited and a poster promoting the intervention was perceived as ineffective. Consultant leadership and specialty ownership of the process were perceived to be critical in the success of the intervention. Antibiotic stewardship programs which address social factors may have greater efficacy to optimize antimicrobial prescribing. © 2018 Royal Australasian College of Surgeons.

Structural Biology and the Design of New Therapeutics: From HIV and Cancer to Mycobacterial Infections: A Paper Dedicated to John Kendrew.

PubMed

Thomas, Sherine E; Mendes, Vitor; Kim, So Yeon; Malhotra, Sony; Ochoa-Montaño, Bernardo; Blaszczyk, Michal; Blundell, Tom L

2017-08-18

Interest in applications of protein crystallography to medicine was evident, as the first high-resolution structures emerged in the 50s and 60s. In Cambridge, Max Perutz and John Kendrew sought to understand mutations in sickle cell and other genetic diseases related to hemoglobin, while in Oxford, the group of Dorothy Hodgkin became interested in long-lasting zinc-insulin crystals for treatment of diabetes and later considered insulin redesign, as synthetic insulins became possible. The use of protein crystallography in structure-guided drug discovery emerged as enzyme structures allowed the identification of potential inhibitor-binding sites and optimization of interactions of hits using the structure of the target protein. Early examples of this approach were the use of the structure of renin to design antihypertensives and the structure of HIV protease in design of AIDS antivirals. More recently, use of structure-guided design with fragment-based drug discovery, which reduces the size of screening libraries by decreasing complexity, has improved ligand efficiency in drug design and has been used to progress three oncology drugs through clinical trials to FDA approval. We exemplify current developments in structure-guided target identification and fragment-based lead discovery with efforts to develop new antimicrobials for mycobacterial infections. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mycobacterium intracellulare infection of the shoulder and spine in a patient with steroid-treated systemic Lupus erythematosus

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

Zvetina, J.R.; Rubinstein, H.; Demos, T.C.

1982-05-01

Atypical mycobacterial infections of bone are rare. A patient with systemic lupus erythematosus treated with steroids developed an M. intracellulare infection of the shoulder and spine. These infections are insidious and diagnosis is difficult. Marked involvement of one joint, large effusion, or aspirated small synovial fragments suggest an atypical tuberculous joint infection.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

PubMed

Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

2008-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Abdominal candidiasis is a hidden reservoir of echinocandin resistance.

PubMed

Shields, Ryan K; Nguyen, M Hong; Press, Ellen G; Clancy, Cornelius J

2014-12-01

FKS mutant Candida isolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin. Candida glabrata (29%) and Candida albicans (14%) mutants were identified. Multidrug-resistant bacteria were recovered from 83% of FKS mutant infections. Mutations were associated with prolonged echinocandin exposure (P = 0.01), breakthrough infections (P = 0.03), and therapeutic failures despite source control interventions (100%). Abdominal candidiasis is a hidden reservoir for the emergence of echinocandin-resistant Candida. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

PubMed Central

Behler, Friederike; Maus, Regina; Bohling, Jennifer; Knippenberg, Sarah; Kirchhof, Gabriele; Nagata, Masahiro; Jonigk, Danny; Izykowski, Nicole; Mägel, Lavinia; Welte, Tobias; Yamasaki, Sho

2014-01-01

The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTR mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice. PMID:25332121

Decoding the similarities and differences among mycobacterial species

PubMed Central

Vedithi, Sundeep Chaitanya; Blundell, Tom L.

2017-01-01

Mycobacteriaceae comprises pathogenic species such as Mycobacterium tuberculosis, M. leprae and M. abscessus, as well as non-pathogenic species, for example, M. smegmatis and M. thermoresistibile. Genome comparison and annotation studies provide insights into genome evolutionary relatedness, identify unique and pathogenicity-related genes in each species, and explore new targets that could be used for developing new diagnostics and therapeutics. Here, we present a comparative analysis of ten-mycobacterial genomes with the objective of identifying similarities and differences between pathogenic and non-pathogenic species. We identified 1080 core orthologous clusters that were enriched in proteins involved in amino acid and purine/pyrimidine biosynthetic pathways, DNA-related processes (replication, transcription, recombination and repair), RNA-methylation and modification, and cell-wall polysaccharide biosynthetic pathways. For their pathogenicity and survival in the host cell, pathogenic species have gained specific sets of genes involved in repair and protection of their genomic DNA. M. leprae is of special interest owing to its smallest genome (1600 genes and ~1300 psuedogenes), yet poor genome annotation. More than 75% of the pseudogenes were found to have a functional ortholog in the other mycobacterial genomes and belong to protein families such as transferases, oxidoreductases and hydrolases. PMID:28854187

Mycobacterial Nucleoside Diphosphate Kinase Blocks Phagosome Maturation in Murine Raw 264.7 Macrophages

PubMed Central

Sun, Jim; Wang, Xuetao; Lau, Alice; Liao, Ting-Yu Angela; Bucci, Cecilia; Hmama, Zakaria

2010-01-01

Background Microorganisms capable of surviving within macrophages are rare, but represent very successful pathogens. One of them is Mycobacterium tuberculosis (Mtb) whose resistance to early mechanisms of macrophage killing and failure of its phagosomes to fuse with lysosomes causes tuberculosis (TB) disease in humans. Thus, defining the mechanisms of phagosome maturation arrest and identifying mycobacterial factors responsible for it are key to rational design of novel drugs for the treatment of TB. Previous studies have shown that Mtb and the related vaccine strain, M. bovis bacille Calmette-Guérin (BCG), disrupt the normal function of host Rab5 and Rab7, two small GTPases that are instrumental in the control of phagosome fusion with early endosomes and late endosomes/lysosomes respectively. Methodology/Principal Findings Here we show that recombinant Mtb nucleoside diphosphate kinase (Ndk) exhibits GTPase activating protein (GAP) activity towards Rab5 and Rab7. Then, using a model of latex bead phagosomes, we demonstrated that Ndk inhibits phagosome maturation and fusion with lysosomes in murine RAW 264.7 macrophages. Maturation arrest of phagosomes containing Ndk-beads was associated with the inactivation of both Rab5 and Rab7 as evidenced by the lack of recruitment of their respective effectors EEA1 (early endosome antigen 1) and RILP (Rab7-interacting lysosomal protein). Consistent with these findings, macrophage infection with an Ndk knocked-down BCG strain resulted in increased fusion of its phagosome with lysosomes along with decreased survival of the mutant. Conclusion Our findings provide evidence in support of the hypothesis that mycobacterial Ndk is a putative virulence factor that inhibits phagosome maturation and promotes survival of mycobacteria within the macrophage. PMID:20098737

[Globalization: challenges in abdominal surgery for migrants and refugees].

PubMed

Wilhelm, T J; Post, S

2018-03-01

The increasing number of refugees, migrants and international travelers influences the surgical spectrum of abdominal diseases. The aim of this review is to familiarize surgeons with specific diseases which are endemic in the patients' countries of origin and are likely to be diagnosed with increasing incidence in Germany. Low levels of hygiene in the countries of origin or refugee camps is associated with a high incidence of numerous infections, such as helminth infections, typhoid fever or amoebiasis, which if untreated can cause surgical emergencies. Historically, some of them were common in Germany but have been more or less eradicated because of the high socioeconomic standard. Echinococcosis and Chagas disease are frequently treated surgically while schistosomiasis can mimic intestinal cancer. Abdominal tuberculosis presents in a variety of abdominal pathologies and frequently causes diagnostic uncertainty. Sigmoid volvulus has a very low incidence among Europeans, but is one of the most common abdominal surgical conditions of adults in endemic countries. The number of patients who eventually undergo surgery for these conditions might be relatively low; however, surgeons must be aware of them and consider them as differential diagnoses in refugees and migrants with acute or chronic abdominal symptoms.

Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats.

PubMed

Pepple, Kathryn L; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L; Carlson, Eric; Van Gelder, Russell N

2015-12-01

The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and vitreous of both models and may be a

Solar Disinfection of MODS Mycobacterial Cultures in Resource-Poor Settings

PubMed Central

Nathavitharana, Ruvandhi; Coronel, Jorge; Moore, David A. J.

2007-01-01

Introduction Safe disposal of TB culture material in which the infectious burden of clinical samples has been greatly amplified is an important challenge in resource-limited settings. The bactericidal capacity of solar cookers has been demonstrated previously for conventional bacteria and contaminated clinical waste. We investigated the use of a simple solar cooker for the sterilization of mycobacterial broth cultures from the microscopic observation drug susceptibility assay (MODS). Methods Simulated TB culture materials were prepared by inoculating 24-well MODS plates with 500 µL of a known concentration of Mycobacterium bovis BCG. In a series of experiments, samples were simultaneously placed inside a box-type solar cooker and control box and removed at timepoints between 15 minutes and 6 hours. Quantitative cultures were performed using retrieved samples to determine sterilization effect. Results All cultures from the control box were positive at or within 1–4 logs of inoculation concentration. Simulated culture plates at concentrations from 103colony-forming-units (CFU)/ml to 107 CFU/ml were completely sterilized after only one hour of cooker exposure, at temperatures between 50–102°C. At 109 CFU/ml (far in excess of diagnostic cultures), it was only possible to recover mycobacterial growth in plates removed after 15 minutes. By 30 minutes all plates were effectively sterilized. Discussion Solar disinfection provides a very effective, safe and low-cost alternative to conventional equipment used for disposal of mycobacterial culture material. Effect of climatic conditions and optimal operating procedure remain to be defined. PMID:17971863

Subcutaneous aspergillosis with coexisting atypical mycobacterial infection.

PubMed

Duraipandian, Jeyakumari; Rengasamy, Gopal; Madasamy, Balamurugan; Kulanthaivelu, Ambedkarraj; Subramanian, Girija

2010-01-01

A 60-year-old woman, a known diabetic and asthmatic, was admitted for acute exacerbation of chronic obstructive pulmonary disease. Physical examination revealed two soft nodules in the left infra axillary region. Fine needle aspiration cytology (FNAC) showed fungal granulomatous reaction suggestive of fungal infection. Periodic acid Schiff stain (PAS stain) revealed PAS positive, acutely branching, septate fungal hyphae. Wet mount of the aspirate revealed plenty of pus cells and branching septate hyphae. Ziehl-Neelsen (ZN) stain showed moderate numbers of acid fast bacilli. Culture yielded Aspergillus flavus and Mycobacterium fortuitum.

Mycobacterium smegmatis infection of a prosthetic total knee arthroplasty.

PubMed

Saffo, Zaid; Ognjan, Anthony

2016-01-01

The most common organisms causing prosthetic knee joint infections are staphylococci. However, arthroplasty infections with atypical microbial pathogens, such as Mycobacteria can occur. Due to the rarity of mycobacterial prosthetic joint infections, diagnosis, treatment, and management of these atypical infections represent a clinical challenge. A 71-year old female post-operative day 40 after a left total knee arthroplasty was hospitalized secondary to left knee pain and suspected arthroplasty infection. She had failed outpatient oral antimicrobial treatment for superficial stitch abscess; and outpatient IV/Oral antimicrobials for a clinical postoperative septic bursitis. Ultimately, resection arthroplasty with operative tissue acid fast bacterial cultures demonstrated growth of the Mycobacterium smegmatis group. Post-operatively, she completed a combination course of oral doxycycline and levofloxacin and successfully completed a replacement arthroplasty with clinical and microbial resolution of the infection. To our knowledge, literature review demonstrates three case of knee arthroplasty infection caused by the Mycobacterium smegmatis group. Correspondingly, optimal surgical procedures and antimicrobial management including antimicrobial selection, treatment duration are not well defined. Presently, the best treatment options consists of two step surgical management including prosthesis hardware removal followed by extended antimicrobial therapy, followed by consideration for re-implantation arthroplasty. Our case illustrates importance of considering atypical mycobacterial infections in post-operative arthroplasty infections not responding to traditional surgical manipulations and antimicrobials. For an arthroplasty infection involving the atypical Mycobacterium smegmatis group, two step arthroplasty revision, including arthroplasty resection, with a combination of oral doxycycline and levofloxacin can lead to successful infection resolution, allowing for a

Abdominal pain in children with sickle cell disease.

PubMed

Rhodes, Melissa M; Bates, David Gregory; Andrews, Tina; Adkins, Laura; Thornton, Jennifer; Denham, Jolanda M

2014-02-01

The differential diagnosis of abdominal pain is broad in any child, and further complicated in children with sickle cell disease (SCD). Acute causes of abdominal pain may require emergent surgery, such as for appendicitis or obstruction caused by a bezoar. Rapid intervention is necessary and life-saving in children with SCD and acute splenic or hepatic sequestration. The majority of children with SCD presenting to the physician's office or emergency department will have subacute reasons for their abdominal pain, including but not limited to constipation, urinary tract infection, peptic ulcer disease, and cholecystitis. Vaso-occlusive pain often presents in children as abdominal pain, but is a diagnosis of exclusion. The case of a 10-year-old girl with intermittent abdominal pain is used as a starting point to review the pathophysiology, diagnosis, and treatment of the most acute and common causes of abdominal pain in children with SCD.

Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice.

PubMed

Zheng, Mingquan; Horne, William; McAleer, Jeremy P; Pociask, Derek; Eddens, Taylor; Good, Misty; Gao, Bin; Kolls, Jay K

2016-01-04

Interleukin 22 (IL-22) is an IL-10-related cytokine produced by T helper 17 (Th17) cells and other immune cells that signals via IL-22 receptor alpha 1 (IL-22Ra1), which is expressed on epithelial tissues, as well as hepatocytes. IL-22 has been shown to have hepatoprotective effects that are mediated by signal transducer and activator of transcription 3 (STAT3) signaling. However, it is unclear whether IL-22 can directly regulate antimicrobial programs in the liver. To test this hypothesis, hepatocyte-specific IL-22Ra1 knockout (Il22Ra1(Hep-/-)) and Stat3 knockout (Stat3(Hep-/-)) mice were generated and subjected to intra-abdominal infection with Klebsiella pneumoniae, which results in liver injury and necrosis. We found that overexpression of IL-22 or therapeutic administration of recombinant IL-22 (rIL-22), given 2 h postinfection, significantly reduced the bacterial burden in both the liver and spleen. The antimicrobial activity of rIL-22 required hepatic Il22Ra1 and Stat3. Serum from rIL-22-treated mice showed potent bacteriostatic activity against K. pneumoniae, which was dependent on lipocalin 2 (LCN2). However, in vivo, rIL-22-induced antimicrobial activity was only partially reduced in LCN2-deficient mice. We found that rIL-22 also induced serum amyloid A2 (SAA2) and that SAA2 had anti-K. pneumoniae bactericidal activity in vitro. These results demonstrate that IL-22, through IL-22Ra1 and STAT3 singling, can induce intrinsic antimicrobial activity in the liver, which is due in part to LCN2 and SAA2. Therefore, IL-22 may be a useful adjunct in treating hepatic and intra-abdominal infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Peripheral blood leucocytes show differential expression of tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection: a prospective matched cohort study.

PubMed

Alonso, S; Mayol, X; Nonell, L; Salvans, S; Pascual, M; Pera, M

2017-05-01

Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may induce overexpression of tumour progression-related genes in immune cells. The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leucocytes (PBL) after surgery for colorectal cancer. Prospective matched cohort study. Patients undergoing surgery for colorectal cancer were included. Patients who had anastomotic leak or intra-abdominal abscess were included in the infection group (n = 23) and matched with patients without complications for the control group (n = 23). PBL were isolated from postoperative blood samples. Total RNA was extracted and hybridized to the Affymetrix Human Gene 1.0 ST microarray. Patients in the infection group displayed 162 upregulated genes and 146 downregulated genes with respect to the control group. Upregulated genes included examples coding for secreted cytokines involved in tumour growth and invasion (S100P, HGF, MMP8, MMP9, PDGFC, IL1R2). Infection also upregulated some proangiogenic genes (CEP55, TRPS1) and downregulated some inhibitors of angiogenesis (MME, ALOX15, CXCL10). Finally, some inhibitors (HP, ORM1, OLFM4, IRAK3) and activators (GNLY, PRF1, FGFBP2) of antitumour immunity were upregulated and downregulated, respectively, suggesting that the inflammatory environment caused by a postoperative infection favours immune evasion mechanisms of the tumour. Analysis of PBL shows differential expression of certain tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection, which in turn may promote the growth of residual cancer cells to become recurrent tumours. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Effect of perioperative oxygen supplementation on 30-day surgical site infection rate in abdominal, gynecologic, and breast surgery: the ISO2 randomized controlled trial.

PubMed

Thibon, Pascal; Borgey, France; Boutreux, Sébastien; Hanouz, Jean-Luc; Le Coutour, Xavier; Parienti, Jean-Jacques

2012-09-01

Benefits and limitations of supplementation with 80% fraction of inspired oxygen for preventing surgical site infections have not yet been clearly defined. Some studies have reported benefits in colorectal surgery, whereas trials in abdominal and gynecologic surgery have reported either no effect or a deleterious effect. Controlled, randomized, assessor-blind multicenter trial, the ISO2 study, comparing the effects of hyperoxygenation (fraction of inspired oxygen, 80%) with those of 30% oxygen on the frequency of surgical site infections in routine abdominal, gynecologic, and breast surgery on 434 patients. Patients not seen in consultation after discharge were contacted. In total, 208 patients received 30% perioperative oxygen and 226 received 80%. There was no difference between the two groups for baseline, intraoperative, and postoperative characteristics, except for oxygen saturation at closure, higher in the 80% group (P=0.01). The frequency of 30-day surgical site infections was 7.2% (15/208) in the 30% group and 6.6% (15/226) in the 80% group (relative risk, 0.92; 95% CI [0.46-1.84], P=0.81). Frequency of adverse events (nausea and vomiting, sternal pain, cough, hypotension) was similar in the two groups. Desaturation and bradycardia were more frequent in the 30% group. In an updated meta-analysis including the result of this trial and those of eight published randomized trials, the overall relative risk was 0.97; 95% CI (0.68-1.40), I2 (inconsistency degree)=73%, (P=0.88). The routine use of hyperoxygenation throughout abdominal, gynecologic, and breast surgery had no effect on the frequency of 30-day surgical site infections and was not accompanied by more frequent adverse effects.

Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity.

PubMed

Bhasin, Shalender; Parker, Robert A; Sattler, Fred; Haubrich, Richard; Alston, Beverly; Umbleja, Triin; Shikuma, Cecilia M

2007-03-01

Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown. The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity. IN this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV-positive men with abdominal obesity (waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm) and total testosterone 125-400 ng/dl, or bioavailable testosterone less than 115 ng/dl, or free testosterone less than 50 pg/ml on stable antiretroviral regimen, and HIV RNA less than 10,000 copies per milliliter were randomized to receive 10 g testosterone gel or placebo daily for 24 wk. Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0, 12, and 24. We used an intention-to-treat approach and nonparametric statistical methods. Baseline characteristics were balanced between groups. In 75 subjects evaluated, median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups (testosterone 0.3%, placebo 3.1%, P = 0.75). Total (testosterone -1.5%, placebo 4.3%, P = 0.04) and sc (testosterone-7.2%, placebo 8.1%, P < 0.001) abdominal fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk, and appendicular fat mass by dual energy x-ray absorptiometry (all P < 0.001), whereas whole body and trunk fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen (P = 0.01), neck (P = 0.08), and breast size (P = 0.01) at wk 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M. tuberculosis? 2. How does M. tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M. tuberculosis? 4. What is the mechanism of "endogenous reactivation" of dormant M. tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-alpha. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome after Abdominal Wall Reconstruction: Quaternary Syndromes?

PubMed

Kirkpatrick, A W; Nickerson, D; Roberts, D J; Rosen, M J; McBeth, P B; Petro, C C; Berrevoet, Frederik; Sugrue, M; Xiao, Jimmy; Ball, C G

2017-06-01

Reconstruction with reconstitution of the container function of the abdominal compartment is increasingly being performed in patients with massive ventral hernia previously deemed inoperable. This situation places patients at great risk of severe intra-abdominal hypertension and abdominal compartment syndrome if organ failure ensues. Intra-abdominal hypertension and especially abdominal compartment syndrome may be devastating systemic complications with systematic and progressive organ failure and death. We thus reviewed the pathophysiology and reported clinical experiences with abnormalities of intra-abdominal pressure in the context of abdominal wall reconstruction. Bibliographic databases (1950-2015), websites, textbooks, and the bibliographies of previously recovered articles for reports or data relating to intra-abdominal pressure, intra-abdominal hypertension, and the abdominal compartment syndrome in relation to ventral, incisional, or abdominal hernia repair or abdominal wall reconstruction. Surgeons should thus consider and carefully measure intra-abdominal pressure and its resultant effects on respiratory parameters and function during abdominal wall reconstruction. The intra-abdominal pressure post-operatively will be a result of the new intra-peritoneal volume and the abdominal wall compliance. Strategies surgeons may utilize to ameliorate intra-abdominal pressure rise after abdominal wall reconstruction including temporizing paralysis of the musculature either temporarily or semi-permanently, pre-operative progressive pneumoperitoneum, permanently removing visceral contents, or surgically releasing the musculature to increase the abdominal container volume. In patients without complicating shock and inflammation, and in whom the abdominal wall anatomy has been so functionally adapted to maximize compliance, intra-abdominal hypertension may be transient and tolerable. Intra-abdominal hypertension/abdominal compartment syndrome in the specific setting of

Helicobacter pylori gastritis in a child with sickle cell anemia and recurrent abdominal pain.

PubMed

Kennedy, L; Mahoney, D H; Redel, C A

1997-01-01

Recurrent abdominal pain is a common complaint in children with sickle cell disease. Helicobacter pylori gastritis has recently been described in association with recurrent abdominal pain in children. A case report is given of a 16-year-old black male with hemoglobin SS disease presenting with recurrent abdominal pain and hematemesis. Endoscopic exam of the upper gastrointestinal tract revealed gastritis, and biopsy confirmed H. pylori infection. Serology studies demonstrated increased anti-H. pylori antibody titers. The young man responded well to treatment, with resolution of his symptoms. Helicobacter pylori infection is a new diagnostic consideration for children with recurrent abdominal pain and should be included in the differential diagnosis of children with sickle cell disease, especially when abdominal pain is recurrent and accompanied by vomiting. Larger case studies will be necessary to determine the true incidence of H. pylori in children with sickle cell disease and recurrent abdominal pain.

Comparison of clinical and laboratory findings between those with pulmonary tuberculosis and those with nontuberculous mycobacterial lung disease.

PubMed

Thanachartwet, Vipa; Desakorn, Varunee; Duangrithi, Duangjai; Chunpongthong, Pongsak; Phojanamongkolkij, Kamol; Jitruckthai, Pasakorn; Kasetjaroen, Yuttichai; Pitisuttithum, Punnee

2014-01-01

In tuberculosis endemic areas, patients with sputum positive for acid-fast bacilli (AFB) are usually diagnosed and treated for pulmonary tuberculosis. The diagnosis of nontuberculous mycobacteria (NTM) lung disease is often ascertained only after lung disease progression occurs, increasing the risk of severe morbidity and mortality. We conducted a matched case-control study among a prospective cohort of 300 patients with newly diagnosed AFB-positive sputum in Thailand during 2010-2012. We compared clinical and laboratory parameters and outcomes among patients with pulmonary tuberculosis, NTM lung disease and NTM colonization. A mycobacterial culture was performed in all patients. Ten patients with NTM lung disease were compared to 50 patients with pulmonary tuberculosis and 10 patients with NTM colonization. The presence of diabetes mellitus or human immunodeficiency virus infection, were associated with NTM lung disease (p = 0.030). Patients with NTM lung disease had a significantly lower body weight prior to treatment (p = 0.021), a higher body weight change from baseline (p = 0.038), and were more likely to have cavitations on chest radiograph (p = 0.033) than those with NTM colonization. In tuberculosis endemic areas, mycobacterial identification should be performed among patients with impaired immune function. NTM lung disease treatment should be considered in patients with NTM sputum isolates who have a history of significant weight loss or cavitations on chest radiography.

Temporary Abdominal Closure Combined With an Irrigating System Utilizing Hypochlorous Acid Solution to Decrease Abdominal Mucopurulence

PubMed Central

Matthews, Marc R.; Quan, Asia N.; Weir, Alexandra S.; Foster, Kevin N.; Caruso, Daniel M.

2018-01-01

Introduction: Leaving the abdominal cavity open is a well-described and frequently utilized technique in the treatment of severe intra-abdominal sepsis. Irrigation through a negative pressure wound therapy device is a technique employed to assist in the closure of wounds as well as the reduction of bacterial contamination. Furthermore, hypochlorous acid has been found to be safe and effective in microorganismal elimination from extremity wounds. There is no literature regarding the infusion of hypochlorous solution into the abdominal cavity for intra-abdominal sepsis or mucopurulent abscesses or biofilm. Objectives: A 47-year-old man with granulomatosis polyangiitis was started on weekly rituximab. After 4 infusions, skin sloughing, ultimately diagnosed as toxic epidermal necrolysis, developed. During the hospital course, he developed sepsis and bowel perforation necessitating an exploratory laparotomy. The abdomen was left open with a temporary abdominal closure using the Abthera open abdomen negative wound therapy device; however, the abdomen remained infected with visually diffuse, thickening mucopurulence despite multiple washouts. Therefore, a VAC Vera-Flo irrigation device was combined with the Abthera open abdomen negative wound therapy device and cyclical irrigation of hypochlorous acid. After 72 hours, the purulence visually was improved and no adverse events were recorded with the placement of intra-abdominal hypochlorous acid. Conclusions: The combination of two medical devices for the intra-abdominal instillation of irrigation is considered “off-label use” from the manufacturer's recommendations. In addition, the repeated instillation of hypochlorous acid solution has not been described but was noted to have visually decreased the contaminated effluent within the intra-abdominal fluid. PMID:29527250

Options for Closure of the Infected Abdomen

PubMed Central

Campbell, Chris A.; Rosenberger, Laura H.; Politano, Amani D.; Davies, Stephen W.; Riccio, Lin M.; Sawyer, Robert G.

2012-01-01

Abstract Background The infected abdomen poses substantial challenges to surgeons, and often, both temporary and definitive closure techniques are required. We reviewed the options available to close the abdominal wall defect encountered frequently during and after the management of complicated intra-abdominal infections. Methods A comprehensive review was performed of the techniques and literature on abdominal closure in the setting of intra-abdominal infection. Results Temporary abdominal closure options include the Wittmann Patch, Bogota bag, vacuum-assisted closure (VAC), the AbThera™ device, and synthetic or biologic mesh. Definitive reconstruction has been described with mesh, components separation, and autologous tissue transfer. Conclusion Reconstructing the infected abdomen, both temporarily and definitively, can be accomplished with various techniques, each of which is associated with unique advantages and disadvantages. Appropriate judgment is required to optimize surgical outcomes in these complex cases. PMID:23216525

Rare Orbital Infections ~ State of the Art ~ Part II

PubMed Central

Hamed-Azzam, Shirin; AlHashash, Islam; Briscoe, Daniel; Rose, Geoffrey E; Verity, David H.

2018-01-01

Infections of the orbit and periorbita are relatively frequent. Identifying unusual organisms is crucial because they can cause severe local and systemic morbidity, despite their rarity. Opportunistic infections of the orbit should be considered mainly in debilitated or immunocompromised patients. The key to successful management includes a high index of suspicion, prompt diagnosis, and addressing the underlying systemic disease. This review summarizes unusual infectious processes of the orbit, including mycobacterial, fungal, and parasitic infections, as well as their pathophysiology, symptoms, signs, and treatment. PMID:29719648

Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats

PubMed Central

Pepple, Kathryn L.; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L.; Carlson, Eric; Van Gelder, Russell N.

2015-01-01

Purpose The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. Methods In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Results Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Conclusions Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and

Rapid-Growing Mycobacteria Infections in Medical Tourists: Our Experience and Literature Review.

PubMed

Singh, Mansher; Dugdale, Caitlin M; Solomon, Isaac H; Huang, Anne; Montgomery, Mary W; Pomahac, Bohdan; Yawetz, Sigal; Maguire, James H; Talbot, Simon G

2016-09-01

"Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States. The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively. A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures. Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution. We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios. 5 Therapeutic. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to Mycobacterium bovis infection.

PubMed

Su, Feng; Wang, Yongsheng; Liu, Guanghui; Ru, Kun; Liu, Xin; Yu, Yuan; Liu, Jun; Wu, Yongyan; Quan, Fusheng; Guo, Zekun; Zhang, Yong

2016-03-01

Bovine tuberculosis results from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis family. Worldwide, M. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. Generating M. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing M. bovis infections. In this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding human β-defensin 3 (HBD3), which confers resistance to mycobacteria in vitro. We first generated alveolar epithelial cells expressing HBD3 under the control of the bovine MUC1 promoter, and confirmed that these cells secreted HBD3 and possessed anti-mycobacterial capacity. We then generated and identified transgenic cattle by somatic cell nuclear transfer. The cleavage and blastocyst formation rates of genetically modified embryos provided evidence that monoclonal transgenic bovine fetal fibroblast cells have an integral reprogramming ability that is similar to that of normal cells. Five genetically modified cows were generated, and their anti-mycobacterial capacities were evaluated. Alveolar epithelial cells and macrophages from these cattle expressed higher levels of HBD3 protein compared with non-transgenic cells and possessed effective anti-mycobacterial capacity. These results suggest that the overall risk of M. bovis infection in transgenic cattle is efficiently reduced, and support the development of genetically modified animals as an effective tool to reduce M. bovis infection. © 2016 Federation of European Biochemical Societies.

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

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

Hubin, Elizabeth A.; Fay, Allison; Xu, Catherine

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impedemore » transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD.« less

A Complicated Thread: Abdominal Actinomycosis in a Young Woman with Crohn Disease.

PubMed

Nahum, Ari; Filice, Gregory; Malhotra, Ashish

2017-01-01

Crohn disease is a chronic inflammatory condition that primarily affects the gastrointestinal tract. Typical manifestations include fever, weight loss, fatigue, and abdominal pain, and abdominal abscesses and fistulae are frequent complications. Abdominal actinomycosis is a subacute or indolent disease associated with Actinomyces spp. Symptoms can be very similar to those of Crohn disease, and fistulae are also common. Since ulcerations in the intestinal tract are thought to be caused by Actinomyces escaping from the gut lumen and establishing intra-abdominal infection, it seems likely that abdominal actinomycosis may occur in patients with inflammatory bowel disease. We report a case of abdominal actinomycosis in a woman with active Crohn disease.

Anti-mycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica.

PubMed

Singh, Rambir; Hussain, Shariq; Verma, Rajesh; Sharma, Poonam

2013-05-13

To find out the anti-mycobacterial potential of Cassia sophera (C. sophera), Urtica dioica (U. dioica), Momordica dioica, Tribulus terrestris and Coccinia indica plants against multi-drug resistant (MDR) strain of Mycobacterium tuberculosis (M. tuberculosis). Plant materials were extracted successively with solvents of increasing polarity. Solvent extracts were screened for anti-mycobacterial activity against fast growing, non-pathogenic mycobacterium strain, Mycobacterium semegmatis, by disk diffusion method. The active extracts were tested against MDR and clinical isolates of M. tuberculosis by absolute concentration and proportion methods. The active extracts were subjected to bio-autoassay on TLC followed by silica column chromatography for isolation of potential drug leads. Hexane extract of U. dioica (HEUD) and methanol extract of C. sophera (MECS) produced inhibition zone of 20 mm in disc diffusion assay and MIC of 250 and 125 μ g/mL respectively in broth dilution assay against Mycobacterium semegmatis. Semipurified fraction F2 from MECS produced 86% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. F18 from HEUD produced 81% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. Phytochemical analysis indicated that anti-mycobacterial activity of MECS may be due to presence of alkaloids or flavonoids and that of HEUD due to terpenoids. C. sophera and U. dioica plant extracts exhibited promising anti-mycobacterial activity against MDR strain of M. tuberculosis. This is the first report of anti-mycobacterial activity form C. sophera. This study showed possibility of purifying novel anti-mycobacterial compound(s) from C. sophera and U. dioica. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009–2014

PubMed Central

Wagner, Dirk; de Roux, Andrés; Diel, Roland; Hohmann, David; Hickstein, Lennart; Welte, Tobias; Rademacher, Jessica

2016-01-01

We analyzed routine statutory health insurance claim data to determine prevalence of nontuberculous mycobacterial pulmonary disease in Germany. Documented prevalence rates of this nonnotifiable disease increased from 2.3 to 3.3 cases/100,000 population from 2009 to 2014. Prevalence showed a strong association with advanced age and chronic obstructive pulmonary disease. PMID:27191473

Evaluation of abdominal pain in the AIDS patient.

PubMed Central

Potter, D A; Danforth, D N; Macher, A M; Longo, D L; Stewart, L; Masur, H

1984-01-01

Acquired immune deficiency syndrome (AIDS) is a recently recognized entity characterized by a deficiency in cell mediated immune response. The syndrome is manifested by the development of otherwise rare malignant neoplasms and severe life-threatening opportunistic infections. Case histories of five AIDS patients evaluated for abdominal pain are presented to demonstrate the unusual spectrum of intra-abdominal pathology that may be encountered in the AIDS patient. As the number of patients with AIDS continues to escalate, surgical evaluation and intervention will be required more frequently. An understanding of this syndrome and its complications is mandatory for the surgeon to adequately evaluate AIDS patients with abdominal pain. PMID:6322708

[Application of antiseptic dekasan in urgent abdominal surgery].

PubMed

Fomin, P D; Lissov, A I; Kozlov, S N; Mikhal'chishin, S N

2009-01-01

Experience in local application of antiseptic Dekasan in the complex treatment of abdominal infections of various origins are presented. The clinical and economic efficacy of the drug application is notice.

Inhaled Antibiotics for Lower Airway Infections

PubMed Central

Quon, Bradley S.; Goss, Christopher H.

2014-01-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post–lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized “off-label” to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated. PMID:24673698

Inhaled antibiotics for lower airway infections.

PubMed

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Disseminated infection with Mycobacterium tilburgii in a male immunocompromised patient.

PubMed

Temmerman, Sarah; Vandekerckhove, Linos; Sermijn, Erica; Vogelaers, Dirk; Claeys, Geert; Vaneechoutte, Mario; Cools, Piet; Callens, Steven

2014-05-01

Mycobacterium tilburgii is a nonculturable nontuberculous mycobacterium identifiable only by molecular methods. We report a case of disseminated M. tilburgii infection illustrating the importance of 16S rRNA gene sequencing to determine the responsible mycobacterial pathogen and the difficulties in tailoring antimycobacterial treatment in the absence of a culturable organism.

Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

PubMed Central

Tsoulfa, G; Rook, G A; Van-Embden, J D; Young, D B; Mehlert, A; Isenberg, D A; Hay, F C; Lydyard, P M

1989-01-01

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat. PMID:2930263

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

PubMed Central

Hubin, Elizabeth A; Fay, Allison; Xu, Catherine; Bean, James M; Saecker, Ruth M; Glickman, Michael S; Darst, Seth A; Campbell, Elizabeth A

2017-01-01

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the −10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD. DOI: http://dx.doi.org/10.7554/eLife.22520.001 PMID:28067618

Gastrointestinal injuries from blunt abdominal trauma in children.

PubMed

Ameh, E A; Nmadu, P T

2004-04-01

To determine the pattern, presentation and outcome of gastrointestinal injuries from blunt abdominal trauma in children. A retrospective study. Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Twenty one children managed for gastrointestinal injuries from blunt trauma from 1984-2002. The pattern, presentation, management and outcome of gastrointestinal injuries from blunt trauma. In the 19 year period, 1984-2002, 92 children were treated for blunt abdominal trauma, 21(23%) of who had injuries to the gastrointestinal tract. Three presenting after 24 hours had evidence of peritonitis. In six children with isolated gastrointestinal tract (GIT) injury who presented within two hours, abdominal signs were vague at initial evaluation but became marked over a few hours at repeated examination. In eight with associated intraabdominal injuries, abdominal signs were marked at initial examination and five presented with shock. Free peritoneal air was present on plain abdominal and chest radiograph in three of ten patients, dilated bowel loops in six and fluid levels in one. Diagnostic peritoneal lavage or paracentesis was positive in four patients with isolated GIT injuries and eight with associated intraabdominal injuries. There were 24 injuries in the 21 patients consisting of 15 perforations, five contusions, two seromuscular tears, and two gangrene from mesenteric injury. The small intestine was involved in 11 patients, colon six, stomach five, duodenum one and rectum one. Seven (35%) patients had associated extraabdominal injuries. Treatment consisted of simple closure of perforations, over sewing of contusions, resection and anastomosis for gangrene and repair with protective stoma for the rectal injury. One patient each developed prolonged ileus, urinary tract infection and chest infection, respectively postoperatively. Mortality was 28%, all of who had associated intraabdominal or extraabdominal injuries. Gastrointestinal injury from blunt abdominal trauma in

The acylation state of mycobacterial lipomannans modulates innate immunity response through toll-like receptor 2.

PubMed

Gilleron, Martine; Nigou, Jérôme; Nicolle, Delphine; Quesniaux, Valérie; Puzo, Germain

2006-01-01

Detection of Mycobacterium tuberculosis antigens by professional phagocytes via toll-like receptors (TLR) contributes to controlling chronic M. tuberculosis infection. Lipomannans (LM), which are major lipoglycans of the mycobacterial envelope, were recently described as agonists of TLR2 with potent activity on proinflammatory cytokine regulation. LM correspond to a heterogeneous population of acyl- and glyco-forms. We report here the purification and the complete structural characterization of four LM acyl-forms from Mycobacterium bovis BCG using MALDI MS and 2D (1)H-(31)P NMR analyses. All this biochemical work provided the tools to investigate the implication of LM acylation degree on its proinflammatory activity. The latter was ascribed to the triacylated LM form, essentially an agonist of TLR2, using TLR2/TLR1 heterodimers for signaling. Altogether, these findings shed more light on the molecular basis of LM recognition by TLR.

Neutralization or Absence of the Interleukin-23 Pathway Does Not Compromise Immunity to Mycobacterial Infection▿

PubMed Central

Chackerian, Alissa A.; Chen, Shi-Juan; Brodie, Scott J.; Mattson, Jeanine D.; McClanahan, Terrill K.; Kastelein, Robert A.; Bowman, Edward P.

2006-01-01

Interleukin-23 (IL-23), a member of the IL-12 family, is a heterodimeric cytokine that is composed of the p40 subunit of IL-12 plus a unique p19 subunit. IL-23 is critical for autoimmune inflammation, in part due to its stimulation of the proinflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We examined the role of IL-23 during Mycobacterium bovis BCG infection. We found that IL-23 reduces the bacterial burden and promotes granuloma formation when IL-12 is absent. However, IL-23 does not contribute substantially to host resistance when IL-12 is present, as the ability to control bacterial growth and form granulomata is not affected in IL-23p19-deficient mice and mice treated with a specific anti-IL-23p19 antibody. IL-23p19-deficient mice are also able to mount an effective memory response to secondary infection with BCG. While IL-23p19-deficient mice do not produce IL-17A, this cytokine is not necessary for effective control of infection, and antibody blocking of IL-17A in both wild-type and IL-12-deficient mice also has little effect on the bacterial burden. These data suggest that IL-23 by itself does not play an essential role in the protective immune response to BCG infection; however, the presence of IL-23 can partially compensate for the absence of IL-12. Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection. PMID:16923792

[The cutaneous groin flap for coverage of a full-thickness abdominal wall defect].

PubMed

Doebler, O; Spierer, R

2010-08-01

A full-thickness defect of the abdominal wall is rare and may occur as a complication of extended abdominal surgery procedures. We report about a 69-year-old patient who was presented to our department with a full-thickness abdominal wall defect and a fully exposed collagen-mesh for reconstructive wound closure. 13 operations with resections of necrotic parts of the abdominal wall were performed following a complicated intraabdominal infection. After debridement and mesh explantation, closure of the remaining defect of the lower abdominal region was achieved by a cutaneous groin flap. Georg Thieme Verlag KG Stuttgart New York.

Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial.

PubMed

Diener, Markus K; Knebel, Phillip; Kieser, Meinhard; Schüler, Philipp; Schiergens, Tobias S; Atanassov, Vladimir; Neudecker, Jens; Stein, Erwin; Thielemann, Henryk; Kunz, Reiner; von Frankenberg, Moritz; Schernikau, Utz; Bunse, Jörg; Jansen-Winkeln, Boris; Partecke, Lars I; Prechtl, Gerald; Pochhammer, Julius; Bouchard, Ralf; Hodina, René; Beckurts, K Tobias E; Leißner, Lothar; Lemmens, Hans-Peter; Kallinowski, Friedrich; Thomusch, Oliver; Seehofer, Daniel; Simon, Thomas; Hyhlik-Dürr, Alexander; Seiler, Christoph M; Hackert, Thilo; Reissfelder, Christoph; Hennig, René; Doerr-Harim, Colette; Klose, Christina; Ulrich, Alexis; Büchler, Markus W

2014-07-12

Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598

Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.

PubMed

Bilham, Kirstin; Boyd, Amy C; Preston, Stephen G; Buesching, Christina D; Newman, Chris; Macdonald, David W; Smith, Adrian L

2017-04-06

The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers.

Can early host responses to mycobacterial infection predict eventual disease outcomes?

PubMed

de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

2013-11-01

Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

PubMed

Scriba, Thomas J; Kaufmann, Stefan H E; Henri Lambert, Paul; Sanicas, Melvin; Martin, Carlos; Neyrolles, Olivier

2016-09-01

Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution.

PubMed

Smith, Silvia E; Showers-Corneli, Patrice; Dardenne, Caitlin N; Harpending, Henry H; Martin, Darren P; Beiko, Robert G

2012-01-01

The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer (M. abscessus to Segniliparus and M. smegmatis to Streptomyces), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case (M. vanbaalenii to Streptomyces) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is

Absence of Mycobacterium bovis infection in dogs and cats residing on infected cattle farms: Michigan, 2002

PubMed Central

WILKINS, M. J.; BARTLETT, P. C.; BERRY, D. E.; PERRY, R. L.; FITZGERALD, S. D.; BERNARDO, T. M.; THOEN, C. O.; KANEENE, J. B.

2008-01-01

SUMMARY A cross-sectional field study was performed to evaluate infection in dogs and cats living on farms with Mycobacterium bovis-infected cattle. The purpose was to determine pet infection status and assess their risk to farm families and/or tuberculosis-free livestock. Data and specimens were collected from 18 cats and five dogs from nine participating farms. ELISA testing for M. bovis and M. avium was conducted. Fifty-one biological samples were cultured; all were negative for M. bovis, although other Mycobacterium species were recovered. No radiographic, serological or skin test evidence of mycobacterial infection was found. These negative results may be due to the low level of M. bovis infection in the cattle and the limited duration of exposure of pets to infected cattle residing on the same farm. No evidence was found to indicate that pets residing on M. bovis-infected Michigan cattle farms pose a risk to humans or M. bovis-free livestock; however, precautionary advice for farm owners was provided. PMID:18325127

Cough physiology in elderly women with nontuberculous mycobacterial lung infections.

PubMed

Tsai, Hsiu-Wen; Fennelly, Kevin; Wheeler-Hegland, Karen; Adams, Sherry; Condrey, Jillian; Hosford, Jennifer L; Davenport, Paul W

2017-05-01

Elderly white, thin, nonsmoking women appear to be more susceptible to lung infections with Mycobacterium avium complex and other nontuberculous mycobacteria (NTM). It has been postulated that such disease in women is related to suppression of their cough. We hypothesized that patients with pulmonary NTM (pNTM) infections may have altered cough physiology compared with unaffected control subjects. We used capsaicin-induced cough to assess the cough reflex in pNTM subjects. Eight elderly white women with stable chronic pNTM infections and six unaffected age-matched control subjects were recruited. There was no significant difference between groups in capsaicin-elicited cough motor response, airflow pattern, or cough frequency. The urge-to-cough (UTC) score at the lowest capsaicin concentration was significantly lower in pNTM than control subjects ( P < 0.05). There were no significant differences in the UTC score between pNTM and control subjects at >50 μM capsaicin. These results suggest lower UTC sensitivity to the lowest concentration of capsaicin in pNTM than control subjects. In other words, the pNTM subjects do not sense a UTC when the stimulus is relatively small. NEW & NOTEWORTHY This study investigates the cough motor response and cough sensitivity in patients with nontuberculous mycobacteria (NTM) infection. In elderly white female pulmonary NTM subjects, we demonstrated a capacity to produce coughs similar to that of age-matched control subjects but decreased cough sensitivity in response to a low dose of capsaicin compared with control subjects. These findings are important to understand the pathophysiological mechanisms resulting in NTM disease in elderly white women and/or the syndrome developing in elderly white female NTM patients. Copyright © 2017 the American Physiological Society.

Severe Disseminated Mycobacterium avium Infection in a Patient with a Positive Serum Autoantibody to Interferon-γ

PubMed Central

Ikeda, Hiroshi; Nakamura, Kiwamu; Ikenori, Mei; Saito, Takahiro; Nagamine, Keisuke; Inoue, Minoru; Sakagami, Takuro; Suzuki, Hiroko; Usui, Mariko; Kanemitsu, Keiji; Matsumoto, Akinori; Shinbo, Takuro

2016-01-01

We herein report a case of disseminated Mycobacterium avium infection that involved both optic nerves, the conjunctiva, the right lower lung, and multiple skin lesions, including a thoracic nodule. The patient was a 65-year-old man without any significant medical history. The pathogen was detected in the patient's eye discharge, sputum, bronchial lavage fluid, and thoracic nodule. Anti-mycobacterial chemotherapy, including clarithromycin, rifampicin, and ethambutol, was administered, and the thoracic nodule was resected. An autoantibody to interferon-γ was detected in the patient's serum. Bilateral swelling of his optic nerves and facial dermatitis improved after initiating anti-mycobacterial chemotherapy. PMID:27746449

Why you should ask your patients about their fishing hobbies.

PubMed

Bakker, C V; Kardaun, S H; Wilting, K R; Diercks, G F H; Horváth, B

2013-09-01

Patients who use immunosuppressive agents, in particular medication that blocks tumour necrosis factor-a, are at risk for mycobacterial infections. Besides the typical Mycobacterium tuberculosis infection, a lso a typical mycobacterial disease may occur. Here we demonstrate two patients with such atypical mycobacterial infection due to swimming and fishing water contact. We propose that patients, before starting with immunosuppressive therapy, are counselled about risk factors for mycobacterial disease.

Cryopreserved arterial allografts for in situ reconstruction of abdominal aortic native or secondary graft infection.

PubMed

Ben Ahmed, Sabrina; Louvancourt, Adrien; Daniel, Guillaume; Combe, Pierre; Duprey, Ambroise; Albertini, Jean-Noël; Favre, Jean-Pierre; Rosset, Eugenio

2018-02-01

The objective of this study was to evaluate the early and long-term outcome of cryopreserved arterial allografts (CAAs) used for in situ reconstruction of abdominal aortic native or secondary graft infection and to identify predictors of mortality. We retrospectively included 71 patients (mean age, 65.2 years [range, 41-84 years]; men, 91.5%) treated for abdominal aortic native or secondary graft infection (65 prosthetic graft infections; 16 of them had secondary aortoenteric fistula, 2 venous graft infections, and 4 mycotic aneurysms) by in situ reconstruction with CAA in the university hospitals of Clermont-Ferrand and Saint-Etienne from 2000 to 2016. The cryopreservation protocol was identical in both centers (-140°C). Early (<30 days) and late (>30 days) mortality and morbidity, reinfection, and CAA patency were assessed. Computed tomography was performed in all survivors. Survival was analyzed with the Kaplan-Meier method. Univariate analyses were performed with the log-rank test and multivariate analysis with the Cox regression model. Mean follow-up was 45 months (0-196 months). Early postoperative mortality rate was 16.9% (11/71). Early postoperative CAA-related mortality rate was 2.8% (2/71); both patients died of proximal anastomotic rupture on postoperative days 4 and 15. Early CAA-related reintervention rate was 5.6% (4/71); all had an anastomotic rupture, and two were lethal. Early postoperative reintervention rate was 15.5% (11/71). Intraoperative bacteriologic samples were positive in 56.3%, and 31% had a sole microorganism. Escherichia coli was more frequently identified in the secondary aortoenteric fistula and Staphylococcus epidermidis in the infected prosthesis. Late CAA-related mortality rate was 2.8%: septic shock at 2 months in one patient and proximal anastomosis rupture at 1 year in one patient. Survival at 1 year, 3 years, and 5 years was 75%, 64%, and 54%, respectively. Multivariate analysis identified type 1 diabetes (hazard

Tetrahydrolipstatin Inhibition, Functional Analyses, and Three-dimensional Structure of a Lipase Essential for Mycobacterial Viability

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

Crellin, Paul K.; Vivian, Julian P.; Scoble, Judith

2010-09-17

The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG{_}6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidentlymore » inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG{_}6394, solved to 2.9 {angstrom} resolution, revealed an {alpha}/{beta} hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG{_}6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.« less

Tetrahydrolipstatin inhibition, functional analyses, and three-dimensional structure of a lipase essential for mycobacterial viability.

PubMed

Crellin, Paul K; Vivian, Julian P; Scoble, Judith; Chow, Frances M; West, Nicholas P; Brammananth, Rajini; Proellocks, Nicholas I; Shahine, Adam; Le Nours, Jerome; Wilce, Matthew C J; Britton, Warwick J; Coppel, Ross L; Rossjohn, Jamie; Beddoe, Travis

2010-09-24

The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG_6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidently inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG_6394, solved to 2.9 Å resolution, revealed an α/β hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG_6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.

WC1+ gamma delta T cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis respond differentially to stimulation with PPD-J.

USDA-ARS?s Scientific Manuscript database

A role for gamma delta T cells in protection against mycobacterial infections including Johne’s disease (JD) has been suggested. In neonatal calves where the risk to infection with Mycobacterium avium subsp. paratuberculosis (MAP) is high, the majority of circulating CD3+ lymphocytes are gamma delta...

Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.

PubMed

Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco

2004-12-15

The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (AAA), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective AAA repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for AAA and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of AAA and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of AAA alone. Except for malignancies of organs requiring major surgical resections, simultaneous AAA repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.

Closure of abdominal wounds by adhesive strips: a clinical trial.

PubMed Central

Webster, D J; Davis, P W

1975-01-01

In a randomized trial of wound closure in 512 abdominal wounds, wounds were closed with either reinforced Steristrip skin closures or interrupted silk sutures. Comparisons were made of wound pain and discomfort, wound infection, discharge, redness, width, and skin reaction. The causes of peeling of the tapes were assessed. The results showed that tapes were significantly more comfortable and that patients preferred them to sutures (P less than 0.01), but wide scars occurred more often. There was no difference in rates of wound infection and no case of allergy to the tapes was seen. Closure of abdominal wounds by these tapes is a satisfactory procedure that could be used more extensively. PMID:1100188

Abdominal Adhesions

MedlinePlus

... Clearinghouse What are abdominal adhesions? Abdominal adhesions are bands of fibrous tissue that can form between abdominal ... Esophagus Stomach Large intestine Adhesion Abdominal adhesions are bands of fibrous tissue that can form between abdominal ...

Abdominal Pain

MedlinePlus

... and Recurrent or Functional Abdominal Pain (RAP or FAP) What is abdominal pain? Abdominal pain , or stomachache, ... recurrent abdominal pain (RAP) or functional abdominal pain (FAP)? If your health care provider has ruled out ...

Technical advances for abdominal wall closure after intestinal and multivisceral transplantation.

PubMed

Gerlach, Undine A; Pascher, Andreas

2012-06-01

Abdominal wall closure after intestinal transplantation (ITX) or multivisceral transplantation (MVTX) is challenging because of the loss of abdominal domain and wall elasticity as a result of previous operations and donor-to-recipient weight and height mismatch. We report on abdominal wall closure management in 30 ITX and MVTX recipients. In 60% of patients (n = 18), a primary abdominal closure (PAC) was achieved, in 40% (n = 12) a staged closure (SAC) was necessary. Patients with PAC had undergone less pretransplant operations and required less posttransplant relaparotomies. They were mainly ITX recipients or more abdominal domain because of a longer intestinal remnant. A literature review revealed different strategies to overcome a failed primary closure. They focus on graft reduction or an enlargement of the abdominal domain. The latter includes temporary coverage with prosthetic materials for SAC. Definite abdominal closure is achieved by skin only closure, or by using acellular dermal matrix, rotational flaps, rectus muscle fascia or abdominal wall grafts. Abdominal wall reconstruction after ITX/MVTX is commonly demanded and can be conducted by different strategies. The technique should be easy to use in a timely manner and should prevent abdominal infections, intestinal fistulation, incisional hernias, and wound dehiscence.

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection.

PubMed

Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

2017-04-01

Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent S. stercoralis infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-β]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-β) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in S. stercoralis -LTB coinfection is reversible (for the most part) by anthelmintic treatment. Copyright © 2017 American Society for Microbiology.

Engineering Mycobacteria for the Production of Self-Assembling Biopolyesters Displaying Mycobacterial Antigens for Use as a Tuberculosis Vaccine.

PubMed

Lee, Jason W; Parlane, Natalie A; Rehm, Bernd H A; Buddle, Bryce M; Heiser, Axel

2017-03-01

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads that were produced in both Escherichia coli and Lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities, which we hypothesized to have the potential to induce immunity. In this study, we aimed to develop PHA beads produced in mycobacteria (mycobacterial PHA biobeads [MBB]) and test their potential as a TB vaccine in a mouse model. As a model organism, nonpathogenic Mycobacterium smegmatis was engineered to produce MBB or MBB with immobilized mycobacterial antigens Ag85A and ESAT-6 on their surface (A:E-MBB). Three key enzymes involved in the poly(3-hydroxybutyric acid) pathway, namely, β-ketothiolase (PhaA), acetoacetyl-coenzyme A reductase (PhaB), and PHA synthase (PhaC), were engineered into E. coli - Mycobacterium shuttle plasmids and expressed in trans Immobilization of specific antigens to the surface of the MBB was achieved by creating a fusion with the PHA synthase which remains covalently attached to the polyester core, resulting in PHA biobeads displaying covalently immobilized antigens. E-MBB, and an M. smegmatis vector control (MVC) were used in a mouse immunology trial, with comparison to phosphate-buffered saline (PBS)-vaccinated and Mycobacterium bovis BCG-vaccinated groups. We successfully produced MBB and A:E-MBB and used them as vaccines to induce a cellular immune response to mycobacterial antigens. IMPORTANCE Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. In this study, we produced polyhydroxyalkanoate (PHA) biobeads in mycobacteria and used them as vaccines to induce a cellular

Engineering Mycobacteria for the Production of Self-Assembling Biopolyesters Displaying Mycobacterial Antigens for Use as a Tuberculosis Vaccine

PubMed Central

Lee, Jason W.; Parlane, Natalie A.; Rehm, Bernd H. A.; Buddle, Bryce M.

2017-01-01

ABSTRACT Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads that were produced in both Escherichia coli and Lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities, which we hypothesized to have the potential to induce immunity. In this study, we aimed to develop PHA beads produced in mycobacteria (mycobacterial PHA biobeads [MBB]) and test their potential as a TB vaccine in a mouse model. As a model organism, nonpathogenic Mycobacterium smegmatis was engineered to produce MBB or MBB with immobilized mycobacterial antigens Ag85A and ESAT-6 on their surface (A:E-MBB). Three key enzymes involved in the poly(3-hydroxybutyric acid) pathway, namely, β-ketothiolase (PhaA), acetoacetyl-coenzyme A reductase (PhaB), and PHA synthase (PhaC), were engineered into E. coli-Mycobacterium shuttle plasmids and expressed in trans. Immobilization of specific antigens to the surface of the MBB was achieved by creating a fusion with the PHA synthase which remains covalently attached to the polyester core, resulting in PHA biobeads displaying covalently immobilized antigens. MBB, A:E-MBB, and an M. smegmatis vector control (MVC) were used in a mouse immunology trial, with comparison to phosphate-buffered saline (PBS)-vaccinated and Mycobacterium bovis BCG-vaccinated groups. We successfully produced MBB and A:E-MBB and used them as vaccines to induce a cellular immune response to mycobacterial antigens. IMPORTANCE Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. In this study, we produced polyhydroxyalkanoate (PHA) biobeads in mycobacteria and used them as vaccines to

Characterization of the receptors for mycobacterial cord factor in Guinea pig.

PubMed

Toyonaga, Kenji; Miyake, Yasunobu; Yamasaki, Sho

2014-01-01

Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

Dynamics of albumin synthetic response to intra-abdominal abscess in patients with gastrointestinal fistula.

PubMed

Zhou, Bo; Ren, Jianan; Han, Gang; Chen, Yu; A, Jiye; Gu, Guosheng; Chen, Jun; Wang, Gefei; Li, Jieshou

2014-04-01

Low serum albumin concentration is a predictor of failure of source control for intra-abdominal infection. However, data on dynamics of albumin synthesis in these patients and to what extent these changes contribute to hypoalbuminemia are relatively scarce. We investigated in a group of patients with gastrointestinal fistula the dynamic response of liver albumin synthesis to intra-abdominal abscess and how these related to hypoalbuminemia and circulating endocrine hormone profiles. Eight gastrointestinal fistula patients scheduled to undergo percutaneous abscess sump drainage were enrolled prospectively to measure albumin synthesis rates at different stages of the inflammatory response (immediately after diagnosis and 7 d following sump drainage when clinical signs of intra-abdominal sepsis had been eradicated). Eight age-, sex-, and body mass index-matched intestinal fistula patients were studied as control patients. Consecutive arterial blood samples were drawn during a primed-constant infusion (priming dose: 4 micromol·kg(-1), infusion rate: 6 micromol·kg(-1)·min(-1)) to determine the incorporation rate of L-[ring-(2)H5]-phenylalanine directly into plasma albumin using gas chromatography/mass spectrometry analysis. Patients suffering from intra-abdominal infection had reduced plasma albumin and total plasma protein concentrations, compared with control patients. Albumin fractional synthesis rates in patients with intra-abdominal abscess were decreased, compared with those in the control group. When the source of infection was removed, albumin synthesis rates returned to control values, whereas albumin concentrations did not differ significantly from the corresponding concentrations in control subjects and patients with intra-abdominal abscess. Despite nutritional intervention, albumin synthesis rate is decreased in intestinal fistula patients with intra-abdominal abscess; albumin synthesis returns to control values during convalescence.

Dynamics of Albumin Synthetic Response to Intra-Abdominal Abscess in Patients with Gastrointestinal Fistula

PubMed Central

Zhou, Bo; Han, Gang; Chen, Yu; A, Jiye; Gu, Guosheng; Chen, Jun; Wang, Gefei; Li, Jieshou

2014-01-01

Abstract Background: Low serum albumin concentration is a predictor of failure of source control for intra-abdominal infection. However, data on dynamics of albumin synthesis in these patients and to what extent these changes contribute to hypoalbuminemia are relatively scarce. We investigated in a group of patients with gastrointestinal fistula the dynamic response of liver albumin synthesis to intra-abdominal abscess and how these related to hypoalbuminemia and circulating endocrine hormone profiles. Methods: Eight gastrointestinal fistula patients scheduled to undergo percutaneous abscess sump drainage were enrolled prospectively to measure albumin synthesis rates at different stages of the inflammatory response (immediately after diagnosis and 7 d following sump drainage when clinical signs of intra-abdominal sepsis had been eradicated). Eight age-, sex-, and body mass index–matched intestinal fistula patients were studied as control patients. Consecutive arterial blood samples were drawn during a primed-constant infusion (priming dose: 4 micromol·kg−1, infusion rate: 6 micromol·kg−1·min−1) to determine the incorporation rate of L-[ring-2H5]-phenylalanine directly into plasma albumin using gas chromatography/mass spectrometry analysis. Results: Patients suffering from intra-abdominal infection had reduced plasma albumin and total plasma protein concentrations, compared with control patients. Albumin fractional synthesis rates in patients with intra-abdominal abscess were decreased, compared with those in the control group. When the source of infection was removed, albumin synthesis rates returned to control values, whereas albumin concentrations did not differ significantly from the corresponding concentrations in control subjects and patients with intra-abdominal abscess. Conclusion: Despite nutritional intervention, albumin synthesis rate is decreased in intestinal fistula patients with intra-abdominal abscess; albumin synthesis returns to

Early Versus Delayed Source Control in Open Abdomen Management for Severe Intra-abdominal Infections: A Retrospective Analysis on 111 Cases.

PubMed

Rausei, Stefano; Pappalardo, Vincenzo; Ruspi, Laura; Colella, Antonio; Giudici, Simone; Ardita, Vincenzo; Frattini, Francesco; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

2018-03-01

Time to source control plays a determinant prognostic role in patients having severe intra-abdominal infections (IAIs). Open abdomen (OA) management became an effective treatment option for peritonitis. Aim of this study was to analyze the correlation between time to source control and outcome in patients presenting with abdominal sepsis and treated by OA. We retrospectively analyzed 111 patients affected by abdominal sepsis and treated with OA from May 2007 to May 2015. Patients were classified according to time interval from first patient evaluation to source control. The end points were intra-hospital mortality and primary fascial closure rate. The in-hospital mortality rate was 21.6% (24/111), and the primary fascial closure rate was 90.9% (101/111). A time to source control ≥6 h resulted significantly associated with a poor prognosis and a lower fascial closure rate (mortality 27.0 vs 9.0%, p = 0.04; primary fascial closure 86 vs 100%, p = 0.02). We observed a direct increase in mortality (and a reduction in closure rate) for each 6-h delay in surgery to source control. Early source control using OA management significantly improves outcome of patients with severe IAIs. This damage control approach well fits to the treatment of time-related conditions, particularly in case of critically ill patients.

Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure.

PubMed

Syal, Kirtimaan; Maiti, Krishnagopal; Naresh, Kottari; Avaji, Prakash Gouda; Chatterji, Dipankar; Jayaraman, Narayanaswamy

2016-10-01

Mycobacterium has evolved distinct cell wall and strategies such as biofilm formation, which helps it to survive in hostile conditions. We have reported previously that arabinofuranoside containing glycolipids exhibit inhibition activities against the above functions of the mycobacterial species M. smegmatis. In search for activities mediated by oligosaccharide glycolipids, we report herein the inhibitory activities of a linear and a branched pentasaccharides having arabinan and mannan moieties. In the presence of the pentasaccharide glycolipids, a significant reduction in mycobacterial growth is observed, concomitant with reductions in sliding motility and colonization through biofilm formation, at the optimal glycolipid concentrations of 50-100 μg mL(-1). Especially the biofilm coat is ruptured by ~80-85 % in the presence of glycolipids. Pentasaccharides alone without the lipidic chain show only a weak effect. The glycolipids are non-toxic, as evaluated through their effect on RBCs. Analysis of the mycolic acid profile of glycolipid treated biofilm shows that α- and epoxy mycolic acids are downregulated significantly, in comparison to glycolipid untreated biofilms. Lipidomics profile analysis through mass spectrometry further reveals profound downregulation of phosphatidylinositol mannosides, acylatedphosphoglycerols and mycolic acid family, namely, keto-, alpha- and methoxymycolic acids.

Comparison of sequential intravenous/oral ciprofloxacin plus metronidazole with intravenous ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections.

PubMed

Wacha, Hannes; Warren, Brian; Bassaris, Harry; Nikolaidis, Paul

2006-08-01

Intra-abdominal infections are a substantial clinical problem and an important cause of morbidity and death in the hospital. Optimal treatment requires both source control and antibiotic therapy. Sequential intravenous (IV) to oral therapy may improve patient convenience and reduce total health care costs. In this randomized, double-blind trial, the efficacy of sequential IV-to-oral ciprofloxacin plus metronidazole was compared with ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal infections. The trial enrolled 531 patients, who began with IV therapy. Patients who improved clinically were switched to oral therapy on day three or later. The clinical and bacteriological responses four to six weeks after the end of therapy and the safety of the two regimens were assessed. To maintain blinding, the patients received placebo IV in the ciprofloxacin group or placebo orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of efficacy. All patients were included in the safety analysis. Of the patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to oral therapy. The clinical success rates were 98.9% and 96.9%, respectively, which were statistically equivalent. The clinical success rates for all patients, including those on continuous IV therapy, were 90.6% and 87.9%. Source control was achieved in more than 90% of the patients. The bacteriological eradication rates were similar in the two groups. Bacterial complications (e.g., surgical site infections, abscesses) were encountered more often in the ceftriaxone plus metronidazole group. Sequential ciprofloxacin plus metronidazole IV-to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole. The switch to oral therapy with ciprofloxacin plus metronidazole was as

Staged abdominal re-operation for abdominal trauma.

PubMed

Taviloglu, Korhan

2003-07-01

To review the current developments in staged abdominal re-operation for abdominal trauma. To overview the steps of damage control laparotomy. The ever increasing importance of the resuscitation phase with current intensive care unit (ICU) support techniques should be emphasized. General surgeons should be familiar to staged abdominal re-operation for abdominal trauma and collaborate with ICU teams, interventional radiologists and several other specialties to overcome this entity.

Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas.

PubMed

Egen, Jackson G; Rothfuchs, Antonio Gigliotti; Feng, Carl G; Winter, Nathalie; Sher, Alan; Germain, Ronald N

2008-02-01

Granulomas play a key role in host protection against mycobacterial pathogens, with their breakdown contributing to exacerbated disease. To better understand the initiation and maintenance of these structures, we employed both high-resolution multiplex static imaging and intravital multiphoton microscopy of Mycobacterium bovis BCG-induced liver granulomas. We found that Kupffer cells directly capture blood-borne bacteria and subsequently nucleate formation of a nascent granuloma by recruiting both uninfected liver-resident macrophages and blood-derived monocytes. Within the mature granuloma, these myeloid cell populations formed a relatively immobile cellular matrix that interacted with a highly dynamic effector T cell population. The efficient recruitment of these T cells was highly dependent on TNF-alpha-derived signals, which also maintained the granuloma structure through preferential effects on uninfected macrophage populations. By characterizing the migration of both innate and adaptive immune cells throughout the process of granuloma development, these studies provide a new perspective on the cellular events involved in mycobacterial containment and escape.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

PubMed

Lightner, A L; McKenna, N P; Tse, C S; Raffals, L E; Loftus, E V; Mathis, K L

2018-03-01

Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable

[Non-tuberculous mycobacterial infections related to esthetic care in France, 2001-2010].

PubMed

Couderc, C; Carbonne, A; Thiolet, J M; Brossier, F; Savey, A; Bernet, C; Ortmans, C; Lecadet-Morin, C; Coudière, I; Aggoune, M; Astagneau, P; Coignard, B; Cambau, E

2011-07-01

Non-tuberculous mycobacteria (NTM) infections usually occur in immunocompromised patients but also in immunocompetent patients following invasive procedures, especially for esthetic purposes. Since 2001, 20 episodes (57 cases) of NTM infections, seven of which (43 cases) were related to esthetic care, have been reported to the regional infection control coordinating centers (RICCC), the local health authorities (LHA), and the national institute for public health surveillance. Four notifications (40 cases) were related to non-surgical procedures performed by general practitioners in private settings: mesotherapy, carboxytherapy, and sclerosis of microvaricosities. The three other notifications (three cases) concerned surgical procedures-lifting and mammary prosthesis. Practice evaluations performed by the RICCC and LHA for five notifications showed deficiency of standard hygiene precautions and tap water misuse for injection equipment cleaning, or skin disinfection. Microbiological investigations (national reference center for mycobacteria) demonstrated the similarity of patient and environmental strains: in one episode (16 cases after mesotherapy), M. chelonae isolated from tap water was similar to those isolated from 11 cases. Healthcare-associated NTM infections are rare but have a potentially severe outcome. These cases stress the need of healthcare-associated infection notifications in outpatient settings. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Disseminated Mycobacterium avium--intracellulare complex infection in a miniature schnauzer.

PubMed

Miller, M A; Greene, C E; Brix, A E

1995-01-01

A two-year-old, spayed female, miniature schnauzer was evaluated for respiratory distress associated with a compressive cervical mass. Generalized mycobacterial infection was diagnosed from aspirates of several enlarged lymph nodes. Tissue specimens further identified Mycobacterium avium--intracellulare using polymerase chain reaction followed by nucleic acid hybridization. Treatment with enrofloxacin, clofazamine, rifampin, and interferon did not result in long-term success.

[Evaluation of mycobacterial microscopy and culture results of Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital: A 3-year analysis].

PubMed

Akduman Alaşehir, Elçin; Balıkçı, Ahmet; Partal, Mualla; Çatmabacak, Gülay; Yaman, Görkem

2016-09-01

Effective diagnosis of tuberculosis is of great importance for transmission control and treatment success. The purpose of this study is to evaluate microscopic examination results of Ehrlich-Ziehl Neelsen (EZN) and Auramine-Rhodamine staining methods and automated BACTEC MGIT 960™ system and Löwenstein-Jensen (L-J) culture results of various clinical samples in the light of recent data from the world and Turkey. Specimens that were sent from various clinics to Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital Microbiology Laboratory from January 2012 to December 2015 were evaluated retrospectively. From a total of 62456 samples; 60923 (97.5%) were pulmonary and 1533 (2.5%) were non-pulmonary samples, especially pleura. 2853 (4.6%) Acid-resistant bacilli (ARB) positivity was detected and mycobacterial culture positivity was in total 12.2%. 7076 (93%) and 535 (7%) mycobacteria other than tuberculosis (MOTT) strains were isolated. In 356 specimens the cultures were negative in despite the positive ARB results. Considering mycobacterial culture as the gold standard; the sensitivity, specificity, positive and negative predictive values of ARB microscopy were 32.8%, 99.4%, 87.5% and 91.4%, respectively. The contamination rates in total were within acceptable limits being 2.7% for L-J and 3.8% for MGIT. Analysis of our data indicated that the sensitivity of microscopy is low and it should be evaluated together with the mycobacterial culture to rule out tuberculosis infection. With the use of fluorescent staining and also L-J and MGIT broth together for routine culture since 2013; ARB false negativity rate was observed to fall to 51.7% from 74.1% compared to the years. The follow-up of data such as the sensitivity of microscopy, culture positivity, false-positivity and false-negativity rates and contamination values is of great importance in terms of assessing compliance with laboratory quality standards and contributing to the surveillance

Infections in solid-organ transplant recipients.

PubMed Central

Patel, R; Paya, C V

1997-01-01

Solid-organ transplantation is a therapeutic option for many human diseases. Infections are a major complication of solid-organ transplantation. All candidates should undergo a thorough infectious-disease screening prior to transplantation. There are three time frames, influenced by surgical factors, the level of immunosuppression, and environmental exposures, during which infections of specific types most frequently occur posttransplantation. Most infections during the first month are related to surgical complications. Opportunistic infections typically occur from the second to the sixth month. During the late posttransplant period (beyond 6 months), transplantation recipients suffer from the same infections seen in the general community. Opportunistic bacterial infections seen in transplant recipients include those caused by Legionella spp., Nocardia spp., Salmonella spp., and Listeria monocytogenes. Cytomegalovirus is the most common cause of viral infections. Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus and others are also significant pathogens. Fungal infections, caused by both yeasts and mycelial fungi, are associated with the highest mortality rates. Mycobacterial, pneumocystis, and parasitic diseases may also occur. PMID:8993860

Rapid identification of clinical mycobacterial isolates by protein profiling using matrix assisted laser desorption ionization-time of flight mass spectrometry.

PubMed

Panda, A; Kurapati, S; Samantaray, J C; Myneedu, V P; Verma, A; Srinivasan, A; Ahmad, H; Behera, D; Singh, U B

2013-01-01

The purpose of this study was to evaluate the identification of Mycobacterium tuberculosis which is often plagued with ambiguity. It is a time consuming process requiring 4-8 weeks after culture positivity, thereby delaying therapeutic intervention. For a successful treatment and disease management, timely diagnosis is imperative. We evaluated a rapid, proteomic based technique for identification of clinical mycobacterial isolates by protein profiling using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Freshly grown mycobacterial isolates were used. Acetonitrile/trifluoroacetic acid extraction procedure was carried out, following which cinnamic acid charged plates were subjected to identification by MALDI-TOF MS. A comparative analysis of 42 clinical mycobacterial isolates using the MALDI-TOF MS and conventional techniques was carried out. Among these, 97.61% were found to corroborate with the standard methods at genus level and 85.36% were accurate till the species level. One out of 42 was not in accord with the conventional assays because MALDI-TOF MS established it as Mycobacterium tuberculosis (log (score)>2.0) and conventional methods established it to be non-tuberculous Mycobacterium. MALDI-TOF MS was found to be an accurate, rapid, cost effective and robust system for identification of mycobacterial species. This innovative approach holds promise for early therapeutic intervention leading to better patient care.

Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy.

PubMed

Liu, Ting-Ting; Weng, Shao-Wen; Wang, Ming-Chung; Huang, Wan-Ting

2016-03-01

Disseminated nontuberculous mycobacteria (NTM) infection with concurrent IgG4-related lymphadenopathy has not been reported. We described a patient with neutralizing autoantibodies to interferon-gamma (IFN-γ) and elevated levels of serum IgG4 presenting with generalized lymphadenopathy and reactive dermatosis. Histologically, lymph nodes (LNs) showed effaced nodal architecture with polymorphic infiltrates, mimicking angioimmunoblastic T-cell lymphoma. Both the absolute number and the ratio of IgG4+ plasma cells to IgG+ plasma cells were increased. Mycobacterium abscessus was isolated from cultures of LNs, and demonstrated by polymerase chain reaction-restriction fragment length polymorphism. The skin biopsy showed neutrophilic dermatosis, consistent with Sweet syndrome. The patient met the criteria of both adult-onset immunodeficiency syndrome and IgG4-related lymphadenopathy. This case provides evidence of disseminated NTM infection with concurrent type III IgG4-related lymphadenopathy in the patient with anti-IFN-γ autoantibodies. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

PubMed Central

2015-01-01

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

PubMed

Ufimtseva, Elena

2015-01-01

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

Paradigm for diagnosing mycobacterial disease: direct detection and differentiation of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria in clinical specimens using multiplex real-time PCR.

PubMed

Kim, Jeong-Uk; Ryu, Dae-Shick; Cha, Choong-Hwan; Park, Seon-Hee

2018-03-20

Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) are clinically different, and the rapid detection and differentiation of M. tuberculosis complex (MTBC) and NTM is crucial for patient management and infection control. Given the slow growth of most pathogenic mycobacteria, nucleic acid amplification assays are excellent tools for direct identification of mycobacteria in clinical specimens. Recently, a multiplex real-time PCR assay was developed that can directly detect 20 mycobacterial species in clinical specimens. Here, we evaluated the diagnostic performance of the assay for diagnosing mycobacterial disease under routine laboratory conditions. A total of 3334 specimens collected from 1437 patients suspected of tuberculosis infection were subjected to acid-fast bacilli staining, conventional culture and the multiplex real-time PCR assay. To evaluate the sensitivity and specificity of the assay, the overall diagnosis of tuberculosis was defined by positive culture plus medical history, and the 2007 American Thoracic Society and Infectious Disease Society of America diagnostic criteria for NTM disease were applied. The sensitivity, specificity, positive predictive value and negative predictive value were 87.5%, 99.6%, 96.1% and 98.5%, respectively, for the detection of MTBC isolates and 53.3%, 99.9%, 95.2%, and 98.9%, respectively, for detecting NTM isolates. Thus, the assay can correctly differentiate between MTBC and NTM isolates in clinical specimens and would be a useful tool for the rapid differentiation of tuberculosis and NTM disease, despite its limited sensitivity for the diagnosis of NTM disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Goal-directed fluid therapy for reducing risk of surgical site infections following abdominal surgery - A systematic review and meta-analysis of randomized controlled trials.

PubMed

Yuan, Jianhu; Sun, Yanxia; Pan, Chuxiong; Li, Tianzuo

2017-03-01

Surgical site infections (SSIs) become a key indicator of quality of care. This meta-analysis aimed to determine the effect of goal-directed fluid therapy (GDFT) on the risk of SSIs after abdominal surgery. MEDLINE, Embase, CINAHL, Scopus, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs), from inception to May 2016 that compared the incidence of SSIs in abdominal surgical patients with or without GDFT treatment. . Data were pooled and risk ratio (RR) as well as weighted mean differences (WMD) with their 95% confidence intervals (CI) was calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). A total of 29 eligible RCTs with 5317 patients were included in this analysis. GDFT significantly reduced the incidence of SSIs after abdominal surgery. The pooled RR was 0.74 (95% CI: 0.63 to 0.86) with low heterogeneity (I 2  = 4%). Length of hospital stay was significantly reduced in the GDFT group (WMD: -1.16 days, 95% CI: -1.92 to -0.40, p = 0.003; I 2  = 81%). This systematic review suggests that perioperative GDFT is associated with a reduction in the incidence of SSIs after abdominal surgery. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Rapid Identification of Mycobacterial Whole Cells in Solid and Liquid Culture Media by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry ▿

PubMed Central

Lotz, Aurélie; Ferroni, Agnès; Beretti, Jean-Luc; Dauphin, Brunhilde; Carbonnelle, Etienne; Guet-Revillet, Hélène; Veziris, Nicolas; Heym, Béate; Jarlier, Vincent; Gaillard, Jean-Louis; Pierre-Audigier, Catherine; Frapy, Eric; Berche, Patrick; Nassif, Xavier; Bille, Emmanuelle

2010-01-01

Mycobacterial identification is based on several methods: conventional biochemical tests that require several weeks for accurate identification, and molecular tools that are now routinely used. However, these techniques are expensive and time-consuming. In this study, an alternative method was developed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). This approach allows a characteristic mass spectral fingerprint to be obtained from whole inactivated mycobacterial cells. We engineered a strategy based on specific profiles in order to identify the most clinically relevant species of mycobacteria. To validate the mycobacterial database, a total of 311 strains belonging to 31 distinct species and 4 species complexes grown in Löwenstein-Jensen (LJ) and liquid (mycobacterium growth indicator tube [MGIT]) media were analyzed. No extraction step was required. Correct identifications were obtained for 97% of strains from LJ and 77% from MGIT media. No misidentification was noted. Our results, based on a very simple protocol, suggest that this system may represent a serious alternative for clinical laboratories to identify mycobacterial species. PMID:20943874

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance

PubMed Central

2010-01-01

Background The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance. Results Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG → TCG (Glu → Ser) at codon 469 of rpoB gene. Conclusions This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control. PMID:20236539

Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.

PubMed

Monin, Leticia; Mehta, Shail; Elsegeiny, Waleed; Gopal, Radha; McAleer, Jeremy P; Oury, Tim D; Kolls, Jay; Khader, Shabaana A

2018-03-01

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. Copyright © 2018 American Society for Microbiology.

[Characterisation of Candida sp. isolated from patients after abdominal surgery].

PubMed

Adámková, V; Vaňková, A; Ulrych, J; Matek, K

2017-01-01

Intraabdominal candidiasis (IAC) is the predominant type of invasive candidiasis after candidemia. The majority of epidemiological studies on Candida are focused only on bloodstream infections. Nevertheless, the role of blood cultures has limited application in patients with abdominal candidiasis. IAC, which includes peritonitis and intraabdominal abscesses, may occur in around 40% of patients following repeat gastrointestinal (GI) surgery or GI perforation. Retrospective analysis of culture isolates of Candida sp. from clinical specimens of patients after abdominal surgery. The study period was from January 1 to October 31, 2016. Our study of 33 patients with findings of Candida sp. from the abdominal cavity found a mortality of 15.2%, the most frequent strain being C. albicans and C. glabrata. All strains of Candida sp. were susceptible to echinocandins. Candida sp. is part of normal microbiota of the gastrointestinal tract and its isolation is often difficult to interpret. Unfortunately, the pathophysiologic importance of Candida isolation from the abdominal space is not completely clear in many clinical situations.Key words: invasive candidiasis intra-abdominal candidiasis laboratory diagnostics.

Temporary abdominal closure with zipper-mesh device for management of intra-abdominal sepsis.

PubMed

Utiyama, Edivaldo Massazo; Pflug, Adriano Ribeiro Meyer; Damous, Sérgio Henrique Bastos; Rodrigues, Adilson Costa; Montero, Edna Frasson de Souza; Birolini, Claudio Augusto Vianna

2015-01-01

to present our experience with scheduled reoperations in 15 patients with intra-abdominal sepsis. we have applied a more effective technique consisting of temporary abdominal closure with a nylon mesh sheet containing a zipper. We performed reoperations in the operating room under general anesthesia at an average interval of 84 hours. The revision consisted of debridement of necrotic material and vigorous lavage of the involved peritoneal area. The mean age of patients was 38.7 years (range, 15 to 72 years); 11 patients were male, and four were female. forty percent of infections were due to necrotizing pancreatitis. Sixty percent were due to perforation of the intestinal viscus secondary to inflammation, vascular occlusion or trauma. We performed a total of 48 reoperations, an average of 3.2 surgeries per patient. The mesh-zipper device was left in place for an average of 13 days. An intestinal ostomy was present adjacent to the zipper in four patients and did not present a problem for patient management. Mortality was 26.6%. No fistulas resulted from this technique. When intra-abdominal disease was under control, the mesh-zipper device was removed, and the fascia was closed in all patients. In three patients, the wound was closed primarily, and in 12 it was allowed to close by secondary intent. Two patients developed hernia; one was incisional and one was in the drain incision. the planned reoperation for manual lavage and debridement of the abdomen through a nylon mesh-zipper combination was rapid, simple, and well-tolerated. It permitted effective management of severe septic peritonitis, easy wound care and primary closure of the abdominal wall.

Pulmonary Non-tuberculous Mycobacterial Infections in Category II Failures from National Tuberculosis Programme.

PubMed

Dholakia, Y N; Shah, D P

2015-01-01

Pulmonary infections due to non-tuberculous mycobacteria (NTM) are increasingly being reported. These can mimic drug-resitant tubercuolosis. A diagnosis of NTM infections needs a high degree of clinical suspicion and repeated isolation of the organism on culture. NTM infections occur commonly in immunocompromised individuals and in people with lung abnormalities. Currently there are no guidelines on drug combinations and the duration of treatment is not adequately defined. Two cases of pulmonary infection with NTM in immune-competent individuals are described in the present report. Although the bacteriological, radiological and clinical response to treatment was good; early discontinuation of treatment resulted in recurrence and change in drug susceptibility pattern, suggesting the need for prolonged treatment for achieving cure.

A green fluorescent protein-based assay for high-throughput ligand-binding studies of a mycobacterial biotin protein ligase.

PubMed

Bond, Thomas E H; Sorenson, Alanna E; Schaeffer, Patrick M

2017-12-01

Biotin protein ligase (BirA) has been identified as an emerging drug target in Mycobacterium tuberculosis due to its essential metabolic role. Indeed, it is the only enzyme capable of covalently attaching biotin onto the biotin carboxyl carrier protein subunit of the acetyl-CoA carboxylase. Despite recent interest in this protein, there is still a gap in cost-effective high-throughput screening assays for rapid identification of mycobacterial BirA-targeting inhibitors. We present for the first time the cloning, expression, purification of mycobacterial GFP-tagged BirA and its application for the development of a high-throughput assay building on the principle of differential scanning fluorimetry of GFP-tagged proteins. The data obtained in this study reveal how biotin and ATP significantly increase the thermal stability (ΔT m =+16.5°C) of M. tuberculosis BirA and lead to formation of a high affinity holoenzyme complex (K obs =7.7nM). The new findings and mycobacterial BirA high-throughput assay presented in this work could provide an efficient platform for future anti-tubercular drug discovery campaigns. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ocular localization of mycobacterial lesions in tank-reared juvenile cobia, Rachycentron canadum.

PubMed

Phillips, A C N; Suepaul, R; Soto, E

2017-12-01

Severe clinical mycobacteriosis with consistent ocular lesion localization was diagnosed in a population of 800 juvenile tank-reared Cobia (Rachycentron canadum) which experienced a sudden increase in mortality approximately 5 months after arriving into Trinidad and Tobago from Florida, USA. Moderate daily mortality (15-20 animals per day) persisted for just over 1 month. Moribund fish displayed circling behaviour and had an open-mouth gape upon death. Fish consistently presented with bilateral exophthalmia, corneal cloudiness and hyphema. Non-branching acid-fast rods were detected in aqueous humour touch preparations. Histological analysis revealed severe bilateral intra-ocular granulomatous responses in all specimens. Mycobacterium sp. was identified using a real-time PCR assay detecting the RNA polymerase β-subunit (rpoB) gene in different tissue samples. Specimens did not present with characteristic granulomatous responses usually seen in viscera. To the best of our knowledge, this represents only the third documentation of piscine mycobacterial infection presenting with only localized ocular lesions, and the second documented case of mycobacteriosis in cobia. It is, however, the first documentation of an ocular presentation of mycobacteriosis in a marine species and is the first documentation of such a presentation in cobia. © 2017 John Wiley & Sons Ltd.

Surgical management of cutaneous infection caused by atypical mycobacteria after penetrating injury: the hidden dangers of horticulture.

PubMed

Holland, J; Smith, C; Childs, P A; Holland, A J

1997-02-01

We identified two patients in a 12-month period who presented with cutaneous infection and secondary lymph node involvement from atypical mycobacterial infection after minor gardening injuries. One patient had a coinfection with Nocardia asteroides. Both patients required multiple surgical interventions, despite appropriate antibiotic therapy, before resolution of the disease. The course of the infection was characterized by chronic relapses with complete healing at 12 to 18 months after the original injury. The identification and management of this clinical problem are reviewed.

Effect of Apoptotic Cell Recognition on Macrophage Polarization and Mycobacterial Persistence

PubMed Central

de Oliveira Fulco, Tatiana; Andrade, Priscila Ribeiro; de Mattos Barbosa, Mayara Garcia; Pinto, Thiago Gomes Toledo; Ferreira, Paula Fernandez; Ferreira, Helen; da Costa Nery, José Augusto; Real, Suzana Côrte; Borges, Valéria Matos; Moraes, Milton Ozório; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

2014-01-01

Intracellular Mycobacterium leprae infection modifies host macrophage programming, creating a protective niche for bacterial survival. The milieu regulating cellular apoptosis in the tissue plays an important role in defining susceptible and/or resistant phenotypes. A higher density of apoptotic cells has been demonstrated in paucibacillary leprosy lesions than in multibacillary ones. However, the effect of apoptotic cell removal on M. leprae-stimulated cells has yet to be fully elucidated. In this study, we investigated whether apoptotic cell removal (efferocytosis) induces different phenotypes in proinflammatory (Mϕ1) and anti-inflammatory (Mϕ2) macrophages in the presence of M. leprae. We stimulated Mϕ1 and Mϕ2 cells with M. leprae in the presence or absence of apoptotic cells and subsequently evaluated the M. leprae uptake, cell phenotype, and cytokine pattern in the supernatants. In the presence of M. leprae and apoptotic cells, Mϕ1 macrophages changed their phenotype to resemble the Mϕ2 phenotype, displaying increased CD163 and SRA-I expression as well as higher phagocytic capacity. Efferocytosis increased M. leprae survival in Mϕ1 cells, accompanied by reduced interleukin-15 (IL-15) and IL-6 levels and increased transforming growth factor beta (TGF-β) and IL-10 secretion. Mϕ1 cells primed with M. leprae in the presence of apoptotic cells induced the secretion of Th2 cytokines IL-4 and IL-13 in autologous T cells compared with cultures stimulated with M. leprae or apoptotic cells alone. Efferocytosis did not alter the Mϕ2 cell phenotype or cytokine secretion profile, except for TGF-β. Based on these data, we suggest that, in paucibacillary leprosy patients, efferocytosis contributes to mycobacterial persistence by increasing the Mϕ2 population and sustaining the infection. PMID:25024361

GenoMycDB: a database for comparative analysis of mycobacterial genes and genomes.

PubMed

Catanho, Marcos; Mascarenhas, Daniel; Degrave, Wim; Miranda, Antonio Basílio de

2006-03-31

Several databases and computational tools have been created with the aim of organizing, integrating and analyzing the wealth of information generated by large-scale sequencing projects of mycobacterial genomes and those of other organisms. However, with very few exceptions, these databases and tools do not allow for massive and/or dynamic comparison of these data. GenoMycDB (http://www.dbbm.fiocruz.br/GenoMycDB) is a relational database built for large-scale comparative analyses of completely sequenced mycobacterial genomes, based on their predicted protein content. Its central structure is composed of the results obtained after pair-wise sequence alignments among all the predicted proteins coded by the genomes of six mycobacteria: Mycobacterium tuberculosis (strains H37Rv and CDC1551), M. bovis AF2122/97, M. avium subsp. paratuberculosis K10, M. leprae TN, and M. smegmatis MC2 155. The database stores the computed similarity parameters of every aligned pair, providing for each protein sequence the predicted subcellular localization, the assigned cluster of orthologous groups, the features of the corresponding gene, and links to several important databases. Tables containing pairs or groups of potential homologs between selected species/strains can be produced dynamically by user-defined criteria, based on one or multiple sequence similarity parameters. In addition, searches can be restricted according to the predicted subcellular localization of the protein, the DNA strand of the corresponding gene and/or the description of the protein. Massive data search and/or retrieval are available, and different ways of exporting the result are offered. GenoMycDB provides an on-line resource for the functional classification of mycobacterial proteins as well as for the analysis of genome structure, organization, and evolution.

Clinical significance of mycobacterial genotyping in Mycobacterium avium lung disease in Korea.

PubMed

Kim, S-Y; Lee, S-T; Jeong, B-H; Jeon, K; Kim, J-W; Shin, S J; Koh, W-J

2012-10-01

A recent study in Japan found that mycobacterial genotyping was associated with disease progression and susceptibility to certain drugs in Mycobacterium avium lung disease. However, it is not known whether this association is true in other populations. To investigate the association between mycobacterial genotype, clinical characteristics and the progression of M. avium lung disease in Korean patients. A total of 102 M. avium clinical isolates were genotyped using M. avium tandem repeats-variable number of tandem repeats (MATR-VNTR). MATR-VNTR typing demonstrated a high discriminatory power and genetic diversity for molecular epidemiological studies of M. avium. In the phylogenetic tree, the M. avium clinical isolates were divided into three major clusters: A, B and C. Cluster A was observed most frequently (64/102, 63%), whereas cluster C was found in a minor proportion of the isolates (8/102, 8%). However, there was no association between the clinical characteristics, disease progression and drug susceptibility and the phylogenetic tree based on VNTR genotyping. MATR-VNTR genotyping may be useful for epidemiological studies of M. avium lung disease; however, no association was found between the specific VNTR genotypes of M. avium and the clinical characteristics of Korean patients.

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

[Abdominal trauma].

PubMed

Sido, B; Grenacher, L; Friess, H; Büchler, M W

2005-09-01

Blunt abdominal trauma is much more frequent than penetrating abdominal trauma in Europe. As a consequence of improved quality of computed tomography, even complex liver injuries are increasingly being treated conservatively. However, missed hollow viscus injuries still remain a problem, as they considerably increase mortality in multiply injured patients. Laparoscopy decreases the rate of unnecessary laparotomies in perforating abdominal trauma and helps to diagnose injuries of solid organs and the diaphragm. However, the sensitivity in detecting hollow viscus injuries is low and the role of laparoscopy in blunt abdominal injury has not been defined. If intra-abdominal bleeding is difficult to control in hemodynamically unstable patients, damage control surgery with packing of the liver, total splenectomy, and provisional closure of hollow viscus injuries is of importance. Definitive surgical treatment follows hemodynamic stabilization and restoration of hemostasis. Injuries of the duodenum and pancreas after blunt abdominal trauma are often associated with other intra-abdominal injuries and the treatment depends on their location and severity.

Domain Requirements for DNA Unwinding by Mycobacterial UvrD2, an Essential DNA Helicase†

PubMed Central

Sinha, Krishna Murari; Stephanou, Nicolas C.; Unciuleac, Mihaela-Carmen; Glickman, Michael S.; Shuman, Stewart

2008-01-01

Mycobacterial UvrD2 is a DNA-dependent ATPase with 3′ to 5′ helicase activity. UvrD2 is an atypical helicase, insofar as its N-terminal ATPase domain resembles the superfamily I helicases UvrD/PcrA, yet it has a C-terminal HRDC domain, which is a feature of RecQ-type superfamily II helicases. The ATPase and HRDC domains are connected by a CxxC-(14)-CxxC tetracysteine module that defines a new clade of UvrD2-like bacterial helicases found only in Actinomycetales. By characterizing truncated versions of Mycobacterium smegmatis UvrD2, we show that whereas the HRDC domain is not required for ATPase or helicase activities in vitro, deletion of the tetracysteine module abolishes duplex unwinding while preserving ATP hydrolysis. Replacing each of the CxxC motifs with a double-alanine variant AxxA had no effect on duplex unwinding, signifying that the domain module, not the cysteines, is crucial for function. The helicase activity of a truncated UvrD2 lacking the tetracysteine and HRDC domains was restored by the DNA-binding protein Ku, a component of the mycobacterial NHEJ system and a cofactor for DNA unwinding by the paralogous mycobacterial helicase UvrD1. Our findings indicate that coupling of ATP hydrolysis to duplex unwinding can be achieved by protein domains acting in cis or trans. Attempts to disrupt the M. smegmatis uvrD2 gene were unsuccessful unless a second copy of uvrD2 was present elsewhere in the chromosome, indicating that UvrD2 is essential for growth of M. smegmatis. PMID:18702526

Chronic abdominal wall pain misdiagnosed as functional abdominal pain.

PubMed

van Assen, Tijmen; de Jager-Kievit, Jenneke W A J; Scheltinga, Marc R; Roumen, Rudi M H

2013-01-01

The abdominal wall is often neglected as a cause of chronic abdominal pain. The aim of this study was to identify chronic abdominal wall pain syndromes, such as anterior cutaneous nerve entrapment syndrome (ACNES), in a patient population diagnosed with functional abdominal pain, including irritable bowel syndrome, using a validated 18-item questionnaire as an identification tool. In this cross-sectional analysis, 4 Dutch primary care practices employing physicians who were unaware of the existence of ACNES were selected. A total of 535 patients ≥18 years old who were registered with a functional abdominal pain diagnosis were approached when they were symptomatic to complete the questionnaire (maximum 18 points). Responders who scored at least the 10-point cutoff value (sensitivity, 0.94; specificity, 0.92) underwent a diagnostic evaluation to establish their final diagnosis. The main outcome was the presence and prevalence of ACNES in a group of symptomatic patients diagnosed with functional abdominal pain. Of 535 patients, 304 (57%) responded; 167 subjects (31%) recently reporting symptoms completed the questionnaire. Of 23 patients who scored above the 10-point cutoff value, 18 were available for a diagnostic evaluation. In half of these subjects (n = 9) functional abdominal pain (including IBS) was confirmed. However, the other 9 patients were suffering from abdominal wall pain syndrome, 6 of whom were diagnosed with ACNES (3.6% prevalence rate of symptomatic subjects; 95% confidence interval, 1.7-7.6), whereas the remaining 3 harbored a painful lipoma, an abdominal herniation, and a painful scar. A clinically relevant portion of patients previously diagnosed with functional abdominal pain syndrome in a primary care environment suffers from an abdominal wall pain syndrome such as ACNES.

Mycobacterium fortuitum Infection at Umbilical Hernioplasty Site

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev; Shenoy, Vishnu Prasad

2017-01-01

Non Tuberculous Mycobacteria (NTM) are a group of rapidly growing mycobacteria and are generally considered to be of low virulence. Of late, there has been an increase in incidence of infections due to these organisms. Among them, Mycobacterium fortuitum, M. chelonae and M. abscessus are the common species which have been identified. Though they are occasionally implicated in pulmonary infections, NTM are very commonly associated with cutaneous infections, especially surgical site infections. Identification of NTM infection at such sites should be suspected when there is delayed healing of the wound. Histopathological Examination (HPE) of the wound site may reveal a classical picture of granulomas, epithelioid cells and giant cells which may lead to a suspicion of tuberculosis. It is important to perform mycobacterial culture and sensitivity testing of the wound tissue as this helps to differentiate tuberculous and non tuberculous infections. Here, we present a case of a patient who underwent mesh hernioplasty for umbilical hernia and was diagnosed with M. fortuitum infection at the site of umbilical hernioplasty. PMID:29207758

Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli.

PubMed

Alexandre, K; Chau, F; Guérin, F; Massias, L; Lefort, A; Cattoir, V; Fantin, B

2016-07-01

Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli. Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal fluid (PF) and spleen were collected; 24 h survival and sterility rates were assessed. Temocillin MICs were 8, 16, 32, and 256 mg/L for the susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains, respectively. In mice treated with temocillin, significant bacterial reduction was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and KPC-3-producing strains (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) for mice infected with the susceptible strain and KPC-2-, KPC-3- and OXA-48-producing strains, respectively. In a lethal-infection model with bacteraemia from intra-abdominal origin, temocillin retained significant activity in PF, blood and spleen and prevented death in mice by effectively working against KPC-producing E. coli with temocillin MICs ≤16 mg/L. © The Author 2016. 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.

Low serum vitamin D levels in type 2 diabetes patients are associated with decreased mycobacterial activity.

PubMed

Herrera, María Teresa; Gonzalez, Yolanda; Hernández-Sánchez, Fernando; Fabián-San Miguel, Guadalupe; Torres, Martha

2017-09-07

Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels. In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human β defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38). Twenty-seven type 2 diabetes mellitus patients had inadequate inactive vitamin D levels (<50 nM). The percentages of M. tuberculosis phagocytosis between monocytes were similar across groups according to microscopy. Intracellular mycobacterial growth was similar in infected monocytes from both groups. However, M. tuberculosis growth was significantly higher in monocytes obtained from type 2 diabetes mellitus patients and lower vitamin D levels after 1-h (D0) and 72-h (D3) post-infection (p ≤ 0.05). LL-37, human β defensin-2 and IL-10 mRNA expression were similar between monocytes across groups; vitamin D serum levels and LL-37, human β defensin-2 and IL-10 expression were not correlated. Nitric oxide production was significantly higher in healthy volunteers than in type 2 diabetes mellitus patients with low vitamin D serum levels at D3 post-infection (p ≤ 0.05). Our results show that monocytes from type 2 diabetes mellitus patients and low vitamin D serum levels show an impaired ability to control the intracellular growth of M. tuberculosis, which is not associated with significant decrease of LL-37 or human β defensin-2 expression. Vitamin D could be the link between diabetes and tuberculosis susceptibility.

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study).

PubMed

Sartelli, Massimo; Abu-Zidan, Fikri M; Catena, Fausto; Griffiths, Ewen A; Di Saverio, Salomone; Coimbra, Raul; Ordoñez, Carlos A; Leppaniemi, Ari; Fraga, Gustavo P; Coccolini, Federico; Agresta, Ferdinando; Abbas, Asrhaf; Abdel Kader, Saleh; Agboola, John; Amhed, Adamu; Ajibade, Adesina; Akkucuk, Seckin; Alharthi, Bandar; Anyfantakis, Dimitrios; Augustin, Goran; Baiocchi, Gianluca; Bala, Miklosh; Baraket, Oussama; Bayrak, Savas; Bellanova, Giovanni; Beltràn, Marcelo A; Bini, Roberto; Boal, Matthew; Borodach, Andrey V; Bouliaris, Konstantinos; Branger, Frederic; Brunelli, Daniele; Catani, Marco; Che Jusoh, Asri; Chichom-Mefire, Alain; Cocorullo, Gianfranco; Colak, Elif; Costa, David; Costa, Silvia; Cui, Yunfeng; Curca, Geanina Loredana; Curry, Terry; Das, Koray; Delibegovic, Samir; Demetrashvili, Zaza; Di Carlo, Isidoro; Drozdova, Nadezda; El Zalabany, Tamer; Enani, Mushira Abdulaziz; Faro, Mario; Gachabayov, Mahir; Giménez Maurel, Teresa; Gkiokas, Georgios; Gomes, Carlos Augusto; Gonsaga, Ricardo Alessandro Teixeira; Guercioni, Gianluca; Guner, Ali; Gupta, Sanjay; Gutierrez, Sandra; Hutan, Martin; Ioannidis, Orestis; Isik, Arda; Izawa, Yoshimitsu; Jain, Sumita A; Jokubauskas, Mantas; Karamarkovic, Aleksandar; Kauhanen, Saila; Kaushik, Robin; Kenig, Jakub; Khokha, Vladimir; Kim, Jae Il; Kong, Victor; Koshy, Renol; Krasniqi, Avidyl; Kshirsagar, Ashok; Kuliesius, Zygimantas; Lasithiotakis, Konstantinos; Leão, Pedro; Lee, Jae Gil; Leon, Miguel; Lizarazu Pérez, Aintzane; Lohsiriwat, Varut; López-Tomassetti Fernandez, Eudaldo; Lostoridis, Eftychios; Mn, Raghuveer; Major, Piotr; Marinis, Athanasios; Marrelli, Daniele; Martinez-Perez, Aleix; Marwah, Sanjay; McFarlane, Michael; Melo, Renato Bessa; Mesina, Cristian; Michalopoulos, Nick; Moldovanu, Radu; Mouaqit, Ouadii; Munyika, Akutu; Negoi, Ionut; Nikolopoulos, Ioannis; Nita, Gabriela Elisa; Olaoye, Iyiade; Omari, Abdelkarim; Ossa, Paola Rodríguez; Ozkan, Zeynep; Padmakumar, Ramakrishnapillai; Pata, Francesco; Pereira Junior, Gerson Alves; Pereira, Jorge; Pintar, Tadeja; Pouggouras, Konstantinos; Prabhu, Vinod; Rausei, Stefano; Rems, Miran; Rios-Cruz, Daniel; Sakakushev, Boris; Sánchez de Molina, Maria Luisa; Seretis, Charampolos; Shelat, Vishal; Simões, Romeo Lages; Sinibaldi, Giovanni; Skrovina, Matej; Smirnov, Dmitry; Spyropoulos, Charalampos; Tepp, Jaan; Tezcaner, Tugan; Tolonen, Matti; Torba, Myftar; Ulrych, Jan; Uzunoglu, Mustafa Yener; van Dellen, David; van Ramshorst, Gabrielle H; Vasquez, Giorgio; Venara, Aurélien; Vereczkei, Andras; Vettoretto, Nereo; Vlad, Nutu; Yadav, Sanjay Kumar; Yilmaz, Tonguç Utku; Yuan, Kuo-Ching; Zachariah, Sanoop Koshy; Zida, Maurice; Zilinskas, Justas; Ansaloni, Luca

2015-01-01

To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Mycobacterial culture

MedlinePlus

... test to look for the bacteria that cause tuberculosis and other infections caused by similar bacteria. How ... order this test if you have signs of tuberculosis or a related infection. Normal Results If there ...

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

PubMed

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Complex sacral abscess 8 years after abdominal sacral colpopexy.

PubMed

Collins, Sarah A; Tulikangas, Paul K; LaSala, Christine A; Lind, Lawrence R

2011-08-01

Sacral colpopexy is an effective, durable repair for women with apical vaginal or uterovaginal prolapse. There are few reports of serious complications diagnosed in the remote postoperative period. A 74-year-old woman presented 8 years after undergoing posthysterectomy abdominal sacral colpopexy using polypropylene mesh. Posterior vaginal mesh erosion had been diagnosed several months before presentation. She suffered severe infectious complications including an infected thrombus in the inferior vena cava, sacral osteomyelitis, and a complex abscess with presacral and epidural components. Surgical exploration revealed an abscess cavity surrounding the mesh. Although minor complications commonly occur after sacral colpopexy using abdominal mesh, serious and rare postoperative infectious complications may occur years postoperatively.

Mycobacterial infection in Northern snakehead (Channa argus) from the Potomac River catchment

USGS Publications Warehouse

Densmore, Christine L.; Iwanowicz, L.R.; Henderson, A.P.; Iwanowicz, D.D.; Odenkirk, J.S.

2016-01-01

The Northern snakehead, Channa argus (Cantor), is a non-native predatory fish that has become established regionally in some temperate freshwater habitats within the United States. Over the past decade, Northern snakehead populations have developed within aquatic ecosystems throughout the eastern USA, including the Potomac River system within Virginia, Maryland and Washington, D.C. Since this species was initially observed in this region in 2002, the population has expanded considerably (Odenkirk & Owens 2007). In the Chesapeake Bay watershed, populations of Northern snakehead exist in the lower Potomac River and Rappahannock Rivers on the Western shore of the Bay, and these fish have also been found in middle or upper reaches of river systems on the Eastern shore of the Bay, including the Nanticoke and Wicomico Rivers among others. Over the past several years, many aspects of Northern snakehead life history in the Potomac River have been described, including range and dispersal patterns, microhabitat selection and diet (Lapointe, Thorson & Angermeier 2010; Saylor, Lapointe & Angermeier 2012; Lapointe, Odenkirk & Angermeier 2013). However, comparatively little is known about their health status including susceptibility to parasitism and disease and their capacity to serve as reservoirs of disease for native wildlife. Although considered hardy by fisheries biologists, snakehead fish have demonstrated susceptibility to a number of described piscine diseases within their native range and habitat in Asia. Reported pathogens of significance in snakehead species in Asia include snakehead rhabdovirus (Lio-Po et al. 2000), aeromonad bacteria (Zheng, Cao & Yang 2012), Nocardia (Wang et al. 2007) andMycobacterium spp. (Chinabut, Limsuwan & Chantatchakool 1990; ). Mycobacterial isolates recovered from another snakehead species (Channa striata) in the previous studies have included M. marinum and M. fortuitum, as identified through molecular

Management of intra-abdominal hypertension and abdominal compartment syndrome: a review

PubMed Central

2014-01-01

Patients in the intensive care unit (ICU) are at risk of developing of intra abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Aim: This review seeks to define IAH and ACS, identify the aetiology and presentation of IAH and ACS, identify IAP measurement techniques, identify current management and discuss the implications of IAH and ACS for nursing practice. A search of the electronic databases was supervised by a health librarian. The electronic data bases Cumulative Index of Nursing and Allied Health Literature (CINAHL); Medline, EMBASE, and the World Wide Web was undertaken from 1996- January 2011 using MeSH and key words which included but not limited to: abdominal compartment syndrome, intra -abdominal hypertension, intra-abdominal pressure in adult populations met the search criteria and were reviewed by three authors using a critical appraisal tool. Data derived from the retrieved material are discussed under the following themes: (1) etiology of intra-abdominal hypertension; (2) strategies for measuring intra-abdominal pressure (3) the manifestation of abdominal compartment syndrome; and (4) the importance of nursing assessment, observation and interventions. Intra-abdominal pressure (IAP) and abdominal compartment syndrome (ACS) have the potential to alter organ perfusion and compromise organ function. PMID:24499574

Infected Aneurysm after Endoscopic Submucosal Dissection.

PubMed

Gen, Shiko; Usui, Ryuichi; Sasaki, Takaya; Nobe, Kanako; Takahashi, Aya; Okudaira, Keisuke; Ikeda, Naofumi

2016-01-01

A 79-year-old man on hemodialysis was hospitalized for further investigation. Early gastric cancer was diagnosed by gastrointestinal endoscopy and endoscopic submucosal dissection (ESD) was performed. Fever and abdominal pain thereafter developed, and a severe inflammatory response was observed on a blood test. Contrast computed tomography (CT) showed ulcer-like projections and soft tissue surrounding the aorta, from the celiac to left renal artery. An infected aneurysm was diagnosed. Although infected aneurysms developing after laparoscopic cholecystectomy or biopsy of contiguous esophageal duplication cyst have been reported, those developing after ESD have not. When fever and abdominal pain develop after ESD, an infected aneurysm should be considered and contrast CT performed.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

PubMed

Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

2017-10-01

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Determining the mode of action of anti-mycobacterial C17 diyne natural products using expression profiling: evidence for fatty acid biosynthesis inhibition.

PubMed

Li, Haoxin; Cowie, Andrew; Johnson, John A; Webster, Duncan; Martyniuk, Christopher J; Gray, Christopher A

2016-08-11

The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, their mode of action remains largely undetermined in microbes. Gene expression profiling was therefore used to determine the transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol and panaxydol to better characterize the mode of action of these C17 diynes. Our analyses identified 704 and 907 transcripts that were differentially expressed in M. smegmatis after treatment with falcarinol and panaxydol respectively. Principal component analysis suggested that the C17 diynes exhibit a mode of action that is distinct to commonly used antimycobacterial drugs. Functional enrichment analysis and pathway enrichment analysis revealed that cell processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid synthesis were responsive to falcarinol and panaxydol treatment at the transcriptome level in M. smegmatis. The modes of action of the two C17 diynes were also predicted through Prediction of Activity Spectra of Substances (PASS). Based upon convergence of these three independent analyses, we hypothesize that the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid synthesis, in mycobacteria. Based on transcriptomic responses, it is suggested that the C17 diynes act differently than other anti-mycobacterial compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis.

The Host Response to a Clinical MDR Mycobacterial Strain Cultured in a Detergent-Free Environment: A Global Transcriptomics Approach.

PubMed

Leisching, Gina; Pietersen, Ray-Dean; Mpongoshe, Vuyiseka; van Heerden, Carel; van Helden, Paul; Wiid, Ian; Baker, Bienyameen

2016-01-01

During Mycobacterium tuberculosis (M.tb) infection, the initial interactions between the pathogen and the host cell determines internalization and innate immune response events. It is established that detergents such as Tween alter the mycobacterial cell wall and solubilize various lipids and proteins. The implication of this is significant since induced changes on the cell wall affect macrophage uptake and the immune response to M.tb. Importantly, during transmission between hosts, aerosolized M.tb enters the host in its native form, i.e. in a detergent-free environment, thus in vitro and in vivo studies should mimic this as closely as possible. To this end, we have optimized a procedure for growing and processing detergent-free M.tb and assessed the response of murine macrophages (BMDM) infected with multi drug-resistant M.tb (R179 Beijing 220 clinical isolate) using RNAseq. We compared the effects of the host response to M.tb cultured under standard laboratory conditions (Tween 80 containing medium -R179T), or in detergent-free medium (R179NT). RNAseq comparisons reveal 2651 differentially expressed genes in BMDMs infected with R179T M.tb vs. BMDMs infected with R179NT M.tb. A range of differentially expressed genes involved in BMDM receptor interaction with M.tb (Mrc1, Ifngr1, Tlr9, Fpr1 and Itgax) and pro-inflammatory cytokines/chemokines (Il6, Il1b, Tnf, Ccl5 and Cxcl14) were selected for analysis through qPCR. BMDMs infected with R179NT stimulate a robust inflammatory response. Interestingly, R179NT M.tb induce transcription of Fpr1, a receptor which detects bacterial formyl peptides and initiates a myriad of immune responses. Additionally we show that the host components Cxcl14, with an unknown role in M.tb infection, and Tlr9, an emerging role player, are only stimulated by infection with R179NT M.tb. Taken together, our results suggest that the host response differs significantly in response to Tween 80 cultured M.tb and should therefore not be used in

Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis.

PubMed

Tantry, Subramanyam J; Markad, Shankar D; Shinde, Vikas; Bhat, Jyothi; Balakrishnan, Gayathri; Gupta, Amit K; Ambady, Anisha; Raichurkar, Anandkumar; Kedari, Chaitanyakumar; Sharma, Sreevalli; Mudugal, Naina V; Narayan, Ashwini; Naveen Kumar, C N; Nanduri, Robert; Bharath, Sowmya; Reddy, Jitendar; Panduga, Vijender; Prabhakar, K R; Kandaswamy, Karthikeyan; Saralaya, Ramanatha; Kaur, Parvinder; Dinesh, Neela; Guptha, Supreeth; Rich, Kirsty; Murray, David; Plant, Helen; Preston, Marian; Ashton, Helen; Plant, Darren; Walsh, Jarrod; Alcock, Peter; Naylor, Kathryn; Collier, Matthew; Whiteaker, James; McLaughlin, Robert E; Mallya, Meenakshi; Panda, Manoranjan; Rudrapatna, Suresh; Ramachandran, Vasanthi; Shandil, Radha; Sambandamurthy, Vasan K; Mdluli, Khisi; Cooper, Christopher B; Rubin, Harvey; Yano, Takahiro; Iyer, Pravin; Narayanan, Shridhar; Kavanagh, Stefan; Mukherjee, Kakoli; Balasubramanian, V; Hosagrahara, Vinayak P; Solapure, Suresh; Ravishankar, Sudha; Hameed P, Shahul

2017-02-23

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.

Sophora flavescens protects against mycobacterial Trehalose Dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages.

PubMed

Liu, Dehua; Chan, Ben Chung-Lap; Cheng, Ling; Tsang, Miranda Sin-Man; Zhu, Jing; Wong, Chun-Wai; Jiao, Delong; Chan, Helen Yau-Tsz; Leung, Ping Chung; Lam, Christopher Wai-Kei; Wong, Chun Kwok

2018-03-02

The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface. Moreover, FSF reduced adhesion molecule (LFA-1) expression on MH-S cells after TDM stimulation. Furthermore, FSF treatment on TDM-activated lung epithelial (MLE-12) cells significantly downregulated macrophage chemoattractant protein (MCP-1/CCL2) expression, which in turn reduced the in vitro migration of MH-S to MLE-12 cells. In addition, FSF increased the clearance of mycobacterium bacteria (Mycobacterium aurum) in macrophages. FSF mainly affected the Mincle-Syk-Erk signaling pathway in TDM-activated MH-S cells. In TDM-induced mouse granulomas model, oral administration with FSF significantly suppressed lung granulomas formation and inflammation. These findings collectively implicated an anti-inflammatory role of FSF on MTB-mediated granulomatous inflammation, thereby providing evidence of FSF as an efficacious adjunct treatment during mycobacterial infection.

Engineering new mycobacterial vaccine design for HIV–TB pediatric vaccine vectored by lysine auxotroph of BCG

PubMed Central

Saubi, Narcís; Gea-Mallorquí, Ester; Ferrer, Pau; Hurtado, Carmen; Sánchez-Úbeda, Sara; Eto, Yoshiki; Gatell, Josep M; Hanke, Tomáš; Joseph, Joan

2014-01-01

In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)–mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA2auxo. We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA2auxo vaccine strain. The BCG.HIVA2auxo vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice–compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on “double” auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth. PMID:26015961

Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

PubMed

Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

2018-05-11

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

Reduced transcript stabilization restricts TNF-alpha expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan.

PubMed

Basler, Tina; Holtmann, Helmut; Abel, Jens; Eckstein, Torsten; Baumer, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

2010-01-01

Despite the critical role that TNF-alpha plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn's disease. We found that in MAP infected macrophages, TNF-alpha gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF-alpha transcriptional one could not fully explain the differential TNF-alpha mRNA expression, suggesting that there must be a substantial contribution by post-transcriptional mechanisms.Accordingly, we found reduced TNF-alpha mRNA stability in MAP-infected macrophages. Further comparison of MAP- and MS-infected macrophages revealed that lower TNF-alpha mRNA stability combined with lower mRNA and protein expression in MAP-infected macrophages correlated with lower p38 MAPK phosphorylation. These findings were independent of viability of MAP and MS. We demonstrate that the major mycobacterial cell-wall lipoglycan LM of MAP and MS induced TNF-alpha mRNA transcription,but only the MS-LM induced p38 MAPK-dependent transcript stabilization. Overall, our data suggest that pathogenic mycobacteria cause weak p38 and TNF-alpha mRNA stabilization as a result of their structural cell-wall components such as LM and thereby, restrict TNF-alpha expression in macrophages.

Abdominal epilepsy as an unusual cause of abdominal pain: a case report.

PubMed

Yunus, Yilmaz; Sefer, Ustebay; Dondu, Ulker Ustebay; Ismail, Ozanli; Yusuf, Ehi

2016-09-01

Abdominal pain, in etiology sometimes difficult to be defined, is a frequent complaint in childhood. Abdominal epilepsy is a rare cause of abdominal pain. In this article, we report on 5 year old girl patient with abdominal epilepsy. Some investigations (stool investigation, routine blood tests, ultrasonography (USG), electrocardiogram (ECHO) and electrocardiograpy (ECG), holter for 24hr.) were done to understand the origin of these complaints; but no abnormalities were found. Finally an EEG was done during an episode of abdominal pain and it was shown that there were generalized spikes especially precipitated by hyperventilation. The patient did well on valproic acid therapy and EEG was normal 1 month after beginning of the treatment. The cause of chronic recurrent paroxymal abdominal pain is difficult for the clinicians to diagnose in childhood. A lot of disease may lead to paroxysmal gastrointestinal symptoms like familial mediterranean fever and porfiria. Abdominal epilepsy is one of the rare but easily treatable cause of abdominal pain. In conclusion, abdominal epilepsy should be suspected in children with recurrent abdominal pain.

Clinical characteristics of ceftriaxone plus metronidazole in complicated intra-abdominal infection

PubMed Central

2015-01-01

Purpose Empirical antibiotics in complicated intra-abdominal infection (c-IAI), such as secondary peritonitis are a first step of treatment. Empirical antibiotic regimen is very diverse. Ceftriaxone plus metronidazole regimen (CMR) is one of the empirical antibiotic regimens used in treatment of c-IAI. However, although CMR is a widely used empirical antibiotic regimen, study regarding success, failure or efficacy of CMR has been poorly understood. This retrospective study is conducted to compare the clinical efficacy of this regimen in c-IAI according to clinical characteristics. Methods The subjects were patients in this hospital who were diagnosed as secondary peritonitis between 2009 and 2013. Retrospective analysis was performed based on the records made after surgery regarding clinical characteristics including albumin level, blood pressure, pulse rate, respiration rate, smoking, age, sex, body mass index, hemoglobin, coexisting disease, leukocytosis, and APACHE (acute physiology and chronic health evaluation) II score. Results A total of 114 patients were enrolled. In univariated analysis, the success and failure of CMR showed significant association with preoperative low albumin, old age, and preoperative tachycardia. In multivariated analysis, low albumin and preoperative tachycardia were significant. Conclusion It is thought that an additional antibiotic treatment plan is necessary in patients with low albumin and tachycardia when the empirical antibiotic regimen is CMR in c-IAI. Conduct of research through well-designed prospective randomized clinical study is also necessary in order to evaluate the appropriateness of CMR and decide on a proper empirical antibiotic regimen between many regimens in c-IAI based on our country. PMID:26131444

Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model

PubMed Central

Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie

2018-01-01

Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800

Evolution of granulomas in lungs of mice infected aerogenically with Mycobacterium tuberculosis.

PubMed

Cardona, P J; Llatjós, R; Gordillo, S; Díaz, J; Ojanguren, I; Ariza, A; Ausina, V

2000-08-01

Aerogenous infection of C57Bl/6 mice with a virulent strain of Mycobacterium tuberculosis (CL 511) leads to the formation of primary granulomas in the lung where neutrophils, macrophages and subsequently, lymphocytes accumulate progressively around an initial cluster of infected macrophages. The spread of infection through the lung parenchyma gives rise to secondary granulomas featuring numerous lymphocytes that surround a small number of infected macrophages. Afterwards, foamy macrophages add an outer layer to the granulomas, which characteristically respect the pulmonary interstitium and remain confined within the alveolar spaces. This feature, in conjunction with the constant presence of M. tuberculosis in the products of broncho-alveolar lavage, suggests that the upward bronchial migration of infected macrophages may contribute significantly to pulmonary dissemination of mycobacterial infection. The latter would be in agreement with the persistence of chronic pulmonary infection in spite of a concomitant strong T helper 1 cell response.

Genome Sequence of Mycobacterium hassiacum DSM 44199, a Rare Source of Heat-Stable Mycobacterial Proteins

PubMed Central

Tiago, Igor; Maranha, Ana; Mendes, Vitor; Alarico, Susana; Moynihan, Patrick J.; Clarke, Anthony J.; Macedo-Ribeiro, Sandra; Pereira, Pedro J. B.

2012-01-01

Mycobacterium hassiacum is a rapidly growing mycobacterium isolated from human urine and so far the most thermophilic among mycobacterial species. Its thermotolerance and phylogenetic relationship to M. tuberculosis render its proteins attractive tools for crystallization and structure-guided drug design. We report the draft genome sequence of M. hassiacum DSM 44199. PMID:23209251

Synthesis, structure-activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents.

PubMed

Raju, B China; Rao, R Nageswara; Suman, P; Yogeeswari, P; Sriram, D; Shaik, Thokhir Basha; Kalivendi, Shasi Vardhan

2011-05-15

Series of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 7a-7zb, 8a-8d and 9a-9d were synthesized and screened for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H(37)Rv (MTB) and cytotoxicity against three human cancer cell lines including A549, SK-N-SH and HeLa. The results indicate that six compounds are more potent and 7za is most effective anti-mycobacterial derivative compared to the standard drugs Ethambutol and Ciprofloxacin. However, 12 compounds exhibited cytotoxicity against human neuroblastoma cell line; amongst them the compound 7v is most effective compared to the standard drug Doxorubicin. This is the first report assigning in vitro anti-mycobacterial, anticancer and structure-activity relationship for this new class of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Histamine plays an essential regulatory role in lung inflammation and protective immunity in the acute phase of Mycobacterium tuberculosis infection.

PubMed

Carlos, D; Fremond, C; Samarina, A; Vasseur, V; Maillet, I; Ramos, S G; Erard, F; Quesniaux, V; Ohtsu, H; Silva, C L; Faccioli, L H; Ryffel, B

2009-12-01

The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Recent data suggest a regulatory role of histamine not only in the innate but also in the adaptive immune response. We used a model of pulmonary Mycobacterium tuberculosis infection in histamine-deficient mice lacking histidine decarboxylase (HDC(-/-)), the histamine-synthesizing enzyme. To confirm that mycobacterial infection induced histamine production, we exposed mice to M. tuberculosis and compared responses in C57BL/6 (wild-type) and HDC(-/-) mice. Histamine levels increased around fivefold above baseline in infected C57BL/6 mice at day 28 of infection, whereas only small amounts were detected in the lungs of infected HDC(-/-) mice. Blocking histamine production decreased both neutrophil influx into lung tissue and the release of proinflammatory mediators, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), in the acute phase of infection. However, the accumulation and activation of CD4(+) T cells were augmented in the lungs of infected HDC(-/-) mice and correlated with a distinct granuloma formation that contained abundant lymphocytic infiltration and reduced numbers of mycobacteria 28 days after infection. Furthermore, the production of IL-12, gamma interferon, and nitric oxide, as well as CD11c(+) cell influx into the lungs of infected HDC(-/-) mice, was increased. These findings indicate that histamine produced after M. tuberculosis infection may play a regulatory role not only by enhancing the pulmonary neutrophilia and production of IL-6 and TNF-alpha but also by impairing the protective Th1 response, which ultimately restricts mycobacterial growth.

Kocuria kristinae infection during adalimumab treatment.

PubMed

Kolikonda, Murali K; Jayakumar, Priyanga; Sriramula, Srividya; Lippmann, Steven

2017-03-01

A common inhabitant of skin, the Kocuria kristinae of the Micrococcaceae family, has gained attention in recent years because it can induce pathology in humans. Reported is a Kocuria kristinae-caused abdominal abscess in a patient treated for rheumatoid arthritis with adalimumab. The tumor necrosis factor (TNF) inhibitor drugs are known to cause various bacterial, viral, and fungal infections. This is the first known case where an opportunistic infection with Kocuria has presented with an abdominal abscess in an immunocompromised individual who is on long term TNF inhibitors.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome in Association with Ruptured Abdominal Aortic Aneurysm in the Endovascular Era: Vigilance Remains Critical

PubMed Central

Bozeman, Matthew C.; Ross, Charles B.

2012-01-01

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events. PMID:22454763

Intra-abdominal hypertension and abdominal compartment syndrome in association with ruptured abdominal aortic aneurysm in the endovascular era: vigilance remains critical.

PubMed

Bozeman, Matthew C; Ross, Charles B

2012-01-01

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events.

Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus: differences from other mycobacterial isoforms and implications for selective inhibition.

PubMed

Cocaign, Angélique; Kubiak, Xavier; Xu, Ximing; Garnier, Guillaume; Li de la Sierra-Gallay, Inès; Chi-Bui, Linh; Dairou, Julien; Busi, Florent; Abuhammad, Areej; Haouz, Ahmed; Dupret, Jean Marie; Herrmann, Jean Louis; Rodrigues-Lima, Fernando

2014-11-01

Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural and functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme is endogenously expressed and functional in both the rough and smooth M. abscessus morphotypes. The crystal structure of (MYCAB)NAT1 at 1.8 Å resolution reveals that it is more closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In particular, structural and physicochemical differences from other mycobacterial NATs were found in the active site. Peculiarities of (MYCAB)NAT1 were further supported by kinetic and docking studies showing that the enzyme was poorly inhibited by the piperidinol inhibitor of mycobacterial NATs. This study describes the first structure of an antibiotic-modifying enzyme from M. abscessus and provides bases to better understand the substrate/inhibitor-binding specificities among mycobacterial NATs and to identify/optimize specific inhibitors. These data should also contribute to the understanding of the mechanisms that are responsible for the pathogenicity and extensive chemotherapeutic resistance of M. abscessus.

Abdominal Assessment.

PubMed

Fritz, Deborah; Weilitz, Pamela Becker

2016-03-01

Abdominal pain is one of the most common complaints by patients, and assessment of abdominal pain and associated symptoms can be challenging for home healthcare providers. Reasons for abdominal pain are related to inflammation, organ distention, and ischemia. The history and physical examination are important to narrow the source of acute or chronic problems, identify immediate interventions, and when necessary, facilitate emergency department care.

Conservative management of mesh-site infection in hernia repair surgery: a case series.

PubMed

Meagher, H; Clarke Moloney, M; Grace, P A

2015-04-01

The aim of this study is to assess the outcome of conservative management of infected mesh grafts following abdominal wall hernia repair. This study retrospectively examined the charts of patients who developed mesh-site infection following surgery for abdominal hernia repair to determine how effective conservative management in the form of antibiotics and wound management was on the resolution of infection and wound healing. Over a period of 30 months, 13 patients developed infected mesh grafts post-hernia repair surgery. Twelve patients were successfully treated conservatively with local wound care and antibiotics if clinically indicated. One patient returned to theatre to have the infected mesh removed. Of the patients that healed eleven were treated with negative pressure wound therapy (VAC(®)). This series of case studies indicate that conservative management of abdominal wall-infected hernia mesh cases is likely to be successful.

Systems-level modeling of mycobacterial metabolism for the identification of new (multi-)drug targets.

PubMed

Rienksma, Rienk A; Suarez-Diez, Maria; Spina, Lucie; Schaap, Peter J; Martins dos Santos, Vitor A P

2014-12-01

Systems-level metabolic network reconstructions and the derived constraint-based (CB) mathematical models are efficient tools to explore bacterial metabolism. Approximately one-fourth of the Mycobacterium tuberculosis (Mtb) genome contains genes that encode proteins directly involved in its metabolism. These represent potential drug targets that can be systematically probed with CB models through the prediction of genes essential (or the combination thereof) for the pathogen to grow. However, gene essentiality depends on the growth conditions and, so far, no in vitro model precisely mimics the host at the different stages of mycobacterial infection, limiting model predictions. These limitations can be circumvented by combining expression data from in vivo samples with a validated CB model, creating an accurate description of pathogen metabolism in the host. To this end, we present here a thoroughly curated and extended genome-scale CB metabolic model of Mtb quantitatively validated using 13C measurements. We describe some of the efforts made in integrating CB models and high-throughput data to generate condition specific models, and we will discuss challenges ahead. This knowledge and the framework herein presented will enable to identify potential new drug targets, and will foster the development of optimal therapeutic strategies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The frequency and treatment of pneumothorax associated with pulmonary nontuberculous mycobacterial infection.

PubMed

Ikeda, Masaki; Takahashi, Koji; Komatsu, Teruya; Tanaka, Toru; Kato, Tatsuo; Fujinaga, Takuji

2017-02-01

Characteristics of pneumothorax associated with nontuberculous mycobacterium (NTM) infection are rarely reported, especially in terms of surgical treatments. Our objectives were to show the tendency and clinical courses of pneumothorax due to NTM and discuss the way of therapy in our hospital. We retrospectively analyzed 557 patients with NTM infection over a period of 5 years at the Nagara Medical Center. A total of 12 out of the 557 patients (2.2%) suffered from pneumothorax caused by NTM infection without other pulmonary diseases. The diagnosis of all NTM cases was mycobacterium avium complex. Of these 12 patients, three required observation only (25%), five required drainage only (42%), and four required surgery after drainage (33%). The four surgically treated patients suffered from empyema as well as pneumothorax. They were in worse nutritional condition than non-surgically treated patients. For the patients requiring surgery, we selected reasonable surgical methods; we sutured the fistula of lung in all cases and covered it with muscle or omentum or polyglycolic acid sheets without a case in which endobronchial embolization was performed in advance before surgery. Finally, all pneumothorax healed. Thereafter, three of these four patients took unfavorable courses: progressing malnutrition, complications worsening or contralateral pneumothorax. We should select an appropriate treatment including surgery against NTM-associated pneumothorax without losing an opportunity because of its intractability and exhausting effect.

Abdominal Aortic Aneurysm

MedlinePlus

... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life ... familydoctor.org editorial staff Categories: Family Health, Men, Seniors, WomenTags: abdominal aorta, abdominal aortic aneurysm, abdominal pain, ...

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

Structure of a novel sulfate-containing mycobacterial glycolipid.

PubMed

López Marín, L M; Lanéelle, M A; Promé, D; Lanéelle, G; Promé, J C; Daffé, M

1992-11-17

We described previously the unusual structures of the two major C-mycoside glycopeptidolipids from Mycobacterium fortuitum biovar. peregrinum. More polar glycolipids, potentially more interesting in terms of antigenicity, were also present in the strains. A combination of FAB mass spectrometry, NMR, chemical analyses, and radiolabeling was successfully applied to these glycolipids to arrive at the unexpected and novel structure for the more polar compound. This consisted of the "orthodox" basic structure of the apolar C-mycosides, modified at the alaninol end by the presence of a sulfate group on position 2 of a 3,4-di-O-methylrhamnosyl residue. This novel and second class of sulfate-containing mycobacterial glycolipid may provide a chemical basis for the differentiation and classification of members of the M. fortuitum complex, the main group causing human diseases among the many fast-growing mycobacteria widely distributed in nature.

Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility.

PubMed

Guerra-Laso, José M; Raposo-García, Sara; García-García, Silvia; Diez-Tascón, Cristina; Rivero-Lezcano, Octavio M

2015-02-01

Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected monocytes from both healthy elderly individuals (a tuberculosis susceptibility group) and elderly tuberculosis patients with M. tuberculosis, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns for these genes, regardless of whether they were obtained from younger or older patients. Only one of the detected genes corresponded to a cytokine: IL26, a member of the interleukin-10 (IL-10) cytokine family which we found to be down-regulated in infected monocytes from tuberculosis patients. Non-infected monocytes secreted IL-26 constitutively but they reacted strongly to M. tuberculosis infection by decreasing IL-26 production. Furthermore, IL-26 serum concentrations appeared to be lower in the tuberculosis patients. When whole blood was infected, IL-26 inhibited the observed pathogen-killing capability. Although lymphocytes expressed IL26R, the receptor mRNA was not detected in either monocytes or neutrophils, suggesting that the inhibition of anti-mycobacterial activity may be mediated by lymphocytes. Additionally, IL-2 concentrations in infected blood were lower in the presence of IL-26. The negative influence of IL-26 on the anti-mycobacterial activity and its constitutive presence in both serum and monocyte supernatants prompt us to propose IL26 as a candidate gene for tuberculosis susceptibility. © 2014 John Wiley & Sons Ltd.

Scarless abdominal fat graft harvest for neurosurgical procedures: technical note.

PubMed

Trinh, Victoria T; Duckworth, Edward A M

2015-02-01

Background Abdominal fat grafts are often harvested for use in skull base reconstruction and cerebrospinal fluid (CSF) leak repairs, and for operations traversing the nasal sinuses or mastoid bone. Although the endoscopic transnasal surgery has gained significant popularity, in part because it is considered "scarless," a common adjunct, the abdominal fat graft, can result in a disfiguring scar across the abdomen. Objective This is the first report of a scarless abdominal fat graft technique for skull base reconstruction. Methods Ten patients with a median age of 56.5 years (range: 45-73 years) underwent endoscopic transsphenoidal tumor resection with intraumbilical fat graft harvest. Careful circumferential fat dissection at the umbilicus, with progressive retraction of the graft, was crucial to ensure maximal visualization and to prevent injury to the subcutaneous vessels and rectus fascia. Results Following reconstruction of the sellar skull base, all patients did well postoperatively with no evidence of CSF leak. At 12-week follow-up for all patients, there was no evidence of scar, intracavity hematoma, or wound infection. Conclusions Fat graft harvest through an intraumbilical incision results in a scar-free abdominal harvest, and is a useful procedural adjunct to complement "scarless" brain surgery.

Regulatory T Cells Subvert Mycobacterial Containment in Patients Failing Extensively Drug-resistant TB Treatment.

PubMed

Davids, Malika; Pooran, Anil S; Pietersen, Elize; Wainwright, Helen C; Binder, Anke; Warren, Robin; Dheda, Keertan

2018-02-09

The advent of extensively (XDR-TB) and totally drug-resistant TB, with limited or no treatment options, has facilitated renewed interest in host directed immunotherapy, particularly for therapeutically destitute patients. However, the selection and utility of such approaches depend upon understanding the host immune response in XDR-TB, which hitherto remains unexplored. To determine the host immunological profile in patients with XDR-TB, compared to drug-sensitive TB, using peripheral blood and explanted lung tissue. Blood and explanted lung tissue were obtained from patients with XDR-TB (n=31), drug-sensitive TB (DS-TB, n=20) and presumed latent-TB infection (LTBI, n=20). T-cell phenotype (Th1/Th2/Th17/Tregs) was evaluated in all patient groups, and Treg function assessed in XDR-TB non-responders by co-culturing PPD pre-primed effector T-cells with H37Rv-infected monocyte-derived macrophages, with or without autologous Tregs. Mycobacterial containment was evaluated by counting colony-forming units. Patients failing XDR-TB treatment had an altered immuno-phenotype characterized by a substantial increase in the frequency (median; IQR) of CD4+CD25+FoxP3+ regulatory T-cells (11.5; 5.9-15.2) compared to DS-TB (3.4 %; 1.6-5.73; p < 0.001) and presumed LTBI (1.8 % 1.2-2.3; p < 0.001), which was unrelated to disease duration. Tregs isolated from XDR-TB patients suppressed T-cell proliferation (up to 90%) and subverted containment of H37Rv-infected monocyte-derived macrophages (by 30%; p= 0.03) by impairing effector T-cell function through a mechanism independent of direct cell-to-cell contact, IL-10, TGF-beta and CTLA-4. Collectively, these data suggest that Tregs may be contributing to immune dysfunction, and bacterial persistence, in patients with XDR-TB. The relevant cellular pathways may serve as potential targets for immunotherapeutic intervention.

Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

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

Drumm, J.; Mi, K; Bilder, P

Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant failsmore » to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.« less

[Opportunistic infections and sarcoidosis].

PubMed

Jamilloux, Y; Bernard, C; Lortholary, O; Kerever, S; Lelièvre, L; Gerfaud-Valentin, M; Broussolle, C; Valeyre, D; Sève, P

2017-05-01

Opportunistic infections (OI) are uncommon in sarcoidosis (1 to 10%) and mostly occur in patients with previously diagnosed disease or can rarely be the presenting manifestation. The most common OIs are, in descending order: aspergillosis, cryptococcosis, and mycobacterial infections. Treatment with corticosteroids is the most frequent risk factor for OI occurrence during sarcoidosis but immunosuppressive drugs and therapy with anti-TNFα are also risk factors. Overall, clinical presentation, treatment, and outcome are identical to that occur in other conditions complicated with the occurrence of OIs. However, some atypical presentations of OIs can mimic sarcoidosis exacerbation and misdiagnosis may lead clinicians to increase immunosuppression, causing worsening of the OI. The meticulous collection of patient's history along with factors differentiating OI from sarcoidosis exacerbation is key factor to optimally manage these patients. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

PubMed Central

Mazuski, John E.; Gasink, Leanne B.; Armstrong, Jon; Broadhurst, Helen; Stone, Greg G.; Rank, Douglas; Llorens, Lily; Newell, Paul; Pachl, Jan

2016-01-01

Background. When combined with ceftazidime, the novel non–β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28–35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of −12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, −3.5%; 95% confidence interval −8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (−2.4%; −6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (−0.8%; −4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal

Impaired IFNγ-Signaling and Mycobacterial Clearance in IFNγR1-Deficient Human iPSC-Derived Macrophages.

PubMed

Neehus, Anna-Lena; Lam, Jenny; Haake, Kathrin; Merkert, Sylvia; Schmidt, Nico; Mucci, Adele; Ackermann, Mania; Schubert, Madline; Happle, Christine; Kühnel, Mark Philipp; Blank, Patrick; Philipp, Friederike; Goethe, Ralph; Jonigk, Danny; Martin, Ulrich; Kalinke, Ulrich; Baumann, Ulrich; Schambach, Axel; Roesler, Joachim; Lachmann, Nico

2018-01-09

Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of interferon gamma (IFNγ) immunity and is characterized by severe infections by weakly virulent mycobacteria. Although IFNγ is the macrophage-activating factor, macrophages from these patients have never been studied. We demonstrate the generation of heterozygous and compound heterozygous (iMSMD-cohet) induced pluripotent stem cells (iPSCs) from a single chimeric patient, who suffered from complete autosomal recessive IFNγR1 deficiency and received bone-marrow transplantation. Loss of IFNγR1 expression had no influence on the macrophage differentiation potential of patient-specific iPSCs. In contrast, lack of IFNγR1 in iMSMD-cohet macrophages abolished IFNγ-dependent phosphorylation of STAT1 and induction of IFNγ-downstream targets such as IRF-1, SOCS-3, and IDO. As a consequence, iMSMD-cohet macrophages show impaired upregulation of HLA-DR and reduced intracellular killing of Bacillus Calmette-Guérin. We provide a disease-modeling platform that might be suited to investigate novel treatment options for MSMD and to gain insights into IFNγ signaling in macrophages. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Intra-abdominal hypertension and abdominal compartment syndrome in pediatrics. A review.

PubMed

Thabet, Farah Chedly; Ejike, Janeth Chiaka

2017-10-01

To consolidate pediatric intensivists' understanding of the pathophysiology, definition, incidence, monitoring, and management of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS); and to highlight the characteristics related to the pediatric population. This is a narrative review article that utilized a systematic search of the medical literature published in the English language between January 1990 and august 2016. Studies were identified by conducting a comprehensive search of Pub Med databases. Search terms included "intra-abdominal hypertension and child", "intra-abdominal hypertension and pediatrics", "abdominal compartment syndrome and child", and "abdominal compartment syndrome and pediatrics". Intra-abdominal hypertension and ACS are associated with a number of pathophysiological disturbances and increased morbidity and mortality. These conditions have been well described in critically ill adults. In children, the IAH and the ACS have a reported incidence of 13% and 0.6 to 10% respectively; they carry similar prognostic impact but are still under-diagnosed and under-recognized by pediatric health care providers. Intra-abdominal hypertension and ACS are conditions that are regularly encountered in critically ill children. They are associated with an increased morbidity and mortality. Early recognition, prevention and timely management of this critical condition are necessary to improve its outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Plain abdominal radiography in acute abdominal pain; past, present, and future

PubMed Central

Gans, Sarah L; Stoker, Jaap; Boermeester, Marja A

2012-01-01

Several studies have demonstrated that a diagnosis based solely on a patient’s medical history, physical examination, and laboratory tests is not reliable enough, despite the fact that these aspects are essential parts of the workup of a patient presenting with acute abdominal pain. Traditionally, imaging workup starts with abdominal radiography. However, numerous studies have demonstrated low sensitivity and accuracy for plain abdominal radiography in the evaluation of acute abdominal pain as well as various specific diseases such as perforated viscus, bowel obstruction, ingested foreign body, and ureteral stones. Computed tomography, and in particular computed tomography after negative ultrasonography, provides a better workup than plain abdominal radiography alone. The benefits of computed tomography lie in decision-making for management, planning of a surgical strategy, and possibly even avoidance of negative laparotomies. Based on abundant available evidence, major advances in diagnostic imaging, and changes in the management of certain diseases, we can conclude that there is no place for plain abdominal radiography in the workup of adult patients with acute abdominal pain presenting in the emergency department in current practice. PMID:22807640

Cutaneous atypical mycobacteriosis in a clouded leopard (Neofelis nebulosa).

PubMed

Cerveny, Shannon N S; Thompson, Michelle E; Corner, Sarah M; Swinford, Amy K; Coke, Rob L

2013-09-01

A 16-yr-old male clouded leopard (Neofelis nebulosa) was presented for lethargy and anorexia. A cutaneous abdominal mass extending from the pubis to just caudal to the xiphoid process was present. A biopsy revealed histologic lesions consistent with an atypical mycobacterial infection consisting of diffuse, severe, pyogranulomatous dermatitis and panniculitis, with clear vacuoles and 3-5 microm, intravacuolar, faintly eosinophilic, filamentous bacilli that stained positively with FiteFaraco modified acid-fast stain. The clouded leopard had biochemical findings suggestive of chronic renal failure and euthanasia was elected. Histological evaluation of tissues collected at postmortem examination revealed multicentric B-cell lymphoma involving the oral cavity, liver, spleen, and multiple lymph nodes, bilateral testicular seminomas, thyroid follicular cell adenoma, thyroid C cell adenoma, and biliary cystadenomas. Bacterial culture and molecular sequencing identified the causative agent of the cutaneous abdominal mass as belonging to the Mycobacterium fortuitum group.

Abdominal Trauma Revisited.

PubMed

Feliciano, David V

2017-11-01

Although abdominal trauma has been described since antiquity, formal laparotomies for trauma were not performed until the 1800s. Even with the introduction of general anesthesia in the United States during the years 1842 to 1846, laparotomies for abdominal trauma were not performed during the Civil War. The first laparotomy for an abdominal gunshot wound in the United States was finally performed in New York City in 1884. An aggressive operative approach to all forms of abdominal trauma till the establishment of formal trauma centers (where data were analyzed) resulted in extraordinarily high rates of nontherapeutic laparotomies from the 1880s to the 1960s. More selective operative approaches to patients with abdominal stab wounds (1960s), blunt trauma (1970s), and gunshot wounds (1990s) were then developed. Current adjuncts to the diagnosis of abdominal trauma when serial physical examinations are unreliable include the following: 1) diagnostic peritoneal tap/lavage, 2) surgeon-performed ultrasound examination; 3) contrast-enhanced CT of the abdomen and pelvis; and 4) diagnostic laparoscopy. Operative techniques for injuries to the liver, spleen, duodenum, and pancreas have been refined considerably since World War II. These need to be emphasized repeatedly in an era when fewer patients undergo laparotomy for abdominal trauma. Finally, abdominal trauma damage control is a valuable operative approach in patients with physiologic exhaustion and multiple injuries.

Management of complex abdominal wall defects associated with penetrating abdominal trauma.

PubMed

Arul, G Suren; Sonka, B J; Lundy, J B; Rickard, R F; Jeffery, S L A

2015-03-01

The paradigm of Damage Control Surgery (DCS) has radically improved the management of abdominal trauma, but less well described are the options for managing the abdominal wall itself in an austere environment. This article describes a series of patients with complex abdominal wall problems managed at the UK-led Role 3 Medical Treatment Facility (MTF) in Camp Bastion, Afghanistan. Contemporaneous review of a series of patients with complex abdominal wall injuries who presented to the Role 3 MTF between July and November 2012. Five patients with penetrating abdominal trauma associated with significant damage to the abdominal wall were included. All patients were managed using DCS principles, leaving the abdominal wall open at the end of the first procedure. Subsequent management of the abdominal wall was determined by a multidisciplinary team of general and plastic surgeons, intensivists and specialist nurses. The principles of management identified included minimising tissue loss on initial laparotomy by joining adjacent wounds and marginal debridement of dead tissue; contraction of the abdominal wall was minimised by using topical negative pressure dressing and dermal-holding sutures. Definitive closure was timed to allow oedema to settle and sepsis to be controlled. Closure techniques include delayed primary closure with traction sutures, components separation, and mesh closure with skin grafting. A daily multidisciplinary team discussion was invaluable for optimal decision making regarding the most appropriate means of abdominal closure. Dermal-holding sutures were particularly useful in preventing myostatic contraction of the abdominal wall. A simple flow chart was developed to aid decision making in these patients. This flow chart may prove especially useful in a resource-limited environment in which returning months or years later for closure of a large ventral hernia may not be possible. Published by the BMJ Publishing Group Limited. For permission to use

Systemic classification for a new diagnostic approach to acute abdominal pain in children.

PubMed

Kim, Ji Hoi; Kang, Hyun Sik; Han, Kyung Hee; Kim, Seung Hyo; Shin, Kyung-Sue; Lee, Mu Suk; Jeong, In Ho; Kim, Young Sil; Kang, Ki-Soo

2014-12-01

With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

Systemic Classification for a New Diagnostic Approach to Acute Abdominal Pain in Children

PubMed Central

Kim, Ji Hoi; Kang, Hyun Sik; Han, Kyung Hee; Kim, Seung Hyo; Shin, Kyung-Sue; Lee, Mu Suk; Jeong, In Ho; Kim, Young Sil

2014-01-01

Purpose With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. Methods From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. Results The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. Conclusion Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children. PMID:25587522

Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra-abdominal infection and/or pneumonia.

PubMed

Rodriguez-Osorio, Carlos A; Lima, Guadalupe; Herrera-Caceres, Jaime O; Villegas-Torres, Beatriz E; Zuñiga, Joaquin; Ponce-de-Leon, Sergio; Llorente, Luis; Sifuentes-Osornio, Jose

2013-06-01

Sepsis is a leading cause of death around the world, and 73-83% of all sepsis cases requiring attention in intensive care units are linked to intra-abdominal infection (IAI) or pneumonia. The activation of innate immunity is central to the manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role in this activation process. The 299G and 399I alleles of TLR4 have been linked with an increased risk of Gram-negative bacteria (GNB) infections and septic shock in some populations. This case-control study evaluated the prevalence of D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05-12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS), confirming the co-segregation of these alleles in this population. Furthermore, the patients with a GNB infection and severe sepsis were not carriers of the risk alleles. In summary, this report shows that the frequency of the D299G and T399I polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms among different populations. Consequently, this study was not able to detect associations between TLR4 polymorphisms and sepsis in this population. Copyright © 2013 Elsevier B.V. All rights reserved.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and

Identification of the Infection Source of an Outbreak of Mycobacterium Chelonae Keratitis After Laser in Situ Keratomileusis.

PubMed

Nascimento, Heloisa; Viana-Niero, Cristina; Nogueira, Christiane Lourenço; Martins Bispo, Paulo José; Pinto, Fernando; de Paula Pereira Uzam, Camila; Matsumoto, Cristianne Kayoko; Oliveira Machado, Antônia Maria; Leão, Sylvia Cardoso; Höfling-Lima, Ana Luisa; de Freitas, Denise

2018-01-01

Nontuberculous mycobacteria keratitis is a rare but challenging complication of laser in situ keratomileusis (LASIK). This study was conducted to determine the source(s) of infection in a cluster of cases of keratitis after LASIK and to describe this outbreak and patients' outcomes. In this retrospective, case series, single-center study, 86 patients were included who underwent LASIK or photorefractive keratectomy between December 2011 and February 2012. Corneal scrapes from the affected eyes, samples of tap and distilled water, water from the reservoir of the distilling equipment, steamer, and autoclave cassette; antiseptic and anesthetic solutions and surgical instrument imprints were cultivated in liquid and on solid media. Gram-negative bacteria and yeasts were identified using automated systems and mycobacteria by polymerase chain reaction-restriction enzyme analysis of the hsp65 gene (PRA-hsp65) and DNA sequencing. Mycobacterial isolates were typed by pulsed-field gel electrophoresis. The cases and outcomes are described. The main outcome measure was identification of the source(s) of the mycobacterial infections. Eight (15 eyes) of 86 patients (172 eyes) who underwent LASIK developed infections postoperatively; no patients who underwent photorefractive keratectomy developed infections. Mycobacterium chelonae was isolated from 4 eyes. The distilled water collected in the surgical facility contained the same M. chelonae strain isolated from the patients' eyes. Different gram-negative bacteria and yeasts were isolated from samples collected at the clinic but not from the patients' eyes. Tap water distilled locally in surgical facilities may be a source of infection after ocular surgery and its use should be avoided.

The value of plain abdominal radiographs in management of abdominal emergencies in Luth.

PubMed

Ashindoitiang, J A; Atoyebi, A O; Arogundade, R A

2008-01-01

The plain abdominal x-ray is still the first imaging modality in diagnosis of acute abdomen. The aim of this study was to find the value of plain abdominal x-ray in the management of abdominal emergencies seen in Lagos university teaching hospital. The accurate diagnosis of the cause of acute abdominal pain is one of the most challenging undertakings in emergency medicine. This is due to overlapping of clinical presentation and non-specific findings of physical and even laboratory data of the multifarious causes. Plain abdominal radiography is one investigation that can be obtained readily and within a short period of time to help the physician arrive at a correct diagnosis The relevance of plain abdominal radiography was therefore evaluated in the management of abdominal emergencies seen in Lagos over a 12 month period (April 2002 to March 2003). A prospective study of 100 consecutively presenting patients with acute abdominal conditions treated by the general surgical unit of Lagos University Teaching Hospital was undertaken. All patients had supine and erect abdominal x-ray before any therapeutic intervention was undertaken. The diagnostic features of the plain films were compared with final diagnosis to determine the usefulness of the plain x-ray There were 54 males and 46 females (M:F 1.2:1). Twenty-four percent of the patients had intestinal obstruction, 20% perforated typhoid enteritis; gunshot injuries and generalized peritonitis each occurred in 13%, blunt abdominal trauma in 12%, while 8% and 10% had acute appendicitis and perforated peptic ulcer disease respectively. Of 100 patients studied, 54% had plain abdominal radiographs that showed positive diagnostic features. Plain abdominal radiograph showed high sensitivity in patients with intestinal obstruction 100% and perforated peptic ulcer 90% but was less sensitive in patients with perforated typhoid, acute appendicitis, and blunt abdominal trauma and generalized peritonitis. In conclusion, this study

Evaluation of the levels of metalloproteinsase-2 in patients with abdominal aneurysm and abdominal hernias.

PubMed

Antoszewska, Magdalena

2013-05-01

Abdominal aortic aneurysms and abdominal hernias become an important health problems of our times. Abdominal aortic aneurysm and its rupture is one of the most dangerous fact in vascular surgery. There are some theories pointing to a multifactoral genesis of these kinds of diseases, all of them assume the attenuation of abdominal fascia and abdominal aortic wall. The density and continuity of these structures depend on collagen and elastic fibers structure. Reducing the strength of the fibers may be due to changes in the extracellular matrix (ECM) by the proteolytic enzymes-matrix metalloproteinases (MMPs) that degrade extracellular matrix proteins. These enzymes play an important role in the development of many disease: malignant tumors (colon, breast, lung, pancreas), cardiovascular disease (myocardial infarction, ischemia-reperfusion injury), connective tissue diseases (Ehler-Danlos Syndrome, Marfan's Syndrome), complications of diabetes (retinopathy, nephropathy). One of the most important is matrix metalloproteinase-2 (MMP-2). The aim of the study was an estimation of the MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia, and in patients with only abdominal aortic aneurysm. The study involved 88 patients aged 42 to 89 years, including 75 men and 13 women. Patients were divided into two groups: patients with abdominal aortic aneurysm and primary abdominal hernia (45 persons, representing 51.1% of all group) and patients with only abdominal aortic aneurysm (43 persons, representing 48,9% of all group). It was a statistically significant increase in MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia compared to patients with only abdominal aortic aneurysm. It was a statistically significant increase in the prevalence of POCHP in patients with only abdominal aortic aneurysm compared to patients with abdominal aortic aneurysm and primary abdominal hernia. Statistically significant

Valganciclovir (VGCV) followed by cytomegalovirus (CMV) hyperimmune globulin compared to VGCV for 200 days in abdominal organ transplant recipients at high risk for CMV infection: A prospective, randomized pilot study.

PubMed

Fleming, James N; Taber, David J; Weimert, Nicole A; Nadig, Satish; McGillicuddy, John W; Bratton, Charles F; Baliga, Prabhakar K; Chavin, Kenneth D

2017-12-01

With the advent of effective antivirals against cytomegalovirus (CMV), use of CMV hyperimmune globulin (HIG) has decreased. Although antiviral prophylaxis in patients at high risk for CMV is effective, many patients still have late infection, never developing antibodies sufficient to achieve immunity. Utilizing a combination of antiviral and CMV HIG may allow patients to achieve immunity and decrease late CMV infections. This was a prospective randomized, open-label, pilot study comparing valganciclovir (VGCV) prophylaxis for 200 days vs VGCV for 100 days followed by CMV HIG in abdominal transplant recipients at high risk for CMV. The primary outcome was a comparison of late CMV disease. Forty patients were randomized to VGCV for 200 days (n = 20) or VGCV for 100 days followed by 3 doses of monthly CMV HIG (n = 20). Numerically, more overall CMV infections occurred in the CMV HIG group (45 vs 20%, P = .09). No differences in overall CMV infections or late CMV disease were seen between groups (20% vs 15%, P = 1.00 and 0 vs 0, P = 1.00). All CMV disease occurred within 200 days, with 63% occurring while patients were on VGCV. No differences were found in toxicities, graft function, or rejection between groups. Patients with CMV infection at any time had a higher body weight than those who did not have an infection (82 vs 95 kg, P = .049). Use of CMV HIG sequentially with prophylaxis may be an effective and affordable prophylactic regimen in abdominal transplant recipients at high risk for CMV, and warrants larger prospective study. Increased monitoring for patients with obesity may be warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Experience with Clotteau-Prémont's technique in abdominal wall hernias. Preliminary report].

PubMed

Soto-Dávalos, Baltazar Alberto; Del Pozzo-Magaña, José Antonio; Luna-Martínez, Javier

2006-01-01

Incisional hernias account for at least a third of abdominal wall hernias. There are different techniques of repair that include the use of prosthetic materials, which has lowered the hernia recurrence rate. Nonetheless, its use in case of rejection or infection requires other techniques with local tissue. The use of prosthetic material in a contaminated environment is contraindicated because the risk of infection and recurrence rate is unacceptably high. In order to compare two repair techniques for abdominal wall hernias in terms of complications and recurrence to be used as an alternative for hernia repair in patients with abdominal wall hernias, we conducted, between January 2000 and January 2004, an observational, longitudinal, retrospective, non-randomized matched control case study in patients with abdominal wall hernia. A total of 30 patients were studied and were divided into two groups of 15 patients each. Subjects were matched for sex, age and hernia type (group A, mesh treated and group B, Clotteau-Prémont treated) who had at least a 5-month postoperative follow-up. Complication and recurrence rate was assessed and compared. There were no differences between the two groups in complications or recurrence (p <0.05). The average follow-up time was 18.9 +/- 8 months for group A and 15 +/- 7.9 months for group B. Clotteau-Prémont's technique is a safe and feasible alternative procedure with indications in selected patients.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers

PubMed Central

Cohen, Jeffrey I.; Dropulic, Lesia; Hsu, Amy P.; Zerbe, Christa S.; Krogmann, Tammy; Dowdell, Kennichi; Hornung, Ronald L.; Lovell, Jana; Hardy, Nancy; Hickstein, Dennis; Cowen, Edward W.; Calvo, Katherine R.; Pittaluga, Stefania; Holland, Steven M.

2016-01-01

Background. Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. Methods. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Results. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme–like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. Conclusions. GATA2 is the first gene associated with EBV hydroa vacciniforme–like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts. PMID:27169477

Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs.

PubMed

Housman, Genevieve; Malukiewicz, Joanna; Boere, Vanner; Grativol, Adriana D; Pereira, Luiz Cezar M; Silva, Ita de Oliveira; Ruiz-Miranda, Carlos R; Truman, Richard; Stone, Anne C

2015-11-01

Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR. In a trial study in which armadillos were artificially infected with M. leprae, these techniques were specific and sensitive to pathogen detection, while more traditional ELISAs were only specific. These assays were then employed in a case study to detect M. leprae as well as MTBC in wild marmosets. All marmosets were negative for M. leprae DNA, but 14 were positive for the mycobacterial rpoB gene assay. Targeted capture and sequencing of rpoB and other MTBC genes validated the presence of mycobacterial DNA in these samples and revealed that qPCR is useful for identifying mycobacterial-infected animal hosts.

[A commonly seen cause of abdominal pain: abdominal cutaneous nerve entrapment syndrome].

PubMed

Solmaz, Ilker; Talay, Mustafa; Tekindur, Şükrü; Kurt, Ercan

2012-01-01

Although abdominal cutaneous nerve entrapment syndrome (ACNES) is accepted as a rare condition, it is a syndrome that should be diagnosed more commonly when the clinical signs cannot explain the cause of abdominal pain. Abdominal pain is commonly considered by physicians to be based on intra-abdominal causes. Consequently, redundant tests and consultations are requested for these patients, and unnecessary surgical procedures may be applied. Patients with this type of pain are consulted to many clinics, and because their definitive diagnoses cannot be achieved, they are assessed as psychiatric patients. Actually, a common cause of abdominal wall pain is nerve entrapment on the lateral edge of the rectus abdominis muscle. In this paper, we would like to share information about the diagnosis and treatment of a patient who, prior to presenting to us, had applied to different clinics for chronic abdominal pain and had undergone many tests and consultations; abdominal surgery was eventually decided.

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

PubMed

Sýkora, Josef; Huml, Michal; Siala, Konrad; Pomahačová, Renáta; Jehlička, Petr; Liška, Jiří; Kuntscherová, Jana; Schwarz, Jan

2016-10-01

Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 μg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 μg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

Chlamydia Infections

MedlinePlus

... include Abnormal vaginal discharge, which may have a strong smell A burning sensation when urinating Pain during intercourse If the infection spreads, you might get lower abdominal pain, pain during sex, nausea, or fever. Symptoms in men include Discharge from your penis A burning sensation ...

Nutritional status and eating disorders: neglected risks factor for nontuberculous mycobacterial lung disease?

PubMed

Portillo, Karina; Morera, Josep

2012-01-01

Nontuberculous mycobacterial lung disease (NTMLD) in immunocompetent patients is an increasingly important epidemiologic concern. However, risk factors associated with susceptibility to NTMLD are not completely known. A prevalence of NTMLD appears to be rising, mainly in some populations such as middle-aged or elderly thin women, (a group including those with Lady Windermere syndrome) with neither remarkable history of respiratory disease nor smoking habit. Right middle lobe (RML) and lingula are often involved. Various predisposing factors and genetic defects have been described as possible causes of development of NTMLD, namely: voluntary suppression of cough, RML anatomical factors, menopause and mutations in cystic fibrosis transmembrane conductance regulator (CFTR). Malnutrition is also an important and common risk factor associated with other mycobacterial disease like tuberculosis (TB) and its probable association with NTMLD as have been pointed out for some authors. However, a real description of all nutritional aspects and eating habits of patients prior to NTMLD diagnosis is lacking. We hypothesized that malnutrition and eating disorders like anorexia nervosa could be risk factors that may promoting NTMLD. From a clinical viewpoint, if this hypothesis proves to be correct, eating habits and nutritional aspects should be taken into account in the diagnosis process of suspected NTMLD, since they are easily identifiable and treatable conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

MmPPOX inhibits Mycobacterium tuberculosis lipolytic enzymes belonging to the hormone-sensitive lipase family and alters mycobacterial growth.

PubMed

Delorme, Vincent; Diomandé, Sadia V; Dedieu, Luc; Cavalier, Jean-François; Carrière, Frédéric; Kremer, Laurent; Leclaire, Julien; Fotiadu, Frédéric; Canaan, Stéphane

2012-01-01

Lipid metabolism plays an important role during the lifetime of Mycobacterium tuberculosis, the causative agent of tuberculosis. Although M. tuberculosis possesses numerous lipolytic enzymes, very few have been characterized yet at a biochemical/pharmacological level. This study was devoted to the M. tuberculosis lipolytic enzymes belonging to the Hormone-Sensitive Lipase (HSL) family, which encompasses twelve serine hydrolases closely related to the human HSL. Among them, nine were expressed, purified and biochemically characterized using a broad range of substrates. In vitro enzymatic inhibition studies using the recombinant HSL proteins, combined with mass spectrometry analyses, revealed the potent inhibitory activity of an oxadiazolone compound, named MmPPOX. In addition, we provide evidence that MmPPOX alters mycobacterial growth. Overall, these findings suggest that the M. tuberculosis HSL family displays important metabolic functions, thus opening the way to further investigations linking the involvement of these enzymes in mycobacterial growth.

MmPPOX Inhibits Mycobacterium tuberculosis Lipolytic Enzymes Belonging to the Hormone-Sensitive Lipase Family and Alters Mycobacterial Growth

PubMed Central

Delorme, Vincent; Diomandé, Sadia V.; Dedieu, Luc; Cavalier, Jean-François; Carrière, Frédéric; Kremer, Laurent; Leclaire, Julien; Fotiadu, Frédéric; Canaan, Stéphane

2012-01-01

Lipid metabolism plays an important role during the lifetime of Mycobacterium tuberculosis, the causative agent of tuberculosis. Although M. tuberculosis possesses numerous lipolytic enzymes, very few have been characterized yet at a biochemical/pharmacological level. This study was devoted to the M. tuberculosis lipolytic enzymes belonging to the Hormone-Sensitive Lipase (HSL) family, which encompasses twelve serine hydrolases closely related to the human HSL. Among them, nine were expressed, purified and biochemically characterized using a broad range of substrates. In vitro enzymatic inhibition studies using the recombinant HSL proteins, combined with mass spectrometry analyses, revealed the potent inhibitory activity of an oxadiazolone compound, named MmPPOX. In addition, we provide evidence that MmPPOX alters mycobacterial growth. Overall, these findings suggest that the M. tuberculosis HSL family displays important metabolic functions, thus opening the way to further investigations linking the involvement of these enzymes in mycobacterial growth. PMID:23029536

Protozoa as a cause of recurrent abdominal pain in children.

PubMed

Gijsbers, Carolien F M; Schweizer, Joachim J; Büller, Hans A

2013-11-01

The aim of this study was to investigate whether protozoa can be identified as a cause of recurrent abdominal pain (RAP), and whether protozoan infections can be recognized by a specific clinical presentation. For 2 years, all patients (ages 4-16 years) fulfilling the Apley criteria of RAP referred to secondary care were prospectively evaluated for protozoa (Giardia lamblia, Dientamoeba fragilis, Blastocystis hominis) and treated if positive. Re-examination followed at least 10 days after treatment. Disappearance of pain with eradication and a pain-free follow-up of at least 6 months were considered to be indicative of a causal relation with RAP. The predictive value of the characteristics of the pain for protozoan infections was calculated. Of 220 included patients (92 boys, mean age 8.8 years), 215 brought a stool sample; 73 (34%) carried parasites, 10 of whom had 2 parasites, 2 had 3 parasites. Sixty-five patients were treated. Twenty-five (11%) were pain-free after eradication (21 had D fragilis, 8 B hominis, 4 G lamblia), of whom 11 had another infection (2) or constipation (9) as second diagnosis for the pain. Five had recurrence of infection with D fragilis and were again pain-free with eradication. Patients with protozoa as cause of their pain did not show differences with respect to their presentation when compared with patients with an asymptomatic infection and patients without protozoa. Protozoa were found as the cause of pain in 6% to 11% of children with RAP. These patients did not show a characteristic presentation when compared with patients with other causes of abdominal pain.

Functional Dissection of the PE Domain Responsible for Translocation of PE_PGRS33 across the Mycobacterial Cell Wall

PubMed Central

Cascioferro, Alessandro; Donà, Valentina; Delogu, Giovanni; Palù, Giorgio; Bitter, Wilbert; Manganelli, Riccardo

2011-01-01

PE are peculiar exported mycobacterial proteins over-represented in pathogenic mycobacterial species. They are characterized by an N-terminal domain of about 110 amino acids (PE domain) which has been demonstrated to be responsible for their export and localization. In this paper, we characterize the PE domain of PE_PGRS33 (PERv1818c), one of the best characterized PE proteins. We constructed several mutated proteins in which portions of the PE domain were deleted or subjected to defined mutations. These proteins were expressed in different mycobacterial species and their localization was characterized. We confirmed that the PE domain is essential for PE_PGRS33 surface localization, and demonstrated that a PE domain lacking its first 30 amino acids loses its function. However, single amino acid substitutions in two regions extremely well conserved within the N-terminal domain of all PE proteins had some effect on the stability of PE_PGRS33, but not on its localization. Using Mycobacterium marinum we could show that the type VII secretion system ESX-5 is essential for PE_PGRS33 export. Moreover, in M. marinum, but not in Mycobacterium bovis BCG and in Mycobacterium tuberculosis, the PE domain of PE_PGRS33 is processed and secreted into the culture medium when expressed in the absence of the PGRS domain. Finally, using chimeric proteins in which different portions of the PERv1818c domain were fused to the N-terminus of the green fluorescent protein, we could hypothesize that the first 30 amino acids of the PE domain contain a sequence that allows protein translocation. PMID:22110736

Molecular basis of mycobacterial lipid antigen presentation by CD1c and its recognition by αβ T cells

PubMed Central

Roy, Sobhan; Ly, Dalam; Li, Nan-Sheng; Altman, John D.; Piccirilli, Joseph A.; Moody, D. Branch; Adams, Erin J.

2014-01-01

CD1c is a member of the group 1 CD1 family of proteins that are specialized for lipid antigen presentation. Despite high cell surface expression of CD1c on key antigen-presenting cells and the discovery of its mycobacterial lipid antigen presentation capability, the molecular basis of CD1c recognition by T cells is unknown. Here we present a comprehensive functional and molecular analysis of αβ T-cell receptor (TCR) recognition of CD1c presenting mycobacterial phosphomycoketide antigens. Our structure of CD1c with the mycobacterial phosphomycoketide (PM) shows similarities to that of CD1c-mannosyl-β1-phosphomycoketide in that the A' pocket accommodates the mycoketide alkyl chain; however, the phosphate head-group of PM is shifted ∼6 Å in relation to that of mannosyl-β1-PM. We also demonstrate a bona fide interaction between six human TCRs and CD1c-mycoketide complexes, measuring high to moderate affinities. The crystal structure of the DN6 TCR and mutagenic studies reveal a requirement of five complementarity determining region (CDR) loops for CD1c recognition. Furthermore, mutagenesis of CD1c reveals residues in both the α1 and α2 helices involved in TCR recognition, yet not entirely overlapping among the examined TCRs. Unlike patterns for MHC I, no archetypical binding footprint is predicted to be shared by CD1c-reactive TCRs, even when recognizing the same or similar antigens. PMID:25298532

Focused abdominal sonography for trauma (FAST) in blunt paediatric abdominal trauma.

PubMed

Faruque, Ahmad Vaqas; Qazi, Saqib Hamid; Khan, Muhammad Arif Mateen; Akhtar, Wassem; Majeed, Amina

2013-03-01

To evaluate the role of focussed abdominal sonography for trauma in blunt paediatric abdominal trauma patients, and to see if the role of computed tomography scan could be limited to only those cases in which sonography was positive. The retrospective study covered 10 years, from January 1,2000 to December 31,2009, and was conducted at the Department of Radiology and Department of Emergency Medicine, Aga Khan University Hospital, Karachi. It comprised cases of 174 children from birth to 14 years who had presented with blunt abdominal trauma and had focussed abdominal sonography for trauma done at the hospital. The findings were correlated with computed tomography scan of the abdomen and clinical follow-up. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of focussed abdominal sonography for trauma were calculated for blunt abdominal trauma. SPSS 17 was used for statistical analysis. Of the total 174 cases, 31 (17.81%) were later confirmed by abdominal scan. Of these 31 children, sonography had been positive in 29 (93.54%) children. In 21 (67.74%) of the 31 children, sonograpy had been true positive; 8 (25%) (8/31) were false positive; and 2 (6%) (2/31) were false negative. There were 6 (19.3%) children in which sonography was positive and converted to laparotomy. There was no significant difference on account of gender (p>0.356). Focussed abdominal sonography for trauma in the study had sensitivity of 91%, specificity of 95%, positive predictive value of 73%, and negative predictive value of 73% with accuracy of 94%. All patients who had negative sonography were discharged later, and had no complication on clinical follow-up. Focussed abdominal sonography for trauma is a fairly reliable mode to assess blunt abdominal trauma in children. It is a useful tool to pick high-grade solid and hollow viscous injury. The results suggest that the role of computed tomography scan can be limited to those cases in which focussed

Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease.

PubMed

Lightner, Amy L; Raffals, Laura E; Mathis, Kellie L; Cima, Robert R; Tse, Chung Sang; Pemberton, John H; Dozois, Eric J; Loftus, Edward V

2017-02-01

Vedolizumab was recently approved by the Food and Drug Administration for the treatment of moderate to severe ulcerative colitis [UC] and Crohn's disease [CD]. No study to date has examined the rate of postoperative infectious complications among patients who received vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among inflammatory bowel disease [IBD] patients who received vedolizumab within 12 weeks of an abdominal operation as compared to patients who received tumour necrosis factor α [TNFα] inhibitors or no biological therapy. A retrospective chart review between May 1, 2014 and December 31, 2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort comprised patients who received vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biological therapy. In total, 94 patients received vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications [53%], 35 of which were surgical site infections [SSIs] [36%]. The vedolizumab group experienced significantly higher rates of any postoperative infection [53% vs 33% anti-TNF and 28% non-biologics; p<0.001] and SSI [37% vs 10% and 13%; p<0.001]. On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative SSI [p<0.001]. Thirty-seven per cent of IBD patients who received vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biological therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Menarche? A Case of Abdominal Pain and Vaginal Bleeding in a Preadolescent Girl.

PubMed

Riney, Lauren C; Reed, Jennifer L; Kruger, Laura L; Brody, Alan J; Pomerantz, Wendy J

2015-11-01

Abdominal pain is one of the most common complaints in the pediatric ED. Because of the broad range of potential diagnoses, it can pose challenges in diagnosis and therapy in the preadolescent girl. An 11-year-old previously healthy girl presented to our pediatric ED with fever, decreased appetite, vaginal bleeding, and abdominal pain. Initial evaluation yielded elevated creatinine levels, leukocytosis with bandemia, elevated inflammatory markers, and urine concerning for a urinary tract infection. She began receiving antibiotics for presumed pyelonephritis and was admitted to the hospital. After worsening respiratory status and continued abdominal pain, a computed tomography scan was obtained and a pelvic foreign body and abscess were identified. Adolescent gynecology was consulted for examination under anesthesia for abscess drainage and foreign body removal. A foreign body in the vagina or uterus can present as vaginal discharge, vaginal bleeding, abdominal pain, dysuria, or hematuria. Because symptoms can be diverse, an intravaginal or uterine foreign body should be considered in the preteen female patient presenting to the ED with abdominal pain. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Laparoscopic treatment of abdominal complications following ventriculoperitoneal shunt

PubMed Central

Grigorean, VT; Onose, G; Popescu, M; Strambu, V; Sandu, AM

2009-01-01

The aim of this study is the evaluation of laparoscopic treatment in abdominal complications following ventriculoperitoneal (VP) shunt. Methods: We report a retrospective study including 17 patients with abdominal complications secondary to VP shunt for hydrocephalus, laparoscopically treated in our department, between 2000 and 2007. Results: Patients' age ranged from 1 to 72 years old (mean age 25.8 years old). Male: female ratio was 1.4. Abdominal complications encountered were: shunt disconnection with intraperitoneal distal catheter migration 47.05% (8/17), infections 23.52% (4/17) such as abscesses and peritonitis, pseudocysts 11.76% (2/17), CSF ascites 5.88% (1/17), inguinal hernia 5.88% (1/17), and shunt malfunction due to excessive length of intraperitoneal tube 5.88% (1/17). Free–disease interval varies from 1 day to 21 years, depending on the type of complication, short in peritoneal irritation syndrome and abscesses (days) and long in ascites, pseudocysts(months– years). Laparoscopic treatment was: extraction of the foreign body in shunt disconnection with intraperitoneal distal catheter migration, evacuation, debridement, lavage and drainage for pseudocysts, abscess and peritonitis, shortening of the tube in shunt malfunction due to excessive length of intraperitoneal tube a nd hernioraphy. One diagnostic laparoscopy was performed in a peritoneal irritation syndrome, which found only CSF ascites. There were no conversions to open surgery. The overall mortality was of 5.88% and postoperative morbidity was of 11.76%. In 7 patients operated for abscesses, peritonitis, pseudocysts, and CSF ascites the shunting system was converted in to a ventriculocardiac shunt. Conclusions: Abdominal complication following VP shunt can be successfully performed laparoscopically. Abdominal surgery required, in selected cases, the repositioning of the distal catheter, frequently as a ventriculocardiac shunt. There are abdominal complications with no indication of

Effects of recombinant granulocyte-colony stimulating factor administration during Mycobacterium avium infection in mice

PubMed Central

Gonçalves, A S; Appelberg, R

2001-01-01

Granulocyte colony-stimulating factor (G-CSF) administration in vivo has been shown to improve the defence mechanisms against infection by different microbes. Here we evaluated a possible protective role of this molecule in a mouse model of mycobacterial infection. The administration of recombinant G-CSF promoted an extensive blood neutrophilia but failed to improve the course of Mycobacterium avium infection in C57Bl/6 or beige mice. G-CSF administration also failed to improve the efficacy of a triple chemotherapeutic regimen (clarithromycin + ethambutol + rifabutin). G-CSF treatment did not protect interleukin-10 gene disrupted mice infected with M. avium. Spleen cells from infected mice treated with G-CSF had a decreased priming for antigen-specific production of interferon gamma compared to control infected mice. Our data do not substantiate previous reports on the protective activity of G-CSF in antimycobacterial immunity using mouse models. PMID:11422200

Necrotizing Fasciitis of the Abdominal Wall Caused by Serratia Marcescens

PubMed Central

Lakhani, Naheed A.; Narsinghani, Umesh; Kumar, Ritu

2015-01-01

In this article, we present the first case of necrotizing fasciitis affecting the abdominal wall caused by Serratia marcescens and share results of a focused review of S. marcescens induced necrotizing fasciitis. Our patient underwent aorto-femoral bypass grafting for advanced peripheral vascular disease and presented 3 weeks postoperatively with pain, erythema and discharge from the incision site in the left lower abdominal wall and underwent multiple debridement of the affected area. Pathology of debrided tissue indicated extensive necrosis involving the adipose tissue, fascia and skeletal muscle. Wound cultures were positive for Serratia marcescens. She was successfully treated with antibiotics and multiple surgical debridements. Since necrotizing fasciitis is a medical and surgical emergency, it is critical to examine infectivity trends, clinical characteristics in its causative spectrum. Using PubMed we found 17 published cases of necrotizing fasciitis caused by Serratia marcescens, and then analyzed patterns among those cases. Serratia marcescens is prominent in the community and hospital settings, and information on infection presentations, risk factors, characteristics, treatment, course, and complications as provided through this study can help identify cases earlier and mitigate poor outcomes. Patients with positive blood cultures and those patients where surgical intervention was not provided or delayed had a higher mortality. Surgical intervention is a definite way to establish the diagnosis of necrotizing infection and differentiate it from other entities. PMID:26294949

Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection

PubMed Central

Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L.; Brown, Michelle L.; Losada, Maria C.; Pedley, Alison; Kartsonis, Nicholas A.

2016-01-01

Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas. In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. PMID:27503659

Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection.

PubMed

Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L; Brown, Michelle L; Losada, Maria C; Pedley, Alison; Kartsonis, Nicholas A; Paschke, Amanda

2016-10-01

Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Intra-abdominal sepsis following pancreatic resection: incidence, risk factors, diagnosis, microbiology, management, and outcome.

PubMed

Behrman, Stephen W; Zarzaur, Ben L

2008-07-01

Intra-abdominal sepsis (IAS) following pancreatectomy is associated with the need for therapeutic intervention and may result in mortality. We retrospectively reviewed patients developing IAS following elective pancreatectomy. Risk factors for the development of sepsis were assessed. The microbiology of these infections was ascertained. The number and type of therapeutic interventions required and infectious-related mortality were recorded. One hundred ninety-six patients had a pancreatectomy performed, 32 (16.3%) of who developed IAS. Infected abdominal collections were diagnosed and therapeutically managed at a mean of 11.8 days after the index procedure (range, 4-33). Eleven of 32 (34%) of these infections were diagnosed on or before postoperative day 6, 10 of who had Whipple procedures. Statistically significant risk factors included an overt pancreatic fistula (18.8% vs 5.5%) and a soft pancreatic remnant (74.2% vs 42.3%), but not the lack of intra-abdominal drainage, an antecedent immunocompromised state, postoperative hemorrhage, or the preoperative placement of a biliary stent. Fifty-five per cent had polymicrobial infections and 26 per cent of isolates were resistant organisms. Nineteen per cent and 48 per cent of patients had an isolate positive for fungus and a Gram-positive organism, respectively. Forty-seven therapeutic interventions were used, including 10 reoperations. Length of stay was significantly prolonged in those with IAS (28.5 vs 15.2 days) and mortality was higher (15.6% vs 1.8%). We conclude: 1) septic morbidity after pancreatectomy is associated with a soft pancreatic remnant and an overt pancreatic fistula and in this series resulted in a prolonged length of stay and a significant increase in procedure-related mortality; 2) infected fluid collections may occur very early in the postoperative period before frank abscess formation, and an early threshold for diagnostic imaging and/or therapeutic intervention should be entertained in those

[Predictive value of procalcitonin in postoperative intra-abdominal infections after definitive operation of intestinal fistulae].

PubMed

Ren, Huajian; Wang, Gefei; Gu, Guosheng; Hu, Qiongyuan; Li, Guanwei; Hong, Zhiwu; Wu, Xiuwen; Ren, Jianan

2017-05-25

To investigate the predictive value of procalcitonin(PCT) in postoperative intra-abdominal infections (IAI) after definitive operation of intestinal fistulae(IF). With the exclusion of emergence operation, preoperative clinical infection, preoperative renal or hepatic dysfunction, and age less than 18 years, a total of 356 consecutive patients who underwent elective digestive tract reconstruction of intestinal fistulae from February 2012 to December 2015 at Intestinal Fistula Center of Jinling Hospital were prospectively enrolled in the study. All the patients were divided into IAI group (26 cases, 21 of anastomosis leakage and 5 of peritoneal abscess) and non-IAI group (330 cases) based on the existence of postoperative IAI. The non-IAI group was then divided into two subgroups of other infection (93 cases) and non-infection(237 cases) according to the presence of other infections. Plasma PCT level, serum CRP concentration and WBC count were assessed preoperatively and on postoperative days (PODs) 1, 3, 5, 7 by immunofluorescence, turbidimetry and automatic blood analyzer, respectively. The predictive value of each marker for IAI was calculated by receiver operating characteristic (ROC) curve. There was no significant difference in general clinical data between IAI and non-IAI group (all P>0.05). The proportions of multi-IF (53.8%, 14/26) and colectomy (61.5%, 16/26) in IAI group were higher than those of non-IAI group [20.0% (66/330), χ 2 =15.847, P=0.000 and 31.2%(103/330), χ 2 =9.961, P=0.002]. Differences of preoperative PCT, CRP and WBC levels among IAI, other infection and non-infection groups were not significant. These three markers all increased obviously and immediately after surgery. PCT and WBC values reached the peak point on POD 1, whereas CRP on POD 3. In IAI group, mean PCT values were (5.4±4.2) μg/L, (2.9±1.9) μg/L and (1.6±1.8) μg/L on POD 1, POD 3 and POD 5, respectively, which were higher than those of other infection group [(4.2±8

Child with Abdominal Pain.

PubMed

Iyer, Rajalakshmi; Nallasamy, Karthi

2018-01-01

Abdominal pain is one of the common symptoms reported by children in urgent care clinics. While most children tend to have self-limiting conditions, the treating pediatrician should watch out for underlying serious causes like intestinal obstruction and perforation peritonitis, which require immediate referral to an emergency department (ED). Abdominal pain may be secondary to surgical or non-surgical causes, and will differ as per the age of the child. The common etiologies for abdominal pain presenting to an urgent care clinic are acute gastro-enteritis, constipation and functional abdominal pain; however, a variety of extra-abdominal conditions may also present as abdominal pain. Meticulous history taking and physical examination are the best tools for diagnosis, while investigations have a limited role in treating benign etiologies.

Unusual Methylobacterium fujisawaense Infection in a Patient with Acute Leukaemia Undergoing Hematopoietic Stem Cell Transplantation: First Case Report

PubMed Central

Fanci, Rosa; Corti, Giampaolo; Bartoloni, Alessandro; Tortoli, Enrico; Mariottini, Alessandro; Pecile, Patrizia

2010-01-01

Microorganisms of the genus Methylobacterium are facultative methylotrophic, gram-negative rods that are ubiquitous in nature and rarely cause human disease, mostly in subjects with preexisting causes of immune depression. Methylobacterium fujisawaense, first proposed as a new species in 1988, has never been reported as a bacterial agent of human infections so far. Here we describe a case of M. fujisawaense infection in a relapsed acute leukaemia undergoing unrelated allogeneic hematopoietic stem cell transplantation. Molecular identification of an M. fujisawaense strain was obtained from multiple mycobacterial blood cultures. PMID:20396386

Abdominal wall fat pad biopsy

MedlinePlus

Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... most common method of taking an abdominal wall fat pad biopsy . The health care provider cleans the ...

Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

PubMed Central

Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

2015-01-01

Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features (“fried eggs” colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

High prevalence of Mycobacterium tuberculosis mixed infection in the capital of moderate tuberculosis incidence country.

PubMed

Hajimiri, Elahe Sadat; Masoomi, Morteza; Ebrahimzadeh, Nayereh; Fateh, Abolfazl; Hadizadeh Tasbiti, Alireza; Rahimi Jamnani, Fatemeh; Bahrmand, Ahmad Reza; Mirsaeidi, Mehdi; Vaziri, Farzam; Siadat, Seyed Davar

2016-04-01

Recent studies using molecular epidemiological techniques have demonstrated mixed infection with multiple strains of Mycobacterium tuberculosis especially in countries with high tuberculosis (TB) burden. We aimed to determine the prevalence of mixed infection among patients with TB in the capital of Iran as a country with moderate incidence rate. Samples were collected randomly from January 2011 to December 2013 in Tehran, capital of Iran. A total of 75 M. tuberculosis isolates were genotyped by 24 loci mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) for screening the mixed infection. Twenty patients (20/75) were identified with mixed infection, and the estimated rate of mixed infection was 26.6%. Thirteen out of the 24 loci were able to detect the mixed infection in our study. Mixed infections occur at high prevalence among studied Iranian TB patients. Further research is inevitable to evaluate the association of mixed infection and disease progression and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The risk of infection to the mother prior, during and after delivery. A registration of nosocomial infections].

PubMed

Hirsch, H A; Niehues, U

1982-09-01

During 5 1/2 years all infections arising in the hospital (nosocomial infections) were registered prospectively by an infection control nurse. The incidence of all nosocomial infections in 3192 maternity patients was 2.1%. In 10,569 women following vaginal deliveries 2.6% and in 1,353 women following Caesarean section 21.1%. The commonest infections were urinary tract infections, endometritis, infections of the abdominal wound or the episiotomy, and a phlebitis of the intravenous infusion site. Measures to prevent infection resulted in a steadily decreasing incidence of infections during the 6 years of registration of nosocomial infections.

Bioprosthetic tissue matrices in complex abdominal wall reconstruction.

PubMed

Broyles, Justin M; Abt, Nicholas B; Sacks, Justin M; Butler, Charles E

2013-12-01

Complex abdominal defects are difficult problems encountered by surgeons in multiple specialties. Although current evidence supports the primary repair of these defects with mesh reinforcement, it is unclear which mesh is superior for any given clinical scenario. The purpose of this review was to explore the characteristics of and clinical relevance behind bioprosthetic tissue matrices in an effort to better clarify their role in abdominal wall reconstruction. We reviewed the peer-reviewed literature on the use of bioprosthetic mesh in human subjects. Basic science articles and large retrospective and prospective reviews were included in author's analysis. The clinical performance and characteristics of 13 bioprosthetic tissue matrices were evaluated. The majority of the products evaluated perform well in contaminated fields, where the risk of wound-healing difficulties is high. Clinical outcomes, which included infection, reherniation, and bulge formation, were variable, and the majority of the studies had a mean follow-up of less than 24 months. Although bioprosthetic matrix has a multitude of indications within the growing field of abdominal wall reconstruction, the functionality, regenerative capacity, and long-term fate of these products have yet to be fully established. Furthermore, the clinical performance, indications, and contraindications for each type of matrix need to be fully evaluated in long-term outcome studies.

Abdominal wall Hydatid cyst: A review a literature with a case report.

PubMed

Salih, Abdulwahid M; Kakamad, F H; Hammood, Zuhair D; Yasin, Bzhwen; Ahmed, Dilshad M

2017-01-01

Hydatid cyst (HC) disease is a serious health problem in endemic areas. It is a parasitic infection that commonly involves liver and lungs while muscular HC is rare. HC of abdominal wall was reported only six times. We reported a 39-year-old male presented with HC of the right loin who was managed surgically with brief literature review. HC should be put in the differential diagnosis of the abdominal wall masses. Its pre-operative diagnosis is important to prevent rupture with subsequent anaphylaxis and recurrence. Surgery is the main modality of treatment. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Recent trends in soft-tissue infection imaging.

PubMed

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-03-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of (18)F-FDG-PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with (111)In-oxine/(99m)Tc-HMPAO labeled autologous white blood cells. The literature on central nervous system infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the postoperative spine, (99m)Tc-ciprofloxacin single-photon emission computed tomography (SPECT) was reported to be >80% sensitive in patients more than 6 months after surgery. FDG-PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/computed tomography (CT) is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune

Recent Trends in Soft Tissue Infection Imaging

PubMed Central

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-01-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, CNS, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of 18F-FDG PET and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of FDG PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with 111In-oxine/99mTc-HMPAO labeled autologous white blood cells. The literature on CNS infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the post-operative spine, 99mTc-ciprofloxacin SPECT was reported to be >80% sensitive in patients more than 6 months post-surgery. FDG PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/CT is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. While an infection specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

PubMed

Young, M; Plosker, G L

2001-01-01

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per

Cutaneous non-tuberculous Mycobacterial infections: a clinical and histopathological study of 17 cases from Lebanon.

PubMed

Abbas, O; Marrouch, N; Kattar, M M; Zeynoun, S; Kibbi, A G; Rached, R A; Araj, G F; Ghosn, S

2011-01-01

Only a few studies characterized cutaneous non-tuberculous Mycobacterium (NTM) infections in this region of the world. Objective  The aim of this study was to describe the epidemiological, clinical and histological findings of cutaneous NTM infections in Lebanon. Retrospective study of 17 patients (19 histological specimens) diagnosed with cutaneous NTM infections and confirmed by culture-based partial sequencing of the 16S rRNA gene at the American University of Beirut Medical Center between 2005 and 2008. Of 17 cases, 14 were caused by Mycobacterium marinum. All patients were immunocompetent except for one. Clinically, the most common presentation was multiple sporotrichoid lesions over an extremity (8/17). Many patients had peculiar presentations including bruise-like patches, herpetiform lesions, annular ulcerated plaques, symmetrical nodules over the buttocks and locally disseminated lesions with surrounding pale halo. Almost all patients cleared their infection on either minocycline or clarithromycin monotherapies. Histologically, a dermal small vessel proliferation with mixed inflammation (granulation tissue-like changes) was identified in 58% of specimens. The most common type of granulomatous inflammation was the suppurative (47%) followed by the tuberculoid (30%), sarcoidal (11%), and palisading (5%) types. Lichenoid granulomatous dermatitis was noted in 42% of cases. Special staining highlighted mycobacteria in only two specimens. The incidence of cutaneous NTM infections is high in our area. Many patients had peculiar clinical presentations. Our study is the second to report the common presence of granulation tissue-like changes as a good histological indicator of cutaneous NTM infections. Minocycline and clarithromycin remain the drugs of choice in our area. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

The Economic Impact of Closed-Incision Negative-Pressure Therapy in High-Risk Abdominal Incisions: A Cost-Utility Analysis.

PubMed

Chopra, Karan; Gowda, Arvind U; Morrow, Chris; Holton, Luther; Singh, Devinder P

2016-04-01

Complex abdominal wall reconstruction is beset by postoperative complications. A recent meta-analysis comparing the use of closed-incision negative-pressure therapy to standard dressings found a statistically significant reduction in surgical-site infection. The use of closed-incision negative-pressure therapy is gaining acceptance in this population; however, the economic impact of this innovative dressing remains unknown. In this study, a cost-utility analysis was performed assessing closed-incision negative-pressure therapy and standard dressings following closure of abdominal incisions in high-risk patients. Cost-utility methodology involved reviewing literature related to closed-incision negative-pressure therapy in abdominal wall surgery, obtaining utility estimates to calculate quality-adjusted life-year scores for successful surgery and surgery complicated by surgical-site infection, summing costs using Medicare Current Procedural Terminology codes, and creating a decision tree illuminating the most cost-effective dressing strategy. One-way sensitivity analysis was performed to assess the robustness of the results. The aforementioned meta-analysis comparing closed-incision negative-pressure therapy to standard dressings included a subset of five studies assessing abdominal wall surgery in 829 patients (260 closed-incision negative-pressure therapy and 569 standard dressings). Decision tree analysis revealed an estimated savings of $1546.52 and a gain of 0.0024 quality-adjusted life-year with closed-incision negative-pressure therapy compared with standard dressings; therefore, closed-incision negative-pressure therapy is a dominant treatment strategy. One-way sensitivity analysis revealed that closed-incision negative-pressure therapy is a cost-effective option when the surgical-site infection rate is greater than 16.39 percent. The use of closed-incision negative-pressure therapy is cost-saving following closure of abdominal incisions in high-risk patients.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

PubMed

Cohen, Jeffrey I; Dropulic, Lesia; Hsu, Amy P; Zerbe, Christa S; Krogmann, Tammy; Dowdell, Kennichi; Hornung, Ronald L; Lovell, Jana; Hardy, Nancy; Hickstein, Dennis; Cowen, Edward W; Calvo, Katherine R; Pittaluga, Stefania; Holland, Steven M

2016-07-01

Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

2012-01-01

Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

Don't Forget the Abdominal Wall: Imaging Spectrum of Abdominal Wall Injuries after Nonpenetrating Trauma.

PubMed

Matalon, Shanna A; Askari, Reza; Gates, Jonathan D; Patel, Ketan; Sodickson, Aaron D; Khurana, Bharti

2017-01-01

Abdominal wall injuries occur in nearly one of 10 patients coming to the emergency department after nonpenetrating trauma. Injuries range from minor, such as abdominal wall contusion, to severe, such as abdominal wall rupture with evisceration of abdominal contents. Examples of specific injuries that can be detected at cross-sectional imaging include abdominal muscle strain, tear, or hematoma, including rectus sheath hematoma (RSH); traumatic abdominal wall hernia (TAWH); and Morel-Lavallée lesion (MLL) (closed degloving injury). These injuries are often overlooked clinically because of (a) a lack of findings at physical examination or (b) distraction by more-severe associated injuries. However, these injuries are important to detect because they are highly associated with potentially grave visceral and vascular injuries, such as aortic injury, and because their detection can lead to the diagnosis of these more clinically important grave traumatic injuries. Failure to make a timely diagnosis can result in delayed complications, such as bowel hernia with potential for obstruction or strangulation, or misdiagnosis of an abdominal wall neoplasm. Groin injuries, such as athletic pubalgia, and inferior costochondral injuries should also be considered in patients with abdominal pain after nonpenetrating trauma, because these conditions may manifest with referred abdominal pain and are often included within the field of view at cross-sectional abdominal imaging. Radiologists must recognize and report acute abdominal wall injuries and their associated intra-abdominal pathologic conditions to allow appropriate and timely treatment. © RSNA, 2017.

Correlation between intra-abdominal pressure and pulmonary volumes after superior and inferior abdominal surgery.

PubMed

Cleva, Roberto de; Assumpção, Marianna Siqueira de; Sasaya, Flavia; Chaves, Natalia Zuniaga; Santo, Marco Aurelio; Fló, Claudia; Lunardi, Adriana C; Jacob Filho, Wilson

2014-07-01

Patients undergoing abdominal surgery are at risk for pulmonary complications. The principal cause of postoperative pulmonary complications is a significant reduction in pulmonary volumes (FEV1 and FVC) to approximately 65-70% of the predicted value. Another frequent occurrence after abdominal surgery is increased intra-abdominal pressure. The aim of this study was to correlate changes in pulmonary volumes with the values of intra-abdominal pressure after abdominal surgery, according to the surgical incision in the abdomen (superior or inferior). We prospectively evaluated 60 patients who underwent elective open abdominal surgery with a surgical time greater than 240 minutes. Patients were evaluated before surgery and on the 3rd postoperative day. Spirometry was assessed by maximal respiratory maneuvers and flow-volume curves. Intra-abdominal pressure was measured in the postoperative period using the bladder technique. The mean age of the patients was 56 ± 13 years, and 41.6% 25 were female; 50 patients (83.3%) had malignant disease. The patients were divided into two groups according to the surgical incision (superior or inferior). The lung volumes in the preoperative period showed no abnormalities. After surgery, there was a significant reduction in both FEV1 (1.6 ± 0.6 L) and FVC (2.0 ± 0.7 L) with maintenance of FEV1/FVC of 0.8 ± 0.2 in both groups. The maximum intra-abdominal pressure values were similar (p=0.59) for the two groups. There was no association between pulmonary volumes and intra-abdominal pressure measured in any of the groups analyzed. Our results show that superior and inferior abdominal surgery determines hypoventilation, unrelated to increased intra-abdominal pressure. Patients at high risk of pulmonary complications should receive respiratory care even if undergoing inferior abdominal surgery.

Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

PubMed

Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

2013-06-01

The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

[Cefamandole as prophylactic A.B. in abdominal surgery. Comparative study of cefamandole versus clindamycin/tobramycin (author's transl)].

PubMed

Iarchy, J

1980-01-01

A prospective, randomized and controlled study of prophylactic A.B. was made in 100 patients prior to abdominal surgery. Fifty patients received 3 x 2 g of cefamandole I.V. within 24 hrs, the first dose being given at the time of anesthetic induction. Postoperative infections occurred in 2% of this group. Fifty patients received the association Clindamycin-Tobramycin (clindamycin 600 mg - tobramycin 80 mg/8 hrs) for 24 hrs, the first dose also at the induction of anesthesia. The complication rate in this group was 18%. The difference between those 2 groups is statistically significant (p less than 0.01). Cefamandole used as a prophylactic antibiotic in abdominal surgery reduces the incidence of postoperative wound infections when compared to the association clindamycin-tobramycin.

Non-tuberculous mycobacterial bloodstream infections in patients with indwelling vascular catheters - the role of sickle cell anaemia.

PubMed

Edun, Babatunde; Shah, Ansal; Durkin, Martin; Whitmire, Melanie; Williams, Shanetta Patterson; Albrecht, Helmut; Al-Hasan, Majdi; Weissman, Sharon

2017-05-01

Few studies have examined risk factors for nontuberculous mycobacteria (NTM) bloodstream infections (BSI) involving indwelling vascular catheters (IDVC). Sickle cell anaemia (HbSS/SC) is known to affect several aspects of the immune system leading to relative immune deficiency. The purpose of this retrospective nested case-control study was to determine if HbSS/SC is a risk factor for NTM BSI among individuals with IDVCs. All NTM IDVC infections (cases) at two tertiary hospitals from 2008 to 2014 were reviewed. Cases were matched 2:1 with controls who had IDVC infections due to organisms other than NTM. Matching criteria included age within 10 years and IDVC infection within three months of index case. Logistic regression was used to identify risk factors for IDVC infection due to NTM. Nineteen NTM BSIs were identified. Three cases were excluded because they did not have IDVCs at the time their BSI was identified. Sixteen cases of NTM IDVC infection were matched to 32 controls with IDVC infections due to other organisms. The mean age of patients with IDVC infections was 48.5 years and 28 (58%) were male. Compared to the control group those with NTM BSI were more likely to have HbSS/SC 38% (6/16) versus 6% (2/32) (p = .006). IDVCs are a risk factor for NTM BSI. Sickle cell anaemia appears to be a risk factor for IDVC infections due to NTM. This study is limited by the small sample size. A larger study is needed to further investigate the association between HbSS/SC and NTM IDVC infections.

Chronic Abdominal Wall Pain.

PubMed

Koop, Herbert; Koprdova, Simona; Schürmann, Christine

2016-01-29

Chronic abdominal wall pain is a poorly recognized clinical problem despite being an important element in the differential diagnosis of abdominal pain. This review is based on pertinent articles that were retrieved by a selective search in PubMed and EMBASE employing the terms "abdominal wall pain" and "cutaneous nerve entrapment syndrome," as well as on the authors' clinical experience. In 2% to 3% of patients with chronic abdominal pain, the pain arises from the abdominal wall; in patients with previously diagnosed chronic abdominal pain who have no demonstrable pathological abnormality, this likelihood can rise as high as 30% . There have only been a small number of clinical trials of treatment for this condition. The diagnosis is made on clinical grounds, with the aid of Carnett's test. The characteristic clinical feature is strictly localized pain in the anterior abdominal wall, which is often mischaracterized as a "functional" complaint. In one study, injection of local anesthesia combined with steroids into the painful area was found to relieve pain for 4 weeks in 95% of patients. The injection of lidocaine alone brought about improvement in 83-91% of patients. Long-term pain relief ensued after a single lidocaine injection in 20-30% of patients, after repeated injections in 40-50% , and after combined lidocaine and steroid injections in up to 80% . Pain that persists despite these treatments can be treated with surgery (neurectomy). Chronic abdominal wall pain is easily diagnosed on physical examination and can often be rapidly treated. Any physician treating patients with abdominal pain should be aware of this condition. Further comparative treatment trials will be needed before a validated treatment algorithm can be established.

Timing of urinary catheter removal after uncomplicated total abdominal hysterectomy: a prospective randomized trial.

PubMed

Ahmed, Magdy R; Sayed Ahmed, Waleed A; Atwa, Khaled A; Metwally, Lobna

2014-05-01

To assess whether immediate (0h), intermediate (after 6h) or delayed (after 24h) removal of an indwelling urinary catheter after uncomplicated abdominal hysterectomy can affect the rate of re-catheterization due to urinary retention, rate of urinary tract infection, ambulation time and length of hospital stay. Prospective randomized controlled trial conducted at Suez Canal University Hospital, Egypt. Two hundred and twenty-one women underwent total abdominal hysterectomy for benign gynecological diseases and were randomly allocated into three groups. Women in group A (73 patients) had their urinary catheter removed immediately after surgery. Group B (81 patients) had the catheter removed 6h post-operatively while in group C (67 patients) the catheter was removed after 24h. The main outcome measures were the frequency of urinary retention, urinary tract infections, ambulation time and length of hospital stay. There was a significantly higher number of urinary retention episodes requiring re-catheterization in the immediate removal group compared to the intermediate and delayed removal groups (16.4% versus 2.5% and 0% respectively). Delayed urinary catheter removal was associated with a higher incidence of urinary tract infections (15%), delayed ambulation time (10.3h) and longer hospital stay (5.6 days) compared to the early (1.4%, 4.1h and 3.2 days respectively) and intermediate (3.7%, 6.8h and 3.4 days respectively) removal groups. Removal of the urinary catheter 6h postoperatively appears to be more advantageous than early or late removal in cases of uncomplicated total abdominal hysterectomy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units

NASA Astrophysics Data System (ADS)

Wu, Yong; Xiong, De-Cai; Chen, Si-Cong; Wang, Yong-Shi; Ye, Xin-Shan

2017-03-01

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

Mycobacterial Antigen Driven Activation of CD14++CD16− Monocytes Is a Predictor of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

PubMed Central

Andrade, Bruno B.; Singh, Amrit; Narendran, Gopalan; Schechter, Melissa E.; Nayak, Kaustuv; Subramanian, Sudha; Anbalagan, Selvaraj; Jensen, Stig M. R.; Porter, Brian O.; Antonelli, Lis R.; Wilkinson, Katalin A.; Wilkinson, Robert J.; Meintjes, Graeme; van der Plas, Helen; Follmann, Dean; Barber, Daniel L.; Swaminathan, Soumya; Sher, Alan; Sereti, Irini

2014-01-01

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response occurring in a subset of TB-HIV co-infected patients initiating anti-retroviral therapy (ART). Here, we examined monocyte activation by prospectively quantitating pro-inflammatory plasma markers and monocyte subsets in TB-HIV co-infected patients from a South Indian cohort at baseline and following ART initiation at the time of IRIS, or at equivalent time points in non-IRIS controls. Pro-inflammatory biomarkers of innate and myeloid cell activation were increased in plasma of IRIS patients pre-ART and at the time of IRIS; this association was confirmed in a second cohort in South Africa. Increased expression of these markers correlated with elevated antigen load as measured by higher sputum culture grade and shorter duration of anti-TB therapy. Phenotypic analysis revealed the frequency of CD14++CD16− monocytes was an independent predictor of TB-IRIS, and was closely associated with plasma levels of CRP, TNF, IL-6 and tissue factor during IRIS. In addition, production of inflammatory cytokines by monocytes was higher in IRIS patients compared to controls pre-ART. These data point to a major role of mycobacterial antigen load and myeloid cell hyperactivation in the pathogenesis of TB-IRIS, and implicate monocytes and monocyte-derived cytokines as potential targets for TB-IRIS prevention or treatment. PMID:25275318

Technique and outcomes of laparoscopic bulge repair after abdominal free flap reconstruction.

PubMed

Lee, Johnson C; Whipple, Lauren A; Binetti, Brian; Singh, T Paul; Agag, Richard

2016-01-21

Bulges and hernias after abdominal free flap surgery are uncommon with rates ranging from as low as 0-36%. In the free flap breast reconstruction population, there are no clear guidelines or optimal strategies to treating postoperative bulges. We describe our minimally invasive technique and outcomes in managing bulge complications in abdominal free flap breast reconstruction patients. A retrospective review was performed on all abdominal free flap breast reconstruction patients at Albany Medical Center from 2011 to 2014. All patients with bulges on clinical exam underwent abdominal CT imaging prior to consultation with a minimally invasive surgeon. Confirmed symptomatic bulges were repaired laparoscopically and patients were monitored regularly in the outpatient setting. Sixty-two patients received a total of 80 abdominal free flap breast reconstructions. Flap types included 41 deep inferior epigastric perforator (DIEP), 36 muscle-sparing transverse rectus abdominus myocutaneous (msTRAM), 2 superficial inferior epigastric artery, and 1 transverse rectus abdominus myocutaneous flap. There were a total of 9 (14.5%) bulge complications, with the majority of patients having undergone msTRAM or DIEP reconstruction. There were no complications, revisions, or recurrences from laparoscopic bulge repair after an average follow-up of 181 days. Although uncommon, bulge formation after abdominal free flap reconstruction can create significant morbidity to patients. Laproscopic hernia repair using composite mesh underlay offers an alternative to traditional open hernia repair and can be successfully used to minimize scarring, infection, and pain to free flap patients who have already undergone significant reconstructive procedures. © 2016 Wiley Periodicals, Inc. Microsurgery, 2016. © 2016 Wiley Periodicals, Inc.

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

PubMed Central

Goodlet, Kellie J; Nicolau, David P; Nailor, Michael D

2016-01-01

Complicated intra-abdominal infections (cIAI) represent a large proportion of all hospital admissions and are a major cause of morbidity and mortality in the intensive care unit. Rising rates of multidrug resistant organisms (MDRO), including extended-spectrum β-lactamase producing Enterobacteriaceae and carbapenem-nonsusceptible Pseudomonas spp., for which there are few remaining active antimicrobial agents, pose an increased challenge to clinicians. Patients with frequent exposures to the health care system or multiple recurrent IAIs are at increased risk for MDRO; however, treatment options have traditionally been limited, in some cases necessitating the utilization of last-line agents with unfavorable side-effect profiles. Ceftolozane/tazobactam and ceftazidime/avibactam are two new cephalosporin and β-lactamase inhibitor combinations with recent US Food and Drug Administration approvals for the treatment of cIAI in combination with metronidazole. Ceftolozane/tazobactam has demonstrated excellent in vitro activity against MDR and extensively drug-resistant Pseudomonas spp., including carbapenem-nonsusceptible strains, while ceftazidime/avibactam effectively inhibits a broad range of β-lactamases, making it an excellent option for the treatment of carbapenem-resistant Enterobacteriaceae. Both agents were shown to be noninferior to meropenem for treatment of cIAI in Phase III trials; however, reduced responses in patients with renal impairment at baseline highlight the importance of routine serum creatinine monitoring and ongoing dose adjustments. This review highlights in vitro and in vivo data of these two agents and suggests their proper place in cIAI treatment to ensure adequate therapy in our most at-risk patients while sparing unnecessary use in patients without MDRO risk factors. PMID:27942218

Modulation of mycobacterial-specific Th1 and Th17 cells in latent tuberculosis by coincident hookworm infection

PubMed Central

George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumaran, Paramasivam Paul; Chandrasekaran, Vedachalam; Nutman, Thomas B.; Babu, Subash

2013-01-01

Hookworm infections and tuberculosis are co-endemic in many parts of the world. It has been suggested that infection with helminth parasites could suppress the predominant Th1 (IFN-γ-mediated) response needed to control Mycobacterium tuberculosis (Mtb) infection and enhance susceptibility to infection and/or disease. To determine the role of coincident hookworm infection on responses at steady state and on Mtb – specific immune responses in latent tuberculosis (TB), we examined the cellular responses in individuals with latent TB with or without concomitant hookworm infection. By analyzing the expression of Th1, Th2 and Th17 subsets of CD4+ T cells, we were able to demonstrate that the presence of coincident hookworm infection significantly diminished both spontaneously expressed and Mtb – specific mono – and dual – functional Th1 and Th17 cells. Hookworm infection, in contrast, was associated with expanded frequencies of mono – and dual – functional Th2 cells at both steady state and upon antigen – stimulation. This differential induction of CD4+ T cell subsets was abrogated upon mitogen stimulation. In addition, coincident hookworm infection was associated with increased adaptive T regulatory (aTreg) cells but not natural regulatory T cells (nTregs) in latent TB. Finally, the CD4+ T cell cytokine expression pattern was also associated with alterations in the systemic levels of Th1 and Th2 cytokines. Thus, coincident hookworm infection exerts a profound inhibitory effect on protective Th1 and Th17 responses in latent tuberculosis and may predispose toward the development of active tuberculosis in humans. PMID:23576678

Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis

PubMed Central

Luo, Qing; Huang, Zhikun; Peng, Yiping; Xiong, Guoliang; Guo, Yang; Jiang, Hong; Li, Junming

2016-01-01

Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis. PMID:27073889

The 100 most-cited articles on non-tuberculous mycobacterial infection from 1995 to 2015.

PubMed

Jhun, B W; Kim, S-Y; Kong, J H; Park, J R; Park, S Y; Shim, M A; Jeon, K; Park, H Y; Shin, S J; Koh, W-J

2017-01-01

Citation analyses aid in assessing quality, trends and future directions of research fields. To identify the most influential articles on infections caused by non-tuberculous mycobacteria (NTM) in the last 20 years. We performed a cited reference search of the Web of Science database from 1995 to 2015. The 100 most cited articles on NTM infections were analysed. The top 100 articles were cited 114-1471 times, and were published from 1995 to 2013. Sixty-five were laboratory-based, basic science articles, with the major topics being pathophysiology (n = 20) and molecular methods for NTM identification (n = 15). Among the 35 non-laboratory studies, major topics were clinical management (n = 15) and epidemiology (n = 14). The top article was a clinical treatise on the management of NTM disease, published in 2007. Although there was a correlation between article rank and journal impact factor (P = 0.043, ρ = -0.202), the five articles from the journals with highest impact factors did not rank among the top 10 articles. A large proportion of influential articles on NTM infection are basic scientific studies, and the most influential articles are not always published in high-impact journals.

Bioprosthetic Tissue Matrices in Complex Abdominal Wall Reconstruction

PubMed Central

Broyles, Justin M.; Abt, Nicholas B.; Sacks, Justin M.

2013-01-01

Background: Complex abdominal defects are difficult problems encountered by surgeons in multiple specialties. Although current evidence supports the primary repair of these defects with mesh reinforcement, it is unclear which mesh is superior for any given clinical scenario. The purpose of this review was to explore the characteristics of and clinical relevance behind bioprosthetic tissue matrices in an effort to better clarify their role in abdominal wall reconstruction. Methods: We reviewed the peer-reviewed literature on the use of bioprosthetic mesh in human subjects. Basic science articles and large retrospective and prospective reviews were included in author’s analysis. The clinical performance and characteristics of 13 bioprosthetic tissue matrices were evaluated. Results: The majority of the products evaluated perform well in contaminated fields, where the risk of wound-healing difficulties is high. Clinical outcomes, which included infection, reherniation, and bulge formation, were variable, and the majority of the studies had a mean follow-up of less than 24 months. Conclusions: Although bioprosthetic matrix has a multitude of indications within the growing field of abdominal wall reconstruction, the functionality, regenerative capacity, and long-term fate of these products have yet to be fully established. Furthermore, the clinical performance, indications, and contraindications for each type of matrix need to be fully evaluated in long-term outcome studies. PMID:25289285

Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

PubMed Central

Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

2015-01-01

Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

The Tribolium homeotic gene Abdominal is homologous to abdominal-A of the Drosophila bithorax complex

NASA Technical Reports Server (NTRS)

Stuart, J. J.; Brown, S. J.; Beeman, R. W.; Denell, R. E.; Spooner, B. S. (Principal Investigator)

1993-01-01

The Abdominal gene is a member of the single homeotic complex of the beetle, Tribolium castaneum. An integrated developmental genetic and molecular analysis shows that Abdominal is homologous to the abdominal-A gene of the bithorax complex of Drosophila. abdominal-A mutant embryos display strong homeotic transformations of the anterior abdomen (parasegments 7-9) to PS6, whereas developmental commitments in the posterior abdomen depend primarily on Abdominal-B. In beetle embryos lacking Abdominal function, parasegments throughout the abdomen are transformed to PS6. This observation demonstrates the general functional significance of parasegmental expression among insects and shows that the control of determinative decisions in the posterior abdomen by homeotic selector genes has undergone considerable evolutionary modification.

The Tribolium homeotic gene Abdominal is homologous to abdominal-A of the Drosophila bithorax complex.

PubMed

Stuart, J J; Brown, S J; Beeman, R W; Denell, R E

1993-01-01

The Abdominal gene is a member of the single homeotic complex of the beetle, Tribolium castaneum. An integrated developmental genetic and molecular analysis shows that Abdominal is homologous to the abdominal-A gene of the bithorax complex of Drosophila. abdominal-A mutant embryos display strong homeotic transformations of the anterior abdomen (parasegments 7-9) to PS6, whereas developmental commitments in the posterior abdomen depend primarily on Abdominal-B. In beetle embryos lacking Abdominal function, parasegments throughout the abdomen are transformed to PS6. This observation demonstrates the general functional significance of parasegmental expression among insects and shows that the control of determinative decisions in the posterior abdomen by homeotic selector genes has undergone considerable evolutionary modification.

Role of routine abdominal ultrasonography in intensified tuberculosis case finding algorithms at HIV clinics in high TB burden settings.

PubMed

Spalgais, Sonam; Agarwal, Upasna; Sarin, Rohit; Chauhan, Devesh; Yadav, Anita; Jaiswal, Anand

2017-05-18

High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics. Retrospective analysis of eight years' data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained. Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases. Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound

[Differential diagnosis of abdominal pain].

PubMed

Frei, Pascal

2015-09-02

Despite the frequency of functional abdominal pain, potentially dangerous causes of abdominal pain need to be excluded. Medical history and clinical examination must focus on red flags and signs for imflammatory or malignant diseases. See the patient twice in the case of severe and acute abdominal pain if lab parameters or radiological examinations are normal. Avoid repeated and useless X-ray exposure whenever possible. In the case of subacute or chronic abdominal pain, lab tests such as fecal calprotectin, helicobacter stool antigen and serological tests for celiac disease are very useful. Elderly patients may show atypical or missing clinical signs. Take care of red herrings and be skeptical whether your initial diagnosis is really correct. Abdominal pain can frequently be an abdominal wall pain.

[Clinical and microbiological characteristics of complicated intra-abdominal infection in Colombia: a multicenter study].

PubMed

Vallejo, Marta; Cuesta, Diana P; Flórez, Luz E; Correa, Adriana; Llanos, Carmen E; Isaza, Berenice; Vanegas, Stella; Osorio, Johanna; Casanova, Lucía; Villegas, María V

2016-06-01

Complicated community-acquired intra-abdominal infections (CA-cIAI) are a common cause of acute abdomen. To identify the clinical and microbiology profile of CA-cIAI in four Colombian hospitals. This is a prospective, descriptive study, between 08-2012 and 09-2014, including patients with CA-cIAI > 15 years. Data collected included: socio-demographic, clinical, diagnosis, and isolates of the first culture obtained aseptically during surgery with antimicrobial susceptibility. 192 patients were included, 62% men, median age 47.3 years. Co-morbidities were present in 38.4%, 13% had been hospitalized in the previous year 13%, and 9.4% had received antibiotics in the last 6 months; 44.3% were admitted for appendicitis, 17.7% for peritonitis and 16.7% for bowel perforation. CA-cIAI were assessed as moderate in 64.1% of the cases and were treated with ampicillin/sulbactam (SAM) and ertapenem. In 70.8% of cases a bacteria was isolated: 65.1% were gramnegative rods (80.0% Escherichia coli, 44.8% of them susceptible to pipercillin/tazobactam, 65.7% to SAM; 11.2 % were K.pneumoniae, 85% was susceptible for SAM; 16.7% were grampositive cocci (28.1% Streptococci viridans group). The median hospital stay was 7 days and 15.1% died. E. coli, K. pneumoniae and S. viridans were the main organisms to consider in an empiric therapy for CA-cIAI and it is important to know the local epidemiology in order to choose the right antibiotic.

Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report.

PubMed

Cohen-Bacrie, Stéphan; David, Marion; Stremler, Nathalie; Dubus, Jean-Christophe; Rolain, Jean-Marc; Drancourt, Michel

2011-09-22

Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.

Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.

PubMed

Thakkar, Kalpesh; Chen, Leon; Tessier, Mary E; Gilger, Mark A

2014-06-01

Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy (EGD) in children. However, little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure. We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain. We conducted a prospective study of 290 children (4-18 years old; mean age, 11.9 ± 3.5 years; 93 girls) who underwent EGD for the primary indication of chronic abdominal pain (216 with at least 1 alarm feature) at a US pediatric gastroenterology referral center. We collected data on demographic features (age, sex), clinical characteristics (alarm features, Rome III criteria), and EGD results for each patient. All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes. Overall, EGD provided an accurate diagnosis for 109 children (38%). Diagnoses included esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%), and Crohn's disease (0.4%). Short-term outcomes were available for 81% of patients with diagnostic findings, and medical therapy was effective in approximately 67% of these children. EGD is valuable for the diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD identified disorders for which medical therapy was effective in 67% of children during the year after diagnosis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Abdominal rectus muscle pyomyositis: Report of a case and review of the literature

PubMed Central

Fountoukis, Tilemachos; Tsatsanidis, Nikolaos; Tilkeridou, Maria; Konstantinou, Ioannis; Fytas, Pantelis; Skandalos, Ioannis

2018-01-01

Pyomyositis is an uncommon primary bacterial infection of skeletal muscles, usually caused by Staphylococcus aureus. Predisposing factors for pyomyositis include immunodeficiency, trauma, injection drug use, concurrent infection and malnutrition. The diagnosis, staging of the disease and differential diagnosis are established by ultrasound, CT and MRI. Treatment involves surgical drainage and antibiotic therapy. We report a case of abdominal rectus muscle pyomyositis, which constitutes, as far as we know, the second reported in bibliography, while Prevotella disiens is firstly reported as causative agent. PMID:29721242

Chronic abdominal wall pain and ultrasound-guided abdominal cutaneous nerve infiltration: a case series.

PubMed

Kanakarajan, Saravanakumar; High, Kristina; Nagaraja, Ravi

2011-03-01

Chronic abdominal wall pain occurs in about 10-30% of patients presenting with chronic abdominal pain. Entrapment of abdominal cutaneous nerves at the lateral border of the rectus abdominis muscle has been attributed as a cause of abdominal wall pain. We report our experience of treating such patients using ultrasound-guided abdominal cutaneous nerve infiltration. We conducted a retrospective audit of abdominal cutaneous nerve infiltration performed in the period between September 2008 to August 2009 in our center. All patients had received local anesthetic and steroid injection under ultrasound guidance. The response to the infiltration was evaluated in the post-procedure telephone review as well as in the follow-up clinic. Brief pain inventory (BPI) and numerical rating scale pain scores were collated from two points: the initial outpatient clinic and the follow up clinic up to 5 months following the injection. Nine patients had abdominal cutaneous nerve injections under ultrasound guidance in the period under review. Six patients reported 50% pain relief or more (responders) while three patients did not. Pain and BPI scores showed a decreasing trend in responders. The median duration of follow-up was 12 weeks. Ultrasound can reliably be used for infiltration of the abdominal cutaneous nerves. This will improve the safety as well as diagnostic utility of the procedure. Wiley Periodicals, Inc.

Abdominal drainage following cholecystectomy: high, low, or no suction?

PubMed Central

McCormack, T. T.; Abel, P. D.; Collins, C. D.

1983-01-01

A prospective trial to assess the effect of suction in an abdominal drain following cholecystectomy was carried out. Three types of closed drainage system were compared: a simple tube drain, a low negative pressure drain, and a high negative pressure drain: 120 consecutive patients undergoing cholecystectomy were randomly allocated to one of the three drainage groups. There was no significant difference in postoperative pyrexia, wound infection, chest infection, or hospital stay. This study failed to demonstrate any clinically useful difference between high negative pressure, low negative pressure, and static drainage system were compared: a simple tube drain, a low negative used, suction is not necessary and a simple tube drain (greater than 6 mm internal diameter) is the most effective form of drainage. PMID:6614773

Specificity of the Tuberculin Skin Test Is Modified by Use of a Protein Cocktail Containing ESAT-6 and CFP-10 in Cattle Naturally Infected with Mycobacterium bovis

PubMed Central

Flores-Villalva, S.; Suárez-Güemes, F.; Espitia, C.; Whelan, A. O.; Vordermeier, M.

2012-01-01

The mycobacterial immunodominant ESAT-6 and CFP-10 antigens are strongly recognizable in tuberculosis-infected cattle, and they do not elicit a response in cattle without infection. In addition, they are absent in most environmental mycobacterial species, and therefore, their use can be an alternative to purified protein derivative (PPD) tuberculin in the development of a more specific skin diagnostic test in cattle. The aim of the current study was to assess the potential of an ESAT-6 and CFP-10 (E6-C10) protein cocktail in a skin test format in naturally tuberculosis-infected and paratuberculosis-infected cattle. We also included MPB83 as a third component in one of the protein cocktail preparations. The protein cocktail was tested at different dose concentrations (5, 10, and 15 μg per protein). The best skin response to the E6-C10 protein cocktail was obtained with 10 μg. Subsequently, this concentration was tested in 2 herds with high and low bovine tuberculosis prevalence, the latter with paratuberculosis coinfection. Our data show that the E6-C10 cocktail allows identification of an important proportion of animals that PPDB is not able to recognize, especially in low-prevalence herds. The protein cocktail did not induce reactions in tuberculosis-free cattle or in paratuberculosis-infected cattle. Addition of MPB83 to the protein cocktail did not make any difference in the skin reaction. PMID:22419675

Specificity of the tuberculin skin test is modified by use of a protein cocktail containing ESAT-6 and CFP-10 in cattle naturally infected with Mycobacterium bovis.

PubMed

Flores-Villalva, S; Suárez-Güemes, F; Espitia, C; Whelan, A O; Vordermeier, M; Gutiérrez-Pabello, J A

2012-05-01

The mycobacterial immunodominant ESAT-6 and CFP-10 antigens are strongly recognizable in tuberculosis-infected cattle, and they do not elicit a response in cattle without infection. In addition, they are absent in most environmental mycobacterial species, and therefore, their use can be an alternative to purified protein derivative (PPD) tuberculin in the development of a more specific skin diagnostic test in cattle. The aim of the current study was to assess the potential of an ESAT-6 and CFP-10 (E6-C10) protein cocktail in a skin test format in naturally tuberculosis-infected and paratuberculosis-infected cattle. We also included MPB83 as a third component in one of the protein cocktail preparations. The protein cocktail was tested at different dose concentrations (5, 10, and 15 μg per protein). The best skin response to the E6-C10 protein cocktail was obtained with 10 μg. Subsequently, this concentration was tested in 2 herds with high and low bovine tuberculosis prevalence, the latter with paratuberculosis coinfection. Our data show that the E6-C10 cocktail allows identification of an important proportion of animals that PPDB is not able to recognize, especially in low-prevalence herds. The protein cocktail did not induce reactions in tuberculosis-free cattle or in paratuberculosis-infected cattle. Addition of MPB83 to the protein cocktail did not make any difference in the skin reaction.

Readmission After Abdominal Surgery for Crohn's Disease: Identification of High-Risk Patients.

PubMed

Mege, Diane; Michelassi, Fabrizio

2018-05-16

Although many predictive factors for postoperative morbidity are known, few data are available about readmission after abdominal surgery for Crohn's disease (CD). The objective of this study is to identify predictive factors and high-risk patients for readmission after abdominal CD surgery. All patients who underwent abdominal surgery for CD in one tertiary referral center between January 2004 and December 2016 were included. Patients who required readmission and those without were compared. Perineal procedures, elective readmissions, and abdominal procedures for non-Crohn's indications were not included. Nine hundred eight abdominal procedures were performed in 712 patients. Readmission rates were 8, 8.5, 8.6, 8.8, and 8.9% at 30, 60, and 90 days and 12 and 60 months, respectively. The main reasons were wound infection (14%), deep abscess (13%), small-bowel obstruction (13%), and dehydration (11%). Eight (11%) patients required percutaneous drainage and 19 (27%) underwent an unplanned surgery. After multivariate analysis, three independent predictive factors for readmission were identified: older age (OR 1.02, 95%CI 1.005-1.04; p < 0.006), a history of previous proctectomy (OR 3, 95%CI 1.2-9, p < 0.02), and higher blood loss volume during surgery (OR 1.0001, 95%CI 1-1.002, p < 0.05). Readmission occurred in 8-9% of abdominal procedures for CD within 1-3 months after surgery and it required unplanned reoperation in a quarter of them. Identification of high-risk groups and knowledge of the more common postoperative complications requiring readmission help in increasing postoperative vigilance to select patients who may benefit from early interventions.

Postoperative outcomes in vedolizumab-treated pediatric patients undergoing abdominal operations for inflammatory bowel disease.

PubMed

Lightner, Amy L; Tse, Chung Sang; Potter, D Dean; Moir, Christopher

2017-10-09

Recent studies have found vedolizumab to be an independent predictor of increased rates of postoperative complications and surgical site infections (SSIs) in adults with inflammatory bowel disease (IBD), but studies in the pediatric surgical population are lacking. We sought to determine the 30-day postoperative infectious complication rate among pediatric IBD patients who received vedolizumab within 12weeks of a major abdominal operation. A retrospective chart review was performed on pediatric IBD patients who underwent an abdominal operation between 5/20/2014 and 6/1/2017. The study cohort was comprised of pediatric patients (≤18years) who received vedolizumab within 12weeks prior to their abdominal operation. The control cohort was all patients operated on for IBD during the same time on anti-TNF therapy within 12weeks of their abdominal operation. Thirteen pediatric patients (5 female) received vedolizumab within 12weeks of an abdominal operation and 36 patients received anti TNF therapy (20 female). There were no differences in the vedolizumab and anti-TNF therapy with regard to sex, median age of diagnosis or operation, IBD type, body mass index (BMI), smoking status, diabetes mellitus (DM), preoperative serum laboratory values, steroid or immunomodulatory use. The number of biologics previously exposed to was significantly higher in the vedolizumab treated patients (p<0.0001). There were no significant differences in operative characteristics including laparoscopic versus open surgery, construction of an anastomosis, or diversion of an anastomosis. There were also no significant differences found in 30-day postoperative complications including nonsurgical site infections (SSIs), all SSIs, small bowel obstruction (SBO)/ileus, hospital readmission, or return to the operating room (ROR). There were four RORs in total: one in the vedolizumab group was for a missed enterotomy and stoma revision; three in the anti-TNF cohort were for ileostomy revisions. None of

Abdominal elephantiasis: a case report.

PubMed

Hanna, Dominique; Cloutier, Richard; Lapointe, Roch; Desgagné, Antoine

2004-01-01

Elephantiasis is a well-known condition in dermatology usually affecting the legs and external genitalia. It is characterized by chronic inflammation and obstruction of the lymphatic channels and by hypertrophy of the skin and subcutaneous tissues. The etiology is either idiopathic or caused by a variety of conditions such as chronic filarial disease, leprosy, leishmaniasis, and chronic recurrent cellulites. Elephantiasis of the abdominal wall is very rare. A complete review of the English and French literature showed only two cases reported in 1966 and 1973, respectively. We report a third case of abdominal elephantiasis and we briefly review this entity. We present the case of a 51-year-old woman who had progressively developed an enormous pediculated abdominal mass hanging down her knees. The skin was thickened, hyperpigmented, and fissured. She had a history of multiple abdominal cellulites. She underwent an abdominal lipectomy. Histopathology of the specimen confirmed the diagnosis of abdominal elephantiasis. Abdominal elephantiasis is a rare disease that represents end-stage failure of lymph drainage. Lipectomy should be considered in the management of this condition.

Acute abdominal pain in patients with lassa fever: Radiological assessment and diagnostic challenges

PubMed Central

Eze, Kenneth C.; Salami, Taofeek A.; Kpolugbo, James U.

2014-01-01

Background: To highlight the problems of diagnosis and management of acute abdomen in patients with lassa fever. And to also highlight the need for high index of suspicion of lassa fever in patients presenting with acute abdominal pain in order to avoid surgical intervention with unfavourable prognosis and nosocomial transmission of infections, especially in Lassa fever-endemic regions. Materials and Methods: A review of experiences of the authors in the management of lassa fever over a 4-year period (2004-2008). Literature on lassa fever, available in the internet and other local sources, was studied in November 2010 and reviewed. Results: Normal plain chest radiographic picture can change rapidly due to pulmonary oedema, pulmonary haemorrhage and acute respiratory distress syndrome. Plain abdominal radiograph may show dilated bowels with signs of paralytic ileus or dynamic intestinal obstruction due to bowel wall haemorrhage or inflamed and enlarged Peyer's patches. Ultrasound may show free intra-peritoneal fluid due to peritonitis and intra-peritoneal haemorrhage. Bleeding into the gall bladder wall may erroneously suggest infective cholecystitis. Pericardial effusion with or without pericarditis causing abdominal pain may be seen using echocardiography. High index of suspicion, antibody testing for lassa fever and viral isolation in a reference laboratory are critical for accurate diagnosis. Conclusion: Patients from lassa fever-endemic regions may present with features that suggest acute abdomen. Radiological studies may show findings that suggest acute abdomen but these should be interpreted in the light of the general clinical condition of the patient. It is necessary to know that acute abdominal pain and vomiting in lassa fever-endemic areas could be caused by lassa fever, which is a medical condition. Surgical option should be undertaken with restraint as it increases the morbidity, may worsen the prognosis and increase the risk of nosocomial transmission

Acute abdominal pain in patients with lassa fever: Radiological assessment and diagnostic challenges.

PubMed

Eze, Kenneth C; Salami, Taofeek A; Kpolugbo, James U

2014-05-01

To highlight the problems of diagnosis and management of acute abdomen in patients with lassa fever. And to also highlight the need for high index of suspicion of lassa fever in patients presenting with acute abdominal pain in order to avoid surgical intervention with unfavourable prognosis and nosocomial transmission of infections, especially in Lassa fever-endemic regions. A review of experiences of the authors in the management of lassa fever over a 4-year period (2004-2008). Literature on lassa fever, available in the internet and other local sources, was studied in November 2010 and reviewed. Normal plain chest radiographic picture can change rapidly due to pulmonary oedema, pulmonary haemorrhage and acute respiratory distress syndrome. Plain abdominal radiograph may show dilated bowels with signs of paralytic ileus or dynamic intestinal obstruction due to bowel wall haemorrhage or inflamed and enlarged Peyer's patches. Ultrasound may show free intra-peritoneal fluid due to peritonitis and intra-peritoneal haemorrhage. Bleeding into the gall bladder wall may erroneously suggest infective cholecystitis. Pericardial effusion with or without pericarditis causing abdominal pain may be seen using echocardiography. High index of suspicion, antibody testing for lassa fever and viral isolation in a reference laboratory are critical for accurate diagnosis. Patients from lassa fever-endemic regions may present with features that suggest acute abdomen. Radiological studies may show findings that suggest acute abdomen but these should be interpreted in the light of the general clinical condition of the patient. It is necessary to know that acute abdominal pain and vomiting in lassa fever-endemic areas could be caused by lassa fever, which is a medical condition. Surgical option should be undertaken with restraint as it increases the morbidity, may worsen the prognosis and increase the risk of nosocomial transmission.

In vitro comparison of intra-abdominal hypertension development after different temporary abdominal closure techniques.

PubMed

Benninger, Emanuel; Labler, Ludwig; Seifert, Burkhardt; Trentz, Otmar; Menger, Michael D; Meier, Christoph

2008-01-01

To compare volume reserve capacity (VRC) and development of intra-abdominal hypertension after different in vitro temporary abdominal closure (TAC) techniques. A model of the abdomen was designed. The abdominal wall was simulated with polychloroprene, a synthetic rubber compound. A lentil-shaped defect of 150 cm(2) was cut into the anterior aspect of the abdominal wall. TAC of this defect was performed by a zipper system (ZS), a bag silo closure (BSC), or a vacuum assisted closure (VAC) with subatmospheric pressures ranging from 0- to 200 mmHg. The model with intact abdominal wall served as reference. The model was filled with water to baseline level. The intra-abdominal pressure was increased in 2 mmHg steps from baseline level (6 mmHg) to 40 mmHg by adding volume to the system according to a standardized protocol. VRC with corresponding intra-abdominal pressure were analyzed and compared for the different TAC techniques. VRC was the highest after BSC at all pressure levels studied (P < 0.05). VAC and ZS resulted in significantly lower VRC compared with BSC and reference (P < 0.05). The magnitude of negative pressure on the VAC did not significantly influence the VRC. In the present in vitro model, BSC demonstrated the highest VRC of all evaluated TAC techniques. Different levels of subatmospheric pressures applied to the VAC did not affect VRC. The results for ZS and VAC indicate that these TAC techniques may increase the risk for recurrent intra-abdominal hypertension and should therefore not be used in high-risk patients during the initial phase after abdominal decompression.

2017 update of the WSES guidelines for emergency repair of complicated abdominal wall hernias.

PubMed

Birindelli, Arianna; Sartelli, Massimo; Di Saverio, Salomone; Coccolini, Federico; Ansaloni, Luca; van Ramshorst, Gabrielle H; Campanelli, Giampiero; Khokha, Vladimir; Moore, Ernest E; Peitzman, Andrew; Velmahos, George; Moore, Frederick Alan; Leppaniemi, Ari; Burlew, Clay Cothren; Biffl, Walter L; Koike, Kaoru; Kluger, Yoram; Fraga, Gustavo P; Ordonez, Carlos A; Novello, Matteo; Agresta, Ferdinando; Sakakushev, Boris; Gerych, Igor; Wani, Imtiaz; Kelly, Michael D; Gomes, Carlos Augusto; Faro, Mario Paulo; Tarasconi, Antonio; Demetrashvili, Zaza; Lee, Jae Gil; Vettoretto, Nereo; Guercioni, Gianluca; Persiani, Roberto; Tranà, Cristian; Cui, Yunfeng; Kok, Kenneth Y Y; Ghnnam, Wagih M; Abbas, Ashraf El-Sayed; Sato, Norio; Marwah, Sanjay; Rangarajan, Muthukumaran; Ben-Ishay, Offir; Adesunkanmi, Abdul Rashid K; Lohse, Helmut Alfredo Segovia; Kenig, Jakub; Mandalà, Stefano; Coimbra, Raul; Bhangu, Aneel; Suggett, Nigel; Biondi, Antonio; Portolani, Nazario; Baiocchi, Gianluca; Kirkpatrick, Andrew W; Scibé, Rodolfo; Sugrue, Michael; Chiara, Osvaldo; Catena, Fausto

2017-01-01

Emergency repair of complicated abdominal wall hernias may be associated with worsen outcome and a significant rate of postoperative complications. There is no consensus on management of complicated abdominal hernias. The main matter of debate is about the use of mesh in case of intestinal resection and the type of mesh to be used. Wound infection is the most common complication encountered and represents an immense burden especially in the presence of a mesh. The recurrence rate is an important topic that influences the final outcome. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013 with the aim to define recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. In 2016, the guidelines have been revised and updated according to the most recent available literature.

Endovascular Repair of an Actively Hemorrhaging Stab Wound Injury to the Abdominal Aorta

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

Hussain, Qasim; Maleux, Geert, E-mail: geert.maleux@uz.kuleuven.ac.be; Heye, Sam

Traumatic injury of the abdominal aorta is rare and potentially lethal (Yeh et al., J Vasc Surg 42(5):1007-1009, 2005; Chicos et al., Chirurgia (Bucur) 102(2):237-240, 2007) as it can result in major retroperitoneal hemorrhage, requiring an urgent open surgery. In case of concomitant bowel injury or other conditions of hostile abdomen, endovascular repair can be an alternative treatment. This case report deals with a 50-year-old man presenting at the emergency ward with three stab wounds: two in the abdomen and one in the chest. During explorative laparotomy, liver laceration and bowel perforation were repaired. One day later, abdominal CT-scan revealedmore » an additional retroperitoneal hematoma associated with an aortic pseudoaneurysm, located anteriorly 3 cm above the aortic bifurcation. Because of the risk of graft infection, an endovascular repair of the aortic injury using a Gore excluder stent-graft was performed. Radiological and clinical follow-up revealed a gradual shrinkage of the pseudo-aneurysm and no sign of graft infection at two years' follow-up.« less

Endovascular repair of an actively hemorrhaging stab wound injury to the abdominal aorta.

PubMed

Hussain, Qasim; Maleux, Geert; Heye, Sam; Fourneau, Inge

2008-01-01

Traumatic injury of the abdominal aorta is rare and potentially lethal (Yeh et al., J Vasc Surg 42(5):1007-1009, 2005; Chicos et al., Chirurgia (Bucur) 102(2):237-240, 2007) as it can result in major retroperitoneal hemorrhage, requiring an urgent open surgery. In case of concomitant bowel injury or other conditions of hostile abdomen, endovascular repair can be an alternative treatment. This case report deals with a 50-year-old man presenting at the emergency ward with three stab wounds: two in the abdomen and one in the chest. During explorative laparotomy, liver laceration and bowel perforation were repaired. One day later, abdominal CT-scan revealed an additional retroperitoneal hematoma associated with an aortic pseudoaneurysm, located anteriorly 3 cm above the aortic bifurcation. Because of the risk of graft infection, an endovascular repair of the aortic injury using a Gore excluder stent-graft was performed. Radiological and clinical follow-up revealed a gradual shrinkage of the pseudo-aneurysm and no sign of graft infection at two years' follow-up.

Definitive Surgical Treatment of Infected or Exposed Ventral Hernia Mesh

PubMed Central

Szczerba, Steven R.; Dumanian, Gregory A.

2003-01-01

Objective To discuss the difficulties in dealing with infected or exposed ventral hernia mesh, and to illustrate one solution using an autogenous abdominal wall reconstruction technique. Summary Background Data The definitive treatment for any infected prosthetic material in the body is removal and substitution. When ventral hernia mesh becomes exposed or infected, its removal requires a solution to prevent a subsequent hernia or evisceration. Methods Eleven patients with ventral hernia mesh that was exposed, nonincorporated, with chronic drainage, or associated with a spontaneous enterocutaneous fistula were referred by their initial surgeons after failed local wound care for definitive management. The patients were treated with radical en bloc excision of mesh and scarred fascia followed by immediate abdominal wall reconstruction using bilateral sliding rectus abdominis myofascial advancement flaps. Results Four of the 11 patients treated for infected mesh additionally required a bowel resection. Transverse defect size ranged from 8 to 18 cm (average 13 cm). Average procedure duration was 3 hours without bowel repair and 5 hours with bowel repair. Postoperative length of stay was 5 to 7 days without bowel repair and 7 to 9 days with bowel repair. Complications included hernia recurrence in one case and stitch abscesses in two cases. Follow-up ranges from 6 to 54 months (average 24 months). Conclusions Removal of infected mesh and autogenous flap reconstruction is a safe, reliable, and one-step surgical solution to the problem of infected abdominal wall mesh. PMID:12616130

Abdominal hernias: Radiological features

PubMed Central

Lassandro, Francesco; Iasiello, Francesca; Pizza, Nunzia Luisa; Valente, Tullio; Stefano, Maria Luisa Mangoni di Santo; Grassi, Roberto; Muto, Roberto

2011-01-01

Abdominal wall hernias are common diseases of the abdomen with a global incidence approximately 4%-5%. They are distinguished in external, diaphragmatic and internal hernias on the basis of their localisation. Groin hernias are the most common with a prevalence of 75%, followed by femoral (15%) and umbilical (8%). There is a higher prevalence in males (M:F, 8:1). Diagnosis is usually made on physical examination. However, clinical diagnosis may be difficult, especially in patients with obesity, pain or abdominal wall scarring. In these cases, abdominal imaging may be the first clue to the correct diagnosis and to confirm suspected complications. Different imaging modalities are used: conventional radiographs or barium studies, ultrasonography and Computed Tomography. Imaging modalities can aid in the differential diagnosis of palpable abdominal wall masses and can help to define hernial contents such as fatty tissue, bowel, other organs or fluid. This work focuses on the main radiological findings of abdominal herniations. PMID:21860678

Respiratory infections associated with anti-TNFα agents.

PubMed

Blanchard, E; Truchetet, M-E; Machelart, I; Séneschal, J; Raherison-Semjen, C

2017-10-01

Anti-TNFα agents have proved effective in the treatment of various inflammatory, rheumatologic, dermatologic, and gastrointestinal diseases. Severe respiratory tract infections of bacterial or fungal origin have emerged as important complications in patients receiving such treatments. The risk of infection due to anti-TNFα therapy is difficult to assess in these patients who are immunocompromised because of the underlying disease itself and of previous or concomitant immunosuppressive drugs. This excessive infection risk seems real, particularly in the first six months following treatment initiation, and higher for patients receiving anti-TNFα monoclonal antibodies than for those receiving soluble TNFα receptor. The involved pathogens are pyogenic bacteria but also Mycobacterium tuberculosis, mostly by reactivation of latent tuberculosis infection, warranting a systematic preventive approach to screening and chemoprophylaxis before initiating the anti-TNFα therapy. In countries with low tuberculosis endemicity, an increased prevalence of nontuberculous mycobacterial infections has been reported. The incidence rate of legionellosis is high in this population. In case of pneumonia, empirical antibiotic therapy should cover Legionella pneumophila. Several cases of histoplasmosis have also been reported and this diagnosis should be suspected in patients who have traveled to endemic areas. Other opportunistic infections have been reported including Pneumocystis pneumonia, aspergillosis, and nocardiosis mostly in patients receiving other immunosuppressive treatments. The risk of infection should be evaluated as an individual risk depending on comorbidities and past or concomitant treatments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Necrotizing infection of the heart.

PubMed

Ballard, David H; Pennington, George Patton; Pennington, George P; Johnson, Joe; Bhalla, Sanjeev; Raptis, Constantine

2018-02-06

A case of necrotizing infection of the heart is presented. A 70-year-old woman presented with vague chest and abdominal pain. CT of the abdomen and pelvis was initially obtained, which demonstrated gas in the myocardium of the left ventricle. Subsequent chest CT, endoscopy, and abdominal surgical exploration did not reveal perforated viscus or diaphragm compromise. At median sternotomy, the inferior wall of the heart was found to be necrotic. Culture of the excised tissue grew E. coli. The patient expired shortly after surgical exploration. Copyright © 2018 Elsevier Inc. All rights reserved.

Mycobacterium bovis Bacille Calmette-Guérin Infection in the CNS Suppresses Experimental Autoimmune Encephalomyelitis and Th17 Responses in an IFN-gamma-independent Manner1

PubMed Central

Lee, JangEun; Reinke, Emily K.; Zozulya, Alla L.; Sandor, Matyas; Fabry, Zsuzsanna

2009-01-01

Multiple sclerosis (MS) and an animal model resembling MS, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases of the central nervous system (CNS) that are suppressed by systemic mycobacterial infection in mice and BCG vaccination in humans. Host defense responses against Mycobacterium in mice are influenced by T lymphocytes and their cytokine products, particularly IFN-γ, which plays a protective regulatory role in EAE. To analyze the counter-regulatory role of mycobacterial infection-induced IFN-γ in the CNS on the function of the pathological Th17 cells and the clinical outcome of EAE, we induced EAE in mice that were intracerebrally infected with Mycobacterium bovis bacille Calmette-Guerin (BCG). Here we demonstrate that intracerebral (i.c.) BCG infection prevented inflammatory cell recruitment to the spinal cord and suppressed the development of EAE. Concomitantly, there was a significant decrease in the frequency of MOG-specific IFN-γ-producing CD4+ T cells in the CNS. IL-17+CD4+ T cell responses were significantly suppressed in i.c. BCG-infected mice following EAE induction regardless of T cell specificity. The frequency of Foxp3+CD4+ T cells in these mice was equivalent to that of control mice. The i.c. BCG infection-induced protection of EAE and suppression of MOG-specific IL-17+CD4+ T cell responses were similar in both wild type (WT) and IFN-γ deficient mice. These data show that live BCG infection in the brain suppresses CNS autoimmunity. These findings also reveal that the regulation of Th17-mediated autoimmunity in the CNS can be independent of IFN-γ-mediated mechanisms. PMID:18941210

Infected Congenital Epicardial Cyst Presenting as Acute Abdomen.

PubMed

Dribin, Timothy; Files, Matthew D; Rudzinski, Erin R; Kaplan, Ron; Stone, Kimberly P

2016-12-01

A previously healthy 3-year-old boy presented to the emergency department with abdominal pain, fever, and emesis. Laboratory and radiologic evaluation for causes of acute abdomen were negative; however, review of the abdominal x-ray demonstrated cardiomegaly with the subsequent diagnosis of pericardial cyst by echocardiogram and computed tomography. The patient underwent surgical decompression and attempted removal of the cystic structure revealing that the cyst originated from the epicardium. His abdominal pain and fever resolved postoperatively and he completed a 3-week course of ceftriaxone for treatment of Propionibacterium acnes infected congenital epicardial cyst. Emergency department physicians must maintain a broad differential in patients with symptoms of acute abdomen to prevent complications from serious cardiac or pulmonary diseases that present with symptoms of referred abdominal pain.

Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review.

PubMed

Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

2014-11-01

Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. A systematic review was conducted. The PubMed, EMBASE and Cochrane databases were searched for studies on the use of abdominal binders after abdominal surgery or abdominoplasty. All types of clinical studies were included. Two independent assessors evaluated the scientific quality of the studies. The primary outcomes were pain, seroma formation and physical function. A total of 50 publications were identified; 42 publications were excluded leaving eight publications counting a total of 578 patients for analysis. Generally, the scientific quality of the studies was poor. Use of abdominal binder revealed a non-significant tendency to reduce seroma formation after laparoscopic ventral herniotomy and a non-significant reduction in pain. Physical function was improved, whereas evidence supports a beneficial effect on psychological distress after open abdominal surgery. Evidence also supports that intra-abdominal pressure increases with the use of abdominal binders. Reduction of pulmonary function during use of abdominal binders has not been revealed. Abdominal binders reduce post-operative psychological distress, but their effect on post-operative pain after laparotomy and seroma formation after ventral hernia repair remains unclear. Due to the sparse evidence and poor quality of the literature, solid conclusions may be difficult to make, and procedure-specific, high-quality randomised clinical trials are warranted.

Importance of Local and Regional Scales in Shaping Mycobacterial Abundance in Freshwater Lakes.

PubMed

Roguet, Adélaïde; Therial, Claire; Catherine, Arnaud; Bressy, Adèle; Varrault, Gilles; Bouhdamane, Lila; Tran, Viet; Lemaire, Bruno J; Vincon-Leite, Brigitte; Saad, Mohamed; Moulin, Laurent; Lucas, Françoise S

2018-05-01

Biogeographical studies considering the entire bacterial community may underestimate mechanisms of bacterial assemblages at lower taxonomic levels. In this context, the study aimed to identify factors affecting the spatial and temporal dynamic of the Mycobacterium, a genus widespread in aquatic ecosystems. Nontuberculous mycobacteria (NTM) density variations were quantified in the water column of freshwater lakes at the regional scale (annual monitoring of 49 lakes in the Paris area) and at the local scale (2-year monthly monitoring in Créteil Lake) by real-time quantitative PCR targeting the atpE gene. At the regional scale, mycobacteria densities in water samples ranged from 6.7 × 10 3 to 1.9 × 10 8 genome units per liter. Density variations were primarily explained by water pH, labile iron, and dispersal processes through the connection of the lakes to a river. In Créteil Lake, no spatial variation of mycobacterial densities was noticed over the 2-year monthly survey, except after large rainfall events. Indeed, storm sewer effluents locally and temporarily increased NTM densities in the water column. The temporal dynamic of the NTM densities in Créteil Lake was associated with suspended solid concentrations. No clear seasonal variation was noticed despite a shift in NTM densities observed over the 2012-2013 winter. Temporal NTM densities fluctuations were well predicted by the neutral community model, suggesting a random balance between loss and gain of mycobacterial taxa within Créteil Lake. This study highlights the importance of considering multiple spatial scales for understanding the spatio-temporal dynamic of bacterial populations in natural environments.

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence.

PubMed

Lipner, Ettie M; Gopi, P G; Subramani, R; Kolappan, C; Sadacharam, K; Kumaran, Paul; Prevots, D Rebecca; Narayanan, P R; Nutman, Thomas B; Kumaraswami, V

2006-05-01

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

Trends in bacterial, mycobacterial, and fungal meningitis in England and Wales 2004-11: an observational study.

PubMed

Okike, Ifeanichukwu O; Ribeiro, Sonia; Ramsay, Mary E; Heath, Paul T; Sharland, Mike; Ladhani, Shamez N

2014-04-01

Meningitis remains one of the most feared infectious diseases worldwide, yet there are few population-based studies on the epidemiology, causes, or trends over time in meningitis, especially in industrialised countries. Our aim was to do such a study using routinely reported data available in England and Wales. In England and Wales, UK National Health Service hospitals routinely report laboratory-confirmed pathogens electronically to Public Health England. Records of all positive bacterial, mycobacterial, and fungal results from cerebrospinal fluid or from blood cultures in patients with clinical meningitis were extracted for analysis. The percentage change in annual incidence was estimated using linear regression analysis of the log of the annual incidence. During 2004-11, 7061 cases of meningitis were reported (mean annual incidence 1·62 per 100,000 people, 95% CI 1·58-1·66), including 2594 cases in children (37%). The incidence of bacterial (1·44 per 100,000 people, 1·41-1·48), fungal (0·09, 0·08-0·10), and mycobacterial (0·09, 0·08-0·09) meningitis remained stable overall and across the age groups, apart from significant year-on-year increases in children younger than 3 months (978 cases; incidence 72·2 per 100,000 people; annual increase 7·4%, 5·1-9·8; p<0·0001) driven mainly by group B streptococci (GBS), and in adults aged 65 years or older (752 cases; incidence 1·2 per 100,000 people; annual increase 3·0%, 1·4-4·8; p<0·0001) primarily because of Escherichia coli. By contrast, meningococcal meningitis rates declined steadily, but remained the most common cause of meningitis in children. Overall, five groups of bacteria accounted for 60% (3790/6286) of bacterial meningitis cases: Neisseria meningitidis (1350 cases, 22%), Streptococcus pneumoniae (1143, 18%), Staphylococcus aureus (652, 10%), GBS (326, 5%), and E coli (319, 5%). In England and Wales, laboratory-based surveillance shows a remarkably stable incidence of bacterial, fungal

Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection

PubMed Central

Silva-Gomes, Sandro; Appelberg, Rui; Larsen, Rasmus; Soares, Miguel Parreira

2013-01-01

Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (Mϕ) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1−/−) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1+/+) controls. Furthermore, Hmox1−/− mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1−/− versus Hmox1+/+ SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected Mϕ, an effect mimicked by exogenous heme administration to M. avium-infected wild-type Mϕ in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in Mϕ, contributing critically to host resistance to Mycobacterium infection. PMID:23630967

Abdominal Aortic Dissections

PubMed Central

Borioni, Raoul; Garofalo, Mariano; De Paulis, Ruggero; Nardi, Paolo; Scaffa, Raffaele; Chiariello, Luigi

2005-01-01

Isolated abdominal aortic dissections are rare events. Their anatomic and clinical features are different from those of atherosclerotic aneurysms. We report 4 cases of isolated abdominal aortic dissection that were successfully treated with surgical or endovascular intervention. The anatomic and clinical features and a review of the literature are also presented. PMID:15902826

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ Transplant Infection Project, a Multicenter, Prospective, Cohort Study.

PubMed

Schuster, Mindy G; Cleveland, Angela A; Dubberke, Erik R; Kauffman, Carol A; Avery, Robin K; Husain, Shahid; Paterson, David L; Silveira, Fernanda P; Chiller, Tom M; Benedict, Kaitlin; Murphy, Kathleen; Pappas, Peter G

2017-01-01

Infection is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Our object was to better define the epidemiology and outcomes of infections after HCT. This was a prospective, multicenter cohort study of HCT recipients and conducted from 2006 to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data were prospectively collected for up to 30 months after HCT using a standardized data collection tool. The median age was 53 years, and median follow up was 413 (range, 5-980) days. The most common reason for HCT was hematologic malignancy (87%). The overall crude mortality was 52%. Death was due to underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231 (52%) cases and occurred early posttransplant (median day 48). Gram-negative bloodstream infections were less frequent than Gram-positive, but it was associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile infection developed in 148 patients (33%) at a median of 27 days post-HCT. There were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection, 4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13 (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial infection. This study lacked standardized antifungal and antiviral prophylactic strategies. Infection remains a significant cause of morbidity and mortality after HCT. Bacteremias and C difficile infection are frequent, particularly in the early posttransplant period. The rate of IFI is approximately 10%. Organ involvement with CMV is infrequent, as are serious infections with VZV and herpes simplex virus, likely reflecting improved prevention

Analysis of 162 colon injuries in patients with penetrating abdominal trauma: concomitant stomach injury results in a higher rate of infection.

PubMed

O'Neill, Patricia A; Kirton, Orlando C; Dresner, Lisa S; Tortella, Bartholomew; Kestner, Mark M

2004-02-01

Fecal contamination from colon injury has been thought to be the most significant factor for the development of surgical site infection (SSI) after trauma. However, there are increasing data to suggest that other factors may play a role in the development of postinjury infection in patients after colon injury. The purpose of this study was to determine the impact of gastric wounding on the development of SSI and nonsurgical site infection (NSSI) in patients with colon injury. Post hoc analysis was performed on data prospectively collected for 317 patients presenting with penetrating hollow viscus injury. One hundred sixty-two patients with colon injury were subdivided into one of three groups: patients with isolated colon wounds (C), patients with colon and stomach wounds with or without other organ injury (C+S), and patients with colon and other organ injury but no stomach injury (C-S) and assessed for the development of SSI and NSSI. Infection rates were also determined for patients who sustained isolated gastric injury (S) and gastric injury in combination with other injuries other than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel-Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by multivariate logistic regression. C+S patients had a higher rate of SSI infection (31%) than C patients (3.6%) (p=0.008) and C-S patients (13%) (p=0.021). Similarly, the incidence of NSSI was also significantly greater in the C+S group (37%) compared with the C patients (7.5%) (p=0.07) and the C-S patients (17%) (p=0.019). There was no difference in the rate of SSI or NSSI between the C and C-S groups (p=0.3 and p=0.24, respectively). The rate of SSI was significantly greater in the C+S patients when compared with the S-C patients (31% vs. 10%, p=0.008), but there was no statistical difference in the rate of NSSI in the C+S group and the S-C group (37

Automated anatomical labeling method for abdominal arteries extracted from 3D abdominal CT images

NASA Astrophysics Data System (ADS)

Oda, Masahiro; Hoang, Bui Huy; Kitasaka, Takayuki; Misawa, Kazunari; Fujiwara, Michitaka; Mori, Kensaku

2012-02-01

This paper presents an automated anatomical labeling method of abdominal arteries. In abdominal surgery, understanding of blood vessel structure concerning with a target organ is very important. Branching pattern of blood vessels differs among individuals. It is required to develop a system that can assist understanding of a blood vessel structure and anatomical names of blood vessels of a patient. Previous anatomical labbeling methods for abdominal arteries deal with either of the upper or lower abdominal arteries. In this paper, we present an automated anatomical labeling method of both of the upper and lower abdominal arteries extracted from CT images. We obtain a tree structure of artery regions and calculate feature values for each branch. These feature values include the diameter, curvature, direction, and running vectors of a branch. Target arteries of this method are grouped based on branching conditions. The following processes are separately applied for each group. We compute candidate artery names by using classifiers that are trained to output artery names. A correction process of the candidate anatomical names based on the rule of majority is applied to determine final names. We applied the proposed method to 23 cases of 3D abdominal CT images. Experimental results showed that the proposed method is able to perform nomenclature of entire major abdominal arteries. The recall and the precision rates of labeling are 79.01% and 80.41%, respectively.

Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections.

PubMed

Bartoletti, Michele; Tedeschi, Sara; Pascale, Renato; Raumer, Luigi; Maraolo, Alberto Enrico; Palmiero, Giulia; Tumietto, Fabio; Cristini, Francesco; Ambretti, Simone; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

2018-03-01

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen. We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves. We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46). TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Functional abdominal pain.

PubMed

Grover, Madhusudan; Drossman, Douglas A

2010-10-01

Functional abdominal pain syndrome (FAPS) is a relatively less common functional gastrointestinal (GI) disorder defined by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006), which points to a more centrally targeted (spinal and supraspinal) basis for the symptoms. However, FAPS is frequently confused with irritable bowel syndrome and other functional GI disorders in which abdominal pain is associated with eating and bowel movements. FAPS also differs from chronic abdominal pain associated with entities such as chronic pancreatitis or chronic inflammatory bowel disease, in which the pain is associated with peripherally acting factors (eg, gut inflammation or injury). Given the central contribution to the pain experience, concomitant psychosocial disturbances are common and strongly influence the clinical expression of FAPS, which also by definition is associated with loss of daily functioning. These factors make it critical to use a biopsychosocial construct to understand and manage FAPS, because gut-directed treatments are usually not successful in managing this condition.

Postoperative intra-abdominal collections using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier at the time of laparotomy for ovarian, fallopian tube, or primary peritoneal cancers.

PubMed

Leitao, Mario M; Natenzon, Anna; Abu-Rustum, Nadeem R; Chi, Dennis S; Sonoda, Yukio; Levine, Douglas A; Gardner, Ginger J; Barakat, Richard R

2009-11-01

To determine whether HA-CMC was associated with the development of postoperative intra-abdominal collections in patients undergoing laparotomy for ovarian, fallopian tube, or primary peritoneal malignancies. We retrospectively identified all laparotomies performed for these malignancies from March 1, 2005 to December 31, 2007. The use of HA-CMC was identified. Laparotomies for malignant bowel obstruction or repair of fistulae were excluded. Intra-abdominal collections, non-infected and infected, were defined as localized intraperitoneal fluid accumulations in the absence of re-accumulating ascites. All other complications were also captured. Appropriate statistical tests were applied using SPSS 15.0. We identified 219 laparotomies with HA-CMC and 204 without HA-CMC. Upper abdominal resections were performed in 65/219 (30%) HA-CMC cases compared to 39/204 (19%) cases without HA-CMC (P=0.01). The rates of large bowel and/or rectal resections were similar in both cohorts. Intra-abdominal collections were seen in 18/219 (8.2%) HA-CMC cases compared to 5/204 (2.5%) cases without HA-CMC (P=0.009). HA-CMC was independently associated with the diagnosis of a postoperative intra-abdominal collection (P=0.01). All but 2 collections developed in patients undergoing debulking procedures. HA-CMC appears to be associated with a higher rate of postoperative intra-abdominal collections. This seems to be greatest in patients who are undergoing a debulking procedure.

Determinants of splenectomy in splenic injuries following blunt abdominal trauma.

PubMed

Akinkuolie, A A; Lawal, O O; Arowolo, O A; Agbakwuru, E A; Adesunkanmi, A R K

2010-02-01

The management of splenic injuries has shifted from splenectomy to splenic preservation owing to the risk of overwhelming post-splenectomy infection (OPSI). This study aimed to identify the factors that determine splenectomy in patients with isolated splenic injuries, with a view to increasing the rate of splenic preservation. Files of 55 patients managed for isolated splenic injuries from blunt abdominal trauma between 1998 and 2007 were retrospectively analysed using a pro forma. Management options were classified into nonoperative, operative salvage and splenectomy. The majority of patients suffered splenic injury as a result of motor vehicle accident (MVA) trauma or falls. Splenectomy was undertaken in 33 (60%) patients, 12 (22%) had non-operative management, and operative salvage was achieved in 10 (18%) patients. Significant determinants of splenectomy were grade of splenic injury, hierarchy of the surgeon, and hierarchy of the assistant. MVA injury and falls accounted for the vast majority of blunt abdominal trauma in this study. The rate and magnitude of energy transferred versus splenic protective mechanisms at the time of blunt abdominal trauma seems to determine the grade of splenic injury. Interest in splenic salvage surgery, availability of technology that enables splenic salvage surgery, and the experience of the surgeon and assistant appear to determine the surgical management. Legislation on vehicle safety and good parental control may reduce the severity of splenic injury in blunt abdominal trauma. When surgery is indicated, salvage surgery should be considered in intermediate isolated splenic injury to reduce the incidence of OPSI.

Abdominal Cystic Echinococcosis Treated with Albendazole. A Pediatric Cohort Study.

PubMed

Moroni, Samanta; Moscatelli, Guillermo; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Freilij, Héctor; Salgueiro, Fabián; Altcheh, Jaime

2016-01-01

Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. Patients (0-18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10-15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention.

[Abdominal traumatic evisceration: reconstruction abdominal wall with biologic mesh and negative pressure therapy].

PubMed

Jiménez Gómez, M; Betancor Rivera, N; Lima Sánchez, J; Hernández Hernández, J R

2016-04-10

Abdominal traumatic evisceration as a result of high energy trauma is uncommon. Once repaired the possible internal damage, an abdominal wall defect of high complexity may exist, whose reconstruction represents a surgical challenge. Politraumatized male with important abdominal muculocutaneous avulsion and evisceration. After initial repair, the patient developed a big eventration in which we use a porcine dermis-derived mesh (Permacol TM ), a safe and effective alternative in abdominal wall repair, thanks to its seamless integration with other tissues, even when exposed. Negative pressure therapy has been used for the management of wound complications after surgical implantation of PermacolTM mesh. We describe our experience with the use of PermacolTM mesh and negative pressure therapy to aid the wound closure after skin necrosis and exposed mesh.

Qualitative Immune Modulation by Interleukin-2 (IL-2) Adjuvant Therapy in Immunological Non Responder HIV-Infected Patients

PubMed Central

Sabbatini, Francesca; Bandera, Alessandra; Ferrario, Giulio; Trabattoni, Daria; Marchetti, Giulia; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

2010-01-01

Background Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs). Methods and Findings PBMC from 12 immunological non-responders (INRs) (CD4+<200/µl, HIV-RNA<50 cp/ml) on combination antiretroviral treatment (cART) were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs) and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01). Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02) and substantial reductions in IL-10 levels were observed. Conclusions IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone. PMID:21124762

Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI)

PubMed Central

Solomkin, Joseph; Hershberger, Ellie; Miller, Benjamin; Popejoy, Myra; Friedland, Ian; Steenbergen, Judith; Yoon, Minjung; Collins, Sylva; Yuan, Guojun; Barie, Philip S.; Eckmann, Christian

2015-01-01

Background. Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae. Methods. ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4–14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24–32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated. Results. Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, −4.2%; 95% confidence interval [CI], −8.91 to .54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, −1.0%; 95% CI, −4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea. Conclusions. Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to

Intra-abdominal pressure during swimming.

PubMed

Moriyama, S; Ogita, F; Huang, Z; Kurobe, K; Nagira, A; Tanaka, T; Takahashi, H; Hirano, Y

2014-02-01

The present study aimed to determine the intra-abdominal pressure during front crawl swimming at different velocities in competitive swimmers and to clarify the relationships between stroke indices and changes in intra-abdominal pressure. The subjects were 7 highly trained competitive collegiate male swimmers. Intra-abdominal pressure was measured during front crawl swimming at 1.0, 1.2 and 1.4 m · s(-1) and during the Valsalva maneuver. Intra-abdominal pressure was taken as the difference between minimum and maximum values, and the mean of 6 stable front crawl stroke cycles was used. Stroke rate and stroke length were also measured as stroke indices. There were significant differences in stroke rate among all velocities (P < 0.05). However, there was no significant difference in stroke length by velocity. Significant within-subject correlations between intra-abdominal pressure and stroke rate or stroke length (P < 0.01) were observed, although there were no significant correlations between intra-abdominal pressure and stroke indices when controlling for swimming velocity. These findings do not appear to support the effectiveness of trunk training performed by competitive swimmers aimed at increasing intra-abdominal pressure. © Georg Thieme Verlag KG Stuttgart · New York.

Abdominal Aortic Aneurysm (AAA)

MedlinePlus

... plaque buildup causes the walls of the abdominal aorta to become weak and bulge outward like a ... treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, is a ...

Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China: SMART China 2011.

PubMed

Zhang, Hui; Yang, Qiwen; Xiao, Meng; Chen, Minjun; Badal, Robert E; Xu, Yingchun

2014-01-01

The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli (GNBs) from intra-abdominal infections (IAIs) in patients worldwide. In 2011, 1 929 aerobic and facultative GNBs from 21 hospitals in 16 cities in China were collected. All isolates were tested using a panel of 12 antimicrobial agents, and susceptibility was determined following the Clinical Laboratory Standards Institute guidelines. Among the Gram-negative pathogens causing IAIs, Escherichia coli (47.3%) was the most commonly isolated, followed by Klebsiella pneumoniae (17.2%), Pseudomonas aeruginosa (10.1%), and Acinetobacter baumannii (8.3%). Enterobacteriaceae comprised 78.8% (1521/1929) of the total isolates. Among the antimicrobial agents tested, ertapenem and imipenem were the most active agents against Enterobacteriaceae, with susceptibility rates of 95.1% and 94.4%, followed by amikacin (93.9%) and piperacillin/tazobactam (87.7%). Susceptibility rates of ceftriaxone, cefotaxime, ceftazidime, and cefepime against Enterobacteriaceae were 38.3%, 38.3%, 61.1%, and 50.8%, respectively. The leastactive agent against Enterobacteriaceae was ampicillin/sulbactam (25.9%). The extended-spectrum β-lactamase (ESBL) rates among E. coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis were 68.8%, 38.1%, 41.2%, and 57.7%, respectively. Enterobacteriaceae were the major pathogens causing IAIs, and the most active agents against the study isolates (including those producing ESBLs) were ertapenem, imipenem, and amikacin. Including the carbapenems, most agents exhibited reduced susceptibility against ESBL-positive and multidrug-resistant isolates.

Immunopathological evaluation of recombinant mycobacterial antigen Hsp65 expressed in Lactococcus lactis as a novel vaccine candidate

PubMed Central

Herrera Ramírez, J. C.; De la Mora, A. Ch.; De la Mora Valle, A.; Lopez-Valencia, G.; Hurtado, R. M. B.; Rentería Evangelista, T. B.; Rodríguez Castillo, J. L.; Rodríguez Gardea, A.; Gómez Gómez, S. D.; Medina-Basulto, G. E.

2017-01-01

Bovine tuberculosis (TBB) is a zoonotic disease distributed worldwide and is of great importance for public health and the livestock industry. Several experimental vaccines against this disease have been evaluated in recent years, yielding varying results. An example is the Bacillus Calmette-Guérin (BCG) vaccine, which has been used extensively in humans and tested in cattle showing mixed results related to protection (0-80%) against Mycobacterium bovis. In this study, we used the food-grade bacterium Lactococcus lactis as an expression system for production of mycobacterial protein Hsp65. For this purpose, the construction of a replicable plasmid in strain NZ9000 L. lactis (pVElepr) was conducted, which expressed the Mycobacterium leprae Hsp65 antigen, and was recognized by traded anti-Hsp65 antibodies. The strain NZ9000-pVElepr was applied to calves that were negative to tuberculin test and the immune response was monitored. The results showed that immune response was not significantly increased in calves with NZ9000-pVElepr with respect to control groups, and no injury was observed in any lung or lymph of the calves. Finally, this study suggest that the recombinant NZ9000 strain of L. lactis may protect against the development of M. bovis infection, although studies with longer exposure to this pathogen are necessary to conclude the matter. PMID:29163649

Atypical mycobacterial infection presenting as persistent skin lesion in a patient with ulcerative colitis.

PubMed

Bamias, Giorgos; Daikos, George L; Siakavellas, Spyros I; Kaltsa, Garyfallia; Smilakou, Stavroula; Katsogridakis, Ioannis; Vafiadis-Zouboulis, Irene; Ladas, Spiros D

2011-01-01

Immunosuppressive drugs are commonly used for the treatment of inflammatory bowel disease. Patients receiving immunosuppressants are susceptible to a variety of infections with opportunistic pathogens. We present a case of skin infection with Mycobacterium chelonae in a 60-year-old Caucasian woman with ulcerative colitis who had been treated with corticosteroids and azathioprine. The disease manifested with fever and rash involving the right leg. Infliximab was administered due to a presumptive diagnosis of pyoderma gangrenosum, leading to worsening of the clinical syndrome and admission to our hospital. Routine cultures from various sites were all negative. However, Ziehl-Neelsen staining of pus from the lesions revealed acid-fast bacilli, and culture yielded a rapidly growing mycobacterium further identified as M. chelonae. The patient responded to a clarithromycin-based regimen. Clinicians should be aware of skin lesions caused by atypical mycobacteria in immunocompromised patients with inflammatory bowel disease. Furthermore, they should be able to thoroughly investigate and promptly treat these conditions.

Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1

PubMed Central

Qualls, Joseph E.; Subramanian, Chitra; Rafi, Wasiulla; Smith, Amber M.; Balouzian, Liza; DeFreitas, Ashley A.; Shirey, Kari Ann; Reutterer, Benjamin; Kernbauer, Elisabeth; Stockinger, Silvia; Decker, Thomas; Miyairi, Isao; Vogel, Stefanie N.; Salgame, Padmini; Rock, Charles O.; Murray, Peter J.

2012-01-01

Nitric oxide (NO) defends against intracellular pathogens but its synthesis must be regulated due to cell and tissue toxicity. During infection, macrophages import extracellular arginine to synthesize NO, generating the byproduct citrulline. Accumulated intracellular citrulline is thought to fuel arginine synthesis catalyzed by argininosuccinate synthase (Ass1) and argininosuccinate lyase (Asl), which would lead to abundant NO production. Instead, we find that citrulline is exported from macrophages during early stages of NO production with < 2% retained for recycling via the Ass1-Asl pathway. Later, extracellular arginine is depleted, and Ass1 expression allows macrophages to synthesize arginine from imported citrulline to sustain NO output. Ass1-deficient macrophages fail to salvage citrulline in arginine-scarce conditions, leading to their inability to control mycobacteria infection. Thus, extracellular arginine fuels rapid NO production in activated macrophages, and citrulline recycling via Ass1 and Asl is a fail-safe system that sustains optimum NO production. PMID:22980328

Uptake and metabolism of fluorescent steroids by mycobacterial cells.

PubMed

Faletrov, Yaroslav; Brzostek, Anna; Plocinska, Renata; Dziadek, Jarosław; Rudaya, Elena; Edimecheva, Irina; Shkumatov, Vladimir

2017-01-01

Fluorescent steroids BODIPY-cholesterol (BPCh) and 7-nitrobenzoxadiazole-4-amino-(NBD)-labeled 22-NBD-chelesterol (22NC) as well as synthesized 20-(NBD)-pregn-5-en-3β-ol (20NP) were found to undergo bioconversions by Mycobacterium tuberculosis H 37 Rv and M. smegmatis mc 2 155. The major fluorescent products were determined to be 4-en-3-one derivatives of the compounds. Degradation of NBD fluorophore was also detected in the cases of 22NC and 20NP, but neither NBD degradation nor steroidal part modification were observed for the synthesized 3-(NBD)-cholestane. Mycobacterial 3β-hydroxysteroid dehydrogenases were concluded to be responsible for the formation of the 4-en-3-one derivatives. All the compounds tested were found to cause staining both membrane lipids and cytosolic lipid droplets when incubated with mycobacteria in different manner, demonstrating ability of the steroids to reside in the compartments. The findings reveal a potential of the compounds for monitoring of steroid interactions with mycobacteria and provide information for design of new probes for this purpose. Copyright © 2016 Elsevier Inc. All rights reserved.

Abdominal emergencies in pediatrics.

PubMed

Coca Robinot, D; Liébana de Rojas, C; Aguirre Pascual, E

2016-05-01

Abdominal symptoms are among the most common reasons for pediatric emergency department visits, and abdominal pain is the most frequently reported symptom. Thorough history taking and physical examination can often reach the correct diagnosis. Knowing the abdominal conditions that are most common in each age group can help radiologists narrow the differential diagnosis. When imaging tests are indicated, ultrasonography is usually the first-line technique, enabling the diagnosis or adding relevant information with the well-known advantages of this technique. Nowadays, plain-film X-ray studies are reserved for cases in which perforation, bowel obstruction, or foreign body ingestion is suspected. It is also important to remember that abdominal pain can also occur secondary to basal pneumonia. CT is reserved for specific indications and in individual cases, for example, in patients with high clinical suspicion of abdominal disease and inconclusive findings at ultrasonography. We review some of the most common conditions in pediatric emergencies, the different imaging tests indicated in each case, and the imaging signs in each condition. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Population-based Incidence of Pulmonary Nontuberculous Mycobacterial Disease in Oregon 2007 to 2012.

PubMed

Henkle, Emily; Hedberg, Katrina; Schafer, Sean; Novosad, Shannon; Winthrop, Kevin L

2015-05-01

Pulmonary nontuberculous mycobacteria (NTM) disease is a chronic, nonreportable illness, making it difficult to monitor. Although recent studies suggest an increasing prevalence of NTM disease in the United States, the incidence and temporal trends are unknown. To describe incident cases and calculate the incidence and temporal trends of pulmonary NTM disease in Oregon. We contacted all laboratories performing mycobacterial cultures on Oregon residents and collected demographic and specimen information for patients with NTM isolated during 2007 to 2012. We defined a case of pulmonary NTM disease using the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. We used similar state-wide mycobacterial laboratory data from 2005 to 2006 to exclude prevalent cases from our calculations. We calculated annual pulmonary NTM disease incidence within Oregon during 2007 to 2012, described cases demographically and microbiologically, and evaluated incidence trends over time using a Poisson model. We identified 1,146 incident pulmonary NTM cases in Oregon residents from 2007 to 2012. The median age was 69 years (range, 0.9-97 yr). Cases were more likely female (56%), but among patients less than 60 years old, disease was more common in male subjects (54%). Most (86%) were Mycobacterium avium/intracellulare cases; 68 (6%) were Mycobacterium abscessus/chelonae cases. Although not statistically significant, incidence increased from 4.8/100,000 in 2007 to 5.6/100,000 in 2012 (P for trend, 0.21). Incidence increased with age, to more than 25/100,000 in patients 80 years of age or older. This is the first population-based estimate of pulmonary NTM disease incidence in a region within the United States. In Oregon, disease incidence rose slightly during 2007 to 2012, and although more common in female individuals overall, disease was more common among male individuals less than 60 years of age.

Abdominal Complications after Severe Burns

DTIC Science & Technology

2009-05-01

abdominal compartment syndrome, schemic bowel, biliary disease, peptic ulcer disease and astritis requiring laparotomy, small bowel obstruction, rimary fungal...abdominal complications was 25%, with Curl- ng’s ulcer the most common malady (54% of the total), ollowed by esophageal lesions (17%), hemorrhagic...complications in- luded trauma exploratory laparotomy, abdominal com- artment syndrome, ischemic bowel, biliary disease, peptic lcer disease and gastritis, large

Complete removal of infected devices and simultaneous implantation of new devices for infective endocarditis after pacemaker implantation.

PubMed

Miura, Takuya; Inoue, Kazushige; Yokota, Takenori; Iwata, Takashi; Yoshitatsu, Masao

2017-02-01

Two cases of infective endocarditis after pacemaker implantation were reported. Complete removal of infected devices was performed under cardiopulmonary bypass, and simultaneous implantation of new devices was performed using epicardial leads and generator on the abdominal wall. The postoperative course was uneventful and recurrence was not recognized. These procedures may be suitable for the patients who depend on the pacemaker or who have repeat bacteremia with other infectious disease or conditions.

The MycoBrowser portal: a comprehensive and manually annotated resource for mycobacterial genomes.

PubMed

Kapopoulou, Adamandia; Lew, Jocelyne M; Cole, Stewart T

2011-01-01

In this paper, we present the MycoBrowser portal (http://mycobrowser.epfl.ch/), a resource that provides both in silico generated and manually reviewed information within databases dedicated to the complete genomes of Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium marinum and Mycobacterium smegmatis. A central component of MycoBrowser is TubercuList (http://tuberculist.epfl.ch), which has recently benefited from a new data management system and web interface. These improvements were extended to all MycoBrowser databases. We provide an overview of the functionalities available and the different ways of interrogating the data then discuss how both the new information and the latest features are helping the mycobacterial research communities. Copyright © 2010 Elsevier Ltd. All rights reserved.

Surface Electromyographic Activity of the Abdominal Muscles During Pelvic-Tilt and Abdominal-Hollowing Exercises.

PubMed

Drysdale, Cheri L.; Earl, Jennifer E.; Hertel, Jay

2004-03-01

OBJECTIVE: To investigate surface electromyographic (EMG) activity of the rectus abdominus and external oblique abdominus muscles during pelvic-tilt and abdominal-hollowing exercises performed in different positions. DESIGN AND SETTING: 2 x 3 (exercise by position) within-subjects design with repeated measures on both factors. All testing was performed in a university laboratory. SUBJECTS: Twenty-six healthy, active young adult females. MEASUREMENTS: Surface EMG activity was recorded from the left and right rectus abdominus and external oblique muscles while the 2 exercises (pelvic tilt and abdominal hollowing) were performed in different positions (standard, legs supported, and legs unsupported). The standard position was supine in the crook-lying position, the supported position was with hips and knees flexed to 90 degrees and legs supported on a platform, and the unsupported position was with hips and knees flexed to 90 degrees without external support. Peak EMG activity was normalized to a maximum voluntary isometric contraction for each muscle. RESULTS: For the rectus abdominus, there was an interaction between position and activity. Abdominal hollowing produced significantly less activity than the pelvic tilt in all positions. The difference between the 2 exercises with the legs unsupported was of a greater magnitude than the other 2 positions. For the external obliques, there was significantly lower activity during the abdominal hollowing compared with the pelvic tilting. The greatest muscle activity occurred with the legs-unsupported position during both exercises. CONCLUSIONS: Abdominal-hollowing exercises produced less rectus abdominus and external oblique activity than pelvic-tilting exercises. Abdominal hollowing may be performed with minimal activation of the large global abdominal muscles.

Blunt abdominal trauma in children.

PubMed

Schonfeld, Deborah; Lee, Lois K

2012-06-01

This review will examine the current evidence regarding pediatric blunt abdominal trauma and the physical exam findings, laboratory values, and radiographic imaging associated with the diagnosis of intra-abdominal injuries (IAI), as well as review the current literature on pediatric hollow viscus injuries and emergency department disposition after diagnosis. The importance of the seat belt sign on physical examination and screening laboratory data remains controversial, although screening hepatic enzymes are recommended in the evaluation of nonaccidental trauma to identify occult abdominal organ injuries. Focused Assessment with Sonography for Trauma (FAST) has modest sensitivity for hemoperitoneum and IAI in the pediatric trauma patient. Patients with concern for undiagnosed IAI, including bowel injury, may be considered for hospital admission and serial abdominal exams without an increased risk of complications, if an exploratory laparotomy is not performed emergently. Although the FAST exam is not recommended as the sole screening tool to rule out IAI in hemodynamically stable trauma patients, it may be used in conjunction with the physical exam and laboratory findings to identify children at risk for IAI. Children with a normal physical exam and normal abdominal CT may not require routine hospitalization after blunt abdominal trauma.

Aggregatibacter actinomycetemcomitans pneumonia with chest and abdominal wall involvement.

PubMed

Storms, Iris; van den Brand, Marre; Schneeberger, Peter; van 't Hullenaar, Nico

2017-04-21

A 54-year-old man presented with a productive cough, chest pain, fever and weight loss. Initial analysis revealed a palpable chest wall mass and consolidation in the left lower lobe and pleural abnormalities on imaging. At that point no infectious cause or malignancy was identified. Microbiological analysis of a needle biopsy from a newly developed abdominal wall mass revealed growth of Aggregatibacter actinomycetemcomitans The patient was successfully treated with antibiotic therapy for 1 year. Aggregatibacter actinomycetemcomitans is a Gram-negative coccobacillus and is part of the normal oral flora. It is capable of causing infections in humans including periodontitis, soft tissue abscesses and systemic invasive infections, most commonly endocarditis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An unusual cause of paediatric abdominal pain: Mesenteric masses accompanied with volvulus.

PubMed

Yang, Chao; Wang, Shan; Zhang, Jun; Kong, Xiang Ru; Zhao, Zhenzhen; Li, Chang Chun

2016-07-01

Volvulus caused by mesenteric masses is rare and may result in serious consequences. This study aimed to better characterize volvulus caused by mesenteric masses in children. A retrospective study was conducted in 24 patients who underwent surgical treatment between January 1994 and January 2014 in one single institution. There were 10 boys and 14 girls. The most frequent findings were abdominal pain (100%), emesis (91.7%) and nausea (83.3%). Physical examination showed positive ileus signs in majority cases, and palpable mass was found in half of the patients. Ultrasound and CT scans revealed mesenteric masses in 21 and 24 patients, and 'whirlpool sign' was observed in 19 and 22 patients, respectively. Emergency laparotomy was performed in all patients. Histological examination revealed that 18 cystic masses were lymphangioma, 5 solid cases were lipoma and the remaining one was lipoblastoma. The postoperative course was uneventful in 22 patients, and postoperative obstruction and incision infection occurred in 2 patients. There was no evidence of recurrence at follow-up. Volvulus caused by mesenteric masses is a rare but potentially life-threatening cause of abdominal pain, which should be considered in the differential diagnosis of paediatric acute abdominal pain.

Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection

PubMed Central

Kalia, Nitin P.; Hasenoehrl, Erik J.; Ab Rahman, Nurlilah B.; Koh, Vanessa H.; Ang, Michelle L. T.; Sajorda, Dannah R.; Hards, Kiel; Grüber, Gerhard; Alonso, Sylvie; Cook, Gregory M.; Berney, Michael; Pethe, Kevin

2017-01-01

The recent discovery of small molecules targeting the cytochrome bc1:aa3 in Mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. The mycobacterial cytochrome bc1:aa3 consists of a menaquinone:cytochrome c reductase (bc1) and a cytochrome aa3-type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. Despite the affinity of Q203 for the bc1:aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters. This raises the possibility that the alternate terminal bd-type oxidase (cytochrome bd oxidase) is capable of maintaining a membrane potential and menaquinol oxidation in the presence of Q203. Here, we show that the electron flow through the cytochrome bd oxidase is sufficient to maintain respiration and ATP synthesis at a level high enough to protect M. tuberculosis from Q203-induced bacterial death. Upon genetic deletion of the cytochrome bd oxidase-encoding genes cydAB, Q203 inhibited mycobacterial respiration completely, became bactericidal, killed drug-tolerant mycobacterial persisters, and rapidly cleared M. tuberculosis infection in vivo. These results indicate a synthetic lethal interaction between the two terminal respiratory oxidases that can be exploited for anti-TB drug development. Our findings should be considered in the clinical development of drugs targeting the cytochrome bc1:aa3, as well as for the development of a drug combination targeting oxidative phosphorylation in M. tuberculosis. PMID:28652330

Role of tissue expansion in abdominal wall reconstruction: A systematic evidence-based review.

PubMed

Wooten, Kimberly E; Ozturk, Cemile Nurdan; Ozturk, Can; Laub, Peter; Aronoff, Nell; Gurunluoglu, Raffi

2017-06-01

Tissue expanders (TEs) can be used to assist primary closure of complicated hernias and large abdominal wall defects. However, there is no consensus regarding the optimal technique, use, or associated risk of TE in abdominal wall reconstruction. A systematic search of PubMed and Embase databases was conducted to identify articles reporting abdominal wall reconstruction with TE techniques. English articles published between 1980 and 2016 were included on the basis of the following inclusion criteria: two-stage TE surgical technique, >3 cases, reporting of postoperative complications, hernia recurrence, and patient-based clinical data. Fourteen studies containing 103 patients (85 adults and 18 children) were identified for analysis. Most patients presented with a skin-grafted ventral hernia (n = 86). The etiology of the hernia was from trauma or prior abdominal surgery. The remaining patients had TE placed before organ transplantation (n = 12) or for congenital abdominal wall defects (n = 5). The location for expander placement was subcutaneous (n = 74), between the internal and external obliques (n = 26), posterior to the rectus sheath (n = 2), and intra-peritoneal (n = 1). Postoperative infections and implant-related problems were the most commonly reported complications after Stage I. The most common complication after Stage II was recurrent hernia, which was observed in 12 patients (11.7%). Five patients with TE died. Complications and mortality were more prevalent in children, immunosuppressed patients, and those with chronic illnesses. Tissue expansion for abdominal wall reconstruction can be successfully used for a variety of carefully selected patients with an acceptable complication and risk profile. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren's syndrome using high-content peptide microarrays.

PubMed

Ferrara, Giovanni; Valentini, Davide; Rao, Martin; Wahlström, Jan; Grunewald, Johan; Larsson, Lars-Olof; Brighenti, Susanna; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

2017-03-01

Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosis patient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosis patient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosis patient sera. Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy. Copyright © 2017. Published by Elsevier Ltd.

The reliability of diagnostic coding and laboratory data to identify tuberculosis and nontuberculous mycobacterial disease among rheumatoid arthritis patients using anti-tumor necrosis factor therapy.

PubMed

Winthrop, Kevin L; Baxter, Roger; Liu, Liyan; McFarland, Bentson; Austin, Donald; Varley, Cara; Radcliffe, LeAnn; Suhler, Eric; Choi, Dongsoek; Herrinton, Lisa J

2011-03-01

Anti-tumor necrosis factor-alpha (anti-TNF) therapies are associated with severe mycobacterial infections in rheumatoid arthritis patients. We developed and validated electronic record search algorithms for these serious infections. The study used electronic clinical, microbiologic, and pharmacy records from Kaiser Permanente Northern California (KPNC) and the Portland Veterans Affairs Medical Center (PVAMC). We identified suspect tuberculosis and nontuberculous mycobacteria (NTM) cases using inpatient and outpatient diagnostic codes, culture results, and anti-tuberculous medication dispensing. We manually reviewed records to validate our case-finding algorithms. We identified 64 tuberculosis and 367 NTM potential cases, respectively. For tuberculosis, diagnostic code positive predictive value (PPV) was 54% at KPNC and 9% at PVAMC. Adding medication dispensings improved these to 87% and 46%, respectively. Positive tuberculosis cultures had a PPV of 100% with sensitivities of 79% (KPNC) and 55% (PVAMC). For NTM, the PPV of diagnostic codes was 91% (KPNC) and 76% (PVAMC). At KPNC, ≥ 1 positive NTM culture was sensitive (100%) and specific (PPV, 74%) if non-pathogenic species were excluded; at PVAMC, ≥1 positive NTM culture identified 76% of cases with PPV of 41%. Application of the American Thoracic Society NTM microbiology criteria yielded the highest PPV (100% KPNC, 78% PVAMC). The sensitivity and predictive value of electronic microbiologic data for tuberculosis and NTM infections is generally high, but varies with different facilities or models of care. Unlike NTM, tuberculosis diagnostic codes have poor PPV, and in the absence of laboratory data, should be combined with anti-tuberculous therapy dispensings for pharmacoepidemiologic research. Copyright © 2010 John Wiley & Sons, Ltd.

[Abdominal ultrasound abnormalities incidentally discovered in patients with asymptomatic HIV in Lome (Togo)].

PubMed

Sonhaye, L; Tchaou, M; Amadou, A; Gbande, P; Assih, K; Djibril, M; Adjenou, K; Redah, D; N'Dakéna, K

2014-01-01

Few studies have examined ultrasound imaging of abdominal manifestations of HIV-AIDS, although these rank second only to its pleuropulmonary manifestations. Thus, this study sought to determine the features of abdominal ultrasound in HIV infection. This prospective, descriptive and analytical study took place in the radiology department of the University Hospital Campus Lomé and covered the three-year period of 2009-2011. It included all patients older than 15 years with positive HIV serology. During the study period, 566 patients met the inclusion criteria. Ultrasound examination showed the liver appeared normal in 153 patients (27.0%), but homogeneously hyperechoic and thus suggestive of hepatic steatosis in 107 (18.9%). The bile duct was dilatated in 12 patients or 2.1%. An anomaly in the corticomedullary differentiation in normal-sized kidneys was noted in 28.1% (159 patients). Diffuse homogeneous hypertrophy of the pancreas was found in 3 patients (0.53%). Splenomegaly was noted in 387 patients (68.4%); the echopattern of the spleen was diffusely micronodular in 6 patients (1.1%). Deep adenopathies were found in 29 patients (5.1%) and ascites in 46 patients (8.1%). Abdominal ultrasound is a medical imaging technique available in developing countries, less expensive than others, which can be considered an alternative to computed tomography (CT) in the countries of sub-Saharan Africa for the exploration of the abdominal manifestations of HIV.

Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts, misconceptions, and practical tips for pathologists.

PubMed

Jain, Deepali; Ghosh, Subha; Teixeira, Lucileia; Mukhopadhyay, Sanjay

2017-11-01

Most pathologists are familiar with the microscopic features of tuberculosis and the need to examine special stains for acid-fast bacteria (AFB) in cases of granulomatous lung disease. However, misconceptions do exist, including the concept that finding AFB in "caseating granulomas" confirms the diagnosis of tuberculosis. This dogma is attributable to the high prevalence of tuberculosis in many countries, as well as unfamiliarity with the microscopic spectrum of non-tuberculous mycobacterial lung disease. This review aims to provide surgical pathologists with practical tips to identify AFB, illustrate the histologic overlap between pulmonary tuberculosis and non-tuberculous mycobacterial lung disease, and highlight the importance of cultures in this setting. M. tuberculosis and non-tuberculous mycobacteria cannot be reliably differentiated either on the basis of the tissue reaction or by bacterial morphology on acid-fast stains. Although a presumptive clinical diagnosis of tuberculosis can be made without culture-confirmation, the only definitive means to determine the true identity of AFB is by cultures or molecular methods. Making this distinction is most critical when AFB are found in incidentally detected lung nodules in geographic locations where the incidence of tuberculosis is low, because in such settings AFB in necrotizing granulomas of the lung are more likely to be non-tuberculous mycobacteria than M. tuberculosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Surface Electromyographic Activity of the Abdominal Muscles During Pelvic-Tilt and Abdominal-Hollowing Exercises

PubMed Central

Drysdale, Cheri L.; Earl, Jennifer E.

2004-01-01

Objective: To investigate surface electromyographic (EMG) activity of the rectus abdominus and external oblique abdominus muscles during pelvic-tilt and abdominal-hollowing exercises performed in different positions. Design and Setting: 2 × 3 (exercise by position) within-subjects design with repeated measures on both factors. All testing was performed in a university laboratory. Subjects: Twenty-six healthy, active young adult females. Measurements: Surface EMG activity was recorded from the left and right rectus abdominus and external oblique muscles while the 2 exercises (pelvic tilt and abdominal hollowing) were performed in different positions (standard, legs supported, and legs unsupported). The standard position was supine in the crook-lying position, the supported position was with hips and knees flexed to 90° and legs supported on a platform, and the unsupported position was with hips and knees flexed to 90° without external support. Peak EMG activity was normalized to a maximum voluntary isometric contraction for each muscle. Results: For the rectus abdominus, there was an interaction between position and activity. Abdominal hollowing produced significantly less activity than the pelvic tilt in all positions. The difference between the 2 exercises with the legs unsupported was of a greater magnitude than the other 2 positions. For the external obliques, there was significantly lower activity during the abdominal hollowing compared with the pelvic tilting. The greatest muscle activity occurred with the legs-unsupported position during both exercises. Conclusions: Abdominal-hollowing exercises produced less rectus abdominus and external oblique activity than pelvic-tilting exercises. Abdominal hollowing may be performed with minimal activation of the large global abdominal muscles. PMID:15085209

The alternate effects of anti-TNFα therapeutics and their role in mycobacterial granulomatous infection in Crohn's disease.

PubMed

Qasem, Ahmad; Naser, Abed Elrahman; Naser, Saleh A

2017-07-01

Crohn's disease is an inflammatory bowel disease that has been debated to be associated with bacterial triggers such as Mycobacterium avium subspecies paratuberculosis (MAP). Standard treatment of Crohn's disease (CD) patients includes a family of immunomodulators and biologics such as Anti-Tumor Necrosis Factor alpha (Anti-TNFα). This cytokine in particular has been known to play vital roles in fighting microbial infections through formation and maintenance of granulomas. Areas covered: This perspective is focused on elucidating the negative effects of using Anti-TNFα therapeutic agents as a treatment option in CD patients who are more likely suspected to have MAP infection, and the role of other immunomodulators in MAP infection. Expert commentary: While treatment with Anti-TNFα is beneficial to reduce inflammation and to provide short term relief to the patients, it also compromises the immune system causing susceptibility to microbial infection. More than 50% of CD patients have shown no response to Anti-TNFα treatment which indicates a demand for introducing novel CD treatment in combination with antibiotics as a future CD treatment plan.