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Sample records for abdominal mycobacterial infection

  1. Mycobacterial Infections

    MedlinePlus

    ... similar to tuberculosis: Cough Weight loss Coughing up blood or mucus Weakness or fatigue Fever and chills Night sweats Lack of appetite and weight loss Medicines can treat these infections, but often more than one is needed to cure the infection.

  2. 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 ...

  3. Sternal mycobacterial infections

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Sternal mycobacterial infections are rare. Due to the rarity, its clinical characteristics, diagnoses, and regular management strategies are still scanty. A total of 76 articles on this topic were obtained by a comprehensive literature collection. The clinical features, diagnosis, management strategies and prognosis were carefully analyzed. There were totally 159 patients including 152 (95%) cases of tuberculosis (TB) and seven (5%) cases of non-TB sternal infections. Sternal mycobacterial infections can be categorized into three types: Primary, secondary, and postoperative, according to the pathogenesis; and categorized into isolated, peristernal, and multifocal, according to the extent of the lesions. Microbiological investigation is more sensitive than medical imaging and Mantoux tuberculin skin test in the diagnosis of sternal infections. Most patients show good responses to the standard four-drug regimen and a surgical intervention was necessary in 28.3% patients. The prognoses of the patients are good with a very low mortality. A delayed diagnosis of sternal mycobacterial infections may bring about recurrent sternal infections and sustained incurability. An early diagnosis and prompt antibiotic regimens may significantly improve the patients' outcomes. PMID:27168857

  4. Therapy of nontuberculous mycobacterial infections.

    PubMed

    Jogi, Reena; Tyring, Stephen K

    2004-01-01

    Mycobacterial infections are increasing in incidence worldwide, partly as a result of the increase in immunocompromised individuals. They cause a large number of cutaneous infections with a broad array of manifestations. Because of their diverse manifestations and sometimes fastidious nature, infections with mycobacteria are often misdiagnosed, leading to delay in and sometimes failure of therapy. In addition, many mycobacteria display both in vitro and in vivo drug resistance to antimicrobial agents. Early recognition of affected patients, initiation of appropriate antimicrobial therapy based on current guidelines, and tailoring of therapy after susceptibility testing is available are therefore essential to the successful treatment of mycobacterial infections. PMID:15571497

  5. The cytopathology of mycobacterial infection.

    PubMed

    Michelow, Pamela; Omar, Tanvier; Field, Andrew; Wright, Colleen

    2016-03-01

    Mycobacterial infection, tuberculosis (TB) in particular, remains one of the world's deadliest communicable diseases in adults and particularly in children, in low and middle income countries. The combination of human immunodeficiency virus (HIV) and TB is often lethal with TB accounting for 25% of deaths in the HIV population. One of the cornerstones for reducing the TB epidemic is early case detection using high quality diagnostic techniques. Cytology, especially fine needle aspiration biopsy (FNAB) is able to diagnose mycobacterial infection in a rapid and cost-effective manner without requiring surgery, thus allowing appropriate management to be quickly instituted. Confirmatory ancillary tests can effectively be performed on cytologic material. In this review, the pertinent cytomorphology of mycobacterial infection in various exfoliative and FNAB specimens is presented, in both immunocompetent and immunosuppressed patients. In the immunosuppressed, the typical cytomorphology of caseating granulomatous inflammation may not be seen but suppurative necrotic inflammation, mycobacterial spindle pseudotumour or a specimen comprised entirely of necrosis may be seen instead. This review includes discussion of currently available ancillary tests that can be performed on cytologic specimens. PMID:26800030

  6. The immunology of mycobacterial infections.

    PubMed

    Chaparas, S D

    1982-01-01

    Mycobacteria are endowed with substances that profoundly affect the immune system. Leprosy and tuberculosis exemplify broad spectra of useful and detrimental immune responses of mycobacterial infections that range from intense potentiation to severe specific adn nonspecific suppression of humoral and cellular immune elements. The cellular hypersensitivity induced by mycobacteria serves as a classical model for the analysis of specific and nonspecific immune mechanisms. Mycobacterial disease are prevalent worldwide and rank among the most important bacterial diseases. The kaleidoscope of immunologic events induced by injected mycobacteria and during infections will be reviewed from the standpoint of pathogenesis, pathology, in vitro and in vivo effects on cellular and humoral arms of the immune response, diagnosis, classification, potentiation and suppression. PMID:7042210

  7. Nontuberculous mycobacterial pulmonary infections

    PubMed Central

    Odell, John A.

    2014-01-01

    Pulmonary infections due to nontuberculous mycobacteria (NTM) are increasingly recognized worldwide. Although over 150 different species of NTM have been described, pulmonary infections are most commonly due to Mycobacterium avium complex (MAC), Mycobacterium kansasii, and Mycobacterium abscessus. The identification of these organisms in pulmonary specimens does not always equate with active infection; supportive radiographic and clinical findings are needed to establish the diagnosis. It is difficult to eradicate NTM infections. A prolonged course of therapy with a combination of drugs is required. Unfortunately, recurrent infection with new strains of mycobacteria or a relapse of infection caused by the original organism is not uncommon. Surgical resection is appropriate in selected cases of localized disease or in cases in which the infecting organism is resistant to medical therapy. Additionally, surgery may be required for infections complicated by hemoptysis or abscess formation. This review will summarize the practical aspects of the diagnosis and management of NTM thoracic infections, with emphasis on the indications for surgery and the results of surgical intervention. The management of NTM disease in patients with human immunodeficiency virus (HIV) infections is beyond the scope of this article and, unless otherwise noted, comments apply to hosts without HIV infection PMID:24624285

  8. CD36 deficiency attenuates experimental mycobacterial infection

    PubMed Central

    2010-01-01

    Background Members of the CD36 scavenger receptor family have been implicated as sensors of microbial products that mediate phagocytosis and inflammation in response to a broad range of pathogens. We investigated the role of CD36 in host response to mycobacterial infection. Methods Experimental Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection in Cd36+/+ and Cd36-/- mice, and in vitro co-cultivation of M. tuberculosis, BCG and M. marinum with Cd36+/+ and Cd36-/-murine macrophages. Results Using an in vivo model of BCG infection in Cd36+/+ and Cd36-/- mice, we found that mycobacterial burden in liver and spleen is reduced (83% lower peak splenic colony forming units, p < 0.001), as well as the density of granulomas, and circulating tumor necrosis factor (TNF) levels in Cd36-/- animals. Intracellular growth of all three mycobacterial species was reduced in Cd36-/- relative to wild type Cd36+/+ macrophages in vitro. This difference was not attributable to alterations in mycobacterial uptake, macrophage viability, rate of macrophage apoptosis, production of reactive oxygen and/or nitrogen species, TNF or interleukin-10. Using an in vitro model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination in vivo (i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within Cd36-/- macrophages. Conclusions Together, these data indicate that CD36 deficiency confers resistance to mycobacterial infection. This observation is best explained by reduced intracellular survival of mycobacteria in the Cd36-/- macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination. PMID:20950462

  9. Mycobacterial Lung Disease Complicating HIV Infection.

    PubMed

    Haas, Michelle K; Daley, Charles L

    2016-04-01

    Mycobacterial infections have caused enormous morbidity and mortality in people living with human immunodeficiency virus (HIV) infection. Of these, the most devastating has been tuberculosis (TB), the leading cause of death among HIV-positive persons globally. TB has killed more people living with HIV than any other infection. Diagnosis of latent TB infection (LTBI) is critical as treatment can prevent emergence of TB disease. Bacteriologic confirmation of TB disease should be sought whenever possible as well as drug susceptibility testing. When detected early, drug susceptible TB is curable. Similar to TB, nontuberculous mycobacteria (NTM) can also produce pulmonary and extrapulmonary infections including disseminated disease that can be fatal. Diagnosis through accurate identification of the pathogenic organism will greatly inform treatment. Depending on the NTM identified, treatment may not be curable. Ultimately, preventive strategies such as initiation of antiretroviral drugs and treatment of LTBI are interventions expected to have significant impacts on control of TB and NTM in the setting of HIV. This chapter will review the impact of pulmonary mycobacterial infections on HIV-positive individuals. PMID:26974300

  10. [Nontuberculous mycobacterial infections of the lung].

    PubMed

    Latshang, Tsogyal D; Lo Cascio, Christian M; Russi, Erich W

    2011-07-01

    Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are generally free-living organisms that are ubiquitous in the environment. Pulmonary disease, especially in older persons with and without underlying lung disease, is caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and signs of MAC lung disease are variable and not specific, but include cough, malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two major clinical presentations include disease in those with underlying lung disease, primarily white, middle-aged or elderly men - often alcoholics and/or smokers with underlying chronic obstructive lung disease, patients in whom MAC develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and those without known underlying lung disease, including non-smoking women over age 50 who have interstitial patterns on chest radiography. M. kansasii infections are endemic in cities with infected tap water. Symptoms of the M. kansasii lung disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid growing Mycobacterium which causes pulmonary infection. The American Thoracic Society and Infectious Disease Society of America's diagnostic criteria for nontuberculous mycobacterial pulmonary infections include both imaging studies consistent with pulmonary disease and recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient. For treatment of MAC lung disease we recommend depending on severity and susceptibility testing a three to four drug treatment with a macrolide, rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid, rifampicin and ethambutol. Surgical management only plays a role in rare and special cases. Treatment should be continued until sputum cultures are consecutively negative for at least one year. PMID

  11. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

    PubMed Central

    Lipner, Ettie M.; Garcia, Benjamin J.; Strong, Michael

    2016-01-01

    Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects. PMID:26751573

  12. Mycobacterial infections in striped bass from Delaware Bay

    USGS Publications Warehouse

    Ottinger, C.A.; Brown, J.J.; Densmore, Christine L.; Starliper, C.E.; Blazer, V.S.; Weyers, H.S.; Beauchamp, K.A.; Rhodes, M.W.; Kator, H.; Gauthier, David T.; Vogelbein, W.K.

    2007-01-01

    Eighty striped bass Morone saxatilis were obtained from Delaware Bay using commercial gill nets set adjacent to Woodland Beach (n = 70) and Bowers Beach (n = 10) in December 2003. Fish were examined for gross lesions. Total lengths (TLs) and eviscerated weights were determined to calculate condition factors (K). Portions of spleens were aseptically harvested for bacterial culture, and portions of spleens, kidneys (anterior and posterior), livers, and gonads were obtained for histological examination. The size distribution of the striped bass was relatively homogeneous; the mean TL was about 600 mm for all samples. Mean K exceeded 0.95 in all samples and was not significantly different (P > 0.05) among samples. Significant differences in mycobacterial infection prevalence (P ??? 0.05) were observed among samples; samples obtained at Woodland Beach (WB) on December 10 (53.8%, n = 13) and December 17 (7.1%, n = 42) exhibited the most striking differences in prevalence. Mycobacterial infection intensity ranged from 1 ?? 102 to 1 ?? 107 colony-forming units per gram of spleen. Acanthocephalan infection prevalence and intensity, non-acid-fast bacterial infection prevalence, and fish sex ratio were also significantly different among the samples (P ??? 0.05). Similar to the mycobacterial infections, differences in sex ratio, acanthocephalan infection, and non-acid-fast bacterial infection were observed between the WB samples taken on December 10 and 17. However, no significant associations (P > 0.05) were observed between sex ratio or these infections and mycobacterial infection. The differences in bacterial and parasite infection prevalence and intensity and fish sex ratio in some samples indicate that these fish had a different history and that the epizootiology of mycobacterial infection in striped bass from Delaware Bay may be relatively complex. ?? Copyright by the American Fisheries Society 2007.

  13. Nontuberculous Mycobacterial Ocular Infections: A Systematic Review of the Literature

    PubMed Central

    Kheir, Wajiha J.; Sheheitli, Huda; Abdul Fattah, Maamoun; Hamam, Rola N.

    2015-01-01

    Nontuberculous or atypical mycobacterial ocular infections have been increasing in prevalence over the past few decades. They are known to cause periocular, adnexal, ocular surface and intraocular infections and are often recalcitrant to medical therapy. These infections can potentially cause detrimental outcomes, in part due to a delay in diagnosis. We review 174 case reports and series on nontuberculous mycobacterial (NTM) ocular infections and discuss etiology, microbiology, risk factors, diagnosis, clinical presentation, and treatment of these infections. History of interventions, trauma, foreign bodies, implants, contact lenses, and steroids are linked to NTM ocular infections. Steroid use may prolong the duration of the infection and cause poorer visual outcomes. Early diagnosis and initiation of treatment with multiple antibiotics are necessary to achieve the best visual outcome. PMID:26106601

  14. Nontuberculous Mycobacterial Infection after Fractionated CO2 Laser Resurfacing

    PubMed Central

    Culton, Donna A.; Miller, Becky A.; Miller, Melissa B.; MacKuen, Courteney; Groben, Pamela; White, Becky; Cox, Gary M.; Stout, Jason E.

    2013-01-01

    Nontuberculous mycobacteria are increasingly associated with cutaneous infections after cosmetic procedures. Fractionated CO2 resurfacing, a widely used technique for photorejuvenation, has been associated with a more favorable side effect profile than alternative procedures. We describe 2 cases of nontuberculous mycobacterial infection after treatment with a fractionated CO2 laser at a private clinic. Densely distributed erythematous papules and pustules developed within the treated area within 2 weeks of the laser procedure. Diagnosis was confirmed by histologic analysis and culture. Both infections responded to a 4-month course of a multidrug regimen. An environmental investigation of the clinic was performed, but no source of infection was found. The case isolates differed from each other and from isolates obtained from the clinic, suggesting that the infection was acquired by postprocedure exposure. Papules and pustules after fractionated CO2 resurfacing should raise the suspicion of nontuberculous mycobacterial infection. PMID:23628077

  15. A hoarse voice: atypical mycobacterial infection of the larynx.

    PubMed

    McEwan, J A; Mohsen, A H; Schmid, M L; McKendrick, M W

    2001-11-01

    Myobacterium malmoense is a non-tuberculous mycobacterium that most commonly causes pulmonary infection, particularly in patients with underlying pulmonary disease or immunodeficiency. We describe a case of Mycobacterium malmoense infection of the larynx in a previously well middle-aged woman, which has previously not been reported. The case highlights the importance of considering atypical mycobacterial infection in the differential diagnosis of laryngeal lesions. PMID:11779312

  16. 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.

  17. Seals, seal trainers, and mycobacterial infection.

    PubMed

    Thompson, P J; Cousins, D V; Gow, B L; Collins, D M; Williamson, B H; Dagnia, H T

    1993-01-01

    In 1986, three seals died in a marine park in Western Australia; culture of postmortem tissue suggested infection with Mycobacterium bovis. In 1988, a seal trainer who had been employed at the Western Australian marine park until 1985 developed pulmonary tuberculosis caused by M. bovis while working in a zoo 3,000 km away on the east coast of Australia. Culture characteristics, biochemical behavior, sodium dodecyl sulphate polyacrylamide gel electrophoresis, and restriction endonuclease analysis suggested that the strains of M. bovis infecting the seals and trainer were identical but unique and differed from reference strains and local cattle strains of M. bovis. The infection in both the seals and the trainer had a destructive but indolent course. This is the first time that M. bovis has been observed in seals and the first time that tuberculous infection has been documented to be transmitted from seals to humans. Further investigation of the extent of tuberculous infection in seal populations elsewhere in the world seems warranted, and those working with seals and other marine animals should be monitored for infection. PMID:8420412

  18. Production of matrix metalloproteinases in response to mycobacterial infection.

    PubMed

    Quiding-Järbrink, M; Smith, D A; Bancroft, G J

    2001-09-01

    Matrix metalloproteinases (MMPs) constitute a large family of enzymes with specificity for the various proteins of the extracellular matrix which are implicated in tissue remodeling processes and chronic inflammatory conditions. To investigate the role of MMPs in immunity to mycobacterial infections, we incubated murine peritoneal macrophages with viable Mycobacterium bovis BCG or Mycobacterium tuberculosis H37Rv and assayed MMP activity in the supernatants by zymography. Resting macrophages secreted only small amounts of MMP-9 (gelatinase B), but secretion increased dramatically in a dose-dependent manner in response to either BCG or M. tuberculosis in vitro. Incubation with mycobacteria also induced increased MMP-2 (gelatinase A) activity. Neutralization of tumor necrosis alpha (TNF-alpha), and to a lesser extent interleukin 18 (IL-18), substantially reduced MMP production in response to mycobacteria. Exogenous addition of TNF-alpha or IL-18 induced macrophages to express MMPs, even in the absence of bacteria. The immunoregulatory cytokines gamma interferon (IFN-gamma), IL-4, and IL-10 all suppressed BCG-induced MMP production, but through different mechanisms. IFN-gamma treatment increased macrophage secretion of TNF-alpha but still reduced their MMP activity. Conversely, IL-4 and IL-10 seemed to act by reducing the amount of TNF-alpha available to the macrophages. Finally, infection of BALB/c or severe combined immunodeficiency (SCID) mice with either BCG or M. tuberculosis induced substantial increases in MMP-9 activity in infected tissues. In conclusion, we show that mycobacterial infection induces MMP-9 activity both in vitro and in vivo and that this is regulated by TNF-alpha, IL-18, and IFN-gamma. These findings indicate a possible contribution of MMPs to tissue remodeling processes that occur in mycobacterial infections. PMID:11500442

  19. Biomarker Discovery in Subclinical Mycobacterial Infections of Cattle

    PubMed Central

    Janagama, Harish K.; Widdel, Andrea; Vulchanova, Lucy; Stabel, Judith R.; Waters, W. Ray; Palmer, Mitchell V.; Sreevatsan, Srinand

    2009-01-01

    Background Bovine tuberculosis is a highly prevalent infectious disease of cattle worldwide; however, infection in the United States is limited to 0.01% of dairy herds. Thus detection of bovine TB is confounded by high background infection with M. avium subsp. paratuberculosis. The present study addresses variations in the circulating peptidome based on the pathogenesis of two biologically similar mycobacterial diseases of cattle. Methodology/Principal Findings We hypothesized that serum proteomes of animals in response to either M. bovis or M. paratuberculosis infection will display several commonalities and differences. Sera prospectively collected from animals experimentally infected with either M. bovis or M. paratuberculosis were analyzed using high-resolution proteomics approaches. iTRAQ, a liquid chromatography and tandem mass spectrometry approach, was used to simultaneously identify and quantify peptides from multiple infections and contemporaneous uninfected control groups. Four comparisons were performed: 1) M. bovis infection versus uninfected controls, 2) M. bovis versus M. paratuberculosis infection, 3) early, and 4) advanced M. paratuberculosis infection versus uninfected controls. One hundred and ten differentially elevated proteins (P≤0.05) were identified. Vitamin D binding protein precursor (DBP), alpha-1 acid glycoprotein, alpha-1B glycoprotein, fetuin, and serine proteinase inhibitor were identified in both infections. Transthyretin, retinol binding proteins, and cathelicidin were identified exclusively in M. paratuberculosis infection, while the serum levels of alpha-1-microglobulin/bikunin precursor (AMBP) protein, alpha-1 acid glycoprotein, fetuin, and alpha-1B glycoprotein were elevated exclusively in M. bovis infected animals. Conclusions/Significance The discovery of these biomarkers has significant impact on the elucidation of pathogenesis of two mycobacterial diseases at the cellular and the molecular level and can be applied in the

  20. Nontuberculous Mycobacterial Infections in Cystic Fibrosis.

    PubMed

    Martiniano, Stacey L; Nick, Jerry A; Daley, Charles L

    2016-03-01

    Nontuberculous mycobacteria (NTM) are important emerging cystic fibrosis (CF) pathogens, with estimates of prevalence ranging from 6% to 13%. Diagnosis of NTM disease in patients with CF is challenging, as the infection may remain indolent in some, without evidence of clinical consequence, whereas other patients suffer significant morbidity and mortality. Treatment requires prolonged periods of multiple drugs and varies depending on NTM species, resistance pattern, and extent of disease. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in CF patients is a research priority, as a lifelong strategy is needed for this high-risk population. PMID:26857770

  1. Innate Immune Effectors in Mycobacterial Infection

    PubMed Central

    Saiga, Hiroyuki; Shimada, Yosuke; Takeda, Kiyoshi

    2011-01-01

    Tuberculosis, which is caused by infection with Mycobacterium tuberculosis (Mtb), remains one of the major bacterial infections worldwide. Host defense against Mtb is mediated by a combination of innate and adaptive immune responses. In the last 15 years, the mechanisms for activation of innate immunity have been elucidated. Toll-like receptors (TLRs) have been revealed to be critical for the recognition of pathogenic microorganisms including mycobacteria. Subsequent studies further revealed that NOD-like receptors and C-type lectin receptors are responsible for the TLR-independent recognition of mycobacteria. Several molecules, such as active vitamin D3, secretary leukocyte protease inhibitor, and lipocalin 2, all of which are induced by TLR stimulation, have been shown to direct innate immune responses to mycobacteria. In addition, Irgm1-dependent autophagy has recently been demonstrated to eliminate intracellular mycobacteria. Thus, our understanding of the mechanisms for the innate immune response to mycobacteria is developing. PMID:21274449

  2. Mycobacterial Infection after Cosmetic Procedure with Botulinum Toxin A

    PubMed Central

    Saeb-Lima, Marcela; Solis-Arreola, Gerardo-Victor

    2015-01-01

    We report a case of mycobacterial infection at the sites of previous injections of botulinum toxin A in a 45-year-old woman. She presented with erythematous, swollen, warm, and tender plaques and nodules at the points of injection from which a biopsy was taken, demonstrating a deep dermal and hypodermal abscessified epithelioid granulomatous inflammatory infiltrate in which some acid-fast bacilli were identified with Ziehl-Neelsen and Fite-Faraco stains. The lesion was first treated with clarithromycin plus azithromycin, to which rifampicin was later added. A good therapeutic response was obtained. PMID:26023629

  3. Immune biology of macaque lymphocyte populations during mycobacterial infection

    PubMed Central

    LAI, X; SHEN, Y; ZHOU, D; SEHGAL, P; SHEN, L; SIMON, M; QIU, L; LETVIN, N L; CHEN, Z W

    2003-01-01

    Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette–Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and γδ T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and γδ T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of γδ T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and γδ T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded αβ and γδ T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and γδ T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates. PMID:12869023

  4. Management of Nontuberculous Mycobacterial Infection in The Elderly

    PubMed Central

    Mirsaeidi, Mehdi; Farshidpour, Maham; Ebrahimi, Golnaz; Aliberti, Stefano; Falkinham, Joseph O

    2014-01-01

    The incidence of nontuberculous mycobacteria (NTM) has increased over the last decades. Elderly people are more susceptible to NTM and experience increased morbidities. NTM incidence is expected to rise due to an increasing elderly population at least up to 2050. Given the importance of NTM infection in the elderly, an increasing interest exists in studying NTM characteristics in aged population. In this review, we summarize the characteristics of NTM infection among elderly patients. We focus on epidemiology, clinical presentation, and treatment options of NTM in this age group. We highlight the differences in the diagnosis and treatment between rapid and slow growing mycobacterial infections. The current recommendation for treatment of NTM is discussed. We debate if in vitro susceptibility testing has a role in treatment of NTM. Drug-drug interaction between antibiotics used to treat NTM and other medications, particularly warfarin, is another important issue that we discuss. Finally, we review the prognosis of NTM disease in elderly patients. PMID:24685313

  5. Phagocyte NADPH oxidase, chronic granulomatous disease and mycobacterial infections.

    PubMed

    Deffert, Christine; Cachat, Julien; Krause, Karl-Heinz

    2014-08-01

    Infection of humans with Mycobacterium tuberculosis remains frequent and may still lead to death. After primary infection, the immune system is often able to control M. tuberculosis infection over a prolonged latency period, but a decrease in immune function (from HIV to immunosenescence) leads to active disease. Available vaccines against tuberculosis are restricted to BCG, a live vaccine with an attenuated strain of M. bovis. Immunodeficiency may not only be associated with an increased risk of tuberculosis, but also with local or disseminated BCG infection. Genetic deficiency in the reactive oxygen species (ROS)-producing phagocyte NADPH oxidase NOX2 is called chronic granulomatous disease (CGD). CGD is among the most common primary immune deficiencies. Here we review our knowledge on the importance of NOX2-derived ROS in mycobacterial infection. A literature review suggests that human CGD patient frequently have an increased susceptibility to BCG and to M. tuberculosis. In vitro studies and experiments with CGD mice are incomplete and yielded - at least in part - contradictory results. Thus, although observations in human CGD patients leave little doubt about the role of NOX2 in the control of mycobacteria, further studies will be necessary to unequivocally define and understand the role of ROS. PMID:24916152

  6. Management of nontuberculous mycobacterial infection in the elderly.

    PubMed

    Mirsaeidi, Mehdi; Farshidpour, Maham; Ebrahimi, Golnaz; Aliberti, Stefano; Falkinham, Joseph O

    2014-04-01

    The incidence of nontuberculous mycobacteria (NTM) has increased over the last decades. Elderly people are more susceptible to NTM and experience increased morbidities. NTM incidence is expected to rise due to an increasing elderly population at least up to 2050. Given the importance of NTM infection in the elderly, an increasing interest exists in studying NTM characteristics in the aged population. In this review, we summarize the characteristics of NTM infection among elderly patients. We focus on epidemiology, clinical presentation, and treatment options of NTM in this age group. We highlight the differences in the diagnosis and treatment between rapid and slow growing mycobacterial infections. The current recommendation for treatment of NTM is discussed. We debate if in vitro susceptibility testing has a role in the treatment of NTM. Drug-drug interaction between antibiotics used to treat NTM and other medications, particularly warfarin, is another important issue that we discuss. Finally, we review the prognosis of NTM disease in elderly patients. PMID:24685313

  7. Disseminated nontuberculous mycobacterial infections in sickle cell anemia patients.

    PubMed

    Thorell, Emily A; Sharma, Mukta; Jackson, Mary Anne; Selvarangan, Rangaraj; Woods, Gerald M

    2006-10-01

    Nontuberculous mycobacteria (NTM) are ubiquitous in nature and have been implicated in skin/soft-tissue, pulmonary, middle ear, bone, and surgical/traumatic wound infections. Disseminated disease occurs infrequently and almost exclusively in the immunocompromised. We describe the first 2 reported cases of disseminated Mycobacterium fortuitum infection in teenagers with sickle hemoglobinopathy. Both had central venous catheters (CVCs), frequent admissions for vaso-occlusive painful episode and received hydroxyurea. Diagnosis was confirmed by multiple positive blood cultures and pulmonary dissemination occurred in both. Both had successful treatment after CVC removal and combination drug therapy. Positive cultures persisted in 1 patient due to drug resistance emphasizing the need for accurate susceptibility data. NTM infection should be added to the list of pathogens in sickle cell patients with CVCs and fever. Investigation for disseminated disease should be undertaken based on clinical signs and symptoms. Although some routine blood culture systems can identify NTM, specific mycobacterial blood culture is optimal. Removal of involved CVCs is essential and treatment of NTM must be guided by susceptibilities. As dissemination almost always occurs in those with impaired cellular immunity, human immunodeficiency virus testing should be performed. Hydroxyurea may be a risk factor for dissemination and needs further evaluation. PMID:17023829

  8. [The bacteriology of tuberculosis and non-tuberculosis mycobacterial infections].

    PubMed

    Wyplosz, B; Truffot-Pernot, C; Robert, J; Jarlier, V; Grosset, J

    1997-12-01

    Changing incidence and nature of mycobacterial infections subsequent to the historical regression of tuberculosis and the acquired human immunodeficiency syndrome (AIDS) epidemic, as well as the development of new technical tools for molecular biology, have profoundly modified the methods used for the bacteriological diagnosis of mycobacteria infections. Although microscopic search for acid-fast bacilli, culture and antibiotic resistance tests on Löwenstein-Jensen medium remain the reference methods, more rapid and sophisticated methods are now available. Culture on radiolabeled media using the Bactec system has shortened the delay for positive culture and interpretable antibiotic sensitivity tests. Molecular techniques allow: 1) rapid identification of the most frequently isolated mycobacteria strains, including the most frequent laboratory contaminant M. gordonae, with genome probes; 2) genome typing of M. tuberculosis strains to trace interhuman transmission, detect recurrence or exogenous reinfection or demonstrate laboratory contamination; 3) rapid detection of rifampicin resistance; and 4) direct detection of M. tuberculosis and M. avium in pathological specimens. The role of mycobacteria in the environment causing opportunistic infections, atypical mycobacteria or non-tuberculosis mycobacteria (NTM), particularly the aviaire complex, has grown considerably. Isolation and identification relies on methods used to detect bacilli as well as blood cultures and analysis of fecal matter. NTM are naturally resistant to most of the antituberculosis antibiotics but are sometimes sensitive to aminoglycosides, fluoroquinolones or new macrolides. PMID:9496590

  9. Drug testing in mouse models of tuberculosis and nontuberculous mycobacterial infections.

    PubMed

    Nikonenko, Boris V; Apt, Alexander S

    2013-05-01

    Mice as a species are susceptible to tuberculosis infection while mouse inbred strains present wide spectrum of susceptibility/resistance to this infection. However, non-tuberculosis Mycobacterial infections usually cannot be modeled in mice of common inbred strains. Introduction of specific properties, such as gene mutations, recombinants, targeted gene knockouts significantly extended the use of mice to mimic human Mycobacterial infections, including non-tuberculosis ones. This review describes the available mouse models of tuberculosis and non-tuberculosis infections and drug therapy in these models. Mouse models of non-tuberculosis infections are significantly less developed than tuberculosis models, hampering the development of therapies. PMID:23491715

  10. Patient Report and Review of Rapidly Growing Mycobacterial Infection after Cardiac Device Implantation

    PubMed Central

    Hirsh, David S.; Goswami, Neela D.

    2016-01-01

    Mycobacterial infections resulting from cardiac implantable electronic devices are rare, but as more devices are implanted, these organisms are increasingly emerging as causes of early-onset infections. We report a patient with an implantable cardioverter-defibrillator pocket and associated bloodstream infection caused by an organism of the Mycobacterium fortuitum group, and we review the literature regarding mycobacterial infections resulting from cardiac device implantations. Thirty-two such infections have been previously described; most (70%) were caused by rapidly growing species, of which M. fortuitum group species were predominant. When managing such infections, clinicians should consider the potential need for extended incubation of routine cultures or dedicated mycobacterial cultures for accurate diagnosis; combination antimicrobial drug therapy, even for isolates that appear to be macrolide susceptible, because of the potential for inducible resistance to this drug class; and the arrhythmogenicity of the antimicrobial drugs traditionally recommended for infections caused by these organisms. PMID:26890060

  11. Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.

    PubMed

    Levitte, Steven; Adams, Kristin N; Berg, Russell D; Cosma, Christine L; Urdahl, Kevin B; Ramakrishnan, Lalita

    2016-08-10

    The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection. PMID:27512905

  12. Myeloid Growth Factors Promote Resistance to Mycobacterial Infection by Curtailing Granuloma Necrosis through Macrophage Replenishment.

    PubMed

    Pagán, Antonio J; Yang, Chao-Tsung; Cameron, James; Swaim, Laura E; Ellett, Felix; Lieschke, Graham J; Ramakrishnan, Lalita

    2015-07-01

    The mycobacterial ESX-1 virulence locus accelerates macrophage recruitment to the forming tuberculous granuloma. Newly recruited macrophages phagocytose previously infected apoptotic macrophages to become new bacterial growth niches. Granuloma macrophages can then necrose, releasing mycobacteria into the extracellular milieu, which potentiates their growth even further. Using zebrafish with genetic or pharmacologically induced macrophage deficiencies, we find that global macrophage deficits increase susceptibility to mycobacterial infection by accelerating granuloma necrosis. This is because reduction in the macrophage supply below a critical threshold decreases granuloma macrophage replenishment to the point where apoptotic infected macrophages, failing to get engulfed, necrose. Reducing macrophage demand by removing bacterial ESX-1 offsets the susceptibility of macrophage deficits. Conversely, increasing macrophage supply in wild-type fish by overexpressing myeloid growth factors induces resistance by curtailing necrosis. These findings may explain the susceptibility of humans with mononuclear cytopenias to mycobacterial infections and highlight the therapeutic potential of myeloid growth factors in tuberculosis. PMID:26159717

  13. A focus on intra-abdominal infections

    PubMed Central

    2010-01-01

    Complicated intra-abdominal infections are an important cause of morbidity and are frequently associated with poor prognosis, particularly in higher risk patients. Well defined evidence-based recommendations for intra-abdominal infections treatment are partially lacking because of the limited number of randomized-controlled trials. Factors consistently associated with poor outcomes in patients with intra-abdominal infections include increased illness severity, failed source control, inadequate empiric antimicrobial therapy and healthcare-acquired infection. Early prognostic evaluation of complicated intra-abdominal infections is important to select high-risk patients for more aggressive therapeutic procedures. The cornerstones in the management of complicated intra-abdominal infections are both source control and antibiotic therapy. The timing and the adequacy of source control are the most important issues in the management of intra-abdominal infections, because inadequate and late control of septic source may have a negative effect on the outcomes. Recent advances in interventional and more aggressive techniques could significantly decrease the morbidity and mortality of physiologically severe complicated intra-abdominal infections, even if these are still being debated and are yet not validated by limited prospective trials. Empiric antimicrobial therapy is nevertheless important in the overall management of intra-abdominal infections. Inappropriate antibiotic therapy may result in poor patient outcomes and in the appearance of bacterial resistance. Antimicrobial management is generally standardised and many regimens, either with monotherapy or combination therapy, have proven their efficacy. Routine coverage especially against Enterococci and candida spp is not always recommended, but can be useful in particular clinical conditions. A de escalation approach may be recommended in patients with specific risk factors for multidrug resistant infections such as

  14. Species distribution in human immunodeficiency virus-related mycobacterial infections: implications for selection of initial treatment.

    PubMed

    Montessori, V; Phillips, P; Montaner, J; Haley, L; Craib, K; Bessuille, E; Black, W

    1996-06-01

    Management of mycobacterial infection is species specific; however, treatment is prompted by positive smears or cultures, often several weeks before species identification. The objective of this study was to determine the species distribution of mycobacterial isolates from various body sites in patients infected with human immunodeficiency virus (HIV). All mycobacterial isolates recovered at St. Paul's Hospital (Vancouver, British Columbia, Canada) from April 1989 to March 1993 were reviewed. Among 357 HIV-positive patients with mycobacterial infections, 64% (96) of the sputum isolates were Mycobacterium avium complex (MAC), 18% were Mycobacterium tuberculosis, and 17% were Mycobacterium kansasii. Lymph node involvement (25 patients) was due to either MAC (72%) or M. tuberculosis (24%). Two hundred ninety-eight episodes of mycobacteremia were due to MAC (98%), M. tuberculosis (1%), and M. kansasii (1%). Similarly, cultures of 84 bone marrow biopsy specimens (99%), 19 intestinal biopsy specimens (100%), and 30 stool specimens (97%) yielded predominantly MAC. These results have implications for initial therapy, particularly in areas where rapid methods for species identification are not readily available. Because of considerable geographic variation, development of guidelines for selection of initial therapy depends on regional determination of species distribution in HIV-related mycobacterial infections. PMID:8783698

  15. Multiplex PCR assay for immediate identification of the infecting species in patients with mycobacterial disease.

    PubMed Central

    Kox, L F; Jansen, H M; Kuijper, S; Kolk, A H

    1997-01-01

    Rapid identification of infecting mycobacterial species enables appropriate medical care decisions to be made. Our aim was to demonstrate the clinical usefulness of the multiplex PCR assay, a test based on PCR, which permits direct identification of 12 mycobacterial species in clinical specimens. A total of 259 specimens from 177 patients who had clinical symptoms of mycobacterial disease but for whom there were difficulties in diagnosis were tested. Specimens were analyzed within 48 h of receipt of the sample. Mycobacteria were identified in 102 specimens; 66 specimens contained nontuberculous mycobacteria, and 36 specimens contained Mycobacterium tuberculosis complex mycobacteria. The PCR assay identified the mycobacterial species in 43 (97.7%) of 44 microscopy- and culture-positive specimens and in 15 (93.8%) of 16 culture-positive, microscopy-negative specimens. It also permitted species identification in infections caused by more than one mycobacterial species. For 56 (96.5%) of the 58 specimens from patients with infections caused by opportunistic mycobacteria, the organisms were identified with the PCR assay. The test was useful also for the identification of fastidious mycobacteria, e.g., M. genavense, and those that cannot be cultured, e.g., M. leprae. After resolution of discrepant results, the sensitivity of the PCR assay was 97.9%, the specificity was 96.9%, the positive predictive value was 95.0%, and the negative predictive value was 98.7%. For culture these values were 60.8, 100, 100, and 81.0%, respectively. Thus, the multiplex PCR assay enables prompt diagnosis when rapid identification of infecting mycobacteria is necessary. PMID:9163468

  16. Infected Abdominal Aortic Aneurysm with Helicobacter cinaedi

    PubMed Central

    Iwasawa, Takamasa; Tamura, Atsushi; Lefor, Alan T.

    2016-01-01

    Helicobacter cinaedi is a rare human pathogen which has various clinical manifestations such as cellulitis, bacteremia, arthritis, meningitis, and infectious endocarditis. We report an abdominal aortic aneurysm infected with Helicobacter cinaedi, treated successfully with surgical repair and long-term antimicrobial therapy. PMID:26885430

  17. 2013 WSES guidelines for management of intra-abdominal infections

    PubMed Central

    2013-01-01

    Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The 2013 update of the World Society of Emergency Surgery (WSES) guidelines for the management of intra-abdominal infections contains evidence-based recommendations for management of patients with intra-abdominal infections. PMID:23294512

  18. Husbandry stress exacerbates mycobacterial infections in adult zebrafish, Danio rerio (Hamilton)

    USGS Publications Warehouse

    Ramsay, J.M.; Watral, V.; Schreck, C.B.; Kent, M.L.

    2009-01-01

    Mycobacteria are significant pathogens of laboratory zebrafish, Danio rerio (Hamilton). Stress is often implicated in clinical disease and morbidity associated with mycobacterial infections but has yet to be examined with zebrafish. The aim of this study was to examine the effects of husbandry stressors on zebrafish infected with mycobacteria. Adult zebrafish were exposed to Mycobacterium marinum or Mycobacterium chelonae, two species that have been associated with disease in zebrafish. Infected fish and controls were then subjected to chronic crowding and handling stressors and examined over an 8-week period. Whole-body cortisol was significantly elevated in stressed fish compared to non-stressed fish. Fish infected with M. marinum ATCC 927 and subjected to husbandry stressors had 14% cumulative mortality while no mortality occurred among infected fish not subjected to husbandry stressors. Stressed fish, infected with M. chelonae H1E2 from zebrafish, were 15-fold more likely to be infected than non-stressed fish at week 8 post-injection. Sub-acute, diffuse infections were more common among stressed fish infected with M. marinum or M. chelonae than non-stressed fish. This is the first study to demonstrate an effect of stress and elevated cortisol on the morbidity, prevalence, clinical disease and histological presentation associated with mycobacterial infections in zebrafish. Minimizing husbandry stress may be effective at reducing the severity of outbreaks of clinical mycobacteriosis in zebrafish facilities. ?? 2009 Blackwell Publishing Ltd.

  19. Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut.

    PubMed

    Obieglo, Katja; Feng, Xiaogang; Bollampalli, Vishnu Priya; Dellacasa-Lindberg, Isabel; Classon, Cajsa; Österblad, Markus; Helmby, Helena; Hewitson, James P; Maizels, Rick M; Gigliotti Rothfuchs, Antonio; Nylén, Susanne

    2016-03-01

    Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette-Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4(+) T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus-infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory-secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4(+) T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus-infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test-based diagnosis of microbial infections. PMID:26819205

  20. Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

    PubMed Central

    Obieglo, Katja; Feng, Xiaogang; Bollampalli, Vishnu Priya; Dellacasa-Lindberg, Isabel; Classon, Cajsa; Österblad, Markus; Helmby, Helena; Hewitson, James P.; Maizels, Rick M.

    2016-01-01

    Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette–Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4+ T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus–infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory–secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4+ T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus–infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test–based diagnosis of microbial infections. PMID:26819205

  1. The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and Humans

    PubMed Central

    Tobin, David M.; Vary, Jay C.; Ray, John P.; Walsh, Gregory S.; Dunstan, Sarah J.; Bang, Nguyen D.; Hagge, Deanna A.; Khadge, Saraswoti; King, Mary-Claire; Hawn, Thomas R.; Moens, Cecilia B.; Ramakrishnan, Lalita

    2010-01-01

    SUMMARY Exposure to Mycobacterium tuberculosis produces varied early outcomes, ranging from resistance to infection to progressive disease. Here we report results from a forward genetic screen in zebrafish larvae that identify multiple mutant classes with distinct patterns of innate susceptibility to Mycobacterium marinum. A hypersusceptible mutant maps to the lta4h locus encoding leukotriene A4 hydrolase, which catalyzes the final step in the synthesis of leukotriene B4 (LTB4), a potent chemoattractant and proinflammatory eicosanoid. lta4h mutations confer hypersusceptibility independent of LTB4 reduction, by redirecting eicosanoid substrates to anti-inflammatory lipoxins. The resultant anti-inflammatory state permits increased mycobacterial proliferation by limiting production of tumor necrosis factor. In humans, we find that protection from both tuberculosis and multibacillary leprosy is associated with heterozygosity for LTA4H polymorphisms that have previously been correlated with differential LTB4 production. Our results suggest conserved roles for balanced eicosanoid production in vertebrate resistance to mycobacterial infection. PMID:20211140

  2. A potential target gene for the host-directed therapy of mycobacterial infection in murine macrophages

    PubMed Central

    Bao, Zhang; Chen, Ran; Zhang, Pei; Lu, Shan; Chen, Xing; Yao, Yake; Jin, Xiaozheng; Sun, Yilan; Zhou, Jianying

    2016-01-01

    Mycobacterium tuberculosis (MTB), one of the major bacterial pathogens for lethal infectious diseases, is capable of surviving within the phagosomes of host alveolar macrophages; therefore, host genetic variations may alter the susceptibility to MTB. In this study, to identify host genes exploited by MTB during infection, genes were non-selectively inactivated using lentivirus-based antisense RNA methods in RAW264.7 macrophages, and the cells that survived virulent MTB infection were then screened. Following DNA sequencing of the surviving cell clones, 26 host genes affecting susceptibility to MTB were identified and their pathways were analyzed by bioinformatics analysis. In total, 9 of these genes were confirmed as positive regulators of collagen α-5(IV) chain (Col4a5) expression, a gene encoding a type IV collagen subunit present on the cell surface. The knockdown of Col4a5 consistently suppressed intracellular mycobacterial viability, promoting the survival of RAW264.7 macrophages following mycobacterial infection. Furthermore, Col4a5 deficiency lowered the pH levels of intracellular vesicles, including endosomes, lysosomes and phagosomes in the RAW264.7 cells. Finally, the knockdown of Col4a5 post-translationally increased microsomal vacuolar-type H+-ATPase activity in macrophages, leading to the acidification of intracellular vesicles. Our findings reveal a novel role for Col4a5 in the regulation of macrophage responses to mycobacterial infection and identify Col4a5 as a potential target for the host-directed anti-mycobacterial therapy. PMID:27432120

  3. A potential target gene for the host-directed therapy of mycobacterial infection in murine macrophages.

    PubMed

    Bao, Zhang; Chen, Ran; Zhang, Pei; Lu, Shan; Chen, Xing; Yao, Yake; Jin, Xiaozheng; Sun, Yilan; Zhou, Jianying

    2016-09-01

    Mycobacterium tuberculosis (MTB), one of the major bacterial pathogens for lethal infectious diseases, is capable of surviving within the phagosomes of host alveolar macrophages; therefore, host genetic variations may alter the susceptibility to MTB. In this study, to identify host genes exploited by MTB during infection, genes were non-selectively inactivated using lentivirus-based antisense RNA methods in Raw264.7 macrophages, and the cells that survived virulent MTB infection were then screened. Following DNA sequencing of the surviving cell clones, 26 host genes affecting susceptibility to MTB were identified and their pathways were analyzed by bioinformatics analysis. In total, 9 of these genes were confirmed as positive regulators of collagen α-5(IV) chain (Col4a5) expression, a gene encoding a type IV collagen subunit present on the cell surface. The knockdown of Col4a5 consistently suppressed intracellular mycobacterial viability, promoting the survival of Raw264.7 macrophages following mycobacterial infection. Furthermore, Col4a5 deficiency lowered the pH levels of intracellular vesicles, including endosomes, lysosomes and phagosomes in the Raw264.7 cells. Finally, the knockdown of Col4a5 post-translationally increased microsomal vacuolar-type H+-ATPase activity in macrophages, leading to the acidification of intracellular vesicles. Our findings reveal a novel role for Col4a5 in the regulation of macrophage responses to mycobacterial infection and identify Col4a5 as a potential target for the host-directed anti-mycobacterial therapy. PMID:27432120

  4. Comparative evaluation of in vitro human macrophage models for mycobacterial infection study.

    PubMed

    Mendoza-Coronel, E; Castañón-Arreola, M

    2016-08-01

    Macrophages are phagocytic cells that play a key role maintaining the homeostasis of many tissues. Their function is essential for controlling and eradicating infecting mycobacteria. Human monocytic cell lines such as THP-1 and U937 have provided interesting insights into how mycobacteria subvert the host cell response. However, immortalized cell lines could bring some disadvantages. Here we compare the response of THP-1 and U937 cell lines with human monocyte-derived macrophages (hMDMs) to determine functional differences during infection with different mycobacterial phenotypes (virulent Mycobacterium tuberculosis H37Rv and Mycobacterium bovis, and attenuated M. bovis BCG). The findings of this study indicate that the U937 cell line displays a significantly lower phagocytic capacity than hMDMs and THP-1 macrophages, regardless of the mycobacterial strain. In all cell models, interferon-γ activation leads to up-regulation of interleukin-12 and nitrite production. However, the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of U937 and THP-1 cell lines induces a significant tumor necrosis factor-α production in resting macrophages. However, this state of activation has no effect on the control of intracellular growth of mycobacteria. Moreover, U937 cells show more discrepancies with hMDM than THP-1. This study demonstrates that THP-1 macrophages exhibit closer functional similarities to hMDMs in response to mycobacterial infection, regardless of the strain. PMID:27307103

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:26123801

  6. 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. PMID:26123801

  7. [Intra-abdominal infection and new quinolones].

    PubMed

    Gnocchi, C A

    1999-01-01

    Intra-abdominal infection is defined as the presence of an infectious process within the peritoneal cavity. It may be local or have a systemic consequence generating multiple organic disfunction. Most of the studies report a mortality of 30% in severe intra-abdominal infection. Secondary peritonitis is caused by the loss of integrity of the gastrointestinal apparatus, which contaminates with pathogens the peritoneal cavity. Invariably they are polymicrobial infections, mostly due to facultative anaerobic and anaerobic Gram negative bacilli. Prognosis of peritonitis depends on the struggle between two forces: local and systemic immunity of the host and the volume, nature and length of the contamination. Microorganisms and their products estimulate cellular defenses in the host and activate numerous inflammatory mediators responsible for sepsis. Antibiotic treatment of secondary peritonitis must act mainly against Escherichia coli and Bacteroides fragilis. The adequate and early empirical administration of antibiotics against these bacteria is well established. It is necessary to consider if the infection is localized or generalized and if it is accompanied or not by organic disfunction. It also has to be taken into account if peritonitis is community or hospital-acquired when choosing the antibiotic scheme. In community-acquired peritonitis with low to moderate infections a combination of metronidazole-ceftriaxone, metronidazole-gentamycin or a monodrug like ampicillin-sulbactam may be used. In severe hospital-acquired peritonitis imipenem or the combination piperacillin-tazobactam are effective. New quinolones such as trovafloxacin or clinafloxacin, with excellent activity against aerobes and anaerobes producing intra-abdominal infections, may be effective. Future clinical trials are needed to determine their utility. Tertiary peritonitis represent a systemic inflammatory response with multiorganic failure due to the uncontrolled activation of the inflammatory

  8. Postoperative Abdominal Infection Caused by Corynebacterium minutissimum

    PubMed Central

    Shin, Ji Young; Lee, Woon Kee; Seo, Yiel-Hea

    2014-01-01

    Corynebacterium minutissimum is a non-spore forming, gram-positive, aerobic or facultative anaerobic bacillus. It is the causative organism of erythrasma, a common superficial infection of skin, which typically presents as reddish-brown macular patches. To date, it has rarely been found to cause invasive disease, although other non-diphtheria corynebacteria are becoming increasingly common as opportunistic pathogens. We report on a rare case of abdominal infection due to C. minutissimum in an immunocompetent adult who was successfully treated with intravenous amoxicillin/sulbactam. PMID:25566407

  9. Postoperative Abdominal Infection Caused by Corynebacterium minutissimum.

    PubMed

    Shin, Ji Young; Lee, Woon Kee; Seo, Yiel-Hea; Park, Yoon Soo

    2014-12-01

    Corynebacterium minutissimum is a non-spore forming, gram-positive, aerobic or facultative anaerobic bacillus. It is the causative organism of erythrasma, a common superficial infection of skin, which typically presents as reddish-brown macular patches. To date, it has rarely been found to cause invasive disease, although other non-diphtheria corynebacteria are becoming increasingly common as opportunistic pathogens. We report on a rare case of abdominal infection due to C. minutissimum in an immunocompetent adult who was successfully treated with intravenous amoxicillin/sulbactam. PMID:25566407

  10. Biomarker Discovery in Subclinical Mycobacterial Infections of Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Bovine tuberculosis is a highly prevalent infectious disease of cattle worldwide; however, infection in the United States is limited to 0.01% of dairy herds. Thus detection of bovine TB is confounded by high background infection with M. avium subsp. paratuberculosis. The present study a...

  11. Mycobacterial infection induces a specific human innate immune response

    PubMed Central

    Blischak, John D.; Tailleux, Ludovic; Mitrano, Amy; Barreiro, Luis B.; Gilad, Yoav

    2015-01-01

    The innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5–10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility. PMID:26586179

  12. Developments on drug delivery systems for the treatment of mycobacterial infections.

    PubMed

    Gaspar, M M; Cruz, A; Fraga, A G; Castro, A G; Cruz, M E M; Pedrosa, J

    2008-01-01

    The clinical management of tuberculosis and other mycobacterial diseases with antimycobacterial chemotherapy remains a difficult task. The classical treatment protocols are long-lasting; the drugs reach mycobacteria-infected macrophages in low amounts and/or do not persist long enough to develop the desired antimycobacterial effect; and the available agents induce severe toxic effects. Nanotechnology has provided a huge improvement to pharmacology through the designing of drug delivery systems able to target phagocytic cells infected by intracellular pathogens, such as mycobacteria. Liposomes and nanoparticles of polymeric nature represent two of the most efficient drug carrier systems that after in vivo administration are endocytosed by phagocytic cells and then release the carried agents into these cells. This article reviews the relevant publications describing the effectiveness of the association of antimycobacterial agents with liposomes or nanoparticles for the treatment of mycobacterioses, particularly for Mycobacterium tuberculosis and M. avium infections. The increased therapeutic index of antimycobacterial drugs; the reduction of dosing frequency; and the improvement of solubility of hydrophobic agents, allowing the administration of higher doses, have been demonstrated in experimental infections. These advantages may lead to new therapeutic protocols that will improve patient compliance and, consequently, lead to a more successful control of mycobacterial infections. The potential therapeutic advantages resulting from the use of non-invasive administration routes for nanoparticulate systems are also discussed. PMID:18473884

  13. Host Response to Nontuberculous Mycobacterial Infections of Current Clinical Importance

    PubMed Central

    Orme, Ian M.

    2014-01-01

    The nontuberculous mycobacteria are a large group of acid-fast bacteria that are very widely distributed in the environment. While Mycobacterium avium was once regarded as innocuous, its high frequency as a cause of disseminated disease in HIV-positive individuals illustrated its potential as a pathogen. Much more recently, there is growing evidence that the incidence of M. avium and related nontuberculous species is increasing in immunocompetent individuals. The same has been observed for M. abscessus infections, which are very difficult to treat; accordingly, this review focuses primarily on these two important pathogens. Like the host response to M. tuberculosis infections, the host response to these infections is of the TH1 type but there are some subtle and as-yet-unexplained differences. PMID:24914222

  14. Two Episodes of Cutaneous Non-Tuberculous Mycobacterial Infection in a Patient with Psoriasis

    PubMed Central

    Chan, Wai Sze Agnes; Tee, Shang-Ian; Chandran, Nisha Su Yien; Pan, Jiun Yit

    2015-01-01

    Non-tuberculous mycobacteria (NTM) are a group of environmental pathogens, which cause a broad spectrum of disease. The incidence of NTM infection is increasing, especially in immunocompromized patients. The past three decades also saw a rapid increase in the incidence of NTM infection involving otherwise healthy subjects. We report a case of cutaneous NTM infection in a 79-year-old Chinese woman, who was receiving methotrexate for psoriasis. Mycobacterial culture grew Mycobacterium abscessus, and the lesions cleared with a combination of oral clarithromycin, ciprofloxacin and doxycycline. Interestingly, she then developed a second episode of cutaneous NTM infection with Mycobacterium haemophilum over the same body region, five years after stoppage of methotrexate. Both episodes were separated in time and involved different species, indicating that they were independent from each other. We further discuss the risk factors for cutaneous NTM infection, treatment, and highlight the need for diagnostic vigilance. PMID:26236445

  15. Two Episodes of Cutaneous Non-Tuberculous Mycobacterial Infection in a Patient with Psoriasis.

    PubMed

    Chan, Wai Sze Agnes; Tee, Shang-Ian; Chandran, Nisha Su Yien; Pan, Jiun Yit

    2015-05-21

    Non-tuberculous mycobacteria (NTM) are a group of environmental pathogens, which cause a broad spectrum of disease. The incidence of NTM infection is increasing, especially in immunocompromized patients. The past three decades also saw a rapid increase in the incidence of NTM infection involving otherwise healthy subjects. We report a case of cutaneous NTM infection in a 79-year-old Chinese woman, who was receiving methotrexate for psoriasis. Mycobacterial culture grew Mycobacterium abscessus, and the lesions cleared with a combination of oral clarithromycin, ciprofloxacin and doxycycline. Interestingly, she then developed a second episode of cutaneous NTM infection with Mycobacterium haemophilum over the same body region, five years after stoppage of methotrexate. Both episodes were separated in time and involved different species, indicating that they were independent from each other. We further discuss the risk factors for cutaneous NTM infection, treatment, and highlight the need for diagnostic vigilance. PMID:26236445

  16. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

    PubMed Central

    Kreins, Alexandra Y.; Ciancanelli, Michael J.; Okada, Satoshi; Kong, Xiao-Fei; Ramírez-Alejo, Noé; Kilic, Sara Sebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Mahdaviani, Seyed Alireza; Ailal, Fatima; Bousfiha, Aziz; Mansouri, Davood; Nievas, Elma; Ma, Cindy S.; Rao, Geetha; Bernasconi, Andrea; Sun Kuehn, Hye; Niemela, Julie; Stoddard, Jennifer; Deveau, Paul; Cobat, Aurelie; El Azbaoui, Safa; Sabri, Ayoub; Lim, Che Kang; Sundin, Mikael; Avery, Danielle T.; Halwani, Rabih; Grant, Audrey V.; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Migaud, Melanie; Deswarte, Caroline; Alsina, Laia; Kotlarz, Daniel; Klein, Christoph; Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Cormier-Daire, Valerie; Rose-John, Stefan; Picard, Capucine; Hammarstrom, Lennart; Puel, Anne; Al-Muhsen, Saleh; Abel, Laurent; Chaussabel, Damien; Rosenzweig, Sergio D.; Minegishi, Yoshiyuki; Tangye, Stuart G.; Bustamante, Jacinta; Casanova, Jean-Laurent

    2015-01-01

    Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans. PMID:26304966

  17. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome.

    PubMed

    Kreins, Alexandra Y; Ciancanelli, Michael J; Okada, Satoshi; Kong, Xiao-Fei; Ramírez-Alejo, Noé; Kilic, Sara Sebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Mahdaviani, Seyed Alireza; Ailal, Fatima; Bousfiha, Aziz; Mansouri, Davood; Nievas, Elma; Ma, Cindy S; Rao, Geetha; Bernasconi, Andrea; Sun Kuehn, Hye; Niemela, Julie; Stoddard, Jennifer; Deveau, Paul; Cobat, Aurelie; El Azbaoui, Safa; Sabri, Ayoub; Lim, Che Kang; Sundin, Mikael; Avery, Danielle T; Halwani, Rabih; Grant, Audrey V; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Migaud, Melanie; Deswarte, Caroline; Alsina, Laia; Kotlarz, Daniel; Klein, Christoph; Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Cormier-Daire, Valerie; Rose-John, Stefan; Picard, Capucine; Hammarstrom, Lennart; Puel, Anne; Al-Muhsen, Saleh; Abel, Laurent; Chaussabel, Damien; Rosenzweig, Sergio D; Minegishi, Yoshiyuki; Tangye, Stuart G; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stéphanie

    2015-09-21

    Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans. PMID:26304966

  18. Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.

    PubMed

    López-García, Sonia; Castañeda-Sanchez, Jorge Ismael; Jiménez-Arellanes, Adelina; Domínguez-López, Lilia; Castro-Mussot, Maria Eugenia; Hernández-Sanchéz, Javier; Luna-Herrera, Julieta

    2015-01-01

    Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-β) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-β and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated). PMID:26287131

  19. The vesicle-associated function of NOD2 as a link between Crohn's disease and mycobacterial infection.

    PubMed

    Nabatov, Alexey A

    2015-01-01

    Although Crohn's disease (CD) etiology remains unclear, a growing body of evidence suggests that CD may include an infectious component, with Mycobacterium avium subsp. paratuberculosis (MAP) being the most likely candidate for this role. However, the molecular mechanism of the MAP involvement in CD pathogenesis remains unclear. The polymorphism of the NOD2 gene, coding for an intracellular pattern recognition receptor, is a factor of predisposition to mycobacterial infections and CD. Recent findings on NOD2 interactions and functions provide the missing pieces in the puzzle of a NOD2-mediated mechanism common for mycobacterial infections and CD. Implications of these new findings for the development of a better understanding and treatments of CD and mycobacterial infections are discussed. PMID:25653718

  20. The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection.

    PubMed

    Torraca, Vincenzo; Cui, Chao; Boland, Ralf; Bebelman, Jan-Paul; van der Sar, Astrid M; Smit, Martine J; Siderius, Marco; Spaink, Herman P; Meijer, Annemarie H

    2015-03-01

    The recruitment of leukocytes to infectious foci depends strongly on the local release of chemoattractant mediators. The human CXC chemokine receptor 3 (CXCR3) is an important node in the chemokine signaling network and is expressed by multiple leukocyte lineages, including T cells and macrophages. The ligands of this receptor originate from an ancestral CXCL11 gene in early vertebrates. Here, we used the optically accessible zebrafish embryo model to explore the function of the CXCR3-CXCL11 axis in macrophage recruitment and show that disruption of this axis increases the resistance to mycobacterial infection. In a mutant of the zebrafish ortholog of CXCR3 (cxcr3.2), macrophage chemotaxis to bacterial infections was attenuated, although migration to infection-independent stimuli was unaffected. Additionally, attenuation of macrophage recruitment to infection could be mimicked by treatment with NBI74330, a high-affinity antagonist of CXCR3. We identified two infection-inducible CXCL11-like chemokines as the functional ligands of Cxcr3.2, showing that the recombinant proteins exerted a Cxcr3.2-dependent chemoattraction when locally administrated in vivo. During infection of zebrafish embryos with Mycobacterium marinum, a well-established model for tuberculosis, we found that Cxcr3.2 deficiency limited the macrophage-mediated dissemination of mycobacteria. Furthermore, the loss of Cxcr3.2 function attenuated the formation of granulomatous lesions, the typical histopathological features of tuberculosis, and led to a reduction in the total bacterial burden. Prevention of mycobacterial dissemination by targeting the CXCR3 pathway, therefore, might represent a host-directed therapeutic strategy for treatment of tuberculosis. The demonstration of a conserved CXCR3-CXCL11 signaling axis in zebrafish extends the translational applicability of this model for studying diseases involving the innate immune system. PMID:25573892

  1. The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection

    PubMed Central

    Torraca, Vincenzo; Cui, Chao; Boland, Ralf; Bebelman, Jan-Paul; van der Sar, Astrid M.; Smit, Martine J.; Siderius, Marco; Spaink, Herman P.; Meijer, Annemarie H.

    2015-01-01

    The recruitment of leukocytes to infectious foci depends strongly on the local release of chemoattractant mediators. The human CXC chemokine receptor 3 (CXCR3) is an important node in the chemokine signaling network and is expressed by multiple leukocyte lineages, including T cells and macrophages. The ligands of this receptor originate from an ancestral CXCL11 gene in early vertebrates. Here, we used the optically accessible zebrafish embryo model to explore the function of the CXCR3-CXCL11 axis in macrophage recruitment and show that disruption of this axis increases the resistance to mycobacterial infection. In a mutant of the zebrafish ortholog of CXCR3 (cxcr3.2), macrophage chemotaxis to bacterial infections was attenuated, although migration to infection-independent stimuli was unaffected. Additionally, attenuation of macrophage recruitment to infection could be mimicked by treatment with NBI74330, a high-affinity antagonist of CXCR3. We identified two infection-inducible CXCL11-like chemokines as the functional ligands of Cxcr3.2, showing that the recombinant proteins exerted a Cxcr3.2-dependent chemoattraction when locally administrated in vivo. During infection of zebrafish embryos with Mycobacterium marinum, a well-established model for tuberculosis, we found that Cxcr3.2 deficiency limited the macrophage-mediated dissemination of mycobacteria. Furthermore, the loss of Cxcr3.2 function attenuated the formation of granulomatous lesions, the typical histopathological features of tuberculosis, and led to a reduction in the total bacterial burden. Prevention of mycobacterial dissemination by targeting the CXCR3 pathway, therefore, might represent a host-directed therapeutic strategy for treatment of tuberculosis. The demonstration of a conserved CXCR3-CXCL11 signaling axis in zebrafish extends the translational applicability of this model for studying diseases involving the innate immune system. PMID:25573892

  2. Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection.

    PubMed

    Scharn, Caitlyn R; Collins, Angela C; Nair, Vidhya R; Stamm, Chelsea E; Marciano, Denise K; Graviss, Edward A; Shiloh, Michael U

    2016-06-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth. PMID:27183573

  3. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection

    PubMed Central

    Renna, Maurizio; Schaffner, Catherine; Brown, Karen; Shang, Shaobin; Tamayo, Marcela Henao; Hegyi, Krisztina; Grimsey, Neil J.; Cusens, David; Coulter, Sarah; Cooper, Jason; Bowden, Anne R.; Newton, Sandra M.; Kampmann, Beate; Helm, Jennifer; Jones, Andrew; Haworth, Charles S.; Basaraba, Randall J.; DeGroote, Mary Ann; Ordway, Diane J.; Rubinsztein, David C.; Floto, R. Andres

    2011-01-01

    Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens. PMID:21804191

  4. Plasma Membrane Profiling Reveals Upregulation of ABCA1 by Infected Macrophages Leading to Restriction of Mycobacterial Growth

    PubMed Central

    Long, Jing; Basu Roy, Robindra; Zhang, Yanjia J.; Antrobus, Robin; Du, Yuxian; Smith, Duncan L.; Weekes, Michael P.; Javid, Babak

    2016-01-01

    The plasma membrane represents a critical interface between the internal and extracellular environments, and harbors multiple proteins key receptors and transporters that play important roles in restriction of intracellular infection. We applied plasma membrane profiling, a technique that combines quantitative mass spectrometry with selective cell surface aminooxy-biotinylation, to Bacille Calmette–Guérin (BCG)-infected THP-1 macrophages. We quantified 559 PM proteins in BCG-infected THP-1 cells. One significantly upregulated cell-surface protein was the cholesterol transporter ABCA1. We showed that ABCA1 was upregulated on the macrophage cell-surface following infection with pathogenic mycobacteria and knockdown of ABCA1 resulted in increased mycobacterial survival within macrophages, suggesting that it may be a novel mycobacterial host-restriction factor. PMID:27462310

  5. The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS).

    PubMed

    Horsburgh, C R; Selik, R M

    1989-01-01

    We analyzed cases of disseminated nontuberculous mycobacterial infection (DNTM) in patients with AIDS reported to the Centers for Disease Control. Between 1981 and 1987, 2,269 cases were reported. In 96% of cases, infection was caused by M. avium complex (MAC). The number of cases has risen steadily since 1981, but the rate as a percentage of AIDS cases has remained stable at 5.5%. DNTM was seen less frequently in AIDS cases with Kaposi's sarcoma than in other AIDS cases (p less than 0.01). Rates of DNTM were lower in Hispanics and declined with age but were not significantly different by patient sex or means of acquiring HIV infection. Rates of disseminated MAC varied by geographic region from 3.9% to 7.8% (p less than 0.0001). As assessed by helper/suppressor T-cell ratios, AIDS patients with DNTM were not more immunologically impaired than those with other opportunistic infections. Life table analysis revealed that AIDS patients with DNTM survived a shorter time (median, 7.4 months) than did other AIDS patients (median, 13.3 months; p less than 0.0001). We conclude that DNTM is acquired by unpreventable environmental exposures. Because DNTM adversely affects survival of AIDS patients, effective therapeutic agents must be vigorously sought. PMID:2912355

  6. Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.

    PubMed

    Deffert, Christine; Schäppi, Michela G; Pache, Jean-Claude; Cachat, Julien; Vesin, Dominique; Bisig, Ruth; Ma Mulone, Xiaojuan; Kelkka, Tiina; Holmdahl, Rikard; Garcia, Irene; Olleros, Maria L; Krause, Karl-Heinz

    2014-09-01

    Patients with chronic granulomatous disease (CGD) lack generation of reactive oxygen species (ROS) through the phagocyte NADPH oxidase NOX2. CGD is an immune deficiency that leads to frequent infections with certain pathogens; this is well documented for S. aureus and A. fumigatus, but less clear for mycobacteria. We therefore performed an extensive literature search which yielded 297 cases of CGD patients with mycobacterial infections; M. bovis BCG was most commonly described (74%). The relationship between NOX2 deficiency and BCG infection however has never been studied in a mouse model. We therefore investigated BCG infection in three different mouse models of CGD: Ncf1 mutants in two different genetic backgrounds and Cybb knock-out mice. In addition, we investigated a macrophage-specific rescue (transgenic expression of Ncf1 under the control of the CD68 promoter). Wild-type mice did not develop severe disease upon BCG injection. In contrast, all three types of CGD mice were highly susceptible to BCG, as witnessed by a severe weight loss, development of hemorrhagic pneumonia, and a high mortality (∼ 50%). Rescue of NOX2 activity in macrophages restored BCG resistance, similar as seen in wild-type mice. Granulomas from mycobacteria-infected wild-type mice generated ROS, while granulomas from CGD mice did not. Bacterial load in CGD mice was only moderately increased, suggesting that it was not crucial for the observed phenotype. CGD mice responded with massively enhanced cytokine release (TNF-α, IFN-γ, IL-17 and IL-12) early after BCG infection, which might account for severity of the disease. Finally, in wild-type mice, macrophages formed clusters and restricted mycobacteria to granulomas, while macrophages and mycobacteria were diffusely distributed in lung tissue from CGD mice. Our results demonstrate that lack of the NADPH oxidase leads to a markedly increased severity of BCG infection through mechanisms including increased cytokine production and

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

    PubMed Central

    2014-01-01

    Background 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. Methods 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. Results 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%). Conclusions 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. PMID:24885916

  8. Increased Incidence of Cutaneous Nontuberculous Mycobacterial Infection, 1980 to 2009: A Population-Based Study

    PubMed Central

    Wentworth, Ashley B.; Drage, Lisa A.; Wengenack, Nancy L.; Wilson, John W.; Lohse, Christine M.

    2013-01-01

    Objectives To determine the incidence and clinical characteristics of cutaneous nontuberculous mycobacterial (NTM) infection during the past 30 years and whether the predominant species have changed. Patients and Methods Using Rochester Epidemiology Project data, we identified Olmsted County, Minnesota, residents with cutaneous NTM infections between January 1, 1980, and December 31, 2009, examining the incidence of infection, patient demographic and clinical features, the mycobacterium species, and therapy. Results Forty patients (median age, 47 years; 58% female [23 of 40]) had positive NTM cultures plus 1 or more clinical signs. The overall age- and sex-adjusted incidence of cutaneous NTM infection was 1.3 per 100,000 person-years (95% CI, 0.9–1.7 per 100,000 person-years). The incidence increased with age at diagnosis (P = .003) and was higher in 2000 to 2009 (2.0 per 100,000 person-years; 95% CI, 1.3–2.8 per 100,000 person-years) than in 1980 to 1999 (0.7 per 100,000 person-years; 95% CI, 0.3–1.1 per 100,000 person-years) (P = .002). The distal extremities were the most common sites of infection (27 of 39 patients [69%]). No patient had human immunodeficiency virus infection, but 23% (9 of 39) were immunosuppressed. Of the identifiable causes, traumatic injuries were the most frequent (22 of 29 patients [76%]). The most common species were Mycobacterium marinum (17 of 38 patients [45%]) and Mycobacterium chelonae/Mycobacterium abscessus (12 of 38 patients [32%]). In the past decade (2000–2009), 15 of 24 species (63%) were rapidly growing mycobacteria compared with only 4 of 14 species (29%) earlier (1980–1999) (P = .04). Conclusion The incidence of cutaneous NTM infection increased nearly 3-fold during the study period. Rapidly growing mycobacteria were predominant during the past decade. PMID:23218797

  9. High Mortality of Disseminated Non-Tuberculous Mycobacterial Infection in HIV-Infected Patients in the Antiretroviral Therapy Era

    PubMed Central

    Kobayashi, Tetsuro; Nishijima, Takeshi; Teruya, Katsuji; Aoki, Takahiro; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

    2016-01-01

    Background Little information is available on the mortality and risk factors associated with death in disseminated non-tuberculous mycobacterial infection (dNTM) in HIV-infected patients in the ART-era. Methods In a single-center study, HIV-infected dNTM with positive NTM culture from sterile sites between 2000 and 2013 were analysed. The clinical characteristics at commencement of anti-mycobacterial treatment (baseline) were compared between those who survived and died. Results Twenty-four patients were analyzed. [The median CD4 27/μL (range 2–185)]. Mycobacterium avium and M. intracellulare accounted for 20 (83%) and 3 (13%) of isolated NTM. NTM bacteremia was diagnosed in 15 (63%) patients. Seven (29%) patients died, and NTM bacteremia was significantly associated with mortality (p = 0.022). The baseline CD4 count was significantly lower in the non-survivors than the survivors (median 7/μL versus 49, p = 0.034). Concomitant AIDS-defining diseases or malignancies were not associated with mortality. Immune-reconstitution syndrome (IRS) occurred to 19 (79%) patients (8 paradoxical and 11 unmasking), and prognosis tended to be better in unmasking-IRS than the other patients (n = 13) (p = 0.078). Patients with paradoxical-IRS had marginally lower CD4 count and higher frequency of bacteremia than those with unmasking-IRS (p = 0.051, and 0.059). Treatment with systemic corticosteroids was applied in 63% and 55% of patients with paradoxical and unmasking-IRS, respectively. Conclusion dNTM in HIV-infected patients resulted in high mortality even in the ART-era. NTM bacteremia and low CD4 count were risk factors for death, whereas patients presented with unmasking-IRS had marginally better prognosis. IRS occurred in 79% of the patients, suggesting difficulty in the management of dNTM. PMID:26985832

  10. [Uncommon mycobacterial infections in domestic and zoo animals: four cases with special emphasis on pathology].

    PubMed

    Steiger, K; Ellenberger, C; Schüppel, K F; Richter, E; Schmerbach, K; Krautwald-Junghanns, M E; Wünnemann, K; Eulenberger, K; Schoon, H A

    2003-09-01

    Infections caused by classical tubercle bacilli are rare during the last years. Nevertheless, diseases caused by other mycobacteria have to be considered clinically and in diagnostic pathology especially in cases of immunosuppression and due to their potential zoonosis risk. An infection by mycobacteria was diagnosed in four animals (Mayotte Maki, Blue-headed Parrot, Patagonian sealion, Beagle) necropsied between 1995 and 2002 in the Institute of Veterinary-Pathology of the University of Leipzig. The Maki, the blue-headed parrot and the dog showed a disseminated character of the disease caused by Mycobacterium genavense (monkey and bird) resp. Mycobacterium avium (dog), while an open chronical tuberculosis of the lungs due to a pathogenic member of Mycobacterium tuberculosis complex was observed in the seal. All these bacteria are potential causes of zoonoses. So, if granulomatous or disseminated histiocytic alterations are detected in diagnostic pathology, mycobacterial infections should always be included in differential diagnoses and require careful aetiological investigations by histopathological and bacteriological methods. PMID:14560447

  11. Conserved Immune Recognition Hierarchy of Mycobacterial PE/PPE Proteins during Infection in Natural Hosts

    PubMed Central

    Vordermeier, H. Martin; Hewinson, R. Glyn; Wilkinson, Robert J.; Wilkinson, Katalin A.; Gideon, Hannah P.; Young, Douglas B.; Sampson, Samantha L.

    2012-01-01

    The Mycobacterium tuberculosis genome contains two large gene families encoding proteins of unknown function, characterized by conserved N-terminal proline and glutamate (PE and PPE) motifs. The presence of a large number of PE/PPE proteins with repetitive domains and evidence of strain variation has given rise to the suggestion that these proteins may play a role in immune evasion via antigenic variation, while emerging data suggests that some family members may play important roles in mycobacterial pathogenesis. In this study, we examined cellular immune responses to a panel of 36 PE/PPE proteins during human and bovine infection. We observed a distinct hierarchy of immune recognition, reflected both in the repertoire of PE/PPE peptide recognition in individual cows and humans and in the magnitude of IFN-γ responses elicited by stimulation of sensitized host cells. The pattern of immunodominance was strikingly similar between cattle that had been experimentally infected with Mycobacterium bovis and humans naturally infected with clinical isolates of M. tuberculosis. The same pattern was maintained as disease progressed throughout a four-month course of infection in cattle, and between humans with latent as well as active tuberculosis. Detailed analysis of PE/PPE responses at the peptide level suggests that antigenic cross-reactivity amongst related family members is a major determinant in the observed differences in immune hierarchy. Taken together, these results demonstrate that a subset of PE/PPE proteins are major targets of the cellular immune response to tuberculosis, and are recognized at multiple stages of infection and in different disease states. Thus this work identifies a number of novel antigens that could find application in vaccine development, and provides new insights into PE/PPE biology. PMID:22870206

  12. Treatment Experience of Severe Abdominal Infection after Orthotopic Liver Transplantation

    PubMed Central

    Wang, Y-G; Wu, J-S; Jiang, B; Wang, J-H; Liu, C-P; Peng, C; Tian, B-Z

    2015-01-01

    ABSTRACT This study aims to investigate the causes and treatment experience of severe abdominal infection after orthotopic liver transplantation. Clinical data were retrospectively analysed in perioperative severe abdominal infection of 186 orthotopic liver transplantation cases from March 2004 to November 2011. Among the 186 patients, 16 cases had severe abdominal infection: five cases had bile duct anastomotic leakage-inducing massive hydrops and infection under liver interstice, 10 cases had extensive bleeding of surgical wound leading to massive haematocele and infection around the liver, and one case had postoperative lower oesophageal fistula leakage causing massive hydrops and infection under the left diaphragm. After definite diagnosis, 12 cases underwent surgery within three days, with no death. Among the four cases that underwent surgery three days after diagnosis, one case died of multiple-organ failure five days after abdominal cavity exploration, which was performed 21 days after liver transplantation. Severe abdominal infections after liver transplantation were the most common causes of death in perioperative liver transplantation. Comprehensive treatment with efficacious antibiotics, multiple-organ support, controlled surgical removal of the lesion, and adequate drainage establishment was the key to the entire treatment. PMID:26426173

  13. Mycobacterium tuberculosis Rv1265 promotes mycobacterial intracellular survival and alters cytokine profile of the infected macrophage.

    PubMed

    Luo, Hongping; Zeng, Jie; Huang, Qinqin; Liu, Minqiang; Abdalla, Abualgasim Elgaili; Xie, Longxiang; Wang, Huan; Xie, Jianping

    2016-03-01

    Mycobacterium tuberculosis cAMP and underlying regulatory network are crucial for its survival and thrive in the presence of numerous stresses mounted by the host. Our studies mainly focus on the cAMP-induced M. tuberculosis gene Rv1265, which was shown to be up-regulated under hypoxia and during macrophage infection by addition of exogenous cAMP. To explore the role of Rv1265 in host-pathogen interactions, Rv1265 was expressed in a non-pathogenic Mycobacterium smegmatis. We found that Rv1265 was associated with cell envelope and can up-regulate some cell wall fatty acid components, especially the C26:0. The survival of the recombinant Ms_Rv1265 was enhanced within macrophages and under stress conditions such as low pH and SDS. Macrophages infected with Ms_Rv1265 increased transcription of pro-inflammatory cytokines IL-1β, IL-6, and IL-12 P40 and anti-inflammatory cytokine IL-10 possibly through activation of NF-κB and ERK1/2 pathway. Our findings indicate that Rv1265 can enhance mycobacterial survival within macrophages, and perturb the cytokine profile of macrophage. PMID:26156642

  14. Thioridazine in PLGA nanoparticles reduces toxicity and improves rifampicin therapy against mycobacterial infection in zebrafish.

    PubMed

    Vibe, Carina Beatrice; Fenaroli, Federico; Pires, David; Wilson, Steven Ray; Bogoeva, Vanya; Kalluru, Raja; Speth, Martin; Anes, Elsa; Griffiths, Gareth; Hildahl, Jon

    2016-08-01

    Encapsulating antibiotics such as rifampicin in biodegradable nanoparticles provides several advantages compared to free drug administration, including reduced dosing due to localized targeting and sustained release. Consequently, these characteristics reduce systemic drug toxicity. However, new nanoformulations need to be tested in complex biological systems to fully characterize their potential for improved drug therapy. Tuberculosis, caused by infection with the bacterium Mycobacterium tuberculosis, requires lengthy and expensive treatment, and incomplete therapy contributes to an increasing incidence of drug resistance. Recent evidence suggests that standard therapy may be improved by combining antibiotics with bacterial efflux pump inhibitors, such as thioridazine. However, this drug is difficult to use clinically due to its toxicity. Here, we encapsulated thioridazine in poly(lactic-co-glycolic) acid nanoparticles and tested them alone and in combination with rifampicin nanoparticles, or free rifampicin in macrophages and in a zebrafish model of tuberculosis. Whereas free thioridazine was highly toxic in both cells and zebrafish embryos, after encapsulation in nanoparticles no toxicity was detected. When combined with rifampicin nanoparticles, the nanoparticles loaded with thioridazine gave a modest increase in killing of both Mycobacterium bovis BCG and M. tuberculosis in macrophages. In the zebrafish, the thioridazine nanoparticles showed a significant therapeutic effect in combination with rifampicin by enhancing embryo survival and reducing mycobacterial infection. Our results show that the zebrafish embryo is a highly sensitive indicator of drug toxicity and that thioridazine nanoparticle therapy can improve the antibacterial effect of rifampicin in vivo. PMID:26573343

  15. Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.

    PubMed

    Garza-Cuartero, L; O'Sullivan, J; Blanco, A; McNair, J; Welsh, M; Flynn, R J; Williams, D; Diggle, P; Cassidy, J; Mulcahy, G

    2016-07-01

    Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has an annual incidence in cattle of 0.5% in the Republic of Ireland and 4.7% in the UK, despite long-standing eradication programmes being in place. Failure to achieve complete eradication is multifactorial, but the limitations of diagnostic tests are significant complicating factors. Previously, we have demonstrated that Fasciola hepatica infection, highly prevalent in these areas, induced reduced sensitivity of the standard diagnostic tests for BTB in animals co-infected with F. hepatica and M. bovis. This was accompanied by a reduced M. bovis-specific Th1 immune response. We hypothesized that these changes in co-infected animals would be accompanied by enhanced growth of M. bovis. However, we show here that mycobacterial burden in cattle is reduced in animals co-infected with F. hepatica. Furthermore, we demonstrate a lower mycobacterial recovery and uptake in blood monocyte-derived macrophages (MDM) from F. hepatica-infected cattle which is associated with suppression of pro-inflammatory cytokines and a switch to alternative activation of macrophages. However, the cell surface expression of TLR2 and CD14 in MDM from F. hepatica-infected cattle is increased. These findings reflecting the bystander effect of helminth-induced downregulation of pro-inflammatory responses provide insights to understand host-pathogen interactions in co-infection. PMID:27108767

  16. 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

  17. Use of siRNA molecular beacons to detect and attenuate mycobacterial infection in macrophages

    PubMed Central

    George, Remo; Cavalcante, Renata; Jr, Celso Carvalho; Marques, Elyana; Waugh, Jonathan B; Unlap, M Tino

    2015-01-01

    Tuberculosis is one of the leading infectious diseases plaguing mankind and is mediated by the facultative pathogen, Mycobacterium tuberculosis (MTB). Once the pathogen enters the body, it subverts the host immune defenses and thrives for extended periods of time within the host macrophages in the lung granulomas, a condition called latent tuberculosis (LTB). Persons with LTB are prone to reactivation of the disease when the body’s immunity is compromised. Currently there are no reliable and effective diagnosis and treatment options for LTB, which necessitates new research in this area. The mycobacterial proteins and genes mediating the adaptive responses inside the macrophage is largely yet to be determined. Recently, it has been shown that the mce operon genes are critical for host cell invasion by the mycobacterium and for establishing a persistent infection in both in vitro and in mouse models of tuberculosis. The YrbE and Mce proteins which are encoded by the MTB mce operons display high degrees of homology to the permeases and the surface binding protein of the ABC transports, respectively. Similarities in structure and cell surface location impute a role in cell invasion at cholesterol rich regions and immunomodulation. The mce4 operon is also thought to encode a cholesterol transport system that enables the mycobacterium to derive both energy and carbon from the host membrane lipids and possibly generating virulence mediating metabolites, thus enabling the bacteria in its long term survival within the granuloma. Various deletion mutation studies involving individual or whole mce operon genes have shown to be conferring varying degrees of attenuation of infectivity or at times hypervirulence to the host MTB, with the deletion of mce4A operon gene conferring the greatest degree of attenuation of virulence. Antisense technology using synthetic siRNAs has been used in knocking down genes in bacteria and over the years this has evolved into a powerful tool for

  18. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that 'd T cells from virulent M. bovis infected cattle respond specifically and directly to complex, protein and non-protein mycobacterial anti...

  19. Rituximab as Successful Adjunct Treatment in a Patient With Disseminated Nontuberculous Mycobacterial Infection Due to Acquired Anti–Interferon-γ Autoantibody

    PubMed Central

    Czaja, Christopher A.; Merkel, Patricia A.; Chan, Edward D.; Lenz, Laurel L.; Wolf, Molly L.; Alam, Rafeul; Frankel, Stephen K.; Fischer, Aryeh; Gogate, Shaila; Perez-Velez, Carlos M.; Knight, Vijaya

    2014-01-01

    An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection. PMID:24336756

  20. A Novel Inhibitor of Gyrase B Is a Potent Drug Candidate for Treatment of Tuberculosis and Nontuberculosis Mycobacterial Infections

    PubMed Central

    Jones, Steven M.; Hanzelka, Brian L.; Perola, Emanuele; Shoen, Carolyn M.; Cynamon, Michael H.; Ngwane, Andile H.; Wiid, Ian J.; van Helden, Paul D.; Betoudji, Fabrice; Nuermberger, Eric L.; Thomson, John A.

    2014-01-01

    New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of Mycobacterium tuberculosis in vitro (MICs of 0.03 to 0.30 μg/ml and 0.08 to 5.48 μg/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice in vivo. VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant M. tuberculosis bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of Mycobacterium abscessus, Mycobacterium avium complex, and Mycobacterium kansasii (MICs of 0.1 to 2.0 μg/ml), as well as that of several strains of Nocardia spp. (MICs of 0.1 to 1.0 μg/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of M. tuberculosis than did VXc-486 in vivo. In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized M. tuberculosis infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections. PMID:25534737

  1. A novel inhibitor of gyrase B is a potent drug candidate for treatment of tuberculosis and nontuberculosis mycobacterial infections.

    PubMed

    Locher, Christopher P; Jones, Steven M; Hanzelka, Brian L; Perola, Emanuele; Shoen, Carolyn M; Cynamon, Michael H; Ngwane, Andile H; Wiid, Ian J; van Helden, Paul D; Betoudji, Fabrice; Nuermberger, Eric L; Thomson, John A

    2015-03-01

    New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of Mycobacterium tuberculosis in vitro (MICs of 0.03 to 0.30 μg/ml and 0.08 to 5.48 μg/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice in vivo. VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant M. tuberculosis bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of Mycobacterium abscessus, Mycobacterium avium complex, and Mycobacterium kansasii (MICs of 0.1 to 2.0 μg/ml), as well as that of several strains of Nocardia spp. (MICs of 0.1 to 1.0 μg/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of M. tuberculosis than did VXc-486 in vivo. In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized M. tuberculosis infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections. PMID:25534737

  2. Diphyllobothrium latum infection in a child with recurrent abdominal pain

    PubMed Central

    Lee, Seung Hyun; Park, Hyun

    2015-01-01

    Diphyllobothrium latum infection in humans is not common in Republic of Korea. We report a case of fish tapeworm infection in a 10-year-old boy after ingestion of raw perch about 8 months ago. The patient complained of recurrent abdominal pain and watery diarrhea. A tapeworm, 85 cm in length, without scolex and neck, was spontaneously discharged in the feces of the patient. The patient was treated with 15-mg/kg single dose praziquantel, and follow-up stool examination was negative after one month. There was no evidence of relapse during the next six months. PMID:26692882

  3. Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections ▿ †

    PubMed Central

    Plain, Karren M.; de Silva, Kumudika; Earl, John; Begg, Douglas J.; Purdie, Auriol C.; Whittington, Richard J.

    2011-01-01

    Virulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases. Mycobacterium avium subsp. paratuberculosis is an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased in M. avium subsp. paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells of M. avium subsp. paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses to M. avium subsp. paratuberculosis and other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease. PMID:21730087

  4. MUSASHI-Mediated Expression of JMJD3, a H3K27me3 Demethylase, Is Involved in Foamy Macrophage Generation during Mycobacterial Infection

    PubMed Central

    Singh, Vikas; Karnam, Anupama; Mukherjee, Tanushree; Mahadik, Kasturi; Parikh, Pankti; Singh, Amit; Rajmani, R. S.; Ramachandra, Subbaraya G.; Balaji, Kithiganahalli Narayanaswamy

    2016-01-01

    Foamy macrophages (FM)s harbor lipid bodies that not only assist mycobacterial persistence within the granulomas but also are sites for intracellular signaling and inflammatory mediators which are essential for mycobacterial pathogenesis. However, molecular mechanisms that regulate intracellular lipid accumulation in FMs during mycobacterial infection are not clear. Here, we report for the first time that jumonji domain containing protein (JMJD)3, a demethylase of the repressive H3K27me3 mark, orchestrates the expression of M. tuberculosis H37Rv-, MDR-JAL2287-, H37Ra- and M. bovis BCG-induced genes essential for FM generation in a TLR2-dependent manner. Further, NOTCH1-responsive RNA-binding protein MUSASHI (MSI), targets a transcriptional repressor of JMJD3, Msx2-interacting nuclear target protein, to positively regulate infection-induced JMJD3 expression, FM generation and M2 phenotype. Investigations in in vivo murine models further substantiated these observations. Together, our study has attributed novel roles for JMJD3 and its regulators during mycobacterial infection that assist FM generation and fine-tune associated host immunity. PMID:27532872

  5. MUSASHI-Mediated Expression of JMJD3, a H3K27me3 Demethylase, Is Involved in Foamy Macrophage Generation during Mycobacterial Infection.

    PubMed

    Holla, Sahana; Prakhar, Praveen; Singh, Vikas; Karnam, Anupama; Mukherjee, Tanushree; Mahadik, Kasturi; Parikh, Pankti; Singh, Amit; Rajmani, R S; Ramachandra, Subbaraya G; Balaji, Kithiganahalli Narayanaswamy

    2016-08-01

    Foamy macrophages (FM)s harbor lipid bodies that not only assist mycobacterial persistence within the granulomas but also are sites for intracellular signaling and inflammatory mediators which are essential for mycobacterial pathogenesis. However, molecular mechanisms that regulate intracellular lipid accumulation in FMs during mycobacterial infection are not clear. Here, we report for the first time that jumonji domain containing protein (JMJD)3, a demethylase of the repressive H3K27me3 mark, orchestrates the expression of M. tuberculosis H37Rv-, MDR-JAL2287-, H37Ra- and M. bovis BCG-induced genes essential for FM generation in a TLR2-dependent manner. Further, NOTCH1-responsive RNA-binding protein MUSASHI (MSI), targets a transcriptional repressor of JMJD3, Msx2-interacting nuclear target protein, to positively regulate infection-induced JMJD3 expression, FM generation and M2 phenotype. Investigations in in vivo murine models further substantiated these observations. Together, our study has attributed novel roles for JMJD3 and its regulators during mycobacterial infection that assist FM generation and fine-tune associated host immunity. PMID:27532872

  6. Clinical features and outcomes of Sweet's syndrome associated with non-tuberculous mycobacterial infection and other associated diseases.

    PubMed

    Chaowattanapanit, Suteeraporn; Choonhakarn, Charoen; Chetchotisakd, Ploenchan; Sawanyawisuth, Kittisak; Julanon, Narachai

    2016-05-01

    Sweet's syndrome (SS) is associated with various diseases including non-tuberculous mycobacterial infection (NTM). Recent reports have shown that SS associated with NTM is increasing. Clinical features of SS associated with NTM may be different from SS associated with other associated diseases. The aim of the present study was to compare clinical parameters and treatment outcomes of SS associated with NTM and other associated diseases. Patients from January 2004 to April 2014 diagnosed with SS were retrospectively enrolled. Clinical variables were compared between SS patients with and without NTM infection. There were 51 SS patients during the study period; 36 patients (70.59%) had NTM. Clinical variables between the NTM and other associated diseases were comparable: age, sex, and pattern and locations of skin lesions. Five laboratory factors were significantly different between the groups including white blood cell counts (NTM 25 800 vs 12 850 cells/mm(3) ), lymphocyte percentages (13.0% vs 18.7%), monocytes (3.0% vs 7.2%), blood urea nitrogen (BUN) (11.7 vs 8.1 mg/dL) and serum creatinine (Cr) (1.0 vs 0.7 mg/dL). The presence of markedly high white blood cell counts, a low percentage of mononuclear cells and high BUN/Cr levels in SS may be a clinical clue to recognize the association with NTM infections; particularly in dissemination. PMID:27109150

  7. In vivo gammadelta T cell priming to mycobacterial antigens by primary Mycobacterium tuberculosis infection and exposure to nonpeptidic ligands.

    PubMed Central

    Poccia, F.; Malkovsky, M.; Pollak, A.; Colizzi, V.; Sireci, G.; Salerno, A.; Dieli, F.

    1999-01-01

    BACKGROUND: The recognition of phosphorylated nonpeptidic microbial metabolites by Vgamma9Vdelta2 T cells does not appear to require the presence of MHC molecules or antigen processing, permitting rapid responses against microbial pathogens. These may constitute an important area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vgamma9Vdelta2 T cells in children with primary Mycobacterium tuberculosis (MTB) infections. MATERIALS AND METHODS: Peripheral blood mononuclear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vitro and the reactivity of the Vgamma9Vdelta2 T cell subset with these antigens was determined using proliferation and cytokine assays. Also, responses of gammadelta T cells from rhesus monkeys stimulated with phosphoantigens in vivo were measured. RESULTS: The Vgamma9Vdelta2 T cell responses were highly increased in infected children in comparison with age-matched controls. This augmented Vgamma9Vdelta2 T cell reactivity subsided after successful antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of gammadelta T cell activation in vivo. The in vivo reactivity of Vgamma9Vdelta2 T cells to phosphoantigens was also analyzed in a rhesus monkey model system. Intravenous injections of phosphoantigens induced an activated state of simian Vgamma9Vdelta2 T cells which decreased after 2 months, i.e., with a time course similar to that seen in MTB-infected children. CONCLUSIONS: The increased reactivity of Vgamma9Vdelta2 T cells to phosphoantigens appears to be dependent on constant antigenic exposure. Consequently, the assessment of Vgamma9Vdelta2 responses may be useful for monitoring the efficacy of antimycobacterial therapies. PMID:10449808

  8. 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

  9. Recognition of Stage-Specific Mycobacterial Antigens Differentiates between Acute and Latent Infections with Mycobacterium tuberculosis

    PubMed Central

    Demissie, Abebech; Leyten, Eliane M. S.; Abebe, Markos; Wassie, Liya; Aseffa, Abraham; Abate, Getahun; Fletcher, Helen; Owiafe, Patrick; Hill, Philip C.; Brookes, Roger; Rook, Graham; Zumla, Alimuddin; Arend, Sandra M.; Klein, Michel; Ottenhoff, Tom H. M.; Andersen, Peter; Doherty, T. Mark

    2006-01-01

    Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or α-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB. PMID:16467323

  10. [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. PMID:21440389

  11. 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

  12. Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis.

    PubMed

    Deng, Yating; Ye, Jianqing; 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

  13. Health-related quality of life, comorbidities and mortality in pulmonary nontuberculous mycobacterial infections: A systematic review.

    PubMed

    Yeung, Man Wah; Khoo, Edwin; Brode, Sarah K; Jamieson, Frances B; Kamiya, Hiroyuki; Kwong, Jeffrey C; Macdonald, Liane; Marras, Theodore K; Morimoto, Kozo; Sander, Beate

    2016-08-01

    Nontuberculous mycobacterial (NTM) infections are increasing in disease frequency worldwide. This systematic review examines health-related quality of life (HRQOL), comorbidities and mortality associated with pulmonary NTM disease. We searched MEDLINE, EMBASE, CINAHL, Scopus Life Sciences, conference proceedings and Google (earliest date available to February 2015) for primary studies. Eligible studies compared populations with and without pulmonary NTM disease in high-income jurisdictions. We excluded studies on HIV/AIDS. All languages were accepted. Two reviewers followed MOOSE and PRISMA reporting guidelines and independently appraised quality using STROBE. All studies were summarized qualitatively regardless of quality. Of 3193 citations screened, we included 17 studies mostly from Taiwan (n = 5) and the USA (n = 4). Two studies assessed HRQOL; one assessed comorbidities, 11 assessed mortality, and three assessed multiple outcomes. Populations with pulmonary NTM reported significantly worse or similar HRQOL than the general population, depending on the instruments used. Some suggested greater prevalence of having bronchiectasis (n = 2) and greater risk of developing pulmonary tuberculosis (n = 1). Most (n = 7) suggested no difference in mortality, although only one was age-matched and gender-matched to the general population. Four suggested NTM populations had higher mortality-two of which compared with the general population and were deemed of high quality, while two compared with non-NTM patients from hospital. High clinical heterogeneity in study design may explain discordant results. Bias assessments and controlling for confounding were carried out poorly. No consistent trends were observed although there is suggestion of an increased health burden from respiratory diseases and increased mortality associated with pulmonary NTM disease. PMID:27009804

  14. 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

  15. 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. PMID:26660641

  16. The looming tide of nontuberculous mycobacterial infections in Portugal and Brazil.

    PubMed

    Nunes-Costa, Daniela; Alarico, Susana; Dalcolmo, Margareth Pretti; Correia-Neves, Margarida; Empadinhas, Nuno

    2016-01-01

    Nontuberculous mycobacteria (NTM) are widely disseminated in the environment and an emerging cause of infectious diseases worldwide. Their remarkable natural resistance to disinfectants and antibiotics and an ability to survive under low-nutrient conditions allows NTM to colonize and persist in man-made environments such as household and hospital water distribution systems. This overlap between human and NTM environments afforded new opportunities for human exposure, and for expression of their often neglected and underestimated pathogenic potential. Some risk factors predisposing to NTM disease have been identified and are mainly associated with immune fragilities of the human host. However, infections in apparently immunocompetent persons are also increasingly reported. The purpose of this review is to bring attention to this emerging health problem in Portugal and Brazil and to emphasize the urgent need for increased surveillance and more comprehensive epidemiological data in both countries, where such information is scarce and seriously thwarts the adoption of proper preventive strategies and therapeutic options. PMID:26560840

  17. Bacteriology and drug susceptibility analysis of pus from patients with severe intra-abdominal infection induced by abdominal trauma

    PubMed Central

    ZHANG, SHAOYI; REN, LELE; LI, YOUSHENG; WANG, JIAN; YU, WENKUI; LI, NING; LI, JIESHOU

    2014-01-01

    The aim of the present study was to retrospectively analyze the bacteriology and drug susceptibility of pus flora from abdominal trauma patients with severe intra-abdominal infection (SIAI). A total of 41 patients with SIAI induced by abdominal trauma were enrolled in the study, from which 123 abdominal pus samples were obtained. The results from laboratory microbiology and drug sensitivity were subjected to susceptibility analysis using WHONET software. A total of 297 strains were isolated in which Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 53.5 (159/297), 44.1 (131/297) and 0.7% (2/297), respectively. Anaerobic bacteria accounted for 1.7%. The five predominant bacteria were Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis and Pseudomonas aeruginosa (P. aeruginosa). E. coli was highly susceptible to cefoperazone (91%) and imipenem (98%), while Gram-positive cocci were highly susceptible to teicoplanin (100%) and linezolid (100%). S. aureus was 100% susceptible to vancomycin and K. pneumoniae was highly susceptible to imipenem (100%) and amikacin (79%). P. aeruginosa was the most susceptible to ciprofloxacin (90%). Gram-negative bacterial infection was present in the majority of cases of SIAI. However, a large number of patients were infected by Gram-positive bacteria, particularly S. aureus that exhibited significant resistance to penicillin (100%), oxacillin (100%) and a third-generation cephalosporin antibiotic cefotaxime (95%). Amongst the pathogenic bacteria that cause SIAI, both Gram-negative and Gram-positive bacteria account for a high proportion, so high-level and broad-spectrum antibiotics should be initially used. PMID:24940451

  18. Infected abdominal aortic aneurysm caused by nontyphoid Salmonella in an immunocompromised patient with rheumatoid arthritis.

    PubMed

    Kaneko, Kayoko; Nonomura, Yoshinori; Watanabe, Kaori; Koike, Ryuji; Kubota, Tetsuo; Harigai, Masayoshi; Inoue, Yoshinori; Iwai, Takehisa; Miyasaka, Nobuyuki

    2009-10-01

    Nontyphoid Salmonella strains are important pathogens commonly found worldwide, typically causing gastrointestinal illness. Here, we report a case of a 66-yearold man with an abdominal aortic infected (or so-called mycotic) aneurysm caused by Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis). He had multiple risk factors for atherosclerosis: age over 60, a long history of smoking, an 8-year history of diabetes mellitus, and a 10-year history of rheumatoid arthritis treated with low-dose corticosteroids. Although he had presented with no episode of diarrhea or abdominal pain, the abdominal aortic infected aneurysm was diagnosed by blood cultures and was carefully followed up by computed tomography. An abdominal aneurysmectomy and autogenous in situ reconstruction were successfully performed consequently. Alertness to the possibility of endovascular infection is important, even if there are no symptoms except for persistent fever, when treating Salmonella bacteremia in an immunocompromised patient, particularly when there are associated atherosclerotic risk factors. PMID:19856069

  19. Mycobacterial truncated hemoglobins: from genes to functions.

    PubMed

    Ascenzi, Paolo; Bolognesi, Martino; Milani, Mario; Guertin, Michel; Visca, Paolo

    2007-08-15

    Infections caused by bacteria belonging to genus Mycobacterium are among the most challenging threats for human health. The ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of effective detoxification mechanisms. Mycobacterial truncated hemoglobins (trHbs) have recently been implicated in scavenging of reactive nitrogen species. Individual members from each trHb family (N, O, and P) can be present in the same mycobacterial species. The distinct features of the heme active site structure combined with different ligand binding properties and in vivo expression patterns of mycobacterial trHbs suggest that these globins may accomplish diverse functions. Here, recent genomic, structural and biochemical information on mycobacterial trHbs is reviewed, with the aim of providing further insights into the role of these globins in mycobacterial physiology. PMID:17532149

  20. Lack of IL-1 Receptor-Associated Kinase-4 Leads to Defective Th1 Cell Responses and Renders Mice Susceptible to Mycobacterial Infection.

    PubMed

    Marinho, Fábio V; Fahel, Júlia S; Scanga, Charles A; Gomes, Marco Tulio R; Guimarães, Gabriela; Carvalho, Gabrielle R M; Morales, Stefanny V; Báfica, André; Oliveira, Sergio Costa

    2016-09-01

    The Toll-like and IL-1 family receptors play critical roles in innate and adaptive immunity against intracellular pathogens. Although previous data demonstrated the importance of TLRs and IL-1R signaling events for the establishment of an effective immune response to mycobacteria, the possible function of the adaptor molecule IL-1R-associated kinase (IRAK)-4 against this pathogen has not been addressed. In this study, we determined the role of IRAK-4 in signaling pathways responsible for controlling mycobacterial infections. This kinase is important for the production of IL-12 and TNF-α by macrophages and dendritic cells exposed to mycobacteria. Moreover, Mycobacterium bovis-infected IRAK-4-knockout macrophages displayed impaired MAPK and NF-κB activation. IL-1β secretion and caspase-1 activation were also dependent on IRAK-4 signaling. Mice lacking IRAK-4 showed increased M. bovis burden in spleen, liver, and lungs and smaller liver granulomas during 60 d of infection compared with wild-type mice. Furthermore, 80% of IRAK-4(-/-) mice succumbed to virulent M. tuberculosis within 100 d following low-dose infection. This increased susceptibility to mycobacteria correlated with reduced IFN-γ/TNF-α recall responses by splenocytes, as well as fewer IL-12p70-producing APCs. Additionally, we observed that IRAK-4 is also important for the production of IFN-γ by CD4(+) T cells from infected mice. Finally, THP-1 cells treated with an IRAK-4 inhibitor and exposed to M. bovis showed reduced TNF-α and IL-12, suggesting that the results found in mice can be extended to humans. In summary, these data demonstrate that IRAK-4 is essential for innate and adaptive immunity and necessary for efficient control of mycobacterial infections. PMID:27439514

  1. Nontuberculous mycobacterial osteomyelitis

    PubMed Central

    Bi, Sheng; Hu, Fei-Shu; Yu, Hai-Ying; Xu, Kai-Jin; Zheng, Bei-Wen; Ji, Zhong-Kang; Li, Jun-Jie; Deng, Mei; Hu, Hai-Yang; Sheng, Ji-Fang

    2015-01-01

    Abstract Osteomyelitis caused by nontuberculous mycobacteria (NTM) can have severe consequences and a poor prognosis. Physicians therefore need to be alert to this condition, especially in immunocompromised patients. Although the pathogenesis of NTM osteomyelitis is still unclear, studies in immunodeficient individuals have revealed close relationships between NTM osteomyelitis and defects associated with the interleukin-12–interferon-γ–tumor necrosis factor-α axis, as well as human immunodeficiency virus infection, various immunosuppressive conditions, and diabetes mellitus. Culture and species identification from tissue biopsies or surgical debridement tissue play crucial roles in diagnosing NTM osteomyelitis. Suitable imaging examinations are also important. Adequate surgical debridement and the choice of appropriate, combined antibiotics for long-term anti-mycobacterial chemotherapy, based on in vitro drug susceptibility tests, are the main therapies for these bone infections. Bacillus Calmette–Guerin vaccination might have limited prophylactic value. The use of multiple drugs and long duration of treatment mean that the therapeutic process needs to be monitored closely to detect potential side effects. Adequate duration of anti-mycobacterial chemotherapy together with regular monitoring with blood and imaging tests are key factors determining the recovery outcome in patients with NTM osteomyelitis. PMID:25915177

  2. Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFα blockers

    PubMed Central

    Gomes, Carina Mori Frade; Terreri, Maria Teresa; de Moraes-Pinto, Maria Isabel; Barbosa, Cássia; Machado, Natália Pereira; Melo, Maria Roberta; Pinheiro, Marcelo Medeiros

    2015-01-01

    Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)α blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNF α blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNF α therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNF α blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI. PMID:26560983

  3. Mycobacterial culture

    MedlinePlus

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

  4. Varicella Zoster Infection: A Rare Cause of Abdominal Pain Mimicking Acute Abdomen

    PubMed Central

    Olmez, Deniz; Boz, Alper; Erkan, Nazif

    2009-01-01

    Varicella zoster is an acute viral infection that results from reactivation of a latent varicella zoster virus. It usually occurs in adult population and immune compromised patients. It rarely occurs in healthy children. Here we present a 14 years old male with varicella zoster that had abdominal pain mimicking acute abdomen to alert others who are consulted for the differentiation of acute abdomen and others who may be consulted for pain management. Keywords Varicella zoster; Abdominal pain PMID:22461879

  5. A mycotic abdominal aortic aneurysm caused by Listeria monocytogenes in a patient with HIV infection

    PubMed Central

    Gunst, Jesper Damsgaard; Jensen-Fangel, Søren

    2014-01-01

    A 65-year-old man with HIV infection presented with acute severe abdominal pain radiating to the back. A CT scan revealed an infrarenal abdominal aortic aneurysm, and an aortobifemoral bypass was undertaken. Subsequently, tissue specimens from the aortic wall grew Listeria monocytogenes. The patient received 8 weeks of intravenous antibiotic treatment followed by oral sulfotrim as secondary prophylaxis and made an uneventful recovery. PMID:24443338

  6. A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens

    PubMed Central

    Baumann, Ralf; Kaempfer, Susanne; Chegou, Novel N.; Oehlmann, Wulf; Spallek, Ralf; Loxton, André G.; van Helden, Paul D.; Black, Gillian F.; Singh, Mahavir; Walzl, Gerhard

    2015-01-01

    Elevated antibody responses to Mycobacterium tuberculosis antigens in individuals with latent infection (LTBI) have previously been linked to an increased risk for progression to active disease. Studies in the field focussed mainly on IgG antibodies. In the present study, IgA and/or IgG responses to the mycobacterial protein antigens AlaDH, NarL, 19 kDa, PstS3, and MPT83 were determined in a blinded fashion in sera from 53 LTBI controls, 14 healthy controls, and 42 active TB subjects. Among controls, we found that elevated IgA levels against all investigated antigens were not randomly distributed but concentrated on a subgroup of <30%—with particular high levels in a small subgroup of ~5% comprising one progressor to active TB. Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls. In conclusion, the consistently elevated IgA levels in a subgroup of controls suggest higher mycobacterial load, a risk factor for progression to active TB, and together with high IgG levels may have prognostic potential and should be investigated in future large scale studies. The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases. PMID:26347586

  7. WSES consensus conference: Guidelines for first-line management of intra-abdominal infections

    PubMed Central

    2011-01-01

    Intra-abdominal infections are still associated with high rate of morbidity and mortality. A multidisciplinary approach to the management of patients with intra-abdominal infections may be an important factor in the quality of care. The presence of a team of health professionals from various disciplines, working in concert, may improve efficiency, outcome, and the cost of care. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bologna on July 2010, during the 1st congress of the WSES, involving surgeons, infectious disease specialists, pharmacologists, radiologists and intensivists with the goal of defining recommendations for the early management of intra-abdominal infections. This document represents the executive summary of the final guidelines approved by the consensus conference. PMID:21232143

  8. Aortoiliac Artery Reconstruction Using Bilateral Reversed Superficial Femoral Veins for an Infected Abdominal Aortic Aneurysm

    PubMed Central

    Hirai, Hanako; Yasuhara, Kiyomitsu; Hatori, Kyohei; Miki, Takao; Obayashi, Tamiyuki

    2016-01-01

    Surgical treatment of an infected abdominal aortic aneurysm (IAAA) is difficult and the ideal graft material is a subject of debate. A 60-year-old man with untreated diabetes mellitus was referred to our hospital presenting with fever and left lower abdominal pain. The patient was diagnosed with an IAAA by blood culture and computed tomography. We treated the patient surgically for the IAAA using bilateral reversed superficial femoral veins which were shaped into a bifurcated graft. No signs of recurrent infection or aneurysmal dilation were observed for 3 years after the procedure. PMID:27087879

  9. Cutaneous infection with rapidly-growing mycobacterial infection following heart transplant: a case report and review of the literature.

    PubMed

    Freudenberger, R S; Simafranca, S M

    2006-06-01

    Nontuberculous mycobacteria are ubiquitous and infrequently cause disease in humans, most commonly in immunocompromised hosts. One type of nontuberculous mycobacteria is Mycobacterium abscessus. This rapidly growing mycobacterium is a soil or water saprophyte. It was previously classified as a subspecies of Mycobacterium chelonae; however, current taxonomy now designates it as a separate species. Rapidly growing mycobacteria are resistant to the usual antituberculous drugs. This emphasizes the need for tissue diagnosis and obtaining specimens for culture and drug susceptibility testing. M abscessus has been reported to cause infection in renal transplant patients, but is less well described in cardiac transplant recipients. We report the case of a 65-year-old man who presented 5 years after transplantation for heart failure, with a 2-day history of progressive right lower extremity swelling and redness. He recalled no antecedent trauma and denied any unusual epidemiologic exposure. Medical history included diabetes with peripheral neuropathy and renal insufficiency, hypertension, and right-sided heart failure felt to be due to obstructive sleep apnea. A punch biopsy of the area grew M abscessus sensitive only to clarithromycin (MIC not reported), amikacin (30 microg/mL), and kanamycin (30 microg/mL). On subsequent clinic visits, the patient had decreased leg swelling and resolution of the papular lesions. Ten weeks into antimycobacterial therapy, the patient had an increase in creatinine to 4.9 mg/dL from a baseline of 2.0 with fluid overload necessitating discontinuation of aminoglycoside therapy. He completed 6 months of treatment with oral clarithromycin. We describe these findings and review the literature in this report. PMID:16797350

  10. 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. PMID:26577130

  11. Disseminated Bacillus Calmette-Guérin and Susceptibility to Mycobacterial Infections-Implications on Bacillus Calmette-Guérin Vaccinations.

    PubMed

    Lee, Pamela Pw

    2015-08-01

    Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised. PMID:26477962

  12. Poor oncologic outcomes of hepatocellular carcinoma patients with intra-abdominal infection after hepatectomy

    PubMed Central

    Ruan, Dan-Yun; Lin, Ze-Xiao; Li, Yang; Jiang, Nan; Li, Xing; Wu, Dong-Hao; Wang, Tian-Tian; Chen, Jie; Lin, Qu; Wu, Xiang-Yuan

    2015-01-01

    AIM: To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy. METHODS: We performed a retrospective analysis of 200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September 2003 and June 2011. The patients’ demographics, clinicopathological characteristics and postoperative infectious complications were analyzed. The Clavien-Dindo classification was adopted to assess the severity of complications. The dynamic change in the neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided by the absolute lymphocyte count, after surgery was also investigated. The observation endpoints for this study were recurrence-free survival and overall survival of the patients. Statistical analysis of the survival curves was performed using the Kaplan-Meier method and the log-rank test. The prognostic value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. The cutoff score for each variable was selected based on receiver operating characteristic curve analysis. All statistical tests were two-sided, and significance was set at P < 0.05. RESULTS: The median age of the patients was 49 years, and the majority of patients were male (86%) and had been infected with hepatitis B virus (86%). The 30-d postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (P < 0.001). The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group (P < 0.001). A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis (P = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026). The patients who had an elevated postoperative neutrophil

  13. RP105 Engages Phosphatidylinositol 3-Kinase p110δ To Facilitate the Trafficking and Secretion of Cytokines in Macrophages during Mycobacterial Infection.

    PubMed

    Yu, Chien-Hsiung; Micaroni, Massimo; Puyskens, Andreas; Schultz, Thomas E; Yeo, Jeremy Changyu; Stanley, Amanda C; Lucas, Megan; Kurihara, Jade; Dobos, Karen M; Stow, Jennifer L; Blumenthal, Antje

    2015-10-15

    Cytokines are key regulators of adequate immune responses to infection with Mycobacterium tuberculosis. We demonstrate that the p110δ catalytic subunit of PI3K acts as a downstream effector of the TLR family member RP105 (CD180) in promoting mycobacteria-induced cytokine production by macrophages. Our data show that the significantly reduced release of TNF and IL-6 by RP105(-/-) macrophages during mycobacterial infection was not accompanied by diminished mRNA or protein expression. Mycobacteria induced comparable activation of NF-κB and p38 MAPK signaling in wild-type (WT) and RP105(-/-) macrophages. In contrast, mycobacteria-induced phosphorylation of Akt was abrogated in RP105(-/-) macrophages. The p110δ-specific inhibitor, Cal-101, and small interfering RNA-mediated knockdown of p110δ diminished mycobacteria-induced TNF secretion by WT but not RP105(-/-) macrophages. Such interference with p110δ activity led to reduced surface-expressed TNF in WT but not RP105(-/-) macrophages, while leaving TNF mRNA and protein expression unaffected. Activity of Bruton's tyrosine kinase was required for RP105-mediated activation of Akt phosphorylation and TNF release by mycobacteria-infected macrophages. These data unveil a novel innate immune signaling axis that orchestrates key cytokine responses of macrophages and provide molecular insight into the functions of RP105 as an innate immune receptor for mycobacteria. PMID:26371254

  14. Doripenem in hospital infections: a focus on nosocomial pneumonia, complicated intra-abdominal infections, and complicated urinary tract infections.

    PubMed

    Lo, Tze Shien; Borchardt, Stephanie M; Welch, Justin M; Rohrich, Melissa A; Alonto, Augusto M; Alonto, Anne V

    2009-01-01

    Doripenem is the latest carbapenem on the market to date. Although not an antibiotic in a new class, it offers a glimmer of hope in combating serious infections secondary to multidrug-resistant Gram-negative bacteria when we have not seen a new class of antibacterial, particularly for Gram-negative bacteria, for more than 10 years. In vitro, doripenem exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including extended-spectrum β-lactamase (ESBL) and Amp-C β-lactamase producing Enterobacteriaceae and anaerobes. Doripenem also exhibits better in vitro activity against Pseudomonas aeruginosa compared to other anti-pseudomonal carbapenems. It combines the desirable activities of both imipenem and meropenem. It has similar activity to imipenem against Gram-positive pathogens and has the antimicrobial spectrum of meropenem against Gram-negative organisms. Several randomized clinical trials have demonstrated that doripenem is non-inferior to meropenem, imipenem, piperacillin/tazobactam, or levofloxacin in its efficacy and safety profile in treating a wide range of serious bacterial infections including intra-abdominal infection, complicated urinary tract infection, and nosocomial pneumonia. Due to its wide spectrum of activity and good safety profile it is susceptible to misuse leading to increasing rates of resistance. Judicious use should be considered when using doripenem as a first-line agent or drug of choice for serious infections. Doripenem is a well-tolerated drug with common adverse effects including headache, nausea and diarrhea. Caution should be used in patients with hypersensitivity to carbapenems and adverse reactions to β-lactam agents. Dosage adjustment is needed for patients with renal impairment. Doripenem has demonstrated economic and clinical benefits. It has been shown to reduce hospital length of stay and duration of mechanical ventilation for intensive care unit (ICU) patients. Therefore, doripenem is a

  15. Treatment of an Abdominal Aortic Aneurysm Infected by Coxiella Burnetii Using a Cryopreserved Allograft.

    PubMed

    Jayet, Jérémie; Raux, Maxime; Allaire, Eric; Desgranges, Pascal; Cochennec, Frédéric

    2016-05-01

    Q fever is a worldwide zoonosis caused by an intracellular bacillus named Coxiella burnetii (CB) and is a rare cause of vascular infections. We report a case of abdominal aortic aneurysm infected by CB with bilateral paravertebral abscesses and contiguous spondylodiscitis treated by open repair using a cryopreserved allograft and long-term antibiotic therapy by oral doxycycline and oral hydroxychloroquine for a duration of 18 months. Twenty months after the operation, the patient had no infections signs and vascular complication. PMID:26968369

  16. New technique for treating abdominal surgical site infection using CT woundgraphy and NPWT: A case report

    PubMed Central

    Ito, Eisaku; Yoshida, Masashi; Nakashima, Keigo; Suzuki, Norihiko; Imakita, Tomonori; Tsutsui, Nobuhiro; Ohdaira, Hironori; Kitajima, Masaki; Suzuki, Yutaka

    2016-01-01

    Introduction Negative pressure wound therapy (NPWT) for abdominal surgical site infection (SSI) is becoming increasingly common, although enterocutaneous fistula (ECF) has been reported as a complication. To avoid ECF, we used computed tomography (CT) woundgraphy to evaluate the relationship between the wound and the intestine, and then safely treated the abdominal SSI with NPWT. Case presentation Following a laparoscopic intersphincteric resection for low rectal neuroendocrine tumor and covering ileostomy, a 59-year-old woman underwent stoma closure. Six days after surgery, we diagnosed SSI. We suspected ECF, because the wound was deep and the pus resembled enteric fluid. However, CT woundgraphy showed that the wound was separated from the abdominal cavity and the intestine by the abdominal rectus muscle. Accordingly, we performed NPWT. SSI was cured and the wound was well granulated. Twenty-three days after surgery, the patient was discharged. Eventually, the wound was completely epithelialized. Discussion Although successful NPWT has been reported for open abdominal wounds, ECF is a common complication. ECF can be prevented by separating the wound from the intestine by the omentum or muscle fascia, protecting the intestinal serosa during surgery, and applying low vacuum pressure. The relationships among the wound, the fascia, and the intestine must be evaluated before abdominal SSI treatment. One good method is CT woundgraphy, which evaluates wound extent and depth, closure of muscle fascia, and the relationship between the wound and the intestine. Conclusion We report a case of CT woundgraphy before NPWT for abdominal SSI. CT woundgraphy is a good candidate for evaluating wound condition. PMID:27002290

  17. 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; Sakakhushev, 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. PMID:27429642

  18. Laparoscopic management of intra-abdominal infections: Systematic review of the literature

    PubMed Central

    Coccolini, Federico; Tranà, Cristian; Sartelli, Massimo; Catena, Fausto; Saverio, Salomone Di; Manfredi, Roberto; Montori, Giulia; Ceresoli, Marco; Falcone, Chiara; Ansaloni, Luca

    2015-01-01

    AIM: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections. METHODS: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically. RESULTS: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controlling the source. CONCLUSION: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections. PMID:26328036

  19. Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study

    PubMed Central

    2012-01-01

    The CIAO Study (“Complicated Intra-Abdominal infection Observational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012). Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified. The overall mortality rate was 7.5% (163/2.152). According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission. Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe. PMID:23190741

  20. Obesity and the Risk for Surgical Site Infection in Abdominal Surgery.

    PubMed

    Winfield, Robert D; Reese, Stacey; Bochicchio, Kelly; Mazuski, John E; Bochicchio, Grant V

    2016-04-01

    Obesity is a risk factor for surgical site infection (SSI) after abdominal procedures; however, data characterizing the risk of SSI in obese patients during abdominal procedures are lacking. We hypothesized that obesity is an independent risk factor for SSI across wound classes. We analyzed American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data for 2011. We calculated body mass index (BMI), classifying patients according to National Institute of Health (NIH) BMI groups. We excluded records in which height/weight was not recorded and patients with BMI less than 18.5. We examined patients undergoing open abdominal procedures, performing univariate and multivariate analyses to assess the relative contribution of obesity to SSI. Study criteria were met by 89,148 patients. Obese and morbidly obese patients had significantly greater SSI rates in clean and clean-contaminated cases but not contaminated or dirty/infected cases. Logistic regression confirmed obesity and morbid obesity as being independently associated with the overall SSI development, specifically in clean [Obesity odds ratio (OR) = 1.757, morbid obesity OR = 2.544, P < 0.001] and clean-contaminated (obesity OR = 1.239, morbid obesity OR = 1.287, P < 0.001) cases. Obesity is associated with increased risk of SSI overall, specifically in clean and clean-contaminated abdominal procedures; this is independent of diabetes mellitus. Novel techniques are needed to reduce SSI in this high-risk patient population. PMID:27097626

  1. Mycobacterial infections in adult salmon and steelhead trout returning to the Columbia River Basin and other areas in 1957

    USGS Publications Warehouse

    1959-01-01

    The degree of incidence of acid -fast bacillus infections in adult salmonid fishes was determined. The disease was shown to be widely distributed in the area examined. It is believed the primary source of infection is derived from the hatchery practice of feeding infected salmon products to juvenile fish. One group of marked adults that had been hatchery reared for 370 days showed a 62 percent incidence of infection. A statistical analysis indicated that length of fish is independent of infection

  2. [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

  3. [Nontuberculous mycobacterial pulmonary disease].

    PubMed

    Ringshausen, F C; Rademacher, J

    2016-02-01

    Nontuberculous mycobacteria (NTM) are a group of biologically diverse, ubiquitous and naturally multi-drug resistant bacteria with facultative pathogenicity. Recent data suggest that their clinical significance is increasing worldwide and that susceptible individuals may be at risk for infection via contaminated surfaces and aerosols. These individuals often have a predisposition for chronic respiratory diseases, e. g. bronchiectasis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis and these conditions frequently share the same unspecific signs and symptoms with NTM pulmonary disease (NTM-PD). As a consequence, the diagnosis of NTM-PD, which is established based on clinical, radiological and microbiological criteria, is often delayed. Treating NTM-PD is more demanding than treating pulmonary tuberculosis as therapy is generally more tedious, toxic and expensive as well as being prone to failure. Patient and pathogen-specific factors guide the choice of an appropriate antimicrobial combination regimen, which should comply with national and international recommendations. Adverse events are common, should be anticipated and closely monitored. If infections with infrequently encountered mycobacterial species and severe or refractory disease occur, an interdisciplinary approach should be used, involving infectious disease specialists, experienced thoracic surgeons and referral to an NTM specialist center. PMID:26810111

  4. A Case of Continuous Negative Pressure Wound Therapy for Abdominal Infected Lymphocele after Kidney Transplantation

    PubMed Central

    Franchin, Marco; Tozzi, Matteo; Soldini, Gabriele; Piffaretti, Gabriele

    2014-01-01

    Lymphocele is a common complication after kidney transplantation. Although superinfection is a rare event, it generates a difficult management problem; generally, open surgical drainage is the preferred method of treatment but it may lead to complicated postoperative course and prolonged healing time. Negative pressure wound therapy showed promising outcomes in various surgical disciplines and settings. We present a case of an abdominal infected lymphocele after kidney transplantation managed with open surgery and negative pressure wound therapy. PMID:25374744

  5. Acute Abdominal Pain Caused by an Infected Mesenteric Cyst in a 24-Year-Old Female

    PubMed Central

    Ponten, Joep B.; Zijta, Frank M.

    2016-01-01

    A mesenteric cyst is a rare cause for abdominal pain. This umbrella term includes cystic entities which reside in the mesentery. We present a case of an infected false mesenteric cyst in a 24-year-old female patient without prior surgery or known trauma. Mainstay of treatment involves surgical resection, although less invasive treatments have been described. Prognosis depends on the origin of the cyst. PMID:27190668

  6. Selected overview of nongynecologic surgical intra-abdominal infections. Prophylaxis and therapy.

    PubMed

    Levin, S; Goodman, L J

    1985-11-29

    True prophylaxis of intra-abdominal nongynecologic infections is limited to elective, nonemergency surgery and is best shown in three clean-contaminated surgical procedures. All of these have an infection rate of approximately 10 to 20 percent and include all colon resection surgery, most gastric surgery, and about one third of the cholecystectomies for chronic calculous cholecystitis. Each of these three surgical procedures has a somewhat different pattern of bacterial pathogens. The most useful comparative studies of early preoperative therapy have been performed in cases of suspected appendicitis (50 percent of which usually show perforation or gangrene at the time of surgery) and penetrating abdominal wounds (80 percent of which usually enter some part of the bowel and theoretically soil the peritoneum). These procedures are usually classified as contaminated, with a 20 to 30 percent infection rate, or dirty, with a more than 30 percent infection rate, depending upon several factors. Comparative investigations of intraoperative and postoperative antibiotic therapy of established intra-abdominal infections are more difficult to obtain because of the heterogeneity of the sites, organisms, and medical and surgical therapy. The initial pathogens causing secondary peritonitis and hepatic, perirectal, diverticular, and most other types of intraperitoneal abscesses are mixed coliforms and anaerobes, with emphasis on the anaerobes. Retroperitoneal abscesses, pancreatic abscesses, and biliary tract infections are predominantly caused by coliforms. The organisms responsible for these early infections are usually community-acquired rather than more antibiotic-resistant hospital-acquired bacteria. Considering the availability of a large number of effective broad-spectrum antibacterial agents and therapeutic combinations, it has become increasingly difficult to assess the rightful place of any new prospective antimicrobial regimen unless it has quite unique characteristics

  7. Factors associated with tuberculosis infection, and with anti-mycobacterial immune responses, among five year olds BCG-immunised at birth in Entebbe, Uganda

    PubMed Central

    Lule, Swaib Abubaker; Mawa, Patrice A.; Nkurunungi, Gyaviira; Nampijja, Margaret; Kizito, Dennison; Akello, Florence; Muhangi, Lawrence; Elliott, Alison M.; Webb, Emily L.

    2015-01-01

    Background BCG is used widely as the sole licensed vaccine against tuberculosis, but it has variable efficacy and the reasons for this are still unclear. No reliable biomarkers to predict future protection against, or acquisition of, TB infection following immunisation have been identified. Lessons from BCG could be valuable in the development of effective tuberculosis vaccines. Objectives Within the Entebbe Mother and Baby Study birth cohort in Uganda, infants received BCG at birth. We investigated factors associated with latent tuberculosis infection (LTBI) and with cytokine response to mycobacterial antigen at age five years. We also investigated whether cytokine responses at one year were associated with LTBI at five years of age. Methods Blood samples from age one and five years were stimulated using crude culture filtrates of Mycobacterium tuberculosis in a six-day whole blood assay. IFN-γ, IL-5, IL-13 and IL-10 production was measured. LTBI at five years was determined using T-SPOT.TB® assay. Associations with LTBI at five years were assessed using multivariable logistic regression. Multiple linear regression with bootstrapping was used to determine factors associated with cytokine responses at age five years. Results LTBI prevalence was 9% at age five years. Only urban residence and history of TB contact/disease were positively associated with LTBI. BCG vaccine strain, LTBI, HIV infection, asymptomatic malaria, growth z-scores, childhood anthelminthic treatment and maternal BCG scar were associated with cytokine responses at age five. Cytokine responses at one year were not associated with acquisition of LTBI by five years of age. Conclusion Although multiple factors influenced anti-myocbacterial immune responses at age five, factors likely to be associated with exposure to infectious cases (history of household contact, and urban residence) dominated the risk of LTBI. PMID:25529292

  8. Toxoplasma gondii infection and abdominal hernia: evidence of a new association

    PubMed Central

    2011-01-01

    Background We performed a retrospective, observational study in 1156 adult subjects from the general population of Durango City, Mexico, Fifty five subjects with a history of abdominal hernia repair and 1101 subjects without hernia were examined with enzyme-linked immunoassays for the presence of anti-Toxoplasma IgG and IgM antibodies. Results The seroprevalence of anti-Toxoplasma IgG antibodies and IgG titers was significantly higher in subjects with abdominal hernia repair than those without hernia. There was a tendency for subjects with hernia repair to have a higher seroprevalence of anti-Toxoplasma IgM antibodies than subjects without hernia. The seroprevalence of anti-Toxoplasma IgG antibodies in subjects with hernia repair was significantly higher in subjects ≥ 50 years old than those < 50 years old. Further analysis in subjects aged ≥ 50 years showed that the seroprevalence of anti-Toxoplasma IgG antibodies was also significantly higher in individuals with hernia repair than those without hernia (OR = 2.72; 95% CI: 1.10-6.57). Matching by age and sex further showed that the seroprevalence of Toxoplasma infection was significantly higher in patients with hernia repair than those without hernia (OR: 4.50; 95% CI: 1.22-17.33). Conclusions Results indicate that infection with Toxoplasma is associated with abdominal hernia. The contributing role of infection with Toxoplasma in abdominal hernia was observed mainly in subjects aged ≥ 50 years old. Our results might have clinical, prevention and treatment implications and warrant for further investigation. PMID:21682896

  9. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study

    PubMed Central

    Wu, Qin; Ren, Jianan; Wang, Gefei; Li, Guanwei; Gu, Guosheng; Wu, Xiuwen; Li, Yuan; Chen, Jun; Zhao, Yunzhao; Li, Jieshou

    2016-01-01

    Background Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies. Methods We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors. Results Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors. Conclusions This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients. PMID:26808492

  10. 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

  11. DNA-Launched Alphavirus Replicons Encoding a Fusion of Mycobacterial Antigens Acr and Ag85B Are Immunogenic and Protective in a Murine Model of TB Infection.

    PubMed

    Dalmia, Neha; Klimstra, William B; Mason, Carol; Ramsay, Alistair J

    2015-01-01

    There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr) and antigen 85B (Ag85B), termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNA-launched Vrep may, therefore, represent an effective approach to the development of gene-based vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters. PMID:26317509

  12. Combined megaplex TCR isolation and SMART-based real-time quantitation methods for quantitating antigen-specific T cell clones in mycobacterial infection

    PubMed Central

    Du, George; Qiu, Liyou; Shen, Ling; Sehgal, Probhat; Shen, Yun; Huang, Dan; Letvin, Norman L.; Chen, Zheng W.

    2010-01-01

    Despite recent advances in measuring cellular immune responses, the quantitation of antigen-specific T cell clones in infections or diseases remains challenging. Here, we employed combined megaplex TCR isolation and SMART-based real-time quantitation methods to quantitate numerous antigen-specific T cell clones using limited amounts of specimens. The megaplex TCR isolation covered the repertoire comprised of recombinants from 24 Vβ families and 13 Jβ segments, and allowed us to isolate TCR VDJ clonotypic sequences from one or many PPD-specific IFNγ-producing T cells that were purified by flow cytometry sorting. The SMART amplification technique was then validated for its capacity to proportionally enrich cellular TCR mRNA/cDNA for real-time quantitation of large numbers of T cell clones. SMART amplified cDNA was shown to maintain relative expression levels of TCR genes when compared to unamplified cDNA. While the SMART-based real-time quantitative PCR conferred a detection limit of 10−5 to 10−6 antigen-specific T cells, the clonotypic primers specifically amplified and quantitated the target clone TCR but discriminated other clones that differed by ≥2 bases in the DJ regions. Furthermore, the combined megaplex TCR isolation and SMART-based real-time quantiation methods allowed us to quantitate large numbers of PPD-specific IFNγ-producing T cell clones using as few as 2×106 PBMC collected weekly after mycobacterial infection. This assay system may be useful for studies of antigen-specific T cell clones in tumors, autoimmune and infectious diseases. PMID:16403511

  13. Infective complications after abdominal surgery in patients infected with human immunodeficiency virus: role of CD4+ lymphocytes in prognosis.

    PubMed

    Emparan, C; Iturburu, I M; Ortiz, J; Mendez, J J

    1998-08-01

    Risk factors associated with surgical infections are related to many events that modulate the immune system and affect the surgical procedure. The aim of this study was to determine the influence of low CD4+ lymphocyte counts in 24 patients with human immunodeficiency virus (HIV) undergoing abdominal surgery. Blood samples were obtained, and the lymphocyte population was evaluated perioperatively, as was the nutritional status of the patient. All the patients received selective antibiotic prophylaxis depending on the surgical procedure performed: (1) clean surgery: splenectomies (n = 8); (2) clean-contaminated: cholecystectomy and biliary tract surgery (n = 8); and (3) contaminated: appendectomy (n = 8). Depending on their CD4 count, two groups were formed: one with 200 to 500 cells/ml (n = 11) and the other with < 200 cells/ml (n = 13). When surgical infection was suspected, surgical drainage and microbiologic cultures were undertaken. For statistical evaluation of the groups ANOVA and the chi-square test were used; p < 0.05 was considered significant. Altogether 14 patients (58.3%) had a wound infection, and the mean (+/- SD) CD4 count in those patients was decreased (221.7 +/- 75.1) compared with that of the 10 patients in the uneventful group (386 +/- 81.2). Surgical infection rates were 50% for clean procedures, 62.5% for clean-contaminated procedures, and 62.5% for contaminated surgery. The group of patients with CD4 counts of < 200 cell/ml had an increased incidence of surgical infection, regardless of the type of surgery (p = 0.002). Thus the surgical infection rates with HIV patients undergoing abdominal surgery are dramatically increased. The CD4 and subsequently depressed neutrophil populations increase the risk of surgical infection during major procedures regardless of the type of surgery performed. PMID:9673546

  14. Prevalence of Non-Tuberculosis Mycobacterial Infections among Tuberculosis Suspects in Iran: Systematic Review and Meta-Analysis

    PubMed Central

    Nasiri, Mohammad Javad; Dabiri, Hossein; Darban-Sarokhalil, Davood; Hashemi Shahraki, Abdolrazagh

    2015-01-01

    Introduction The infections due to Non-Tuberculosis Mycobacteria (NTM) are becoming an important health problem in many countries in the world. Globally, an increase in NTM infections has been reported from many countries around the world. However, limited information is available about the prevalence of NTM infections in Iran. Material and Methods The data of the prevalence of NTM infections were collected from databases such as PubMed, Web of science, Cochrane Library, Embase, Scopus, Iranmedex, and Scientific Information Database. Comprehensive Meta-Analysis (V2.0, Biostat) software was used to analyze the data. Results The meta-analyses showed that the prevalence of NTM infections was 10.2% (95% confidence interval [95% CI] 6.3-15.9) among culture-positive cases of tuberculosis (TB) in Iran. The further stratified analyses indicated that the prevalence of NTM was higher in studies that were done after year 2000. Additionally, M. simiae (43.3% [95% CI 36.8-50.0]), M. intracellucar (27.3% [95% CI 0.7-95.5]) and M. fortuitum (22.7% [95% CI 16.1-30.9]) were the most prevalent NTM species, respectively. Discussion The relatively high prevalence of NTM infections (10.2%) among culture positive cases for TB underlines the need for greater enforcement of infection control strategies. Establishment of appropriate diagnostic criteria and management guidelines for NTM diseases and expanding the number and quality of regional reference laboratories may facilitate more accurate action for prevention and control of NTM infections in Iran. PMID:26052701

  15. Parasitic Infection of the Gallbladder: Cystoisospora belli Infection as a Cause of Chronic Abdominal Pain and Acalculous Cholecystitis.

    PubMed

    Martelli, Matthew G; Lee, Johnathan Y

    2016-06-01

    Herein we describe two cases of Cystoisospora belli infection of the gallbladder in patients with chronic abdominal pain and review the published literature to date. C. belli is an intracellular protozoan parasite that typically infects the small bowel of immunocompromised hosts. Little is known of the significance of C. belli infection of the gallbladder at this point as only four cases have been reported as yet, only one of which occurred in an immunocompetent patient. It is often treatable with antibiotics, and the patient's immune status, including HIV testing, should be investigated. Neither of the patients at our institution was found to be immunocompromised, and HIV-1/2 antibody testing was non-reactive in both. PMID:27526491

  16. Mycobacterial infection and the impact of rifabutin treatment in organ transplant recipients: a single-center study.

    PubMed

    Tabarsi, Payam; Farshidpour, Maham; Marjani, Majid; Baghaei, Parvaneh; Yousefzadeh, Amir; Najafizadeh, Katayoon; Sharifkashani, Babak; Javanmard, Pedram; Mansouri, Davood; Masjedi, Mohammadreza; Velayati, Aliakbar

    2015-01-01

    Tuberculosis (TB) is a frequently encountered infection among organ transplant recipients in developing countries, and the incidence of infection after the first year of transplantation is considerably high. In this study, the impact of rifabutin treatment on organ transplant recipients with TB infection was evaluated with respect to the trend of infection, management and outcome. The medical records of 26 post-transplant patients who received an organ transplant between 2004 and 2012 and later diagnosed with TB of different organs were reviewed retrospectively. We retrieved data regarding clinical features as well as treatment and outcomes. The median time interval between transplantation and TB was 36 months (IQR 12-101 months). The most common form of infection was pulmonary/pleural TB. All our subjects received rifabutin instead of rifampin in the anti-TB treatment regime as rifabutin is a less-potent inducer of cytochrome P-450. All patients responded satisfactorily to the treatment and maintained excellent allograft function. Moreover, we did not have any mortality among our recipients. Drug-induced hepatitis was observed in nine (35%) patients. Rifabutin is an excellent alternative medication to rifampin in the setting of TB management. Hepatotoxicity is a potential risk for treatment because of the potential additive toxicity of immunosuppressive drugs. PMID:25579709

  17. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  18. Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections

    PubMed Central

    Chi, Chih-Yu; Lin, Chia-Hao; Ho, Mao-Wang; Ding, Jing-Ya; Huang, Wen-Chi; Shih, Han-Po; Yeh, Chun-Fu; Fung, Chang-Phone; Sun, Hsin-Yun; Huang, Ching-Tai; Wu, Ting-Shu; Chang, Chih-Yen; Liu, Yuag-Meng; Feng, Jia-Yih; Wu, Wei-Kai; Wang, Lih-Shinn; Tsai, Chung-Hao; Ho, Cheng-Mao; Lin, Huang-Shen; Chen, Hung-Jen; Lin, Po-Chang; Liao, Wei-Chin; Chen, Wei-Ting; Lo, Chia-Chi; Wang, Shang-Yu; Kuo, Chen-Yen; Lee, Chen-Hsiang; Ku, Cheng-Lung

    2016-01-01

    Abstract Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM). We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software. Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10–5 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection. In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs. PMID:27336882

  19. Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections.

    PubMed

    Chi, Chih-Yu; Lin, Chia-Hao; Ho, Mao-Wang; Ding, Jing-Ya; Huang, Wen-Chi; Shih, Han-Po; Yeh, Chun-Fu; Fung, Chang-Phone; Sun, Hsin-Yun; Huang, Ching-Tai; Wu, Ting-Shu; Chang, Chih-Yen; Liu, Yuag-Meng; Feng, Jia-Yih; Wu, Wei-Kai; Wang, Lih-Shinn; Tsai, Chung-Hao; Ho, Cheng-Mao; Lin, Huang-Shen; Chen, Hung-Jen; Lin, Po-Chang; Liao, Wei-Chin; Chen, Wei-Ting; Lo, Chia-Chi; Wang, Shang-Yu; Kuo, Chen-Yen; Lee, Chen-Hsiang; Ku, Cheng-Lung

    2016-06-01

    Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software.Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection.In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs. PMID:27336882

  20. Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management of Intra-Abdominal Infections

    PubMed Central

    Hoffmann, Charles; Zak, Matthew; Avery, Lisa; Brown, Jack

    2016-01-01

    Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics. PMID:27025526

  1. Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013–20141

    PubMed Central

    Esposito, Douglas H.; Gaines, Joanna; Ridpath, Alison; Barry, M. Anita; Feldman, Katherine A.; Mullins, Jocelyn; Burns, Rachel; Ahmad, Nina; Nyangoma, Edith N.; Nguyen, Duc B.; Perz, Joseph F.; Moulton-Meissner, Heather A.; Jensen, Bette J.; Lin, Ying; Posivak-Khouly, Leah; Jani, Nisha; Morgan, Oliver W.; Brunette, Gary W.; Pritchard, P. Scott; Greenbaum, Adena H.; Rhee, Susan M.; Blythe, David; Sotir, Mark

    2016-01-01

    During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment. PMID:27434822

  2. Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013-2014(1).

    PubMed

    Schnabel, David; Esposito, Douglas H; Gaines, Joanna; Ridpath, Alison; Barry, M Anita; Feldman, Katherine A; Mullins, Jocelyn; Burns, Rachel; Ahmad, Nina; Nyangoma, Edith N; Nguyen, Duc B; Perz, Joseph F; Moulton-Meissner, Heather A; Jensen, Bette J; Lin, Ying; Posivak-Khouly, Leah; Jani, Nisha; Morgan, Oliver W; Brunette, Gary W; Pritchard, P Scott; Greenbaum, Adena H; Rhee, Susan M; Blythe, David; Sotir, Mark

    2016-08-01

    During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment. PMID:27434822

  3. [Comparative estimation of the application efficacy for ceftriaxon and Hepacef combi preparations in the abdominal infection treatment].

    PubMed

    Boĭko, V V; Ivanova, Iu V

    2012-01-01

    A positive experience was described in the work, concerning application of Hepacef combi (cefoperazon/sulbactam, manufactured by "ARTERIUM" (Corporation, Ukraine) in the treatment of inflammatory-purulent diseases of abdominal organs as a method of empirical therapy. There was the preparation action efficacy estimated together with the diseases outcomes analysis, and possible recommendations for its application suggested. The preparation may be recommended for application as the empirical therapy agent in the abdominal infection treatment. PMID:22642085

  4. Targeting Mycobacterial Enzymes with Natural Products.

    PubMed

    Sieniawska, Elwira

    2015-10-22

    Tuberculosis (TB) is a recurring threat to contemporary civilization. It affects not only those within developing countries, but has also appeared again in places where it was once considered eradicated. TB co-infection in patients infected by HIV is, at the time of writing, the most common cause of death. In the field of searching for new antimycobacterial drug leads, compounds of natural origin still remain a promising source. The review is intended to gather information about natural products (metabolites of plants, fungi, bacteria, and marine sponges) that show activity against mycobacterial enzymes. Here, natural metabolites are presented as being inhibitors/activators of the mycobacterial enzymes involved in mycobacterial growth in vitro (ClpC1, ClpP, MurE ligase, mycothiol S-conjugate amidase, β-ketoacyl-ACP synthase, InhA) and in vivo, as regards the host cell (PtpB). Each enzyme is briefly described so as to generate an understanding of its role in mycobacterial growth and engender a perception of the mechanism of action of the studied natural compounds. Furthermore, after the introduction of the enzyme, its inhibitors are listed and exactly characterized. PMID:26441042

  5. 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

  6. Risk for Mycobacterial Disease among Patients with Rheumatoid Arthritis, Taiwan, 2001–2011

    PubMed Central

    Liao, Tsai-Ling; Lin, Ching-Heng; Shen, Gwan-Han; Chang, Chia-Li; Lin, Chin-Fu

    2015-01-01

    Increasing evidence indicates that the risk of acquiring tuberculosis (TB) and nontuberculous mycobacterial disease is elevated among patients with rheumatoid arthritis (RA). To determine the epidemiology of mycobacterial diseases among RA patients in Asia, we conducted a retrospective cohort study. We used a nationwide database to investigate the association of RA with mycobacterial diseases. The risk for development of TB or nontuberculous mycobacterial disease was 2.28-fold and 6.24-fold higher among RA patients than among the general population, respectively. Among RA patients, risk for development of mycobacterial disease was higher among those who were older, male, or both. Furthermore, among RA patients with mycobacterial infections, the risk for death was increased. Therefore, RA patients, especially those with other risk factors, should be closely monitored for development of mycobacterial disease. PMID:26196158

  7. Non-traumatic hernia of the lateral abdominal wall in a patient infected with the human immunodeficiency virus.

    PubMed

    Fan, Z; Pan, J; Liu, X; Zhuang, C; Ren, J; Yu, H; Tang, S; Wang, S

    2016-07-01

    Introduction There are several classifications for abdominal hernias, and a non-traumatic lateral wall hernia (LAWH) is a rare type. We report the first case of a patient with LAWH infected with the human immunodeficiency virus (HIV). Case History A 53-year-old HIV-infected male presented with an abdominal mass. The patient had a history of treatment with combination antiretroviral therapy. A LAWH was diagnosed based on physical examination and findings of computed tomography. Open mesh repair was undertaken successfully. The patient had no evidence of a recurrent hernia during 11 months of follow-up. Conclusions High intra-abdominal pressure and weak connective tissue can lead to LAWHs. Antiretroviral therapy and lipodystrophy can cause LAWHs in HIV-infected patients. PMID:27241599

  8. Experimental modulation of the reactivity of pleural milky spots (Kampmeier's foci) by Freund's adjuvants, betamethasone and mycobacterial infection.

    PubMed Central

    Pereira, A de D; Aguas, A P; Oliveira, M J; Cabral, J M; Grande, N R

    1994-01-01

    We studied the response of milky spots in the parietal pleura of the rat and mouse to intrapleural instillation of immunomodulatory agents such as complete or incomplete Freund's adjuvants and betamethasone, and also to infection by mycobacteria (M. avium). Both incomplete (mineral oil) and complete (mineral oil plus dead mycobacteria) adjuvants, as well as M. avium infection, induced a striking increase in the size and cellularity of the pleural milky spots whereas betamethasone caused a slight atrophy. The extensive inflammatory infiltrates observed after adjuvant injection differed between milky spots reactive to complete and incomplete Freund's adjuvants. Fifteen days after adjuvant administration, the pleural milky spots of rats were still enlarged and hypercellular but differences were noted in the size of milky spots of the pleura between the 2 adjuvant treatments: animals submitted to injection of complete Freund's adjuvant showed an increase in the size of milky spots from d 3 to d 15, while the size of milky spots of the incomplete Freund's adjuvant treated group showed a decrease in size from d 3 to d 15. The milky spots at d 15 were well organised: reticulin fibres permeated the whole area of the milky spot and the different cell types were evenly distributed. Histiocytes, which were previously confined to the inner layer, were now the main cell type in all areas of milky spots. A moderate number of mast cells and a few eosinophils were also seen. Complete Freund's adjuvant caused the formation of granulomas in the milky spots, a change that was not detected in animals treated with incomplete adjuvant.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7649783

  9. Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study

    PubMed Central

    2014-01-01

    The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001). PMID:24883079

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

    PubMed Central

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

    2016-01-01

    Abstract 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) PMID:27274183

  11. Monstrous Mycobacterial Lipids.

    PubMed

    Seeliger, Jessica; Moody, D Branch

    2016-02-18

    When it comes to lipid diversity, no bacterial genus approaches Mycobacterium. In this issue of Cell Chemical Biology, Burbaud et al. (2016) provide a multi-genic working model for the biosynthesis of trehalose polyphleate (TPP), one of the largest known lipids in mycobacteria. They demonstrate that this lipid is made by diverse mycobacterial species, including those of medical importance. PMID:26971870

  12. 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). PMID:26155003

  13. The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

    PubMed Central

    Kleynhans, Léanie; Du Plessis, Nelita; Allie, Nasiema; Jacobs, Muazzam; Kidd, Martin; van Helden, Paul D.; Walzl, Gerhard

    2013-01-01

    The contraceptive depot medroxyprogesterone acetate (DMPA), with progestin as the single active compound, possesses selective glucocorticoid activity and can alter the expression of glucocorticoid receptor-regulated genes. We therefore propose that pharmacological doses of DMPA used for endocrine therapy could have significant immune modulatory effects and impact on susceptibility to, as well as clinical manifestation and outcome of, infectious diseases. We investigated the effect of contraceptive doses of DMPA in two different murine Mycobacterium tuberculosis models. Multiplex bead array analysis revealed that DMPA altered serum cytokine levels of tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), and interleukin 10 (IL-10) in C57BL/6 mice and gamma interferon (IFN-γ) in BALB/c mice. DMPA also suppressed antigen-specific production of TNF-α, G-CSF, IL-10, and IL-6 and induced the production of IP-10 in C57BL/6 mice. In BALB/c mice, DMPA altered the antigen-specific secretion of IFN-γ, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and monocyte chemotactic protein 1 (MCP-1). Furthermore, we show that C57BL/6 mice treated with doses of DMPA, which result in serum concentrations similar to those observed in contraceptive users, have a significantly higher bacterial load in their lungs. Our data show for the first time that DMPA impacts tuberculosis (TB) disease severity in a mouse model and that the effects of this contraceptive are not confined to infections of the genital tract. This could have major implications for the contraceptive policies not only in developing countries like South Africa but also worldwide. PMID:23381991

  14. Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

    PubMed Central

    Yang, JianWei; Zhang, Yuan; Wang, YongMing; Zhang, JianLei; Zhao, YuanYuan; Dong, WeiLin

    2015-01-01

    The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra-abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, Cmax was 11.151 µg/mL at 5 min after the intravenous injection and t1/2 was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents. PMID:25729270

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

    PubMed Central

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

    2016-01-01

    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 (Il22Ra1Hep−/−) and Stat3 knockout (Stat3Hep−/−) 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. PMID:26729763

  16. 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

    2016-01-01

    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. PMID:26729763

  17. Guideline-Concordant Versus Discordant Antimicrobial Therapy in Patients With Community-Onset Complicated Intra-abdominal Infections.

    PubMed

    Huang, Lori L; Van Schooneveld, Trevor C; Huang, Robert D; Olsen, Keith M; Rupp, Mark E; Gross, Alan E

    2016-07-01

    Overall IDSA/SIS intra-abdominal infection guideline compliance was not associated with improved outcomes; however, there was a longer time to active therapy (P=.024) and higher mortality (P=.077) if empiric therapy was too narrow per guidelines. These findings support the need for the implementation of customized institutional guidelines adapted from the IDSA/SIS guidelines. Infect Control Hosp Epidemiol 2016;37:855-858. PMID:27020310

  18. Optimal times above MICs of ceftibuten and cefaclor in experimental intra-abdominal infections.

    PubMed

    Onyeji, C O; Nicolau, D P; Nightingale, C H; Quintiliani, R

    1994-05-01

    The duration of time that serum drug levels remain above the MIC (time above the MIC) for the pathogen has been shown to be the most significant parameter determining the efficacies of beta-lactam antibiotics. In the described study, we investigated the optimal time above the MIC of ceftibuten and cefaclor using a nonneutropenic mouse model of intra-abdominal infections caused by Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. The abilities of the drugs to protect mice against the organisms were determined in mouse protection tests, and the doses were fractionated to produce various dosing regimens with different times above the MIC. All drug-organism combinations showed a significant correlation (r > 0.9) between drug efficacy and the time above the MIC. Also, with ceftibuten treatment, the different dosing regimens that produced equal times above the MIC resulted in the same efficacy, whereas with cefaclor, an apparent dose-dependent effect was observed. These results showed that for a 100% recovery from K. pneumoniae and E. coli infections, the optimal times above the MIC with ceftibuten treatment were 2.2 and 1.6 h, respectively. Relatively high doses of both antibiotics were required to ensure recovery from S. pneumoniae infections. In vitro time-kill studies demonstrated that cefaclor exhibits a marked inoculum effect against the pathogens, and there was a concentration-dependent killing at a large inoculum size. On the other hand, ceftibuten showed no inoculum effect. It is suggested that optimization of both dose and time above the MIC appears to be necessary for the treatment of S. aureus infections with cefaclor, and this may apply to other beta-lactams tht exhibit marked inoculum effects. PMID:8067747

  19. Mycobacterial signaling through toll-like receptors

    PubMed Central

    Basu, Joyoti; Shin, Dong-Min; Jo, Eun-Kyeong

    2012-01-01

    Studies over the past decade have helped to decipher molecular networks dependent on Toll-like receptor (TLR) signaling, in mycobacteria-infected macrophages. Stimulation of TLRs by mycobacteria and their antigenic components rapidly induces intracellular signaling cascades involved in the activation of nuclear factor-κB and mitogen-activated protein kinase pathways, which play important roles in orchestrating proinflammatory responses and innate defense through generation of a variety of antimicrobial effector molecules. Recent studies have provided evidence that mycobacterial TLR-signaling cross talks with other intracellular antimicrobial innate pathways, the autophagy process and functional vitamin D receptor (VDR) signaling. In this article we describe recent advances in the recognition, responses, and regulation of mycobacterial signaling through TLRs. PMID:23189273

  20. Critical evaluation of ceftolozane–tazobactam for complicated urinary tract and intra-abdominal infections

    PubMed Central

    Giancola, Stephanie E; Mahoney, Monica V; Bias, Tiffany E; Hirsch, Elizabeth B

    2016-01-01

    The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane–tazobactam, a novel β-lactam/β-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some β-lactamase enzymes. Ceftolozane–tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane–tazobactam is a promising carbapenem

  1. 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. PMID:27363829

  2. Efficacy of L-627, a new carbapenem, in the treatment of experimentally induced intra-abdominal infections in rats.

    PubMed

    Nord, C E; Lahnborg, G

    1992-01-01

    A reproducible experimental model of intra-abdominal infections in rats has been devised in order to simulate intra-abdominal sepsis in patients. Pre-operatively, the rats were fed lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of L-627 with the combination of gentamicin plus metronidazole. Eighty per cent of the untreated animals died within three days. Animals treated with L-627 or gentamicin plus metronidazole had significantly decreased mortality and increased cure rates during the experimental period. Only two animals in the two treatment groups died. L-627 seems to be as useful as gentamicin plus metronidazole in the treatment of intra-abdominal infections. PMID:1306152

  3. Ceftazidime-avibactam (CTZ-AVI) as a treatment for hospitalized adult patients with complicated intra-abdominal infections.

    PubMed

    Gardiner, Bradley J; Golan, Yoav

    2016-05-01

    Avibactam, a novel β-lactamase inhibitor, has recently been co-formulated with ceftazidime and approved for use in patients with complicated intra-abdominal and urinary tract infections, where no better treatment alternative exists. The basis for its FDA approval has been the extensive clinical experience with ceftazidime and the demonstration in vitro and in animal models that the addition of avibactam reverses resistance to ceftazidime in extended-spectrum β-lactamase and some carbapenemase-producing Enterobacteriaceae. Early clinical data are promising, with efficacy demonstrated in patients with complicated intra-abdominal and urinary tract infections. This review will summarize the in vitro, animal and clinical data available on this agent to date. PMID:27042762

  4. Autoimmune Hemolytic Anemia Triggered by Infection with Human Parvovirus B19 after Total Abdominal Colectomy for Ulcerative Colitis.

    PubMed

    Iida, Tomoya; Satoh, Shuji; Nakagaki, Suguru; Shimizu, Haruo; Kaneto, Hiroyuki

    2016-01-01

    A 50-year-old man was admitted to our hospital for an adhesive ileus 14 years after total abdominal colectomy for ulcerative colitis (UC). The ileus decreased with conservative treatment, however, autoimmune hemolytic anemia (AIHA) was diagnosed due to worsening anemia, a positive direct Coombs test, low haptoglobin, high lactase dehydrogenase, reticulocytosis, and an increase in the erythroblastic series in a bone-marrow examination. Human parvovirus B19 (PV-B19) IgM and PV-B19 DNA were present, indicating the development of AIHA triggered by an infection with PV-B19. The patient is currently being monitored after spontaneous remission. This is the first report of UC after total abdominal colectomy complicated by AIHA triggered by PV-B19 infection. PMID:26984090

  5. 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

  6. Abdominal CT scan

    MedlinePlus

    ... tumors, including cancer Infections or injury Kidney stones Appendicitis ... also be due to: Abdominal aortic aneurysm Abscesses Appendicitis Bowel wall thickening Retroperitoneal fibrosis Renal artery stenosis ...

  7. Genetic dissection of mycobacterial biofilms.

    PubMed

    Ojha, Anil K; Jacobs, William R; Hatfull, Graham F

    2015-01-01

    Our understanding of the biological principles of mycobacterial tolerance to antibiotics is crucial for developing shorter anti-tuberculosis regimens. Various in vitro approaches have been developed to identify the conditions that promote mycobacterial persistence against antibiotics. In our laboratories, we have developed a detergent-free in vitro growth model, in which mycobacteria spontaneously grow at the air-medium interface as self-organized multicellular structures, called biofilms. Mycobacterial biofilms harbor a subpopulation of drug tolerant persisters at a greater frequency than their planktonic counterpart. Importantly, development of these structures is genetically programmed, and defective biofilms of isogenic mutants harbor fewer persisters. Thus, genetic analysis of mycobacterial biofilms in vitro could potentially be a powerful tool to unravel the biology of drug tolerance in mycobacteria. In this chapter we describe a method for screening biofilm-defective mutants of mycobacteria in a 96-well format, which readily yields a clonally pure mutant for further studies. PMID:25779318

  8. Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections

    PubMed Central

    Skalweit, Marion J

    2015-01-01

    Drug-resistant pathogens have gained a foothold especially in the most vulnerable patient populations, hospitalized and immunocompromised individuals. Furthermore, extended-spectrum β-lactamase and carbapenemase-producing organisms are finding their way even into the community, with patients presenting to the hospital with established colonization and infection with resistant Enterobacteriaceae in particular. Recently, a novel antipseudomonal cephalosporin in combination with an established Class A β-lactamase inhibitor, ceftolozane/tazobactam has been approved by the FDA for use in the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Ceftolozane is a uniquely potent antipseudomonal cephalosporin because of its high affinity for the penicillin-binding proteins of Pseudomonas aeruginosa, its low affinity for the intrinsic Class C β-lactamases of P. aeruginosa, its ability to enter P. aeruginosa through the outer membrane without the utilization of OprD protein, and the fact that it is not a substrate of the often upregulated MexAB/OprM efflux system of P. aeruginosa. The biological chemistry, pharmacokinetics/pharmacodynamics, microbiologic spectrum, and clinical trials that led to the approval of ceftolozane is reviewed. A discussion regarding its potential role in the treatment of complicated intra-abdominal infections and other infectious disease syndromes associated with drug-resistant pathogens follows. PMID:26082619

  9. Malignant peritoneal mesothelioma in a patient with intestinal fistula, incisional hernia and abdominal infection: A case report

    PubMed Central

    HONG, SEN; BI, MIAO-MIAO; ZHAO, PING-WEI; WANG, XU; KONG, QING-YANG; WANG, YONG-TAO; WANG, LEI

    2016-01-01

    Malignant mesothelioma is a rare type of cancer, most commonly associated with exposure to asbestos. Mesothelioma of the peritoneum, the membrane lining the abdominal cavity, is extremely rare. The current study reports the case of a 60-year-old female who presented with intestinal fistula, recurrent incisional hernia and abdominal infection, with no history of asbestos exposure, and was diagnosed with clear cell MPM. Computed tomography scans of the abdomen revealed extensive small bowel adhesions and massive peritoneal effusion. Histological examination of biopsy specimens indicated a diagnosis of malignant peritoneal mesothelioma with clear cell morphology. A laparotomy was performed, with subsequent resection of the bowel with fistula. Follow-up examination performed at 1-year post-surgery revealed that the patient was alive and in generally good health. PMID:26998119

  10. Highlight on Advances in Nontuberculous Mycobacterial Disease in North America

    PubMed Central

    Mirsaeidi, Mehdi; Farshidpour, Maham; Allen, Mary Beth; Ebrahimi, Golnaz; Falkinham, Joseph O.

    2014-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and exist as an important cause of pulmonary infections in humans. Pulmonary involvement is the most common disease manifestation of NTM and the incidence of NTM is growing in North America. Susceptibility to NTM infection is incompletely understood; therefore preventative tools are not well defined. Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is difficult and entails multiple antibiotics and an extended treatment course. Also, there is a considerable variation in treatment management that should be considered before initiating treatment. We highlight the new findings in the epidemiology diagnosis and treatment of mycobacterial infections. We debate new advances regarding NTM infection in cystic fibrosis patients and solid organ transplant recipients. Finally, we introduce a new epidemiologic model for NTM disease based on virulence-exposure-host factors. PMID:25574470

  11. [Hospital management of patients with complicated intra-abdominal infections: pharmacoeconomic evaluations].

    PubMed

    Eandi, Mario

    2008-02-01

    Due to their high incidence and large resource consumption, complicated intra-abdominal infections (cIAIs) represent a heavy burden for the Italian National Health System (NHS) and the Italian society, with estimated annual costs of 1,5 and 3 billions Euro, respectively. The different strategies, monotherapy or antibiotic combinations, indicated for treating cIAIs induce significantly different acquisition and administration costs but substantially equivalent therapeutic results, with average clinical effectiveness rates of 70-80%. This apparent equivalence among different antibiotic protocols presumably depends on the widespread trend to individualize the therapeutic strategy according to the clinical severity and the community or nosocomial origin of cIAIs, as well as on some degree of non-appropriateness when empirically choosing a first-line antibiotic. The average cost for the nosocomial management of cIAI patients depends on several factors: posology and antibiotic drug acquisition and administration costs, days of antibiotic therapy, mix of antibiotic schedules, rates of the therapeutic failures that induce further drug consumption, prolong hospitalization and often require re-intervention and ICU utilization. The introduction in the therapeutic arsenal of a new antibiotic like tigecycline leads to a mild increase of the average antibiotic acquisition and treatment costs per patient: this increase is proportional to the percentage of patients treated with the new antibiotic. According to a decisional model, implemented on international outcome data and Italian costs, the mean cost for first-line antibiotic acquisition and the mean cost for first- and second-line antibiotic treatment represent respectively only 2% and 8% of the mean overall hospitalization cost. The mean hospitalization cost estimated by the model is noticeably higher than the mean value of DRG tariffs presumably reimbursed by the Italian NHS to hospitals for cIAI-related hospitalizations

  12. microRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production

    PubMed Central

    Li, Miao; Wang, Jinli; Fang, Yimin; Gong, Sitang; Li, Meiyu; Wu, Minhao; Lai, Xiaomin; Zeng, Gucheng; Wang, Yi; Yang, Kun; Huang, Xi

    2016-01-01

    Macrophages play a crucial role in host innate anti-mycobacterial defense, which is tightly regulated by multiple factors, including microRNAs. Our previous study showed that a panel of microRNAs was markedly up-regulated in macrophages upon mycobacterial infection. Here, we investigated the biological function of miR-146a during mycobacterial infection. miR-146a expression was induced both in vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO generation, thus promoting mycobacterial survival in macrophages. Inhibition of endogenous miR-146a increased NO production and mycobacterial clearance. Moreover, miR-146a attenuated the activation of nuclear factor κB and mitogen-activated protein kinases signaling pathways during BCG infection, which in turn repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post-transcriptional level. Silencing TRAF6 decreased iNOS expression and NO production in BCG-infected macrophages, while overexpression of TRAF6 reversed miR-146a-mediated inhibition of NO production and clearance of mycobacteria. Therefore, we demonstrated a novel role of miR-146a in the modulation of host defense against mycobacterial infection by repressing NO production via targeting TRAF6, which may provide a promising therapeutic target for tuberculosis. PMID:27025258

  13. Rapid 13C Urea Breath Test to Identify Helicobacter pylori Infection in Emergency Department Patients with Upper Abdominal Pain

    PubMed Central

    Meltzer, Andrew C.; Pierce, Rebecca; Cummings, Derek A.T.; Pines, Jesse M.; May, Larissa; Smith, Meaghan A.; Marcotte, Joseph; McCarthy, Melissa L.

    2013-01-01

    Introduction: In emergency department (ED) patients with upper abdominal pain, management includes ruling out serious diseases and providing symptomatic relief. One of the major causes of upper abdominal pain is an ulcer caused by Helicobacter pylori (H. pylori), which can be treated and cured with antibiotics. We sought to estimate the prevalence of H. pylori infection in symptomatic patients using a convenience sample at a single urban academic ED and demonstrate the feasibility of ED-based testing. Methods: We prospectively enrolled patients with a chief complaint of pain or discomfort in the upper abdomen for 1 year from February 2011 until February 2012 at a single academic urban ED. Enrolled subjects were tested for H. pylori using a rapid point of care 13C Urea Breath Test (UBT) [Exalenz Bioscience]. We compared patient characteristics between those who tested positive versus negative for the disease. Results: A total of 205 patients with upper abdominal pain were tested over 12 months, and 24% (95% confidence interval: 19% to 30%) tested positive for H. pylori. Black subjects were more likely to test positive than white subjects (28% v. 6%, P < 0.001). Other factors, such as age and sex, were not different between the 2 groups. Conclusion: In our ED, H. pylori infection was present in 1 in 4 patients with epigastric pain, and testing with a UBT was feasible. Further study is needed to determine the risk factors associated with infection, the prevalence of H. pylori in other EDs, the effect of the test on ED length of stay and the costeffectiveness of an ED-based test-and-treat strategy. PMID:23687549

  14. Wound Edge Protectors in Open Abdominal Surgery to Reduce Surgical Site Infections: A Systematic Review and Meta-Analysis

    PubMed Central

    Mihaljevic, André L.; Müller, Tara C.; Kehl, Victoria; Friess, Helmut; Kleeff, Jörg

    2015-01-01

    Importance Surgical site infections remain one of the most frequent complications following abdominal surgery and cause substantial costs, morbidity and mortality. Objective To assess the effectiveness of wound edge protectors in open abdominal surgery in reducing surgical site infections. Evidence Review A systematic literature search was conducted according to a prespecified review protocol in a variety of data-bases combined with hand-searches for randomized controlled trials on wound edge protectors in patients undergoing laparotomy. A qualitative and quantitative analysis of included trials was conducted. Findings We identified 16 randomized controlled trials including 3695 patients investigating wound edge protectors published between 1972 and 2014. Critical appraisal uncovered a number of methodological flaws, predominantly in the older trials. Wound edge protectors significantly reduced the rate of surgical site infections (risk ratio 0.65; 95%CI, 0.51–0.83; p = 0.0007; I2 = 52%). The results were robust in a number of sensitivity analyses. A similar effect size was found in the subgroup of patients undergoing colorectal surgery (risk ratio 0.65; 95%CI, 0.44–0.97; p = 0.04; I2 = 56%). Of the two common types of wound protectors double ring devices were found to exhibit a greater protective effect (risk ratio 0.29; 95%CI, 0.15–0.55) than single-ring devices (risk ratio 0.71; 95%CI, 0.54–0.92), but this might largely be due to the lower quality of available data for double-ring devices. Exploratory subgroup analyses for the degree of contamination showed a larger protective effect in contaminated cases (0.44; 95%CI, 0.28–0.67; p = 0.0002, I2 = 23%) than in clean-contaminated surgeries (0.72, 95%CI, 0.57–0.91; p = 0.005; I2 = 46%) and a strong effect on the reduction of superficial surgical site infections (risk ratio 0.45; 95%CI, 0.24–0.82; p = 0.001; I2 = 72%). Conclusions and Relevance Wound edge protectors significantly reduce the rate of

  15. In situ repair of a primary Brucella-infected abdominal aortic aneurysm: long-term follow-up.

    PubMed

    Goudard, Yvain; Pierret, Charles; de La Villéon, Bruno; Mlynski, Amélie; de Kerangal, Xavier

    2013-02-01

    Infected aortic aneurysms represent 0.85 to 1.3% of aortic aneurysms. Most often, the implicated bacteria species are Salmonella sp., Staphylococcus sp. and Streptococcus sp. Brucella-related infected aortic aneurysms are very rare. Most often, they result from endocarditis or from a local septic focus. Combined treatment by antibiotics and surgery is the standard for infectious aneurysms. In the absence of formal factual data, the surgical treatment is still discussed in the literature, especially since endovascular treatments have been in full expansion. We are reporting the case of a female patient presenting with a Brucella-related infra-renal abdominal aortic aneurysm, without primitive infectious source (area) or identified endocarditis. Surgical treatment with in situ prosthetic replacement and omentoplasty in association with adapted antibiotics allowed a favorable outcome with an excellent result after an 8-year follow up. PMID:23380562

  16. Age-dependent humoral responses of children to mycobacterial antigens.

    PubMed Central

    Fairchok, M P; Rouse, J H; Morris, S L

    1995-01-01

    In the United States, disseminated infection with environmental mycobacteria, including the Mycobacterium avium complex, is the most common opportunistic bacterial infection seen in AIDS patients. However, the source and relative degree of exposure to environmental mycobacteria during childhood are unknown. To examine the age-related exposure to mycobacteria, we obtained serum samples from 150 children ranging in age from 6 months to 18 years. Each sample was tested against both M. avium (serovar 1) sonic extracts and mycobacterial lipoarabinomannan, using an enzyme-linked immunosorbent assay (ELISA). All serum samples were also subjected to immunoblot analysis with the sonic extract antigen. These studies established that elevated ELISA values (P < 0.0001) and increased immunoblot reactivity (P < 0.0001) against mycobacterial antigens were both associated with increasing age. The seroreactivity differences were most striking when comparing the age groups of children below the age of 6 with the older age groups. Our results suggest that the development of humoral immune responses to mycobacterial antigens in children correlates with increasing age and that there may be an environmental factor predisposing to mycobacterial exposure which is related to advancing age. PMID:7583921

  17. The use of gentamicin-PMMA chains in abdominal surgery: a pilot study of prophylaxis against wound infection.

    PubMed

    Aubrey, D A; Jenkins, N H; Morgan, W P; Thomas, M

    1986-01-01

    A prospective study was carried out to examine the effectiveness of gentamicin-impregnated polymethylmethacrylate beads in the prevention of wound sepsis after gastro-intestinal surgery. The beads were laid in the abdominal and perineal incisions (61 wounds) of 55 patients at the end of the operative procedures, and were withdrawn in stages from the fifth post-operative day. This method of administration results in a sustained high antibiotic concentration in the wound with low serum and urine concentrations, thus eliminating the dangers of gentamicin toxicity. Wound infection occurred in only 1 instance, a favourable result when compared to historical controls. It is suggested that further controlled studies of this method of topical prophylactic antibiotic administration are indicated. PMID:3714759

  18. Mycobacterial Prevalence and Antibiotic Resistance Frequency Trends in Taiwan of Mycobacterial Clinical Isolates From 2002 to 2014.

    PubMed

    Shiau, Ming-Yuh; Lee, Ming-Shih; Huang, Tian-Lin; Tsai, Jen-Ning; Chang, Yih-Hsin

    2016-03-01

    Tuberculosis, caused by Mycobacterium tuberculosis complex (MTBC) infections, is one of the most widespread infectious diseases worldwide. Nontuberculous mycobacteria (NTM) also cause chronic pulmonary infections, however, NTM infection is generally overlooked.This study analyzed the frequencies of MTBC and NTM clinical isolates from 181,132 specimens obtained from patients in Taiwan suspected of having a pulmonary mycobacterial infection from 2002 to 2014. The resistant rates to 4 first-line antibiotics (isoniazid, ethambutol, rifampicin, and streptomycin) of 9079 clinical MTBC isolates were also examined by the modified agar proportion method.Overall, the mycobacterial isolation rate was 8.65%, and this consisted of MTBC isolation rate of 5.01% and NTM isolation rate of 3.63%. The prevalence of MTBC isolates among the identified mycobacterial strains could be seen to decrease significantly from 82.5% in 2002 to 41.18% in 2014. Notably, the corresponding NTM prevalence increased 3.36 fold from 17.54% in 2002 to 58.82% in 2014. The frequencies of MTBC and NTM isolates showed a reciprocal trend with the crossing over occurring in the years 2010 and 2011. Although the resistance rates of the MTBC isolates to isoniazid and streptomycin were relatively stable over the study period, resistance rates of the MTBC isolates against rifampicin and ethambutol fluctuated across the study period. Overall, the incidence of multidrug resistance was relatively consistent at about 1.74%.The diagnosis, identification, and susceptibility tests for NTM should be standardized and integrated into appropriate clinical settings to cope with the increase in NTM infections. In addition, the documentation of the antibiotic resistance rates of MTBC clinical isolates to the antibiotic treatments most often clinically prescribed over a decade provides valuable clues and reference points for effective mycobacterial control. PMID:27015168

  19. Population Pharmacokinetics of Meropenem in Plasma and Cerebrospinal Fluid of Infants with Suspected or Complicated Intra-Abdominal Infections

    PubMed Central

    SMITH, P. BRIAN; COHEN-WOLKOWIEZ, MICHAEL; CASTRO, LISA M.; POINDEXTER, BRENDA; BIDEGAIN, MARGARITA; WEITKAMP, JOERN-HENDRIK; SCHELONKA, ROBERT L.; WARD, ROBERT M.; WADE, KELLY; VALENCIA, GLORIA; BURCHFIELD, DAVID; ARRIETA, ANTONIO; BHATT-MEHTA, VARSHA; WALSH, MICHELE; KANTAK, ANAND; RASMUSSEN, MAYNARD; SULLIVAN, JANICE E.; FINER, NEIL; BROZANSKI, BEVERLY S.; SANCHEZ, PABLO; ANKER, JOHN VAN DEN; BLUMER, JEFFREY; KEARNS, GREGORY L.; CAPPARELLI, EDMUND V.; ANAND, RAVINDER; BENJAMIN, DANIEL K.

    2011-01-01

    Background Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. Methods Premature and term infants <91 days of age hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20–30 mg/kg of body weight every 8–12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM®. Results Two hundred infants were enrolled and received study drug. One hundred eighty-eight infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23–40) weeks and 21 (1–92) days, respectively. In the final PK model, meropenem clearance (CL) was strongly associated with serum creatinine (SCR) and postmenstrual age (PMA) (CL [L/h/kg] = 0.12*[(0.5/SCR)**0.27]*[(PMA/32.7)**1.46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5–148). Conclusions Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants. PMID:21829139

  20. Drug Targets in Mycobacterial Sulfur Metabolism

    PubMed Central

    Bhave, Devayani P.; Muse, Wilson B.; Carroll, Kate S.

    2011-01-01

    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 in the development of inhibitors of sulfur metabolism enzymes. PMID:17970225

  1. A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections.

    PubMed

    Ma, Yan; Han, Fei; Liang, Jinping; Yang, Jiali; Shi, Juan; Xue, Jing; Yang, Li; Li, Yong; Luo, Meihui; Wang, Yujiong; Wei, Jun; Liu, Xiaoming

    2016-03-01

    Pulmonary tuberculosis caused by a Mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. To date, molecular mechanisms of the pathogenesis of TB are still incompletely understood. In addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for Mycobacteria infections. In an effort to understand the pathogen-host interaction between Mycobacteria and airway epithelial cells in domestic animals, in present study, we investigated the Toll-like receptor (TLR) signaling in bovine and sheep airway epithelial cells in response to an infection of Mycobacterium tuberculosis avirulent H37Ra stain or Mycobacterium bovis BCG vaccine strain, using primary air-liquid interface (ALI) bronchial epithelial culture models. Our results revealed a host and pathogen species-specific TLR-mediated recognition of pathogen-associated molecular patterns (PAMPs), induction and activation of TLR signaling pathways, and substantial induction of inflammatory response in bronchial epithelial cells in response to Mycobacteria infections between these two species. Interestingly, the activation TLR signaling in bovine bronchial epithelial cells induced by Mycobacteria infection was mainly through a myeloid differentiation factor 88 (MyD88)-independent TLR signaling pathway, while both MyD88-dependent and independent TLR signaling cascades could be induced in sheep epithelial cells. Equally noteworthy, a BCG infection was able to induce both MyD88-dependent and independent signaling in sheep and bovine airway epithelial cells, but more robust inflammatory responses were induced in sheep epithelial cells relative to the bovines; whereas an H37Ra infection displayed an ability to mainly trigger a MyD88-independent TLR signaling cascade in these two host species, and induce a more extent expression of

  2. Pelvic and abdominal-wall actinomycotic infection by uterus gateway without genital lesions.

    PubMed

    Brezean, I; Aldoescu, S; Catrina, E; Vâlcu, M; Ionuţ, I; Predescu, G; Degeratu, D; Pantea, I

    2010-01-01

    We hereby aim to account on a case of actinomycotic infection occurred in a female patient with an intrauterine contraceptive device (IUCD). The infection occurred as a pseudo-tumour which raised differential diagnosis issues with a malignant tumour. The diagnosis has been eventually established following the pathologic examination of paraffin-embedded tissues. Although the infection's gateway was the uterus, the subsequent invasion of the parietal, urinary bladder and lateral rectal walls did not seem to affect the fallopian tubes or the ovaries. PMID:20405693

  3. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Promoting effective immunity to Mycobacterium tuberculosis complex pathogens is a challenge that is of interest to the fields of human and veterinary medicine alike. We report that gamma delta T cells from virulent Mycobacterium bovis-infected cattle respond specifically and directly to complex, pro...

  4. Cutaneous mycobacterial spindle cell pseudotumour

    PubMed Central

    Tan, Geok Chin; Yap, Yen Piow; Shiran, Mohd Sidik; Sabariah, Abdul Rahman; Pathmanathan, Rajadurai

    2009-01-01

    Mycobacterial spindle cell pseudotumour (MSCP) has been reported in various sites, including skin, lymph nodes, bone marrow, lung and spleen. Cutaneous lesions are extremely rare and the differential diagnoses include various spindle cell lesions. Literature review shows that this lesion has preponderance for upper limb involvement and occurs largely in immunosuppressed individuals. We report a case of MSCP of the skin due to atypical mycobacterium and discuss the risk of misdiagnosis as a sarcoma. PMID:21686408

  5. Cutaneous mycobacterial spindle cell pseudotumour.

    PubMed

    Tan, Geok Chin; Yap, Yen Piow; Shiran, Mohd Sidik; Sabariah, Abdul Rahman; Pathmanathan, Rajadurai

    2009-01-01

    Mycobacterial spindle cell pseudotumour (MSCP) has been reported in various sites, including skin, lymph nodes, bone marrow, lung and spleen. Cutaneous lesions are extremely rare and the differential diagnoses include various spindle cell lesions. Literature review shows that this lesion has preponderance for upper limb involvement and occurs largely in immunosuppressed individuals. We report a case of MSCP of the skin due to atypical mycobacterium and discuss the risk of misdiagnosis as a sarcoma. PMID:21686408

  6. Clinical characteristics and antimicrobial patterns in complicated intra-abdominal infections: a 6-year epidemiological study in southern China.

    PubMed

    Ouyang, Wenwei; Xue, Huiling; Chen, Yunqin; Gao, Weiguo; Li, Xiaoyan; Wei, Jia; Wen, Zehuai

    2016-03-01

    Complicated intra-abdominal infection (cIAIs) are a common and important cause of morbidity worldwide. In this study, the clinical features, microbiological profiles, antimicrobial patterns and treatments of 3233 cIAI patients (mean age, 47.6 years; 54.7% male) with 3531 hospitalisations from 2008-2013 were retrospectively investigated. The most commonly isolated bacteria were Escherichia coli (47.6%), Klebsiella pneumoniae (16.9%), Enterococcus faecalis (10.4%) and Pseudomonas aeruginosa (8.8%). Ciprofloxacin, aminoglycoside (gentamicin), piperacillin/tazobactam and carbapenems exhibited activity against 53%, 76%, 88% and 100% of extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae isolates, respectively. Pseudomonas aeruginosa isolates exhibited 100%, 95%, 88%, 71% and 76% susceptibility to aminoglycoside (gentamicin), ciprofloxacin, meropenem, imipenem and ceftazidime, respectively, and Enterococcus remained 100% susceptible to vancomycin and linezolid. β-Lactam antibacterials other than penicillin (specifically third-generation cephalosporins) and imidazole derivatives (ornidazole and metronidazole) were the most common first-line treatments. Patients subjected to regimen change after initial antibiotic treatment had predisposing conditions (e.g. older age, more severe co-morbidities) and a higher incidence of P. aeruginosa infection; in addition, these patients encountered a higher average cost of care and worse clinical outcomes compared with those without medication modification. Taken together, these findings indicate the importance of appropriate initial empirical therapy and suggest the use of combination therapy comprising cephalosporins and metronidazole. PMID:26899413

  7. Epidemiology, assessment, and management of excess abdominal fat in persons with HIV infection.

    PubMed

    Moyle, Graeme; Moutschen, Michel; Martínez, Esteban; Domingo, Pere; Guaraldi, Giovanni; Raffi, François; Behrens, Georg; Reiss, Peter

    2010-01-01

    Metabolic and morphologic abnormalities in persons with HIV remain common contributors to stigma and morbidity. Increased abdominal circumference and visceral adiposity were first recognized in the late 1990s, soon after the advent of effective combination antiretroviral therapy. Visceral adiposity is commonly associated with metabolic abnormalities including low HDL-cholesterol, raised triglycerides, insulin resistance, and hypertension, a constellation of risk factors for cardiovascular disease and diabetes mellitus known as "the metabolic syndrome". Medline and conference abstracts were searched to identify clinical research on factors associated with visceral adiposity and randomized studies of management approaches. Data were critically reviewed by physicians familiar with the field. A range of host and lifestyle factors as well as antiretroviral drug choice were associated with increased visceral adiposity. Management approaches included treatment switching and metformin, both of which have shown benefit for insulin-resistant individuals with isolated fat accumulation. Testosterone supplements may also have benefits in a subset of individuals. Supra-physiological doses of recombinant human growth hormone and the growth hormone releasing hormone analog tesamorelin both significantly and selectively reduce visceral fat over 12-24 weeks; however, the benefits are only maintained if doping is continued. In summary, the prevention and management of visceral adiposity remains a substantial challenge in clinical practice. PMID:20216906

  8. Judicious use of prophylactic antimicrobials to reduce abdominal surgical site infections in periparturient cows: part 1 - a risk factor review.

    PubMed

    Dumas, S E; French, H M; Lavergne, S N; Ramirez, C R; Brown, L J; Bromfield, C R; Garrett, E F; French, D D; Aldridge, B M

    2016-06-25

    Surgical site infections (SSI) are an uncommon, but significant, consequence of surgical interventions. There are very few studies investigating SSI risk in veterinary medicine, and even fewer in cattle, despite the fact that major surgeries are commonly conducted on livestock. Furthermore, the suboptimal conditions under which such surgeries are frequently performed on livestock could be considered an important risk factor for the development of SSIs. With increasing public concern over the contribution of veterinary-prescribed antimicrobials to the emergence of antimicrobial-resistant bacteria in people, there is widespread scrutiny and criticism of antimicrobial use in livestock production medicine systems. While the causal link between antimicrobial resistance in livestock and people is heavily debated, it is clear that the prevalence of antimicrobial resistance, in any population, is closely correlated with the antimicrobial 'consumption' within that population. As the veterinary profession explores ways of addressing the emergence and selection of antimicrobial-resistant bacteria in food-producing animals, there is a need for veterinarians and producers to carefully consider all areas of antimicrobial use, and employ an evidence-based approach in designing appropriate clinical protocols. This paper aims to review current knowledge regarding the risk factors related to abdominal SSI in periparturient cows, and to encourage practitioners to judiciously evaluate both their standard operating procedures and their use of antimicrobials in these situations. In a second paper, to be published in a subsequent issue of Veterinary Record, these principles will be used to provide specific evidence-based recommendations for antimicrobial use in bovine abdominal surgery. PMID:27339926

  9. Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group.

    PubMed Central

    Solomkin, J S; Reinhart, H H; Dellinger, E P; Bohnen, J M; Rotstein, O D; Vogel, S B; Simms, H H; Hill, C S; Bjornson, H S; Haverstock, D C; Coulter, H O; Echols, R M

    1996-01-01

    OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. CONCLUSIONS: These results demonstrate statistical equivalence

  10. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab′)2 fragment prolong survival of mice infected with Mycobacterium tuberculosis

    PubMed Central

    HAMASUR, B; HAILE, M; PAWLOWSKI, A; SCHRÖDER, U; KÄLLENIUS, G; SVENSON, S B

    2004-01-01

    Lipoarabinomannan (LAM) is a major structural carbohydrate antigen of the outer surface of Mycobacterium tuberculosis. High antibody titres against LAM are often seen in active tuberculosis (TB). The role of such LAM-specific antibodies in the immune response against TB is unknown. Here we have investigated a monoclonal antibody (MoAb) SMITB14 of IgG1 subclass and its corresponding F(ab′)2 fragment directed against LAM from M. tuberculosis strain H37Rv. MoAb SMITB14 was shown by immunofluorescence to bind to whole cells of the clinical isolate M. tuberculosis strain Harlingen as well as to M. tuberculosis H37Rv. The binding of MoAb SMITB14 to LAM was inhibited by arabinomannan (AM) and oligosaccharides (5·2 kDa) derived from LAM, showing that the MoAb binds specifically to the AM carbohydrate portion of LAM. In passive protection experiments BALB/c mice were infected intravenously with M. tuberculosis Harlingen. MoAb SMITB14 was added intravenously either prior to, or together with, the bacteria. The antibody proved to be protective against the M. tuberculosis infection in terms of a dose-dependent reduction in bacterial load in spleens and lungs, reduced weight loss and, most importantly, increased long-term survival. PMID:15373902

  11. Mycobacterium lentiflavum, a recently identified slow-growing mycobacterial species: clinical significance in immunosuppressed cancer patients and summary of reported cases of infection.

    PubMed

    Safdar, A; Han, X Y

    2005-08-01

    The clinical significance of Mycobacterium lentiflavum, a recently identified nontuberculous mycobacterium, remains uncertain, especially in immunosuppressed cancer patients. The records of all patients in whom M. lentiflavum was identified using a gene sequencing technique between January 2001 and December 2003 were reviewed. The mean age among 12 patients was 51+/-20 years, and 11 (92%) patients had a hematologic malignancy. Six of seven (86%) hematopoietic stem cell transplant recipients had received allogeneic donor grafts. Nine (75%) patients had predisposing risk factors for infection, seven (58%) had severe lymphocytopenia (<400 cells/microl), five (42%) were receiving systemic corticosteroid therapy, and three (25%) had acute graft-versus-host disease. Only 1 of the 12 (8%) patients had evidence of probable pulmonary M. lentiflavum infection. Six M. lentiflavum strains were initially misidentified as Mycobacterium simiae and Mycobacterium avium-intracellulare complex using traditional biochemical tests. Four M. lentiflavum isolates were tested for antimicrobial susceptibility; they were susceptible to isoniazid, ethambutol, clarithromycin, and amikacin, and resistant to rifampin. M. lentiflavum was not clinically significant, even in these severely immunosuppressed cancer patients. PMID:16133412

  12. The Macrophage-Specific Promoter mfap4 Allows Live, Long-Term Analysis of Macrophage Behavior during Mycobacterial Infection in Zebrafish

    PubMed Central

    Walton, Eric M.; Cronan, Mark R.; Beerman, Rebecca W.; Tobin, David M.

    2015-01-01

    Transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. To date, labeling of zebrafish macrophages has been relatively limited, with the most specific expression coming from the mpeg1 promoter. However, mpeg1 transcription at both endogenous and transgenic loci becomes attenuated in the presence of intracellular pathogens, including Salmonella typhimurium and Mycobacterium marinum. Here, we describe mfap4 as a macrophage-specific promoter capable of producing transgenic lines in which transgene expression within larval macrophages remains stable throughout several days of infection. Additionally, we have developed a novel macrophage-specific Cre transgenic line under the control of mfap4, enabling macrophage-specific expression using existing floxed transgenic lines. These tools enrich the repertoire of transgenic lines and promoters available for studying zebrafish macrophage dynamics during infection and inflammation and add flexibility to the design of future macrophage-specific transgenic lines. PMID:26445458

  13. Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study

    PubMed Central

    2012-01-01

    The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012). This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period. Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 912 patients with a mean age of 54.4 years (range 4–98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified. The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality. White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality. PMID:22613202

  14. In Vitro Responsiveness of γδ T Cells from Mycobacterium bovis-Infected Cattle to Mycobacterial Antigens: Predominant Involvement of WC1+ Cells

    PubMed Central

    Smyth, Allister J.; Welsh, Michael D.; Girvin, R. Martyn; Pollock, John M.

    2001-01-01

    It is generally accepted that protective immunity against tuberculosis is generated through the cell-mediated immune (CMI) system, and a greater understanding of such responses is required if better vaccines and diagnostic tests are to be developed. γδ T cells form a major proportion of the peripheral blood mononuclear cells (PBMC) in the ruminant system and, considering data from other species, may have a significant role in CMI responses in bovine tuberculosis. This study compared the in vitro responses of αβ and γδ T cells from Mycobacterium bovis-infected and uninfected cattle. The results showed that, following 24 h of culture of PBMC with M. bovis-derived antigens, the majority of γδ T cells from infected animals became highly activated (upregulation of interleukin-2R), while a lower proportion of the αβ T-cell population showed activation. Similar responses were evident to a lesser degree in uninfected animals. Study of the kinetics of this response showed that γδ T cells remained significantly activated for at least 7 days in culture, while activation of αβ T cells declined during that period. Subsequent analysis revealed that the majority of activated γδ T cells expressed WC1, a 215-kDa surface molecule which is not expressed on human or murine γδ T cells. Furthermore, in comparison with what was found for CD4+ T cells, M. bovis antigen was found to induce strong cellular proliferation but relatively little gamma interferon release by purified WC1+ γδ T cells. Overall, while the role of these cells in protective immunity remains unclear, their highly activated status in response to M. bovis suggests an important role in antimycobacterial immunity, and the ability of γδ T cells to influence other immune cell functions remains to be elucidated, particularly in relation to CMI-based diagnostic tests. PMID:11119493

  15. Mycobacterium tuberculosis Zinc Metalloprotease-1 Assists Mycobacterial Dissemination in Zebrafish.

    PubMed

    Vemula, Mani H; Medisetti, Raghavender; Ganji, Rakesh; Jakkala, Kiran; Sankati, Swetha; Chatti, Kiranam; Banerjee, Sharmistha

    2016-01-01

    Zinc metalloprotease-1 (Zmp1) from Mycobacterium tuberculosis (M.tb), the tuberculosis (TB) causing bacillus, is a virulence factor involved in inflammasome inactivation and phagosome maturation arrest. We earlier reported that Zmp1 was secreted under granuloma-like stress conditions, induced Th2 cytokine microenvironment and was highly immunogenic in TB patients as evident from high anti-Zmp1 antibody titers in their sera. In this study, we deciphered a new physiological role of Zmp1 in mycobacterial dissemination. Exogenous treatment of THP-1 cells with 500 nM and 1 μM of recombinant Zmp1 (rZmp1) resulted in necrotic cell death. Apart from inducing secretion of necrotic cytokines, TNFα, IL-6, and IL-1β, it also induced the release of chemotactic chemokines, MCP-1, MIP-1β, and IL-8, suggesting its likely function in cell migration and mycobacterial dissemination. This was confirmed by Gap closure and Boyden chamber assays, where Zmp1 treated CHO or THP-1 cells showed ∼2 fold increased cell migration compared to the untreated cells. Additionally, Zebrafish-M. marinum based host-pathogen model was used to study mycobacterial dissemination in vivo. Td-Tomato labeled M. marinum (TdM. marinum) when injected with rZmp1 showed increased dissemination to tail region from the site of injection as compared to the untreated control fish in a dose-dependent manner. Summing up these observations along with the earlier reports, we propose that Zmp1, a multi-faceted protein, when released by mycobacteria in granuloma, may lead to necrotic cell damage and release of chemotactic chemokines by surrounding infected macrophages, attracting new immune cells, which in turn may lead to fresh cellular infections, thus assisting mycobacterial dissemination. PMID:27621726

  16. Mycobacterium tuberculosis Zinc Metalloprotease-1 Assists Mycobacterial Dissemination in Zebrafish

    PubMed Central

    Vemula, Mani H.; Medisetti, Raghavender; Ganji, Rakesh; Jakkala, Kiran; Sankati, Swetha; Chatti, Kiranam; Banerjee, Sharmistha

    2016-01-01

    Zinc metalloprotease-1 (Zmp1) from Mycobacterium tuberculosis (M.tb), the tuberculosis (TB) causing bacillus, is a virulence factor involved in inflammasome inactivation and phagosome maturation arrest. We earlier reported that Zmp1 was secreted under granuloma-like stress conditions, induced Th2 cytokine microenvironment and was highly immunogenic in TB patients as evident from high anti-Zmp1 antibody titers in their sera. In this study, we deciphered a new physiological role of Zmp1 in mycobacterial dissemination. Exogenous treatment of THP-1 cells with 500 nM and 1 μM of recombinant Zmp1 (rZmp1) resulted in necrotic cell death. Apart from inducing secretion of necrotic cytokines, TNFα, IL-6, and IL-1β, it also induced the release of chemotactic chemokines, MCP-1, MIP-1β, and IL-8, suggesting its likely function in cell migration and mycobacterial dissemination. This was confirmed by Gap closure and Boyden chamber assays, where Zmp1 treated CHO or THP-1 cells showed ∼2 fold increased cell migration compared to the untreated cells. Additionally, Zebrafish-M. marinum based host–pathogen model was used to study mycobacterial dissemination in vivo. Td-Tomato labeled M. marinum (TdM. marinum) when injected with rZmp1 showed increased dissemination to tail region from the site of injection as compared to the untreated control fish in a dose-dependent manner. Summing up these observations along with the earlier reports, we propose that Zmp1, a multi-faceted protein, when released by mycobacteria in granuloma, may lead to necrotic cell damage and release of chemotactic chemokines by surrounding infected macrophages, attracting new immune cells, which in turn may lead to fresh cellular infections, thus assisting mycobacterial dissemination. PMID:27621726

  17. Treatment of Disseminated Mycobacterial Infection with High-Dose IFN-γ in a Patient with IL-12Rβ1 Deficiency

    PubMed Central

    Alangari, Abdullah A.; Al-Zamil, Fahad; Al-Mazrou, Abdulrahman; Al-Muhsen, Saleh; Boisson-Dupuis, Stéphanie; Awadallah, Sitalbanat; Kambal, Abdelmageed; Casanova, Jean-Laurent

    2011-01-01

    IFN-γ has been used in the treatment of IL-12Rβ1 deficiency patients with disseminated BCG infection (BCGosis), but the optimal dose to reach efficacy is not clear. We used IFN-γ in the treatment of a 2.7-year-old patient with IL-12Rβ1 deficiency and refractory BCG-osis. IFNγ was started at a dose of 50 μg/m2 3 times per week. The dose was upgraded to 100 mcg/m2 after 3 months, then to 200 mcg/m2 6 months afterwards. Serum mycobactericidal activity and lymphocytes number and function were evaluated throughout the study. There was no clinical response to IFN-γ with 50 or 100 μg/m2 doses. However, there was some response to the 200 μg/m2 dose with no additional adverse effects. The serum mycobactericidal activity was not significantly different during the whole treatment period. Lymphocytes proliferation in response to PHA was significantly higher after 3 months of using the highest dose as compared to the lowest dose. The tuberculin skin test reaction remained persistently negative. We conclude that in a patient with IL-12Rβ1 deficiency, IFN-γ at a dose of 200 μg/m2, but not at lower dosages, was found to have a noticeable clinical effect with no additional adverse effects. PMID:21234109

  18. Abdominal Adhesions

    MedlinePlus

    ... Abdominal Adhesions 1 Ward BC, Panitch A. Abdominal adhesions: current and novel therapies. Journal of Surgical Research. 2011;165(1):91– ... are abdominal adhesions and intestinal obstructions ... generally do not require treatment. Surgery is the only way to treat abdominal ...

  19. Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

    PubMed

    Hidalgo, Jose A; Vinluan, Celeste M; Antony, Nishaal

    2016-01-01

    There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz(®), the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations. PMID:27528799

  20. Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections

    PubMed Central

    Hidalgo, Jose A; Vinluan, Celeste M; Antony, Nishaal

    2016-01-01

    There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz®, the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations. PMID:27528799

  1. Superthin Abdominal Wall Glove-Like Flap Combined With Vacuum-Assisted Closure Therapy for Soft Tissue Reconstruction in Severely Burned Hands or With Infection.

    PubMed

    Wang, Fei; Liu, Sheng; Qiu, Le; Ma, Ben; Wang, Jian; Wang, Yong-Jie; Peszel, April; Chen, Xu-Lin

    2015-12-01

    Severe burn and infection to hands always involves the deep structures, such as tendons, joints, and bones. These wounds cannot be closed immediately and therefore creates a high risk for complication. We presented 9 cases with deep dermal burns to the dorsal of the hand (6 electrical burns and 3 thermal crush injuries) with wound infections in 2 cases. The vacuum-assisted closure system was used continuously until the flap reconstruction was performed. A random pattern and superthin abdominal wall skin flap-like glove was designed. The flap was transferred to the defected portion of the dorsum of the hand and resected from the abdominal wall about 3 weeks later. The flaps in 8 of the patients treated by this technique survived completely and partial necrosis of the distal flap occurred in 1 patient. The defect resolved after operative treatment and the function of the hands and fingers were successfully salvaged. All patients resulted in having a satisfactory aesthetic outcome with no or minor discomfort at the abdominal donor area. Integration of the vacuum-assisted closure system and the superthin abdominal wall glove-like flap reconstruction appeared to be successful and should be considered in patients with severely burned hands. PMID:26418768

  2. Inhibitors Selective for Mycobacterial Versus Human Proteasomes

    SciTech Connect

    Lin, G.; Li, D; Sorio de Carvalho, L; Deng, H; Tao, H; Vogt, G; Wu, K; Schneider, J; Chidawanyika, T; et. al.

    2009-01-01

    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-one 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.

  3. OUTCOMES OF CLOSTRIDIUM DIFFICILE INFECTION IN RECIPIENTS OF SOLID ABDOMINAL ORGAN TRANSPLANTS

    PubMed Central

    Hsu, Jennifer L.; Enser, James J.; McKown, Trevor; Leverson, Glen E.; Pirsch, John D.; Hess, Timothy M.; Safdar, Nasia

    2016-01-01

    Knowledge of outcomes of C. difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 years. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 days. In a multivariate analysis, lack of clinical cure at 14 days was predicted by: recurrent episode (0.21, 95% CI 0.06-0.72, p=0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1-0.74, p=0.011), vasopressor support (OR 0.23, 95% CI 0.07-0.76, p=0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2-0.98, p=0.0446.) The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization and 49 patients (29%) died within one year. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed. PMID:24476412

  4. Comparative Gamma Delta T Cell Immunology: A Focus on Mycobacterial Disease in Cattle

    PubMed Central

    Plattner, Brandon L.; Hostetter, Jesse M.

    2011-01-01

    A theme among many pathogenic mycobacterial species affecting both humans and animals is a prolonged asymptomatic or latent period that can last years to decades. The mechanisms that favor progression to active disease are not well understood. Pathogen containment is often associated with an effective cell-mediated or T-helper 1 immune profile. With certain pathogenic mycobacteria, such as Mycobacterium avium subspecies paratuberculosis, a shift to active clinical disease is associated with loss of T-helper 1 immunity and development of an ineffective humoral or T-helper 2 immune response. Recently γδ T cells have been shown to play a role early in mycobacterial infections and have been hypothesized to influence disease outcome. The purpose of this paper is to compare recent advancements in our understanding of γδ T cells in humans, cattle, and mice and to discuss roles of γδ T cells in host response to mycobacterial infection. PMID:21647391

  5. The treatment of rapidly growing mycobacterial infections.

    PubMed

    Kasperbauer, Shannon H; De Groote, Mary Ann

    2015-03-01

    Rapidly growing mycobacteria (RGM) include a diverse group of species. We address the treatment of the most commonly isolated RGM-M abscessus complex, M fortuitum, and M chelonae. The M abscessus complex is composed of 3 closely related species: M abscessus senso stricto (hereafter M abscessus), M massiliense, and M bolletii. Most studies address treatment of M abscessus complex, which accounts for 80% of lung disease caused by RGM and is the second most common RGM to cause extrapulmonary disease (after M fortuitum). The M abscessus complex represent the most drug-resistant nontuberculous mycobacteria and are the most difficult to treat. PMID:25676520

  6. Twenty Years of Mycobacterial Glycans: Furanosides and Beyond.

    PubMed

    Lowary, Todd L

    2016-07-19

    galactofuranose residues. These molecules have now found application in biochemical, immunological, and structural biology investigations, which have shed light on their biosynthesis and how these motifs are recognized by both the innate and adaptive immune systems. More recently, attention has been directed toward the synthesis of another class of immunologically active mycobacterial cell wall glycans, the extractable glycolipids. In this case, efforts have been primarily on phenolic glycolipids, and the compounds synthesized have been used to evaluate their ability to modulate cytokine release. Over the past 20 years, the use of chemical synthesis to provide increasingly complex glycan structures has provided significant benefit to the burgeoning field of mycobacterial glycobiology. Through the efforts of groups from around the globe, access to these compounds is now possible via relatively straightforward methods. As the pool of mycobacterial glycans continues to grow, so too will our understanding of their role in disease, which will undoubtedly lead to new strategies to prevent or treat mycobacterial infections. PMID:27294709

  7. Abdominal mass

    MedlinePlus

    Several conditions can cause an abdominal mass: Abdominal aortic aneurysm can cause a pulsating mass around the navel. ... This could be a sign of a ruptured aortic aneurysm, which is an emergency condition. Contact your health ...

  8. Abdominal mass

    MedlinePlus

    ... Several conditions can cause an abdominal mass: Abdominal aortic aneurysm can cause a pulsating mass around the navel. ... This could be a sign of a ruptured aortic aneurysm, which is an emergency condition. Contact your health ...

  9. Biosynthesis of mycobacterial phosphatidylinositol mannosides.

    PubMed Central

    Morita, Yasu S; Patterson, John H; Billman-Jacobe, Helen; McConville, Malcolm J

    2004-01-01

    All mycobacterial species, including pathogenic Mycobacterium tuberculosis, synthesize an abundant class of phosphatidylinositol mannosides (PIMs) that are essential for normal growth and viability. These glycolipids are important cell-wall and/or plasma-membrane components in their own right and can also be hyperglycosylated to form other wall components, such as lipomannan and lipoarabinomannan. We have investigated the steps involved in the biosynthesis of the major PIM species in a new M. smegmatis cell-free system. A number of apolar and polar PIM intermediates were labelled when this system was continuously labelled or pulse-chase-labelled with GDP-[3H]Man, and the glycan head groups and the acylation states of these species were determined by chemical and enzymic treatments and octyl-Sepharose chromatography respectively. These analyses showed that (1) the major apolar PIM species, acyl-PIM2, can be synthesized by at least two pathways that differ in the timing of the first acylation step, (2) early PIM intermediates containing a single mannose residue can be modified with two fatty acid residues, (3) formation of polar PIM species from acyl-PIM2 is amphomycin-sensitive, indicating that polyprenol phosphate-Man, rather than GDP-Man, is the donor for these reactions, (4) modification of acylated PIM4 with alpha1-2- or alpha1-6-linked mannose residues is probably the branch point in the biosyntheses of polar PIM and lipoarabinomannan respectively and (5) GDP strongly inhibits the synthesis of early PIM intermediates and increases the turnover of polyprenol phosphate-Man. These findings are incorporated into a revised pathway for mycobacterial PIM biosynthesis. PMID:14627436

  10. KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients

    PubMed Central

    2013-01-01

    Background Abdominal surgery carries significant morbidity and mortality, which is in turn associated with an enormous use of healthcare resources. We describe the clinical course of 30 Intensive Care Unit (ICU) patients who underwent abdominal surgery and showed severe infections caused by Klebsiella pneumoniae sequence type (ST) 258 producing K. pneumoniae carbapenemase (KPC-Kp). The aim was to evaluate risk factors for mortality and the impact of a combination therapy of colistin plus recommended regimen or higher dosage of tigecycline. Methods A prospective assessment of severe monomicrobial KPC-Kp infections occurring after open abdominal surgery carried out from August 2011 to August 2012 in the same hospital by different surgical teams is presented. Clinical and surgical characteristics, microbiological and surveillance data, factors associated with mortality and treatment regimens were analyzed. A combination regimen of colistin with tigecycline was used. A high dose of tigecycline was administered according to intra-abdominal abscess severity and MICs for tigecycline. Results The mean age of the patients was 56.6 ± 15 and their APACHE score on admission averaged 22.72. Twenty out of 30 patients came from the surgical emergency unit. Fifteen patients showed intra-abdominal abscess, eight anastomotic leakage, four surgical site infection (SSI) and three peritonitis. The overall crude ICU mortality rate was 40% (12 out of 30 patients). Twelve of the 30 patients were started on a combination treatment of high-dose tigecycline and intravenous colistin. A significantly lower mortality rate was observed among those patients compared to patients treated with approved dose of tigecycline plus colistin. No adverse events were reported with high doses of tigecycline. Conclusions Critically-ill surgical patients are prone to severe post-surgical infectious complications caused by KPC-Kp. Timely microbiological diagnosis and optimizing antibiotic dosing regimens

  11. Outbreak of nontuberculous mycobacterial disease in the central Pacific.

    PubMed

    Lillis, Joseph V; Ansdell, David

    2011-01-01

    Approximately 10% of the island population of Satowan (population, 650 persons), a small, remote coral island in the central Pacific, suffers from an acquired, chronic, disfiguring skin condition known locally as "spam." This skin disease has affected the island population since shortly after World War II. An investigation in 2007 revealed that this skin disease is caused by a nontuberculous mycobacterial infection closely related to Mycobacterium marinum. This article reviews the fascinating history of this skin disease on Satowan, its distinctive clinical presentation, and recommendations for diagnosis and treatment of clinically similar skin lesions in Pacific Islanders. PMID:21095522

  12. Personalized medicine approach in mycobacterial disease

    PubMed Central

    Mirsaeidi, Mehdi

    2014-01-01

    Mycobacterial diseases are a group of illnesses that cause a considerable number of deaths throughout the world, regardless of years of public health control efforts. Personalized medicine is a new but rapidly advancing field of healthcare. Personalized medicine in the field of mycobacteriology may be applied in the different levels of management such as prevention, diagnosis, treatment and prognosis. A genetic predisposition and a protein dysfunction study are recommended to tailor an individual approach in mycobacterial diseases. PMID:25126491

  13. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

    PubMed Central

    Dartois, Véronique

    2015-01-01

    For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. However, most currently used anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution, and this has contributed to the long duration and limited success of current therapies. In this Progress article, I describe new methods to quantify and image drug distribution in infected lung tissue and in mycobacterial cells, and I explore how this technology could be used to design optimized multidrug regimens. PMID:24487820

  14. Case report of fatal Mycobacterium tilburgii infection.

    PubMed

    Akpinar, Timur; Bakkaloglu, Oguz K; Ince, Burak; Tufan, Fatih; Kose, Murat; Poda, Mehves; Tascioglu, Didem; Koksalan, O Kaya; Saka, Bulent; Erten, Nilgun; Buyukbabani, Nesimi; Kilicaslan, Zeki; Tascioglu, Cemil

    2015-07-01

    There are few reports concerning Mycobacterium tilburgii infection in humans because this bacterium is non-cultivatable. Herein, using new molecular techniques, we report the case of an immunocompromised patient with fatal disseminated lymphadenitis that was caused by M. tilburgii.26 years old Caucasian HIV negative female patient presented with abdominal pain. Her clinical assessment revealed disseminated lymphadenitis, that was acid fast bacilli positive. Further molecular evaluation showed the causative agent as M. tilburgii. Despite anti mycobacterial therapy and careful management of intervening complications patient died because of an intraabdominal sepsis. This is the first fatal M. tilburgii infection in the literature. This case points the importance of careful management of patient's immune status and intervening infections besides implementation of effective drug treatment. PMID:25818194

  15. Disseminated herpes zoster infection initially presenting with abdominal pain in patients with lymphoma undergoing conventional chemotherapy: A report of three cases

    PubMed Central

    Okuma, Hitomi Sumiyoshi; Kobayashi, Yukio; Makita, Shinichi; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Suzuki, Tatsuya; Maruyama, Dai; Tobinai, Kensei

    2016-01-01

    Visceral disseminated varicella zoster virus (VZV) disease has a high mortality rate, and occurs in immunocompromised hosts, mostly subsequent to allogeneic stem cell transplantation. Only a few cases of this disease that onset during conventional chemotherapy in patients with lymphoma have been reported. The present study reports the cases of 3 patients with disseminated and visceral VZV infection undergoing treatment for follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. All 3 patients presented with initial symptoms of abdominal pain, and 2 patients demonstrated syndrome of inappropriate antidiuretic hormone and hepatitis. All patients developed widespread cutaneous dissemination, and all had a low cluster of differentiation 4 cell count or lymphocyte count at the time of VZV diagnosis and at least 4 month prior. With intravenous systemic acyclovir therapy (Cases 1 and 3, 1500 mg/day; Case 2, 750 mg/day), the patients achieved complete recovery by day 14 of therapy. Visceral disseminated VZV infection is not limited to patients undergoing stem cell transplantation, and may present with abdominal pain with or without skin eruption. Visceral infection may take a poor clinical course, therefore, in patients with prolonged duration of low lymphocyte count and/or long-term use of steroids, the prophylactic use of acyclovir may be considered. PMID:27446355

  16. Detection of abdominal aortic graft infection: comparison of CT and In-labeled white blood cell scans

    SciTech Connect

    Mark, A.S.; McCarthy, S.M.; Moss, A.A.; Price, D.

    1985-02-01

    Aortic graft infections are a rare but potentially lethal complication of aortic graft surgery. The diagnosis and assessment of the extent of a graft infection is difficult on clinical grounds. A prospective study compared CT and indium-labeled white blood cell (In-WBC) scans in the diagnosis of aortic graft infection. Five patients with aortic graft infection and three patients without aortic graft infection were studied by both methods. CT correctly detected the retroperitoneal extension of the infection in three patients with groin infection; In-WBC scans diagnosed the extension only in one patient. Both CT and In-WBC were positive in two patients with aortic graft infection but no groin infection. Both studies were negative in the three patients without evidence of aortic graft infection. The study suggests that CT is more sensitive than In-WBC in evaluating the extent of aortic graft infection and should be the imaging method of choice.

  17. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  18. Moxifloxacin-loaded nanoemulsions having tocopheryl succinate as the integral component improves pharmacokinetics and enhances survival in E. coli-induced complicated intra-abdominal infection.

    PubMed

    Shukla, Prashant; Verma, Ajeet Kumar; Dwivedi, Pankaj; Yadav, Arti; Gupta, Pramod Kumar; Rath, Srikanta Kumar; Mishra, Prabhat Ranjan

    2014-12-01

    In the present work, a novel nanoemulsion laden with moxifloxacin has been developed for effective management of complicated intra-abdominal infections. Moxifloxacin nanoemulsion fabricated using high pressure homogenization was evaluated for various pharmaceutical parameters, pharmacokinetics (PK) and pharmacodynamics (PD) in rats with E. coli-induced peritonitis and sepsis. The developed nanoemulsion MONe6 (size 168 ± 28 nm and zeta potential (ZP) 24.78 ± 0.45 mV, respectively) was effective for intracellular delivery and sustaining the release of MOX. MONe6 demonstrated improved plasma (AUC(MONe6/MOX) = 2.38-fold) and tissue pharmacokinetics of MOX (AUC(MONe6/MOX) = 2.63 and 1.47 times in lung and liver, respectively). Calculated PK/PD index correlated well with a reduction in bacterial burden in plasma as well as tissues. Enhanced survival on treatment with MONe6 (65.44%) and as compared to the control group (8.22%) was a result of reduction in lipid peroxidation, neutrophil migration, and cytokine levels (TNF-α and IL6) as compared to untreated groups in the rat model of E. coli-induced sepsis. Parenteral nanoemulsions of MOX hold a promising advantage in the therapy of E. coli-induced complicated intra-abdominal infections and is helpful in the prevention of further complications like septic shock and death. PMID:25317848

  19. microRNAs in mycobacterial disease: friend or foe?

    PubMed Central

    Mehta, Manali D.; Liu, Philip T.

    2014-01-01

    As the role of microRNA in all aspects of biology continues to be unraveled, the interplay between microRNAs and human disease is becoming clearer. It should come of no surprise that microRNAs play a major part in the outcome of infectious diseases, since early work has implicated microRNAs as regulators of the immune response. Here, we provide a review on how microRNAs influence the course of mycobacterial infections, which cause two of humanity’s most ancient infectious diseases: tuberculosis and leprosy. Evidence derived from profiling and functional experiments suggests that regulation of specific microRNAs during infection can either enhance the immune response or facilitate pathogen immune evasion. Now, it remains to be seen if the manipulation of host cell microRNA profiles can be an opportunity for therapeutic intervention for these difficult-to-treat diseases. PMID:25076967

  20. Abdominal sounds

    MedlinePlus

    ... during sleep. They also occur normally for a short time after the use of certain medicines and after abdominal surgery. Decreased or absent bowel sounds often indicate constipation. Increased ( hyperactive ) bowel sounds ...

  1. Abdominal MRI

    MedlinePlus

    ... provider if you have: Artificial heart valves Brain aneurysm clips Heart defibrillator or pacemaker Inner ear (cochlear) ... which the test may be performed: Abdominal aortic aneurysm Atheroembolic renal disease Carcinoma of the renal pelvis ...

  2. Abdominal pain

    MedlinePlus

    ... threatening conditions, such as colon cancer or early appendicitis , may only cause mild pain or no pain. ... Food poisoning Stomach flu Other possible causes include: Appendicitis Abdominal aortic aneurysm (bulging and weakening of the ...

  3. Abdominal Pain

    MedlinePlus

    ... can help the overall situation for the child. Teaching kids self-hypnosis [8] or guided imagery [8a] ... related topics? Functional Abdominal Pain (English, French or Spanish)—from The North American Society for Pediatric Gastroenterology, ...

  4. Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production

    PubMed Central

    Yang, Kun; Wu, Yongjian; Xie, Heping; Li, Miao; Ming, Siqi; Li, Liyan; Li, Meiyu; Wu, Minhao; Gong, Sitang; Huang, Xi

    2016-01-01

    Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. PMID:27251437

  5. Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production.

    PubMed

    Yang, Kun; Wu, Yongjian; Xie, Heping; Li, Miao; Ming, Siqi; Li, Liyan; Li, Meiyu; Wu, Minhao; Gong, Sitang; Huang, Xi

    2016-01-01

    Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. PMID:27251437

  6. Clinical and Economic Consequences of Failure of Initial Antibiotic Therapy for Patients with Community-Onset Complicated Intra-Abdominal Infections

    PubMed Central

    Chong, Yong Pil; Bae, In-Gyu; Lee, Sang-Rok; Chung, Jin-Won; Jun, Jae-Bum; Choo, Eun Ju; Moon, Soo-youn; Lee, Mi Suk; Jeon, Min Hyok; Song, Eun Hee; Lee, Eun Jung; Park, Seong Yeon; Kim, Yang Soo

    2015-01-01

    Objectives Complicated intra-abdominal infection (cIAI) is infection that extends beyond the hollow viscus of origin into the peritoneal space, and is associated with either abscess formation or peritonitis. There are few studies that have assessed the actual costs and outcomes associated with failure of initial antibiotic therapy for cIAI. The aims of this study were to evaluate risk factors and impact on costs and outcomes of failure of initial antibiotic therapy for community-onset cIAI. Methods A retrospective study was performed at eleven tertiary-care hospitals. Hospitalized adults with community-onset cIAI who underwent an appropriate source control procedure between August 2008 and September 2011 were included. Failure of initial antibiotic therapy was defined as a change of antibiotics due to a lack of improvement of the clinical symptoms and signs associated with cIAI in the first week. Results A total of 514 patients hospitalized for community-onset cIAI were included in the analysis. The mean age of the patients was 53.3 ± 17.6 years, 72 patients (14%) had health care-associated infection, and 48 (9%) experienced failure of initial antibiotic therapy. Failure of initial antibiotic therapy was associated with increased costs and morbidity. After adjustment for covariates, patients with unsuccessful initial therapy received an additional 2.9 days of parenteral antibiotic therapy, were hospitalized for an additional 5.3 days, and incurred $3,287 in additional inpatient charges. Independent risk factors for failure of initial antibiotic therapy were health care-associated infection, solid cancer, and APACHE II ≥13. Conclusions To improve outcomes and costs in patients with community-onset cIAI, rapid assessment of health care-associated risk factors and severity of disease, selection of an appropriate antibiotic regimen accordingly, and early infection source control should be performed. PMID:25910171

  7. 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

  8. [A case of abdominal wall actinomycosis].

    PubMed

    Kim, Kyung Hoon; Lee, Jin Soo; Cho, Hyeong Jun; Choi, Seung Bong; Cheung, Dae Young; Kim, Jin Il; Lee, In Kyu

    2015-04-01

    Actinomycosis is a chronic suppurative granulomatous infectious disease caused by actinomyces species that is characterized by formation of characteristic clumps called as sulfur granules. Abdominal actinomycosis is a rare disease and is often difficult to diagnose before operation. Abdominal actinomycosis infiltrating into the abdominal wall and adhering to the colon is even rarer. Most abdominal actinomycosis develops after operation, trauma or inflammatory bowel disease, and is also considered as an opportunistic infection in immunocompromised patient with underlying malignancy, diabetes mellitus, human immunodeficiency virus infection, etc. Actinomycosis is diagnosed based on histologic demonstration of sulfur granules in surgically resected specimen or pus, and treatment consists of long-term penicillin based antibiotics therapy with or without surgical resection. Herein, we report an unusual case of abdominal wall actinomycosis which developed in a patient after acupuncture and presented as abdominal wall mass that was first mistaken for abdominal wall invasion of diverticulum perforation. PMID:25896158

  9. Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

    PubMed Central

    Meyhoff, Christian S; Wetterslev, Jørn; Jorgensen, Lars N; Henneberg, Steen W; Simonsen, Inger; Pulawska, Therese; Walker, Line R; Skovgaard, Nina; Heltø, Kim; Gocht-Jensen, Peter; Carlsson, Palle S; Rask, Henrik; Karim, Sharaf; Carlsen, Charlotte G; Jensen, Frank S; Rasmussen, Lars S

    2008-01-01

    Background A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO2 = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO2 = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery. Methods and design The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO2 = 0.80) or 30% oxygen (FiO2 = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power. Discussion This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy. Trial registration ClinicalTrials.gov identifier: NCT00364741. PMID:18945347

  10. Functions and importance of mycobacterial extracellular vesicles.

    PubMed

    Rodriguez, G Marcela; Prados-Rosales, Rafael

    2016-05-01

    The release of cellular factors by means of extracellular vesicles (EVs) is conserved in archaea, bacteria, and eukaryotes. EVs are released by growing bacteria as part of their interaction with their environment and, for pathogenic bacteria, constitute an important component of their interactions with the host. While EVs released by gram-negative bacteria have been extensively studied, the vesicles released by thick cell wall microorganisms like mycobacteria were recognized only recently and are less well understood. Nonetheless, studies of mycobacterial EVs have already suggested roles in pathogenesis, opening exciting new avenues of research aimed at understanding their biogenesis and potential use in antitubercular strategies. In this minireview, we discuss the discovery of mycobacterial vesicles, the current understanding of their nature, content, regulation, and possible functions, as well as their potential therapeutic applications. PMID:27020292

  11. Abdominal thrusts

    MedlinePlus

    ... call 911 . If the person loses consciousness, start CPR . If you are not comfortable performing abdominal thrusts, ... American Red Cross. First Aid/CPR/AED Participant's Manual. 2nd ... Red Cross; 2014. Berg RA, Hemphill R, Abella BS, et al. Part 5: ...

  12. Abdominal Adhesions

    MedlinePlus

    ... Adhesions 1 Ward BC, Panitch A. Abdominal adhesions: current and novel therapies. Journal of Surgical Research. 2011;165(1):91–111. Seek Help for ... and how to participate, visit the NIH Clinical Research Trials and You website ... Foundation for Functional Gastrointestinal Disorders 700 West Virginia ...

  13. Current technology for the treatment of infection following abdominal aortic aneurysm (AAA) fixation by endovascular repair (EVAR).

    PubMed

    Capoccia, L; Mestres, G; Riambau, V

    2014-06-01

    In recent years, in parallel with the increase of endovascular aortic repair (EVAR) procedures performances, a rise of late open surgical removal of EVAR implants has been observed, due to non-endovascularly correctable graft complications. Among them endograft infection is a rare but devastating occurrence, accounting for an incidence ranging from 0.2% to 0.7% in major series, and almost 1% of all causes of endograft explantations. However, a real estimation of the incidence of the problem respect to the number of EVAR implantations is difficult to obtain. Time to infection is usually defined as the period between EVAR and presentation of symptoms that leads to the infection diagnosis. It can be extremely variable, depending on bacterial virulence and host conditions. The diagnosis of an endograft infection is usually based on a combination of clinical symptoms, imaging studies and microbial cultures whenever possible. If computed tomography (CT) scan is employed in almost 100% of infection diagnosis, a combination of fluorodeoxyglucose-positron emission tomography (FDG-PET) and CT scan is nowadays used with increasing frequency in order to rise the likelihood of detecting a graft infection, since even cultures of blood or samples collected from the infected field can sometimes be negative. Complete graft excision seems the best approach whenever a surgical reconstruction could be attempted. In situ reconstruction can be performed by the interposition of an autologous vein, a cryopreserved allograft or a rifampin-soaked Dacron graft. The so-called conventional treatment contemplates the re-establishment of vascularization through extranatomical routes, thus preserving the new graft material from possible contamination by the surgical field just cleaned. When severe comorbid conditions did not allow graft excision, a conservative treatment should be taken into account. It is mainly based on broad-spectrum or culture-specific antibiotic therapy combined, whenever

  14. Metabolomics: Applications and Promise in Mycobacterial Disease.

    PubMed

    Mirsaeidi, Mehdi; Banoei, Mohammad Mehdi; Winston, Brent W; Schraufnagel, Dean E

    2015-09-01

    Until recently, the study of mycobacterial diseases was trapped in culture-based technology that is more than a century old. The use of nucleic acid amplification is changing this, and powerful new technologies are on the horizon. Metabolomics, which is the study of sets of metabolites of both the bacteria and host, is being used to clarify mechanisms of disease, and can identify changes leading to better diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic profiles are arrays of biochemical products of genes in their environment. These complex patterns are biomarkers that can allow a more complete understanding of cell function, dysfunction, and perturbation than genomics or proteomics. Metabolomics could herald sweeping advances in personalized medicine and clinical trial design, but the challenges in metabolomics are also great. Measured metabolite concentrations vary with the timing within a condition, the intrinsic biology, the instruments, and the sample preparation. Metabolism profoundly changes with age, sex, variations in gut microbial flora, and lifestyle. Validation of biomarkers is complicated by measurement accuracy, selectivity, linearity, reproducibility, robustness, and limits of detection. The statistical challenges include analysis, interpretation, and description of the vast amount of data generated. Despite these drawbacks, metabolomics provides great opportunity and the potential to understand and manage mycobacterial diseases. PMID:26196272

  15. Abdominal Aortic Aneurysms: Treatments

    MedlinePlus

    ... information Membership Directory (SIR login) Interventional Radiology Abdominal Aortic Aneurysms Interventional Radiologists Treat Abdominal Aneurysms Nonsurgically Interventional radiologists ...

  16. Perspectives on mycobacterial vacuole-to-cytosol translocation: the importance of cytosolic access.

    PubMed

    Simeone, Roxane; Majlessi, Laleh; Enninga, Jost; Brosch, Roland

    2016-08-01

    Mycobacterium tuberculosis, the infectious agent of human tuberculosis is a master player in circumventing the defense mechanisms of the host immune system. The host-pathogen interaction in the case of an infection with M. tuberculosis is highly complex, involving dedicated mycobacterial virulence factors as well as the action of the innate and adapted immune systems, which determine the outcome of infection. Macrophages play a key role in this process through internalizing the bacterium in a phagosomal vacuole. While this action has normally the function of eliminating invading bacteria, M. tuberculosis employs efficient strategies to prevent its extermination. The question on how-and-where the bacterium succeeds in doing so has interested generations of scientists and still remains a fascinating and important research subject focused on mycobacterial lipids, secretion systems and other contributing factors. This topic is also central to the longstanding and partially controversial discussion on mycobacterial phagosomal rupture and vacuole-to-cytosol translocation, to be reviewed here in more detail. PMID:27247079

  17. Interception of host angiogenic signalling limits mycobacterial growth

    PubMed Central

    Oehlers, Stefan H.; Cronan, Mark R.; Scott, Ninecia R.; Thomas, Monica I.; Okuda, Kazuhide S.; Walton, Eric M.; Beerman, Rebecca W.; Crosier, Philip S.; Tobin, David M.

    2014-01-01

    Pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis1,2. Here we examine the development and consequences of vascularisation of the tuberculous granuloma in the zebrafish-Mycobacterium marinum infection model characterised by organised granulomas with necrotic cores that bear striking resemblance to those of human tuberculosis2. Using intravital microscopy in the transparent larval zebrafish, we show that granuloma formation is intimately associated with angiogenesis. The initiation of angiogenesis in turn coincides with the generation of local hypoxia and transcriptional induction of the canonical pro-angiogenic molecule VEGFA. Pharmacological inhibition of the VEGF pathway suppresses granuloma-associated angiogenesis, reduces infection burden and limits dissemination. Moreover, anti-angiogenic therapies synergise with the first-line anti-tubercular antibiotic rifampicin as well as with the antibiotic metronidazole, which targets hypoxic bacterial populations3. Our data suggest that mycobacteria induce granuloma-associated angiogenesis, which promotes mycobacterial growth and increases spread of infection to new tissue sites. We propose the use of anti-angiogenic agents, now being used in cancer regimens, as a host-targeting TB therapy, particularly in extensively drug-resistant disease where current antibiotic regimens are largely ineffective. PMID:25470057

  18. Trichinella spiralis infection changes immune response in mice performed abdominal heterotopic cardiac transplantation and prolongs cardiac allograft survival time.

    PubMed

    Deng, Gengguo; Deng, Ronghai; Yao, Jianping; Liao, Bing; Chen, Yinghua; Wu, Zhongdao; Hu, Hongxing; Zhou, Xingwang; Ma, Yi

    2016-01-01

    Allograft rejection has been an obstacle for long-term survival of patients for many years. Current strategies for transplant rejection are not as optimal as we expected, especially for long-term treatments. Trichinella spiralis, a nematode parasitized in mammalian muscle and as an invader, maintains harmonious with host in the long term by evading host immune attack. To determine whether T. spiralis infection impacts on allograft rejection, we performed mice cardiac allograft transplantation model by using BALB/c (H-2(b)) mice as donors and C57BL/6 (H-2(b)) mice orally infected with 300 muscle larvae for 28 days as recipients. Graft survival was monitored by daily palpation of the abdomen; histologic change was observed by H&E stain; and CD4(+), CD8(+), CD4(+)IFN-γ(+), and CD4(+)IL-17(+) T cells and regulatory T cells were examined with the use of flow cytometry. Serum cytokine levels were measured by Luminex. Finally, we found that mean survival time of cardiac allografts in T. spiralis group was 23.40 ± 1.99 days, while the vehicle control group was 10.60 ± 0.75 days. Furthermore, we observed alleviated histological changes in the heart allograft, decreased corresponding CD8(+) T cells, suppressed Th1 and Th17 responses, and increased regulatory T cell frequency in a murine cardiac transplantation model at day 7 post-transplantation in experimental group. These data suggest that T. spiralis infection resulted in prolonged allograft survival following murine cardiac transplantation, with suppressed Th1/Th17 responses and augmented regulatory T cells. PMID:26481486

  19. Anaphylaxis, Intra-Abdominal Infections, Skin Lacerations, and Behavioral Emergencies: A Literature Review of Austere Analogs for a near Earth Asteroid Mission

    NASA Technical Reports Server (NTRS)

    Chough, Natacha G.; Watkins, Sharmi; Menon, Anil S.

    2012-01-01

    As space exploration is directed towards destinations beyond low-Earth orbit, the consequent new set of medical risks will drive requirements for new capabilities and more resources to ensure crew health. The Space Medicine Exploration Medical Conditions List (SMEMCL), developed by the Exploration Medical Capability element of the Human Research Program, addresses the risk of "unacceptable health and mission outcomes due to limitations of in-flight medical capabilities". It itemizes 85 evidence-based clinical requirements for eight different mission profiles and identifies conditions warranting further research and technology development. Each condition is given a clinical priority for each mission profile. Four conditions -- intra-abdominal infections, skin lacerations, anaphylaxis, and behavioral emergencies -- were selected as a starting point for analysis. A systematic literature review was performed to understand how these conditions are treated in austere, limited-resource, space-analog environments (i.e., high-altitude and mountain environments, submarines, military deployments, Antarctica, isolated wilderness environments, in-flight environments, and remote, resource-poor, rural environments). These environments serve as analogs to spaceflight because of their shared characteristics (limited medical resources, delay in communication, confined living quarters, difficulty with resupply, variable time to evacuation). Treatment of these four medical conditions in austere environments provides insight into medical equipment and training requirements for exploration-class missions.

  20. Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013

    PubMed Central

    Zhang, Hui; Yang, Qiwen; Liao, Kang; Ni, Yuxing; Yu, Yunsong; Hu, Bijie; Sun, Ziyong; Huang, Wenxiang; Wang, Yong; Wu, Anhua; Feng, Xianju; Luo, Yanping; Hu, Zhidong; Chu, Yunzhuo; Chen, Shulan; Cao, Bin; Su, Jianrong; Gui, Bingdong; Duan, Qiong; Zhang, Shufang; Shao, Haifeng; Kong, Haishen; Badal, Robert E.

    2015-01-01

    To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China. PMID:26482308

  1. Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

    PubMed

    Zhang, Hui; Yang, Qiwen; Liao, Kang; Ni, Yuxing; Yu, Yunsong; Hu, Bijie; Sun, Ziyong; Huang, Wenxiang; Wang, Yong; Wu, Anhua; Feng, Xianju; Luo, Yanping; Hu, Zhidong; Chu, Yunzhuo; Chen, Shulan; Cao, Bin; Su, Jianrong; Gui, Bingdong; Duan, Qiong; Zhang, Shufang; Shao, Haifeng; Kong, Haishen; Badal, Robert E; Xu, Yingchun

    2016-01-01

    To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China. PMID:26482308

  2. Evaluation of Tigecycline Efficacy and Post-Discharge Outcomes in a Clinical Practice Population with Complicated Intra-Abdominal Infection: A Propensity Score–Matched Analysis

    PubMed Central

    Mullins, C. Daniel; Quintana, Alvaro; Eckmann, Christian; Shelbaya, Ahmed; Ernst, Frank R.; Krukas, Michelle R.; Reisman, Arlene

    2016-01-01

    Abstract Background: The utility of tigecycline as compared with other antibiotic therapies in the treatment of patients with complicated intra-abdominal infection (cIAI) and the short- and long-term outcomes of a large cohort of severely ill patients were examined. We provide the first published data on post-discharge events for these patients. Methods: Retrospective data for the cIAI cohort were obtained from a large clinical database. Patients aged ≥18 y were selected for inclusion based on hospitalization with a relevant diagnosis code and procedure code, and guideline-compliant antimicrobial therapy. Propensity scoring was used to reduce treatment-selection bias introduced by the use of observational data. Tigecycline patients were placed into quintiles based on propensity score and were matched 1:3. Results: The final model based on propensity score matching included 2,424 patients: Tigecycline (n = 606) and other antibiotic therapy (n = 1,818). Treatment was successful in 426 (70.3%) tigecycline-treated patients and in 1,294 (71.2%) patients receiving other antibiotics. Similar treatment success occurred across all infection sites. Among survivors, treatment failure was associated with a greater need for all-cause re-hospitalization at 30 d and 180 d. No differences in cIAI-related re-hospitalization and discharge status were observed. Conclusions: Using propensity scores to match populations, similar outcomes were demonstrated between treatment with tigecycline and other antibiotics as expressed by treatment success, the need for re-admission, similar 30-d discharge status, and the need for re-admission at 180 d. PMID:26981640

  3. Evaluation of the effects of ozone therapy in the treatment of intra-abdominal infection in rats

    PubMed Central

    de Souza, Yglesio Moyses; Fontes, Belchor; Martins, Joilson O; Sannomiya, Paulina; Brito, Glacus S.; Younes, Riad N.; Rasslan, Samir

    2010-01-01

    INTRODUCTION The antibacterial effect of ozone (O3) has been described in the extant literature, but the role of O3 therapy in the treatment of certain types of infection remains controversial. OBJECTIVES To evaluate the effect of intraperitoneal (i.p.) O3 application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS Four animal groups were used for the study: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O2 and CLP+O3 groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O3 or CLP+O2 group vs. the cecal ligation/puncture group, and was similar for the CLP+O3 group vs. the CLP+O2 group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O3 group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O2). CONCLUSION Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no improvement on survival rates. PMID

  4. Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis.

    PubMed Central

    Jackett, P S; Bothamley, G H; Batra, H V; Mistry, A; Young, D B; Ivanyi, J

    1988-01-01

    A serological survey was performed in groups of patients with active sputum smear-positive or smear-negative pulmonary tuberculosis, healthy household contacts, and controls. Sera were tested for titers of antibodies which bound to each of five purified mycobacterial antigens by enzyme immunoassay and for competition of binding to single epitopes, using six radiolabeled monoclonal antibodies directed toward corresponding molecules. The evaluation of diagnostic specificity was based on a positive score represented by titers above the cutoff point of 2 standard deviations above the mean titer of a control group. For smear-positive samples, the best sensitivity (83%) was achieved by exclusive use of the 38-kilodalton (kDa) antigen or its corresponding monoclonal antibodies. For smear-negative samples, levels of antibodies binding to the 19-kDa antigen showed a lower sensitivity of 62% compared with the control group or 38% compared with the contact group. Titers of antibody binding to the 14-kDa antigen were raised in Mycobacterium bovis BCG-vaccinated contacts, indicating that the greatest potential of this antigen may be in the detection of infection in a population for which tuberculin testing is unreliable. The results demonstrated the differing antibody responses to each of the tested antigens and distinct associations with the stage of infection or disease. PMID:2466869

  5. Detection and Characterization of Infections and Infection Susceptibility

    ClinicalTrials.gov

    2016-09-10

    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)

  6. Ubiquitination as a Mechanism To Transport Soluble Mycobacterial and Eukaryotic Proteins to Exosomes.

    PubMed

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

    2015-09-15

    Exosomes are extracellular vesicles of endocytic origin that function in intercellular communication. Our previous studies indicate that exosomes released from Mycobacterium 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 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 HEK293 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 HEK293 cells, was transported to exosomes in a 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

  7. Boromycin Kills Mycobacterial Persisters without Detectable Resistance

    PubMed Central

    Moreira, Wilfried; Aziz, Dinah B.; Dick, Thomas

    2016-01-01

    Boromycin is a boron-containing polyether macrolide antibiotic isolated from Streptomyces antibioticus. It was shown to be active against Gram positive bacteria and to act as an ionophore for potassium ions. The antibiotic is ineffective against Gram negative bacteria where the outer membrane appears to block access of the molecule to the cytoplasmic membrane. Here we asked whether boromycin is active against Mycobacterium tuberculosis which, similar to Gram negative bacteria, possesses an outer membrane. The results show that boromycin is a potent inhibitor of mycobacterial growth (MIC50 = 80 nM) with strong bactericidal activity against growing and non-growing drug tolerant persister bacilli. Exposure to boromycin resulted in a rapid loss of membrane potential, reduction of the intracellular ATP level and leakage of cytoplasmic protein. Consistent with boromycin acting as a potassium ionophore, addition of KCl to the medium blocked its antimycobacterial activity. In contrast to the potent antimycobacterial activities of the polyether macrolide, its cytotoxicity and haemolytic activity were low (CC50 = 30 μM, HC50 = 40 μM) with a selectivity index of more than 300. Spontaneous resistant mutants could not be isolated suggesting a mutation frequency of less than 10-9/CFU. Taken together, the results suggests that targeting mycobacterial transmembrane ion gradients may be an attractive chemotherapeutic intervention level to kill otherwise drug tolerant persister bacilli, and to slow down the development of genetic antibiotic resistance. PMID:26941723

  8. Nontuberculous mycobacterial otomastoiditis: a case report.

    PubMed

    Tsai, Li-Tai; Wang, Ching-Yuan; Lin, Chia-Der; Tsai, Ming-Hsui

    2013-01-01

    Nontuberculous mycobacterial otomastoiditis is rare and can be easily confused with various different forms of otitis media. We describe the case of a 50-year-old woman who presented with left-sided chronic otitis media that had persisted for more than 1 year. It was not eradicated by standard antimicrobial therapy and surgical debridement. After appropriate antibiotic therapy for nontuberculous mycobacteria was added to the therapeutic regimen, the patient improved significantly and the lesion had healed by 6 months. Based on our experience with this case, we conclude that early bacterial culture and staining for acid-fast bacilli in ear drainage material or granulation tissue should be performed when standard antimicrobial therapy fails to eradicate chronic otitis media of an undetermined origin that is accompanied by granulation tissue over the external auditory canal or middle ear. Polymerase chain reaction testing is also effective for rapid diagnosis. Surgical debridement and removal of the foreign body can successfully treat nontuberculous mycobacterial otomastoiditis only when effective antimicrobial therapy is also administered. PMID:23354889

  9. Boromycin Kills Mycobacterial Persisters without Detectable Resistance.

    PubMed

    Moreira, Wilfried; Aziz, Dinah B; Dick, Thomas

    2016-01-01

    Boromycin is a boron-containing polyether macrolide antibiotic isolated from Streptomyces antibioticus. It was shown to be active against Gram positive bacteria and to act as an ionophore for potassium ions. The antibiotic is ineffective against Gram negative bacteria where the outer membrane appears to block access of the molecule to the cytoplasmic membrane. Here we asked whether boromycin is active against Mycobacterium tuberculosis which, similar to Gram negative bacteria, possesses an outer membrane. The results show that boromycin is a potent inhibitor of mycobacterial growth (MIC50 = 80 nM) with strong bactericidal activity against growing and non-growing drug tolerant persister bacilli. Exposure to boromycin resulted in a rapid loss of membrane potential, reduction of the intracellular ATP level and leakage of cytoplasmic protein. Consistent with boromycin acting as a potassium ionophore, addition of KCl to the medium blocked its antimycobacterial activity. In contrast to the potent antimycobacterial activities of the polyether macrolide, its cytotoxicity and haemolytic activity were low (CC50 = 30 μM, HC50 = 40 μM) with a selectivity index of more than 300. Spontaneous resistant mutants could not be isolated suggesting a mutation frequency of less than 10(-9)/CFU. Taken together, the results suggests that targeting mycobacterial transmembrane ion gradients may be an attractive chemotherapeutic intervention level to kill otherwise drug tolerant persister bacilli, and to slow down the development of genetic antibiotic resistance. PMID:26941723

  10. Nontuberculous Mycobacterial Disease in Children – Epidemiology, Diagnosis & Management at a Tertiary Center

    PubMed Central

    MacGregor, Duncan; Gonis, Gena; Leslie, David; Sedda, Luigi; Ritz, Nicole; Connell, Tom; Curtis, Nigel

    2016-01-01

    Background There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children. Methods Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia. Results A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6–1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23). Conclusions There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials. PMID:26812154

  11. Mycobacterial MazG Safeguards Genetic Stability via Housecleaning of 5-OH-dCTP

    PubMed Central

    Fan, Xiao-Yong; Ma, Hui; Zhao, Guo-Ping

    2013-01-01

    Generation of reactive oxygen species and reactive nitrogen species in phagocytes is an important innate immune response mechanism to eliminate microbial pathogens. It is known that deoxynucleotides (dNTPs), the precursor nucleotides to DNA synthesis, are one group of the significant targets for these oxidants and incorporation of oxidized dNTPs into genomic DNA may cause mutations and even cell death. Here we show that the mycobacterial dNTP pyrophosphohydrolase MazG safeguards the bacilli genome by degrading 5-OH-dCTP, thereby, preventing it from incorporation into DNA. Deletion of the (d)NTP pyrophosphohydrolase-encoding mazG in mycobacteria leads to a mutator phenotype both under oxidative stress and in the stationary phase of growth, resulting in increased CG to TA mutations. Biochemical analyses demonstrate that mycobacterial MazG can efficiently hydrolyze 5-OH-dCTP, an oxidized nucleotide that induces CG to TA mutation upon incorporation by polymerase. Moreover, chemical genetic analyses show that direct incorporation of 5-OH-dCTP into mazG-null mutant strain of Mycobacterium smegmatis (Msm) leads to a dose-dependent mutagenesis phenotype, indicating that 5-OH-dCTP is a natural substrate of mycobacterial MazG. Furthermore, deletion of mazG in Mycobacterium tuberculosis (Mtb) leads to reduced survival in activated macrophages and in the spleen of infected mice. This study not only characterizes the mycobacterial MazG as a novel pyrimidine-specific housecleaning enzyme that prevents CG to TA mutation by degrading 5-OH-dCTP but also reveals a genome-safeguarding mechanism for survival of Mtb in vivo. PMID:24339782

  12. Abdominal tap

    MedlinePlus

    ... liver Damaged bowel Heart disease Infection Kidney disease Pancreatic disease Tumor (cancerous or noncancerous) Risks There is a ... Kidney Diseases Liver Cancer Liver Diseases Ovarian Cancer Pancreatic Diseases Pancreatitis Peritoneal Disorders Browse the Encyclopedia A.D. ...

  13. Abdominal Aortic Aneurysm (AAA)

    MedlinePlus

    ... Resources Professions Site Index A-Z Abdominal Aortic Aneurysm (AAA) Abdominal aortic aneurysm (AAA) occurs when atherosclerosis ... aortic aneurysm treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, ...

  14. Abdominal CT scan

    MedlinePlus

    ... results may also be due to: Abdominal aortic aneurysm Abscesses Appendicitis Bowel wall thickening Retroperitoneal fibrosis Renal ... Livingstone; 2014:chap 4. Read More Abdominal aortic aneurysm Abdominal aortic aneurysm repair - open Abscess Acute cholecystitis ...

  15. Dynamics of Mycobacteriophage-Mycobacterial Host Interaction: Evidence for Secondary Mechanisms for Host Lethality

    PubMed Central

    Samaddar, Sourabh; Grewal, Rajdeep Kaur; Sinha, Saptarshi; Ghosh, Shrestha

    2015-01-01

    Mycobacteriophages infect mycobacteria, resulting in their death. Therefore, the possibility of using them as therapeutic agents against the deadly mycobacterial disease tuberculosis (TB) is of great interest. To obtain better insight into the dynamics of mycobacterial inactivation by mycobacteriophages, this study was initiated using mycobacteriophage D29 and Mycobacterium smegmatis as the phage-host system. Here, we implemented a goal-oriented iterative cycle of experiments on one hand and mathematical modeling combined with Monte Carlo simulations on the other. This integrative approach lends valuable insight into the detailed kinetics of bacterium-phage interactions. We measured time-dependent changes in host viability during the growth of phage D29 in M. smegmatis at different multiplicities of infection (MOI). The predictions emerging out of theoretical analyses were further examined using biochemical and cell biological assays. In a phage-host interaction system where multiple rounds of infection are allowed to take place, cell counts drop more rapidly than expected if cell lysis is considered the only mechanism for cell death. The phenomenon could be explained by considering a secondary factor for cell death in addition to lysis. Further investigations reveal that phage infection leads to the increased production of superoxide radicals, which appears to be the secondary factor. Therefore, mycobacteriophage D29 can function as an effective antimycobacterial agent, the killing potential of which may be amplified through secondary mechanisms. PMID:26475112

  16. Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV-Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

    PubMed Central

    Glesby, Marshall J.; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N.; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P.

    2013-01-01

    Background Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (−17.5% in rhGH/rosiglitazone and −22.7% in rhGH) but not in the rosiglitazone alone (−2.5%) or control arms (−1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Trial Registration

  17. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat

    PubMed Central

    Mangili, Alexandra; Falutz, Julian; Mamputu, Jean-Claude; Stepanians, Miganush; Hayward, Brooke

    2015-01-01

    Background Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy. Objectives 1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin. Methods Data were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models. Results Metabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44). Conclusions Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin

  18. High mycobacterial diversity in recreational lakes.

    PubMed

    Roguet, A; Therial, C; Saad, M; Boudahmane, L; Moulin, L; Lucas, F S

    2016-05-01

    Although nontuberculous mycobacteria (NTM) are natural inhabitants of freshwater ecosystems, few studies have focused on their distribution in these habitats. Thus, the knowledge about the abundance as well as the composition of NTM remains limited and patchy in these environments. In this context, a prospective study was performed to identify favourable habitats for mycobacteria in two recreational lakes. Mycobacterial density and diversity were measured using quantitative real-time PCR and the MiSeq Illumina platform. For both lakes, five compartments were investigated, i.e. water column, air-water interface, sediment, epilithon and epiphyton biofilms. Nontuberculous mycobacteria were detected in all compartments in large densities and displayed a remarkable diversity. NTM were dominated by fast-growing species. Lakes and compartments appeared to shape mycobacteria assemblage composition as well as their densities. In both lakes, some OTUs assigned to the species level were identified as related to known opportunistic pathogens. PMID:26873594

  19. Cutaneous Mycobacterium abscessus Infection Associated with Mesotherapy Injection.

    PubMed

    Wongkitisophon, Pranee; Rattanakaemakorn, Ploysyne; Tanrattanakorn, Somsak; Vachiramon, Vasanop

    2011-01-01

    Non-tuberculous mycobacterial skin infections have an increasing incidence. In immunocompetent patients, they usually follow local trauma. We present a case of cutaneous Mycobacterium abscessus infection following mesotherapy. The lesions were successfully treated with a combination of clarithromycin, ciprofloxacin, and doxycycline. Atypical mycobacterial infection should be suspected in patients who develop late-onset skin and soft tissue infection after cutaneous injury, injection, and surgical intervention, particularly if they do not respond to conventional antibiotic treatment. PMID:21487459

  20. Mechanistic insight into mycobacterial MmpL protein function.

    PubMed

    Székely, R; Cole, S T

    2016-03-01

    Mycobacterial cell walls are complex structures containing a broad range of unusual lipids, glycolipids and other polymers, some of which act as immunomodulators or virulence determinants. Better understanding of the enzymes involved in export processes would enlighten cell wall biogenesis. Bernut et al. () present the findings of a structural and functional investigation of one of the most important transporter families, the MmpL proteins, members of the resistance-nodulation-cell division (RND) superfamily. A Tyr842His missense mutation in the mmpL4a gene was shown to be responsible for the smooth-to-rough morphotype change of the near untreatable opportunistic pathogen Mycobacterium bolletii due to its failure to export a glycopeptidolipid (GPL). This mutation was pleiotropic and markedly increased virulence in infection models. Tyr842 is well conserved in all actinobacterial MmpL proteins suggesting that it is functionally important and this was confirmed by several approaches including replacing the corresponding residue in MmpL3 of Mycobacterium tuberculosis. Structural modelling combined with experimental results showed Tyr842 to be a critical residue for mediating the proton motive force required for GPL export. This mechanistic insight applies to all MmpL proteins and probably to all RND transporters. PMID:26710752

  1. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer

    PubMed Central

    Hong, Su Jin; Kim, Tae Jung; Lee, Jae-Ho; Park, Jeong-Soo

    2016-01-01

    Abstract To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass-like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed. Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6–7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens. NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID:27367996

  2. Purification of a mycobacterial adhesin for fibronectin.

    PubMed Central

    Ratliff, T L; McCarthy, R; Telle, W B; Brown, E J

    1993-01-01

    Previous studies have demonstrated that mycobacteria attach to fibronectin (FN). The attachment of mycobacteria to FN is considered to be biologically important in Mycobacterium bovis BCG therapy for superficial bladder cancer, initiation of delayed hypersensitivity to mycobacterial antigens, and the phagocytosis of mycobacteria by epithelial cells. Therefore, we purified the mycobacterial receptor for FN. Culture supernatants from 3-week cultures of Mycobacterium vaccae, which contained proteins that bound FN and inhibited the attachment of both M. vaccae and BCG to FN, were used as a source of receptor. Lyophilized M. vaccae supernatants were reconstituted in 0.02 M bis-Tris (pH 6.0) and applied sequentially to an ACA 54 gel filtration column and a DEAE-Sephacel anion-exchange column. A purified inhibitory protein of 55 kDa (p55) was obtained. The purified p55 protein was observed to bind to FN and to inhibit 125I-FN binding to viable BCG in a dose-dependent manner. Polyclonal and monoclonal antibodies to the protein were generated. The resulting polyclonal antiserum blotted a single protein band at 55 kDa in crude M. vaccae supernatants, cross-reacted with a 55-kDa BCG protein by Western blot (immunoblot), and recognized a 55-kDa band that was associated with the BCG cell wall, which is consistent with its function as a FN receptor. A monoclonal immunoglobulin M(lambda) was isolated from mice immunized with purified M. vaccae p55 protein that was not functional in Western blots but inhibited the attachment of viable BCG to FN. These studies demonstrate that a protein or antigenically related proteins with M(r)s of 55,000 function as FN receptors for at least two distinct mycobacteria. Images PMID:8478078

  3. Recurrent abdominal pain in children.

    PubMed

    Buch, Niyaz A; Ahmad, Sheikh Mushtaq; Ahmed, S Zubair; Ali, Syed Wazid; Charoo, B A; Hassan, Masood Ul

    2002-09-01

    Eighty five children with recurrent abdominal pain(RAP) were studied. Organic cause was noticed in 70 cases and non-organic in 15 cases. Giardiasis was the commonest organic cause in 57 (67.0 percent), either alone or with other parasitic infestations. Other organic causes include gallstones (4.7 percent), urinary infections (4.7 percent), esophagitis/gastritis (3.5 percent) and abdominal tuberculosis (2.3 percent). Single parent, school phobia, sibling rivalry, RAP in other family members and nocturnal enuresis are significant factors associated with nonorganic causes PMID:12368527

  4. Imaging infection.

    PubMed

    Ketai, Loren; Jordan, Kirk; Busby, Katrina H

    2015-06-01

    Thoracic imaging is widely used to detect lower respiratory tract infections, identify their complications, and aid in differentiating infectious from noninfectious thoracic disease. Less commonly, the combination of imaging findings and a clinical setting can favor infection with a specific organism. This confluence can occur in cases of bronchiectatic nontuberculous mycobacterial infections in immune-competent hosts, invasive fungal disease among neutropenic patients, Pneumocystis jiroveci pneumonia in patients with AIDS, and in cytomegalovirus infections in patients with recent hematopoietic cell transplantation. These specific diagnoses often depend on computed tomography scanning rather than chest radiography alone. PMID:26024600

  5. 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

  6. Ceftolozane/tazobactam activity tested against aerobic Gram-negative organisms isolated from intra-abdominal and urinary tract infections in European and United States hospitals (2012).

    PubMed

    Sader, Helio S; Farrell, David J; Flamm, Robert K; Jones, Ronald N

    2014-09-01

    Ceftolozane/tazobactam is under clinical development for treatment of complicated intra-abdominal infections (IAI), complicated urinary tract infections (UTI) and ventilator-associated pneumonia. We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Gram-negative aerobic bacteria causing IAI and healthcare-associated UTI (HCA-UTI). The organisms were consecutively collected from January to December 2012 from 59 medical centers located in the United States (USA) and 15 European countries by the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS). The collection included 809 organisms from IAI and 2474 organisms from HCA-UTI, and susceptibility testing was performed by reference broth microdilution methods as described by the Clinical and Laboratory Standards Institute (CLSI) M07-A9 document. Overall, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most frequently isolated pathogens from both infection types. Ceftolozane/tazobactam was very active against E. coli (MIC50/90, 0.25/0.5 mg/L; 98.5-99.9% inhibited at an MIC of ≤8 mg/L) and retained activity against many of the multidrug-resistant (MDR; MIC50/90, 0.5/2->32 mg/L) and ESBL-phenotype strains (MIC50/90, 0.5/2-32 mg/L). Ceftolozane/tazobactam was active against most K. pneumoniae strains (MIC50/90, 0.25/16 mg/L, 88.9-89.6% inhibited at an MIC of ≤8 mg/L), but some ESBL-phenotype (MIC50/90, 4-8/>32 mg/L) and MDR (MIC50/90, 16/>32 mg/L) isolates exhibited elevated MIC values. Ceftolozane/tazobactam was the most active agent tested against P. aeruginosa (MIC50/90, 0.5/4 mg/L; 93.4-95.7% inhibited at ≤8 mg/L) and retained potency against many MDR (MIC50/90, 2-4/>32 mg/L), ceftazidime-nonsusceptible (MIC50/90, 2-4/>32 mg/L) and meropenem-nonsusceptible (MIC50/90, 2/>32 mg/L) strains. Ceftolozane/tazobactam was also active against Klebsiella oxytoca (MIC50/90, ≤0.12-0.25/0.5-1 mg/L), Enterobacter spp. (MIC50/90, 0

  7. An unusual outbreak of nontuberculous mycobacteria in hospital respiratory wards: Association with nontuberculous mycobacterial colonization of hospital water supply network.

    PubMed

    D'Antonio, Salvatore; Rogliani, Paola; Paone, Gregorino; Altieri, Alfonso; Alma, Mario Giuseppe; Cazzola, Mario; Puxeddu, Ermanno

    2016-06-01

    The incidence and prevalence of pulmonary nontuberculous mycobacterial (NTM) infection is increasing worldwide arousing concerns that NTM infection may become a serious health challenge. We recently observed a significant increase of NTM-positive sputa samples from patients referred to respiratory disease wards of a large tertiary hospital in Rome. A survey to identify possible NTM contamination revealed a massive presence of NTM in the hospital water supply network. After decontamination procedures, NTM presence dropped both in water pipelines and sputa samples. We believe that this observation should encourage water network surveys for NTM contamination and prompt decontamination procedures should be considered to reduce this potential source of infection. PMID:27242241

  8. A multicentre, open-label, randomized comparative study of tigecycline versus ceftriaxone sodium plus metronidazole for the treatment of hospitalized subjects with complicated intra-abdominal infections.

    PubMed

    Towfigh, S; Pasternak, J; Poirier, A; Leister, H; Babinchak, T

    2010-08-01

    Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI. PMID:20670293

  9. Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

    PubMed Central

    Niu, Ning-Kui; Yin, Juan-Juan; Yang, Yin-Xue; Wang, Zi-Li; Zhou, Zhi-Wei; He, Zhi-Xu; Chen, Xiao-Wu; Zhang, Xueji; Duan, Wei; Yang, Tianxin; Zhou, Shu-Feng

    2015-01-01

    Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical

  10. Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study.

    PubMed

    Niu, Ning-Kui; Yin, Juan-Juan; Yang, Yin-Xue; Wang, Zi-Li; Zhou, Zhi-Wei; He, Zhi-Xu; Chen, Xiao-Wu; Zhang, Xueji; Duan, Wei; Yang, Tianxin; Zhou, Shu-Feng

    2015-01-01

    Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical

  11. Effects of Insulin-Like Growth Factor (IGF)-I/IGF-Binding Protein-3 Treatment on Glucose Metabolism and Fat Distribution in Human Immunodeficiency Virus-Infected Patients with Abdominal Obesity and Insulin Resistance

    PubMed Central

    Rao, Madhu N.; Mulligan, Kathleen; Tai, Viva; Wen, Michael J.; Dyachenko, Artem; Weinberg, Melissa; Li, Xiaojuan; Lang, Thomas; Grunfeld, Carl; Schwarz, Jean-Marc; Schambelan, Morris

    2010-01-01

    Context: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals. Objective: Our objective was to determine whether IGF-I, complexed to its major binding protein, IGF-binding protein-3 (IGFBP-3), improves glucose metabolism and alters body fat distribution in HIV-infected patients with abdominal obesity and insulin resistance. Methods: We conducted a pilot, open-label study in 13 HIV-infected men with excess abdominal adiposity and insulin resistance to assess the effect of 3 months of treatment with IGF-I/IGFBP-3 on glucose metabolism and fat distribution. Glucose metabolism was assessed by oral glucose tolerance test and hyperinsulinemic-euglycemic clamp. Endogenous glucose production (EGP), gluconeogenesis, whole-body lipolysis, and de novo lipogenesis (DNL) were measured with stable isotope infusions. Body composition was assessed by dual-energy x-ray absorptiometry and abdominal computed tomography scan. Results: Glucose tolerance improved and insulin-mediated glucose uptake increased significantly during treatment. EGP increased under fasting conditions, and suppression of EGP by insulin was blunted. Fasting triglycerides decreased significantly in association with a decrease in hepatic DNL. Lean body mass increased and total body fat decreased, whereas visceral adipose tissue did not change. Conclusions: Treatment with IGF-I/IGFBP-3 improved whole-body glucose uptake and glucose tolerance, while increasing hepatic glucose production. Fasting triglycerides improved, reflecting decreased DNL, and visceral adiposity was unchanged. PMID:20610601

  12. Association of Human Antibodies to Arabinomannan With Enhanced Mycobacterial Opsonophagocytosis and Intracellular Growth Reduction

    PubMed Central

    Chen, Tingting; Blanc, Caroline; Eder, Anke Z.; Prados-Rosales, Rafael; Souza, Ana Camila Oliveira; Kim, Ryung S.; Glatman-Freedman, Aharona; Joe, Maju; Bai, Yu; Lowary, Todd L.; Tanner, Rachel; Brennan, Michael J.; Fletcher, Helen A.; McShane, Helen; Casadevall, Arturo; Achkar, Jacqueline M.

    2016-01-01

    Background. The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain. We investigated the role of Abs to the mycobacterial capsular polysaccharide arabinomannan (AM) and its oligosaccharide (OS) fragments in humans. Methods. Sera obtained from 29 healthy adults before and after primary or secondary bacillus Calmette-Guerin (BCG) vaccination were assessed for Ab responses to AM via enzyme-linked immunosorbent assays, and to AM OS epitopes via novel glycan microarrays. Effects of prevaccination and postvaccination sera on BCG phagocytosis and intracellular survival were assessed in human macrophages. Results. Immunoglobulin G (IgG) responses to AM increased significantly 4–8 weeks after vaccination (P < .01), and sera were able to opsonize BCG and M. tuberculosis grown in both the absence and the presence of detergent. Phagocytosis and intracellular growth inhibition were significantly enhanced when BCG was opsonized with postvaccination sera (P < .01), and these enhancements correlated significantly with IgG titers to AM (P < .05), particularly with reactivity to 3 AM OS epitopes (P < .05). Furthermore, increased phagolysosomal fusion was observed with postvaccination sera. Conclusions. Our results provide further evidence for a role of Ab-mediated immunity to tuberculosis and suggest that IgG to AM, especially to some of its OS epitopes, could contribute to the defense against mycobacterial infection in humans. PMID:27056953

  13. The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity

    PubMed Central

    Wilson, Gillian J.; Marakalala, Mohlopheni J.; Hoving, Jennifer C.; van Laarhoven, Arjan; Drummond, Rebecca A.; Kerscher, Bernhard; Keeton, Roanne; van de Vosse, Esther; Ottenhoff, Tom H.M.; Plantinga, Theo S.; Alisjahbana, Bachti; Govender, Dhirendra; Besra, Gurdyal S.; Netea, Mihai G.; Reid, Delyth M.; Willment, Janet A.; Jacobs, Muazzam; Yamasaki, Sho; van Crevel, Reinout; Brown, Gordon D.

    2015-01-01

    Summary The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8−/− mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8−/− mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man. PMID:25674984

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

    PubMed

    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

  15. 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

  16. Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases.

    PubMed

    Gunn-Moore, Danièlle A; McFarland, Sarah E; Schock, Alex; Brewer, Jacqueline I; Crawshaw, Tim R; Clifton-Hadley, Richard S; Shaw, Darren J

    2011-12-01

    This study investigated 339 cases of feline mycobacterial infection, with histopathology findings from 225 cases, and treatment and outcome information from 184 cases. Tissue samples from cats with cutaneous lesions or suspicious masses at exploratory laparotomy were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study reviewed the files for information about histopathology, treatment and outcome, and blindly reviewed histopathological changes (including staining for acid-fast bacteria [AFB]) in a sub-set of 45 cases. When a cat is suspected of having a mycobacterial infection, accurate identification of the species involved helps to determine possible treatment options and prognosis. The study confirmed that histopathology and the presence of AFB are useful tools in the recognition of mycobacterial infection. Unfortunately, they did little to help determine the species of mycobacteria involved. The study identified a group of cats that were negative for AFB at the primary laboratory, but from which mycobacteria could be cultured; commonly Mycobacterium bovis or Mycobacterium microti. The study also identified a group of cats which where culture negative, despite typical signs of mycobacterial infection and positive AFB staining. Many cases responded favourably to treatment (56% of the cases where information was available), and many cats gained complete remission (42%). However, relapses were common (64%) and often followed by pulmonary and/or systemic spread that may have resulted from treatment with short courses of single drugs. This study shows that the diagnosis and treatment of feline mycobacteriosis is complex and challenging. PMID:22061264

  17. Anti-mycobacterial peptides: from human to phage.

    PubMed

    Teng, Tieshan; Liu, Jiafa; Wei, Hongping

    2015-01-01

    Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the growing problem of M. tuberculosis resistant to conventional antibiotics, especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial peptides have a few advantages, such as low immunogenicity, selective affinity to prokaryotic negatively charged cell envelopes, and diverse modes of action. In this review, we summarize the recent progress in the anti-mycobacterial peptides, highlighting the sources, effectiveness and bactericidal mechanisms of these antimicrobial peptides. Most of the current anti-mycobacterial peptides are derived either from host immune cells, bacterial extraction, or mycobacteriophages. Besides trans-membrane pore formation, which is considered to be the common bactericidal mechanism, many of the anti-mycobacterial peptides have the second non-membrane targets within mycobacteria. Additionally, some antimicrobial peptides play critical roles in innate immunity. However, a few obstacles, such as short half-life in vivo and resistance to antimicrobial peptides, need overcoming before clinical applications. Nevertheless, the multiple functions of anti-mycobacterial peptides, especially direct killing of pathogens and immune-modulators in infectious and inflammatory conditions, indicate that they are promising candidates for future drug development. PMID:25613372

  18. Trends in Susceptibility of Escherichia coli from Intra-Abdominal Infections to Ertapenem and Comparators in the United States According to Data from the SMART Program, 2009 to 2013

    PubMed Central

    Kazmierczak, Krystyna M.; Badal, Robert E.; Hackel, Meredith A.; Bouchillon, Samuel K.; Biedenbach, Douglas J.; Sahm, Daniel F.

    2015-01-01

    Antimicrobial resistance in Enterobacteriaceae, including resistance to carbapenems, is increasing worldwide. However, using U.S. Study for Monitoring Antimicrobial Resistance Trends (SMART) data for 2009 to 2013, no statistically significant decreasing susceptibility trends were found overall for Escherichia coli isolates from patients with intra-abdominal infections. In the subset of isolates from community-associated infections, susceptibility to levofloxacin decreased significantly and the increasing rate of multidrug-resistant E. coli approached statistical significance. In 2013, ertapenem, imipenem, and amikacin showed the highest susceptibility rates (≥99%) and fluoroquinolones the lowest (<70%). The 10 non-ertapenem-susceptible isolates (0.3% of all E. coli isolates) encoded one or more carbapenemases, extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, or non-ESBL β-lactamases. PMID:25801558

  19. Abdominal aortic aneurysm

    MedlinePlus

    ... to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs when an area of the aorta becomes ... blood pressure Male gender Genetic factors An abdominal aortic aneurysm is most often seen in males over age ...

  20. Abdominal x-ray

    MedlinePlus

    ... More Abdominal aortic aneurysm Abdominal pain Acute cholecystitis Acute kidney failure Addison disease Adenomyosis Annular pancreas Aplastic anemia Appendicitis Ascariasis Atheroembolic renal disease Biliary atresia Blind loop syndrome Cholangitis Chronic ...

  1. Granulysin as a Correlate of Immune Response following Mycobacterial Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Correlates of protection following vaccination against TB are needed in the development of improved vaccines against TB. Evaluation of vaccine efficacy is based on measuring IFN gamma levels and antigen-specific proliferation. Granulysin is an antimicrobial protein expressed by T lymphocytes and NK ...

  2. Abattoir-based estimates of mycobacterial infections in Cameroon.

    PubMed

    Egbe, N F; Muwonge, A; Ndip, L; Kelly, R F; Sander, M; Tanya, V; Ngwa, V Ngu; Handel, I G; Novak, A; Ngandalo, R; Mazeri, S; Morgan, K L; Asuquo, A; Bronsvoort, B M de C

    2016-01-01

    Mycobacteria cause major diseases including human tuberculosis, bovine tuberculosis and Johne's disease. In livestock, the dominant species is M. bovis causing bovine tuberculosis (bTB), a disease of global zoonotic importance. In this study, we estimated the prevalence of Mycobacteria in slaughter cattle in Cameroon. A total of 2,346 cattle were examined in a cross-sectional study at four abattoirs in Cameroon. Up to three lesions per animal were collected for further study and a retropharyngeal lymph node was collected from a random sample of non-lesioned animals. Samples were cultured on Lowenstein Jensen media and the BACTEC MGIT 960 system, and identified using the Hain® Genotype kits. A total of 207/2,346 cattle were identified with bTB-like lesions, representing 4.0% (45/1,129), 11.3% (106/935), 23.8% (38/160) and 14.8% (18/122) of the cattle in the Bamenda, Ngaoundere, Garoua and Maroua abattoirs respectively. The minimum estimated prevalence of M. bovis was 2.8% (1.9-3.9), 7.7% (6.1-9.6), 21.3% (15.2-28.4) and 13.1% (7.7-20.4) in the four abattoirs respectively. One M. tuberculosis and three M. bovis strains were recovered from non-lesioned animals. The high prevalence of M. bovis is of public health concern and limits the potential control options in this setting without a viable vaccine as an alternative. PMID:27075056

  3. Abattoir-based estimates of mycobacterial infections in Cameroon

    PubMed Central

    Egbe, N. F.; Muwonge, A.; Ndip, L.; Kelly, R. F.; Sander, M.; Tanya, V.; Ngwa, V. Ngu; Handel, I. G.; Novak, A.; Ngandalo, R.; Mazeri, S.; Morgan, K. L.; Asuquo, A.; Bronsvoort, B. M. de C.

    2016-01-01

    Mycobacteria cause major diseases including human tuberculosis, bovine tuberculosis and Johne’s disease. In livestock, the dominant species is M. bovis causing bovine tuberculosis (bTB), a disease of global zoonotic importance. In this study, we estimated the prevalence of Mycobacteria in slaughter cattle in Cameroon. A total of 2,346 cattle were examined in a cross-sectional study at four abattoirs in Cameroon. Up to three lesions per animal were collected for further study and a retropharyngeal lymph node was collected from a random sample of non-lesioned animals. Samples were cultured on Lowenstein Jensen media and the BACTEC MGIT 960 system, and identified using the Hain® Genotype kits. A total of 207/2,346 cattle were identified with bTB-like lesions, representing 4.0% (45/1,129), 11.3% (106/935), 23.8% (38/160) and 14.8% (18/122) of the cattle in the Bamenda, Ngaoundere, Garoua and Maroua abattoirs respectively. The minimum estimated prevalence of M. bovis was 2.8% (1.9–3.9), 7.7% (6.1–9.6), 21.3% (15.2–28.4) and 13.1% (7.7–20.4) in the four abattoirs respectively. One M. tuberculosis and three M. bovis strains were recovered from non-lesioned animals. The high prevalence of M. bovis is of public health concern and limits the potential control options in this setting without a viable vaccine as an alternative. PMID:27075056

  4. Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

    PubMed Central

    McLean, L.; Winrow, V.; Blake, D.

    1990-01-01

    'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis. PMID:2184873

  5. The clinical management of abdominal ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: a review of current guidelines and recommendations.

    PubMed

    Pericleous, Marinos; Sarnowski, Alexander; Moore, Alice; Fijten, Rik; Zaman, Murtaza

    2016-03-01

    Several pathogenic processes have been implicated in the development of abdominal ascites. Portal hypertension, most usually in the context of liver cirrhosis, can explain about 75% of the cases, whereas infective, inflammatory and infiltrative aetiologies can account for the rest. In this article, we discuss the consensus best practice as published by three professional bodies for the management of ascites, spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). The aim of this study was to compare available clinical guidelines and identify areas of agreement and conflict. We carried out a review of the guidance documentation published by three expert bodies including the British Society of Gastroenterology, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), as well as a wider literature search for ascites, SBP and HRS. Abdominal ultrasonography, diagnostic paracentesis and ascitic fluid cultures are recommended by all three guidelines, especially when there is strong clinical suspicion for infection. EASL and AASLD advocate the use of ascitic amylase and mycobacterial cultures/PCR when there is strong suspicion for tuberculosis and pancreatitis, respectively. Ascitic cytology can be useful when cancer is suspected and has a good diagnostic yield if performed correctly. EASL supports the use of urinary electrolytes for all patients; however, the British Society of Gastroenterology and AASLD only recommend their use for therapy monitoring. All three societies recommend cefotaxime as the antibiotic of choice for SBP and large-volume paracentesis for the management of ascites greater than 5 l in volume. For HRS, cautious diuresis, volume expansion with albumin and the use of vasoactive drugs are recommended. There appears to be good concordance between recommendations by the European, American and British guidelines for the management of ascites and the possible

  6. Abdominal Compartment Hypertension and Abdominal Compartment Syndrome.

    PubMed

    Maluso, Patrick; Olson, Jody; Sarani, Babak

    2016-04-01

    Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are rare but potentially morbid diagnoses. Clinical index of suspicion for these disorders should be raised following massive resuscitation, abdominal wall reconstruction/injury, and in those with space-occupying disorders in the abdomen. Gold standard for diagnosis involves measurement of bladder pressure, with a pressure greater than 12 mm Hg being consistent with IAH and greater than 25 mm Hg being consistent with ACS. Decompressive laparotomy is definitive therapy but paracentesis can be equally therapeutic in properly selected patients. Left untreated, ACS can lead to multisystem organ failure and death. PMID:27016163

  7. Development of a murine mycobacterial growth inhibition assay for evaluating vaccines against Mycobacterium tuberculosis.

    PubMed

    Parra, Marcela; Yang, Amy L; Lim, JaeHyun; Kolibab, Kristopher; Derrick, Steven; Cadieux, Nathalie; Perera, Liyanage P; Jacobs, William R; Brennan, Michael; Morris, Sheldon L

    2009-07-01

    The development and characterization of new tuberculosis (TB) vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of Mycobacterium tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (Mycobacterium bovis BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a modified vaccinia virus strain Ankara [MVA] construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth-inhibitory responses seen in vitro after 1 week of coculture correlated with the protective immune responses detected in vivo at 28 days postchallenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently upregulated cytokines detected in the immune cocultures are gamma interferon, growth differentiation factor 15, interleukin-21 (IL-21), IL-27, and tumor necrosis factor alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues, including product potency and stability. PMID:19458207

  8. Mycobacterial P1-Type ATPases Mediate Resistance to Zinc Poisoning in Human Macrophages

    PubMed Central

    Botella, Hélène; Peyron, Pascale; Levillain, Florence; Poincloux, Renaud; Poquet, Yannick; Brandli, Irène; Wang, Chuan; Tailleux, Ludovic; Tilleul, Sylvain; Charrière, Guillaume M.; Waddell, Simon J.; Foti, Maria; Lugo-Villarino, Geanncarlo; Gao, Qian; Maridonneau-Parini, Isabelle; Butcher, Philip D.; Castagnoli, Paola Ricciardi; Gicquel, Brigitte; de Chastellier, Chantal; Neyrolles, Olivier

    2011-01-01

    Summary Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P1-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race. PMID:21925112

  9. Abdominal Circulatory Interactions.

    PubMed

    Dagar, Gaurav; Taneja, Amit; Nanchal, Rahul S

    2016-04-01

    The abdominal compartment is separated from the thoracic compartment by the diaphragm. Under normal circumstances, a large portion of the venous return crosses the splanchnic and nonsplanchnic abdominal regions before entering the thorax and the right side of the heart. Mechanical ventilation may affect abdominal venous return independent of its interactions at the thoracic level. Changes in pressure in the intra-abdominal compartment may have important implications for organ function within the thorax, particularly if there is a sustained rise in intra-abdominal pressure. It is important to understand the consequences of abdominal pressure changes on respiratory and circulatory physiology. This article elucidates important abdominal-respiratory-circulatory interactions and their clinical effects. PMID:27016167

  10. Acute Abdominal Pain in Children.

    PubMed

    Reust, Carin E; Williams, Amy

    2016-05-15

    Acute abdominal pain accounts for approximately 9% of childhood primary care office visits. Symptoms and signs that increase the likelihood of a surgical cause for pain include fever, bilious vomiting, bloody diarrhea, absent bowel sounds, voluntary guarding, rigidity, and rebound tenderness. The age of the child can help focus the differential diagnosis. In infants and toddlers, clinicians should consider congenital anomalies and other causes, including malrotation, hernias, Meckel diverticulum, or intussusception. In school-aged children, constipation and infectious causes of pain, such as gastroenteritis, colitis, respiratory infections, and urinary tract infections, are more common. In female adolescents, clinicians should consider pelvic inflammatory disease, pregnancy, ruptured ovarian cysts, or ovarian torsion. Initial laboratory tests include complete blood count, erythrocyte sedimentation rate or C-reactive protein, urinalysis, and a pregnancy test. Abdominal radiography can be used to diagnose constipation or obstruction. Ultrasonography is the initial choice in children for the diagnosis of cholecystitis, pancreatitis, ovarian cyst, ovarian or testicular torsion, pelvic inflammatory disease, pregnancy-related pathology, and appendicitis. Appendicitis is the most common cause of acute abdominal pain requiring surgery, with a peak incidence during adolescence. When the appendix is not clearly visible on ultrasonography, computed tomography or magnetic resonance imaging can be used to confirm the diagnosis. PMID:27175718

  11. 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

  12. Phosphorylation Modulates Catalytic Activity of Mycobacterial Sirtuins

    PubMed Central

    Yadav, Ghanshyam S.; Ravala, Sandeep K.; Malhotra, Neha; Chakraborti, Pradip K.

    2016-01-01

    Sirtuins are NAD+-dependent deacetylases involved in the regulation of diverse cellular processes and are conserved throughout phylogeny. Here we report about in vitro transphosphorylation of the only NAD+-dependent deacetylase (mDAC) present in the genome of Mycobacterium tuberculosis by eukaryotic-type Ser/Thr kinases, particularly PknA. The phosphorylated mDAC displayed decreased deacetylase activity compared to its unphosphorylated counterpart. Mass-spectrometric study identified seven phosphosites in mDAC; however, mutational analysis highlighted major contribution of Thr-214 for phosphorylation of the protein. In concordance to this observation, variants of mDAC substituting Thr-214 with either Ala (phospho-ablated) or Glu (phosphomimic) exhibited significantly reduced deacetylase activity suggesting phosphorylation mediated control of enzymatic activity. To assess the role of phosphorylation towards functionality of mDAC, we opted for a sirtuin knock-out strain of Escherichia coli (Δdac), where interference of endogenous mycobacterial kinases could be excluded. The Δdac strain in nutrient deprived acetate medium exhibited compromised growth and complementation with mDAC reversed this phenotype. The phospho-ablated or phosphomimic variant, on the other hand, was unable to restore the functionality of mDAC indicating the role of phosphorylation per se in the process. We further over-expressed mDAC or mDAC-T214A as His-tagged protein in M. smegmatis, where endogenous eukaryotic-type Ser/Thr kinases are present. Anti-phosphothreonine antibody recognized both mDAC and mDAC-T214A proteins in western blotting. However, the extent of phosphorylation as adjudged by scanning the band intensity, was significantly low in the mutant protein (mDAC-T214A) compared to that of the wild-type (mDAC). Furthermore, expression of PknA in the mDAC complemented Δdac strain was able to phosphorylate M. tuberculosis sirtuin. The growth profile of this culture in acetate medium was

  13. Effect of mycobacterial secretory proteins on the cellular integrity and cytokine profile of type II alveolar epithelial cells

    PubMed Central

    Adlakha, Nidhi; Vir, Pooja; Verma, Indu

    2012-01-01

    Background: Pulmonary tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tb). In lungs, alveolar macrophages and type II alveolar epithelial cells serve as a replicative niche for this pathogen. Secretory proteins released by actively replicating tubercle bacilli are known to interact with host cells at the initial stages of infection. To understand the role of these cells in TB pathogenesis, it is important to identify the mycobacterial components involved in interaction with alveolar epithelial cells. Materials and Methods: We fractionated the whole secretory proteome of M. tb H37Rv into 10 narrow molecular mass fractions (A1-A10; <20 kDa to >90 kDa) that were studied for their binding potential with A549; type II alveolar epithelial cell line. We also studied the consequences of this interaction in terms of change in epithelial cell viability by MTT assay and cytokine release by ELISA. Results: Our results show that several mycobacterial proteins bind and confer cytolysis in epithelial cells. Amongst all the fractions, proteins ranging from 35-45 kDa (A5) exhibited highest binding to A549 cells with a consequence of cytolysis of these cells. This fraction (A5) also led to release of various cytokines important in anti-mycobacterial immunity. Conclusion: Fraction A5 (35-45 kDa) of mycobacterial secretory proteome play an important role in mediating M. tb interaction with type II alveolar epithelial cells with the consequences detrimental for the TB pathogenesis. Further studies are being carried out to identify the candidate proteins from this region. PMID:23243342

  14. Clinicopathological Profile of Childhood Primary Abdominal Tumours in Kashmir.

    PubMed

    Khan, Parwez Sajad; Akhter, Zahida; Majeed, Showkat; Wani, Mohd Yousuf; Hayat, Humera

    2015-12-01

    Primary abdominal tumours attract considerable notice because of their serious prognosis, high cost of treatment and the emotional and psychological trauma. Abdominal tumours can present with pain, vomiting, constipation or less commonly intestinal obstruction. The presentation of cancer in children mimic those of childhood conditions like infections particularly viral infections, urinary tract infections, gastro-oesophageal reflux, malnutrition, constipation, lymphadnenitis, glomerulonephritis and congenital urinary tract anomalies. PMID:26730026

  15. Thirteen years of culture-positive M. bovis-BCG infection in an IL-12Rbeta1 deficient patient: treatment and outcome.

    PubMed

    Rosenzweig, S D; Yancoski, J; Bernasconi, A; Krasovec, S; Marciano, B E; Casimir, L; Berberian, G; Símboli, N; Rousseau, M; Calle, G

    2006-03-01

    Patients with mutations in the IFNgamma/IL-12 pathway show an exquisite susceptibility to mycobacterial diseases. An IL-12Rbeta1 deficient patient with impaired intestinal absorption suffered from a 13 year culture-positive Mycobacterium bovis-BCG infection with acquired multidrug resistance. A combined parenteral and enteral anti-mycobacterial treatment, including recombinant IFNgamma, helped to clear his infection. PMID:16181679

  16. 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

  17. Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009-2014.

    PubMed

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

    2016-06-01

    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

  18. Inhaled Amikacin for Treatment of Refractory Pulmonary Nontuberculous Mycobacterial Disease

    PubMed Central

    Shaw, Pamela A.; Glaser, Tanya S.; Bhattacharyya, Darshana; Fleshner, Michelle; Brewer, Carmen C.; Zalewski, Christopher K.; Folio, Les R.; Siegelman, Jenifer R.; Shallom, Shamira; Park, In Kwon; Sampaio, Elizabeth P.; Zelazny, Adrian M.; Holland, Steven M.; Prevots, D. Rebecca

    2014-01-01

    Rationale: Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. Objectives: We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Methods: Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. Measurements and Main Results: The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. Conclusions: In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted. PMID:24460437

  19. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation.

    PubMed

    Abdallah, Abdallah M; Bestebroer, Jovanka; Savage, Nigel D L; de Punder, Karin; van Zon, Maaike; Wilson, Louis; Korbee, Cees J; van der Sar, Astrid M; Ottenhoff, Tom H M; van der Wel, Nicole N; Bitter, Wilbert; Peters, Peter J

    2011-11-01

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5--two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators--during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1β activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. PMID:21957139

  20. Osteopontin: A Novel Cytokine Involved in the Regulation of Mycobacterium avium subsp. paratuberculosis Infection in Periparturient Dairy Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopontin (Opn), an important mediator of the cell-mediated immune response, enhances the host immune response against mycobacterial infections. Infections caused by the intracellular bacterium, Mycobacterium avium subsp. paratuberculosis (MAP), have a devastating impact on the dairy industry. ...

  1. Salmonella Infections

    MedlinePlus

    ... vegetables. You also can get infected after handling pets, especially reptiles like snakes, turtles, and lizards. Symptoms include Fever Diarrhea Abdominal cramps Headache Possible nausea, vomiting, and loss of appetite Symptoms usually last 4-7 days. ...

  2. [The patient with intra-abdominal hypertension].

    PubMed

    Sakka, Samir G

    2016-01-01

    An intra-abdominal hypertension (IAH) defined as a pathological increase in intra-abdominal pressure (IAP) is commonly found on ICU admission or during the ICU stay. Several studies confirmed that an IAH is an independent predictor for mortality of critically ill patients. The abdominal compartment syndrome (ACS) which is defined as a sustained IAP>20 mmHg (with or without an abdominal perfusion pressure [APP]<60mmHg) that is associated with new organ dysfunction or failure has a mortality of up to 60%. In general, an IAH may be induced by several intra-abdominal as well as extra-abdominal conditions. Reduced abdominal wall compliance, intra-abdominal pathologies (either of the peritoneal space or parenchymateous organs) may lead to an IAH. Most commonly, intra-abdominal infections and/or sepsis and severe trauma or burns are predisposing for an IAH. An early sign may be a decrease in urinary output. The effects of an increased IAP on cardiovascular function are well recognized and include negative effects on preload, afterload and contractility. However, all other compartments of the body may be affected by an IAH. Thus, by an increase of the respective compartment pressure, e.g. intracranial pressure, a poly-compartment syndrome may result. Adequate prevention, a forward-looking strategy, and objective techniques for measurement of IAP are required to avoid or early detect an IAH or ACS. Finally, an immediate and consequent interdisciplinary management using conservative, interventional and operative options are necessary to solve an IAH or ACS. PMID:26863642

  3. 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. PMID:16426970

  4. Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential.

    PubMed

    Wehenkel, Annemarie; Bellinzoni, Marco; Graña, Martin; Duran, Rosario; Villarino, Andrea; Fernandez, Pablo; Andre-Leroux, Gwénaëlle; England, Patrick; Takiff, Howard; Cerveñansky, Carlos; Cole, Stewart T; Alzari, Pedro M

    2008-01-01

    Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and virulence of Mycobacterium tuberculosis, the etiological agent of tuberculosis. This pathogen uses 'eukaryotic-like' Ser/Thr protein kinases and phosphatases not only to regulate many intracellular metabolic processes, but also to interfere with signaling pathways of the infected host cell. Disrupting such processes by means of selective inhibitors may thus provide new pharmaceutical weapons to combat the disease. Here we review the current knowledge on Ser/Thr protein kinases and phosphatases in M. tuberculosis, their regulation mechanisms and putative substrates, and we explore their therapeutic potential as possible targets for the development of new anti-mycobacterial compounds. PMID:17869195

  5. Functional plasticity and allosteric regulation of α-ketoglutarate decarboxylase in central mycobacterial metabolism.

    PubMed

    Wagner, Tristan; Bellinzoni, Marco; Wehenkel, Annemarie; O'Hare, Helen M; Alzari, Pedro M

    2011-08-26

    The α-ketoglutarate dehydrogenase (KDH) complex is a major regulatory point of aerobic energy metabolism. Mycobacterium tuberculosis was reported to lack KDH activity, and the putative KDH E1o component, α-ketoglutarate decarboxylase (KGD), was instead assigned as a decarboxylase or carboligase. Here, we show that this protein does in fact sustain KDH activity, as well as the additional two reactions, and these multifunctional properties are shared by the Escherichia coli homolog, SucA. We also show that the mycobacterial enzyme is finely regulated by an additional acyltransferase-like domain and by the action of acetyl-CoA, a powerful allosteric activator able to enhance the concerted protein motions observed during catalysis. Our results uncover the functional plasticity of a crucial node in bacterial metabolism, which may be important for M. tuberculosis during host infection. PMID:21867916

  6. Comparative genomic analysis of Mycobacterium iranicum UM_TJL against representative mycobacterial species suggests its environmental origin

    PubMed Central

    Tan, Joon Liang; Ngeow, Yun Fong; Wee, Wei Yee; Wong, Guat Jah; Ng, Hien Fuh; Choo, Siew Woh

    2014-01-01

    Mycobacterium iranicum is a newly reported mycobacterial species. We present the first comparative study of M. iranicum UM_TJL and other mycobacteria. We found M. iranicum to have a close genetic association with environmental mycobacteria infrequently associated with human infections. Nonetheless, UM_TJL is also equipped with many virulence genes (some of which appear to be the consequence of transduction-related gene transfer) that have been identified in established human pathogens. Taken all together, our data suggest that M. iranicum is an environmental bacterium adapted for pathogenicity in the human host. This comparative study provides important clues and forms the basis for future functional studies on this mycobacterium. PMID:25417557

  7. Reconstruction option of abdominal wounds with large tissue defects

    PubMed Central

    2014-01-01

    Background Abdominal wall defects result from trauma, abdominal wall tumors, necrotizing infections or complications of previous abdominal surgeries. Apart from cosmetics, abdominal wall defects have strong negative functional impact on the patients. Many different techniques exist for abdominal wall repair. Most problematic and troublesome are defects, where major part of abdominal wall had to be resected and tissue for transfer or reconstruction is absent. Case presentation Authors of the article present operative technique, in which reconstruction of abdominal wall was managed by composite polypropylene mesh with absorbable collagen film, creation of granulation tissue with use of NPWT (negative pressure wound therapy), and subsequent split skin grafting. Three patients with massive abdominal wall defect were successfully managed and abdominal wall reconstruction was performed by mentioned technique. Functional and cosmetic effect is acceptable and patients have good postoperative quality of life. Conclusions Patients with giant abdominal defects can benefit from described technique. It serves as the only option, with which abdominal wall is fully reconstructed without need for the secondary intervention. PMID:25103782

  8. 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

  9. Abdominal aortic aneurysm.

    PubMed

    Keisler, Brian; Carter, Chuck

    2015-04-15

    Abdominal aortic aneurysm refers to abdominal aortic dilation of 3.0 cm or greater. The main risk factors are age older than 65 years, male sex, and smoking history. Other risk factors include a family history of abdominal aortic aneurysm, coronary artery disease, hypertension, peripheral artery disease, and previous myocardial infarction. Diagnosis may be made by physical examination, an incidental finding on imaging, or ultrasonography. The U.S. Preventive Services Task Force released updated recommendations for abdominal aortic aneurysm screening in 2014. Men 65 to 75 years of age with a history of smoking should undergo one-time screening with ultrasonography based on evidence that screening will improve abdominal aortic aneurysm-related mortality in this population. Men in this age group without a history of smoking may benefit if they have other risk factors (e.g., family history of abdominal aortic aneurysm, other vascular aneurysms, coronary artery disease). There is inconclusive evidence to recommend screening for abdominal aortic aneurysm in women 65 to 75 years of age with a smoking history. Women without a smoking history should not undergo screening because the harms likely outweigh the benefits. Persons who have a stable abdominal aortic aneurysm should undergo regular surveillance or operative intervention depending on aneurysm size. Surgical intervention by open or endovascular repair is the primary option and is typically reserved for aneurysms 5.5 cm in diameter or greater. There are limited options for medical treatment beyond risk factor modification. Ruptured abdominal aortic aneurysm is a medical emergency presenting with hypotension, shooting abdominal or back pain, and a pulsatile abdominal mass. It is associated with high prehospitalization mortality. Emergent surgical intervention is indicated for a rupture but has a high operative mortality rate. PMID:25884861

  10. Mendelian Susceptibility to Mycobacterial Disease due to IL-12Rβ1 Deficiency in Three Iranian Children

    PubMed Central

    SARRAFZADEH, Shokouh Azam; MAHLOOJIRAD, Maryam; NOURIZADEH, Maryam; CASANOVA, Jean-Laurent; POURPAK, Zahra; BUSTAMANTE, Jacinta; MOIN, Mostafa

    2016-01-01

    Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN-γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombinant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients’ leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimulated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria. PMID:27141500

  11. Mendelian Susceptibility to Mycobacterial Disease due to IL-12Rβ1 Deficiency in Three Iranian Children

    PubMed Central

    SARRAFZADEH, Shokouh azam; MAHLOOJIRAD, Maryam; NOURIZADEH, Maryam; CASANOVA, Jean-Laurent; POURPAK, Zahra; BUSTAMANTE, Jacinta; MOIN, Mostafa

    2016-01-01

    Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN- γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombinant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients’ leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimulated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria. PMID:27114990

  12. Mendelian Susceptibility to Mycobacterial Disease due to IL-12Rβ1 Deficiency in Three Iranian Children.

    PubMed

    Sarrafzadeh, Shokouh Azam; Mahloojirad, Maryam; Nourizadeh, Maryam; Casanova, Jean-Laurent; Pourpak, Zahra; Bustamante, Jacinta; Moin, Mostafa

    2016-03-01

    Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN-γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombinant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients' leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimulated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria. PMID:27141500

  13. [Abdominal pregnancy, institutional experience].

    PubMed

    Bonfante Ramírez, E; Bolaños Ancona, R; Simón Pereyra, L; Juárez García, L; García-Benitez, C Q

    1998-07-01

    Abdominal pregnancy is a rare entity, which has been classified as primary or secondary by Studiford criteria. A retrospective study, between January 1989 and December 1994, realized at Instituto Nacional de Perinatología, found 35,080 pregnancies, from which 149 happened to be ectopic, and 6 of them were abdominal. All patients belonged to a low income society class, age between 24 and 35 years, and average of gestations in 2.6. Gestational age varied from 15 weeks to 32.2 weeks having only one delivery at term with satisfactory postnatal evolution. One patient had a recurrent abdominal pregnancy, with genital Tb as a conditional factor. Time of hospitalization varied from 4 to 5 days, and no further patient complications were reported. Fetal loss was estimated in 83.4%. Abdominal pregnancy is often the sequence of a tubarian ectopic pregnancy an when present, it has a very high maternal mortality reported in world literature, not found in this study. The stated frequency of abdominal pregnancy is from 1 of each 3372, up to 1 in every 10,200 deliveries, reporting in the study 1 abdominal pregnancy in 5846 deliveries. The study had two characteristic entities one, the recurrence and two, the delivery at term of one newborn. Abdominal pregnancy accounts for 4% of all ectopic pregnancies. Clinical findings in abdominal pregnancies are pain, transvaginal bleeding and amenorrea, being the cardinal signs of ectopic pregnancy. PMID:9737070

  14. Recurrent Abdominal Pain

    ERIC Educational Resources Information Center

    Banez, Gerard A.; Gallagher, Heather M.

    2006-01-01

    The purpose of this article is to provide an empirically informed but clinically oriented overview of behavioral treatment of recurrent abdominal pain. The epidemiology and scope of recurrent abdominal pain are presented. Referral process and procedures are discussed, and standardized approaches to assessment are summarized. Treatment protocols…

  15. Targeting the mycobacterial envelope for tuberculosis drug development

    PubMed Central

    Favrot, Lorenza; Ronning, Donald R

    2013-01-01

    The bacterium that causes tuberculosis, Mycobacterium tuberculosis, possesses a rather unique outer membrane composed largely of lipids that possess long-chain and branched fatty acids, called mycolic acids. These lipids form a permeability barrier that prevents entry of many environmental solutes, thereby making these bacteria acid-fast and able to survive extremely hostile surroundings. Antitubercular drugs must penetrate this layer to reach their target. This review highlights drug development efforts that have added to the slowly growing tuberculosis drug pipeline, identified new enzyme activities to target with drugs and increased the understanding of important biosynthetic pathways for mycobacterial outer membrane and cell wall core assembly. In addition, a portion of this review looks at discovery efforts aimed at weakening this barrier to decrease mycobacterial virulence, decrease fitness in the host or enhance the efficacy of the current drug repertoire by disrupting the permeability barrier. PMID:23106277

  16. 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

  17. 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. PMID:27247343

  18. Genetic characterization of mycobacterial l,d-transpeptidases

    PubMed Central

    Sanders, Akeisha N.; Wright, Lori F.

    2014-01-01

    l,d-Transpeptidases (Ldts) catalyse the formation of 3–3 cross-links in peptidoglycans (PGs); however, the role of these enzymes in cell envelope physiology is not well understood. Mycobacterial PG contains a higher percentage of 3–3 cross-links (~30–80 %) than the PG in most other bacteria, suggesting that they are particularly important to mycobacterial cell wall biology. The genomes of Mycobacterium tuberculosis and Mycobacterium smegmatis encode multiple Ldt genes, but it is not clear if they are redundant. We compared the sequences of the Ldt proteins from 18 mycobacterial genomes and found that they can be grouped into six classes. We then constructed M. smegmatis strains lacking single or multiple Ldt genes to determine the physiological consequence of the loss of these enzymes. We report that of the single mutants, only one, ΔldtC (MSMEG_0929, class 5), displayed an increased susceptibility to imipenem – a carbapenem antibiotic that inhibits the Ldt enzymes. The invariant cysteine in the active site of LdtC was required for function, consistent with its role as an Ldt. A triple mutant missing ldtC and both of the class 2 genes displayed hypersusceptibility to antibiotics, lysozyme and d-methionine, and had an altered cellular morphology. These data demonstrated that the distinct classes of mycobacterial Ldts may reflect different, non-redundant functions and that the class 5 Ldt was peculiar in that its loss, alone and with the class 2 proteins, had the most profound effect on phenotype. PMID:24855140

  19. Novel prenyl-linked benzophenone substrate analogues of mycobacterial mannosyltransferases

    PubMed Central

    2004-01-01

    PPM (polyprenol monophosphomannose) has been shown to act as a glycosyl donor in the biosynthesis of the Man (mannose)-rich mycobacterial lipoglycans LM (lipomannan) and LAM (lipoarabinomannan). The Mycobacterium tuberculosis PPM synthase (Mt-Ppm1) catalyses the transfer of Man from GDP-Man to polyprenyl phosphates. The resulting PPM then serves as a donor of Man residues leading to the formation of an α(1→6)LM intermediate through a PPM-dependent α(1→6)mannosyltransferase. In the present study, we prepared a series of ten novel prenyl-related photoactivatable probes based on benzophenone with lipophilic spacers replacing several internal isoprene units. These probes were excellent substrates for the recombinant PPM synthase Mt-Ppm1/D2 and, on photoactivation, several inhibited its activity in vitro. The protection of the PPM synthase activity by a ‘natural’ C75 polyprenyl acceptor during phototreatment is consistent with probe-mediated photoinhibition occurring via specific covalent modification of the enzyme active site. In addition, the unique mannosylated derivatives of the photoreactive probes were all donors of Man residues, through a PPM-dependent mycobacterial α(1→6)mannosyltransferase, to a synthetic Manp(1→6)-Manp-O-C10:1 disaccharide acceptor (where Manp stands for mannopyranose). Photoactivation of probe 7 led to striking-specific inhibition of the M. smegmatis α(1→6)mannosyltransferase. The present study represents the first application of photoreactive probes to the study of mycobacterial glycosyltransferases involved in LM and LAM biosynthesis. These preliminary findings suggest that the probes will prove useful in investigating the polyprenyl-dependent steps of the complex biosynthetic pathways to the mycobacterial lipoglycans, aiding in the identification of novel glycosyltransferases. PMID:15202931

  20. 'Black bronchoscopy': a case of active mycobacterial tuberculosis.

    PubMed

    Inaty, Hanine; Arora, Ayush; Diacovo, Julia M; Mehta, Atul

    2016-07-01

    A 63-year-old male presents with chronic cough and hemoptysis. Computed tomography of the chest revealed a left lower lobe (LLL) area of consolidation with prominent ipsilateral hilar lymphadenopathy. Bronchoscopic airway examination revealed black mucosal discoloration and airway narrowing at the superior segment of the LLL. Bronchoalveolar lavage from the corresponding site grew mycobacterial tuberculosis. The patient's symptoms subsided with anti-tuberculous therapy with a significant decrease in the size of the LLL mass. PMID:27471594

  1. ‘Black bronchoscopy’: a case of active mycobacterial tuberculosis

    PubMed Central

    Inaty, Hanine; Arora, Ayush; Diacovo, Julia M.; Mehta, Atul

    2016-01-01

    A 63-year-old male presents with chronic cough and hemoptysis. Computed tomography of the chest revealed a left lower lobe (LLL) area of consolidation with prominent ipsilateral hilar lymphadenopathy. Bronchoscopic airway examination revealed black mucosal discoloration and airway narrowing at the superior segment of the LLL. Bronchoalveolar lavage from the corresponding site grew mycobacterial tuberculosis. The patient's symptoms subsided with anti-tuberculous therapy with a significant decrease in the size of the LLL mass. PMID:27471594

  2. [Crepitant abdominal cellulitis: a rare clinical presentation of sigmoid tumor].

    PubMed

    Chaib, E; Leal, M C; Onofrio, P L; Nahas, P; de Mello, J B

    1990-01-01

    Unusual infections associated with colorectal tumors may, in some instances, be the sole clue to presence of malignancy. The infections are either related to invasion of tissues or organs in close proximity to the tumor or secondary to distant seeding by transient bacteremia arising from necrotic tumors. The authors present one case of spontaneous crepitant cellulitis in the lower abdominal wall, associated with sigmoid tumor. The patient had abdominal pain in the left iliaca fossa, fever and skin necrosis of the lower abdominal wall in the last 4 hours. At surgery they performed debridement and excision of necrotic tissue (lower abdominal wall) and partial sigmoidectomy with sigmoid colostomy. The patient died 9 months after initial surgery. A study of tumor mass revealed an adenocarcinoma. The presence of crepitant cellulitis in a lower abdominal wall should result in a search for bowel perforation. PMID:2151244

  3. Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection

    PubMed Central

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Rapole, Srikanth; Banerjee, Sharmistha

    2016-01-01

    Mycobacterium tuberculosis (Mtb) is the most common co-infection in HIV patients and a serious co-epidemic. Apart from increasing the risk of reactivation of latent tuberculosis (TB), HIV infection also permits opportunistic infection of environmental non-pathogenic mycobacteria. To gain insights into mycobacterial survival inside host macrophages and identify mycobacterial proteins or processes that influence HIV propagation during co-infection, we employed proteomics approach to identify differentially expressed intracellular mycobacterial proteins during mono- and HIV co-infection of human THP-1 derived macrophage cell lines. Of the 92 proteins identified, 30 proteins were upregulated during mycobacterial mono-infection and 40 proteins during HIV-mycobacteria co-infection. We observed down-regulation of toxin-antitoxin (TA) modules, up-regulation of cation transporters, Type VII (Esx) secretion systems, proteins involved in cell wall lipid or protein metabolism, glyoxalate pathway and branched chain amino-acid synthesis during co-infection. The bearings of these mycobacterial factors or processes on HIV propagation during co-infection, as inferred from the proteomics data, were validated using deletion mutants of mycobacteria. The analyses revealed mycobacterial factors that possibly via modulating the host environment, increased viral titers during co-infection. The study provides new leads for investigations towards hitherto unknown molecular mechanisms explaining HIV-mycobacteria synergism, helping address diagnostics and treatment challenges for effective co-epidemic management. PMID:26916387

  4. Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection.

    PubMed

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Rapole, Srikanth; Banerjee, Sharmistha

    2016-01-01

    Mycobacterium tuberculosis (Mtb) is the most common co-infection in HIV patients and a serious co-epidemic. Apart from increasing the risk of reactivation of latent tuberculosis (TB), HIV infection also permits opportunistic infection of environmental non-pathogenic mycobacteria. To gain insights into mycobacterial survival inside host macrophages and identify mycobacterial proteins or processes that influence HIV propagation during co-infection, we employed proteomics approach to identify differentially expressed intracellular mycobacterial proteins during mono- and HIV co-infection of human THP-1 derived macrophage cell lines. Of the 92 proteins identified, 30 proteins were upregulated during mycobacterial mono-infection and 40 proteins during HIV-mycobacteria co-infection. We observed down-regulation of toxin-antitoxin (TA) modules, up-regulation of cation transporters, Type VII (Esx) secretion systems, proteins involved in cell wall lipid or protein metabolism, glyoxalate pathway and branched chain amino-acid synthesis during co-infection. The bearings of these mycobacterial factors or processes on HIV propagation during co-infection, as inferred from the proteomics data, were validated using deletion mutants of mycobacteria. The analyses revealed mycobacterial factors that possibly via modulating the host environment, increased viral titers during co-infection. The study provides new leads for investigations towards hitherto unknown molecular mechanisms explaining HIV-mycobacteria synergism, helping address diagnostics and treatment challenges for effective co-epidemic management. PMID:26916387

  5. [Case report: strongyloidiosis with chronic abdominal pain].

    PubMed

    Tamer, Gülden Sönmez; Dündar, Devrim

    2008-01-01

    The case was presented here in order to point out that an immunocompetent child might have Strongyloidiosis infection that might be misdiagnosed. A 9 year old male patient who had chronic abdominal pain with a feeling of weakness was treated several times for urinary tract infection. He had never been tested for the presence of parasites. After the patient's complaints occurred again, he presented at our hospital. Strongyloides stercoralis larvae were observed in his feces by microscopy. Albendazol (400 mg/day for three days) was prescribed. After 10 days, the feces of the patient was reexamined and no Strongyloides stercoralis larvae were detected. For this reason, it is important to investigate the possibility of intestinal parasitic infections in children with chronic abdominal pain. PMID:18645954

  6. Post Liposuction Mycobacterium Abscessus Surgical Site Infection in a Returned Medical tourist Complicated by a Paradoxical Reaction During Treatment

    PubMed Central

    Hui, Siong H.; Noonan, Lisa

    2015-01-01

    Rapidly growing mycobacterial skin and soft tissue infections are known to complicate cosmetic surgical procedures. Treatment consists of more surgery and prolonged antibiotic therapy guided by drug susceptibility testing. Paradoxical reactions occurring during antibiotic therapy can further complicate treatment of non-tuberculous mycobacterial infections. We report a case of post liposuction Mycobacterium abscessus surgical site infection in a returned medical tourist and occurrence of paradox during treatment. PMID:26753088

  7. Abdominal ultrasound (image)

    MedlinePlus

    Abdominal ultrasound is a scanning technique used to image the interior of the abdomen. Like the X- ... use high frequency sound waves to produce an image and do not expose the individual to radiation. ...

  8. Abdominal ultrasound (image)

    MedlinePlus

    Abdominal ultrasound is a scanning technique used to image the interior of the abdomen. Like the X-ray, MRI, ... it has its place as a diagnostic tool. Ultrasound scans use high frequency sound waves to produce ...

  9. Abdominal exploration - series (image)

    MedlinePlus

    ... surgical exploration of the abdomen, also called an exploratory laparotomy, may be recommended when there is abdominal ... blunt trauma"). Diseases that may be discovered by exploratory laparotomy include: inflammation of the appendix (acute appendicitis) ...

  10. Abdominal aortic aneurysm

    MedlinePlus

    ... main blood vessel that supplies blood to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs ... dissection). Symptoms of rupture include: Pain in the abdomen or back. The pain may be severe, sudden, ...

  11. Abdominal x-ray

    MedlinePlus

    An abdominal x-ray is an imaging test to look at organs and structures in the abdomen. Organs include the spleen, stomach, and intestines. When the test is done to look at the bladder and kidney structures, ...

  12. Abdominal aortic aneurysm.

    PubMed

    Setacci, Francesco; Galzerano, Giuseppe; De Donato, Gianmarco; Benevento, Domenico; Guerrieri, Massimiliano W; Ruzzi, Umberto; Borrelli, Maria P; Setacci, Carlo

    2016-02-01

    Endovascular repair of abdominal aortic aneurysms has become a milestone in the treatment of patients with abdominal aortic aneurysm. Technological improvement allows treatment in more and more complex cases. This review summarizes all grafts available on the market. A complete review of most important trial on this topic is provided to the best of our knowledge, and technical tips and tricks for standard cases are also included. PMID:26771730

  13. Mycobacterial disease in cats in Great Britain: I. Culture results, geographical distribution and clinical presentation of 339 cases.

    PubMed

    Gunn-Moore, Danièlle A; McFarland, Sarah E; Brewer, Jacqueline I; Crawshaw, Timothy R; Clifton-Hadley, Richard S; Kovalik, Marcel; Shaw, Darren J

    2011-12-01

    This study investigated 339 cases of feline mycobacterial disease from cats with cutaneous lesions or masses found at exploratory laparotomy. Tissue samples were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study assessed which species of culturable mycobacteria were involved, where the cats lived, and their clinical presentation (physical findings, serum biochemistry, radiography, feline leukaemia virus and feline immunodeficiency virus status). Mycobacterium microti was cultured from 19%, Mycobacterium bovis 15%, Mycobacterium avium 7%, non-M avium non-tuberculous mycobacteria 6%, with no growth in 53% of samples. M microti, M bovis and M avium were found in almost mutually exclusive clusters within Great Britain (GB) (ie, M bovis in South-West England/Wales/Welsh Border, M avium in eastern England and M microti south of London and in South-West Scotland). While differences were seen in the clinical presentation and distribution of lesions caused by the different infections, these were not sufficiently different to be diagnostic. Cats commonly presented with single or multiple cutaneous lesions (74%), which were sometimes ulcerated or discharging, located most frequently on the head (54%). Lymph nodes were usually involved (47%); typically the submandibular nodes. Systemic or pulmonary signs were rarely seen (10-16%). When a cat is suspected of having mycobacteriosis, accurate identification of the species involved helps to determine appropriate action. Our findings show that knowing the cat's geographic location can be helpful, while the nature of the clinical presentation is less useful. Most cases of feline mycobacterial disease in GB are cutaneous. PMID:22079343

  14. Characterization of extended-spectrum beta-lactamases and antimicrobial resistance of Klebsiella pneumoniae in intra-abdominal infection isolates in Latin America, 2008-2012. Results of the Study for Monitoring Antimicrobial Resistance Trends.

    PubMed

    Kazmierczak, Krystyna M; Lob, Sibylle H; Hoban, Daryl J; Hackel, Meredith A; Badal, Robert E; Bouchillon, Samuel K

    2015-07-01

    The Study for Monitoring Antimicrobial Resistance Trends has monitored the in vitro activity of several recommended antimicrobials used in the management of intra-abdominal infections (IAIs) globally since 2002. In this report, we document the changing susceptibility patterns to recommended antimicrobials in Klebsiella pneumoniae isolates from patients with IAIs in 11 Latin American countries between 2008 and 2012 and describe the beta-lactamases encoded by phenotypically extended-spectrum beta-lactamase (ESBL)-positive and ertapenem-nonsusceptible isolates. Overall, the incidence of phenotypically ESBL-positive K. pneumoniae did not change significantly from 2008 (40.4%) to 2012 (41.2%) (P > 0.05). However, trend analysis documented an increase in isolates encoding K. pneumoniae carbapenemase (KPC) or both KPC and an ESBL. Decreasing susceptibility (P < 0.05) was noted for cefepime, ceftazidime, ceftriaxone, ertapenem, and imipenem among all K. pneumoniae, as well as for cefepime, cefotaxime, cefoxitin, ceftriaxone, ertapenem, and imipenem among ESBL-positive isolates, while susceptibility of ESBL-negative isolates to ampicillin-sulbactam actually increased (P < 0.05). PMID:25956930

  15. 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

    2011-01-01

    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. PMID:21396338

  16. Intra-abdominal sepsis after hepatic resection.

    PubMed Central

    Pace, R F; Blenkharn, J I; Edwards, W J; Orloff, M; Blumgart, L H; Benjamin, I S

    1989-01-01

    One hundred and thirty hepatic resections performed over an 8-year period were reviewed for evidence of postoperative intra-abdominal sepsis. Of 126 patients who survived for more than 24 hours after operation, 36 developed culture positive intra-abdominal collections (28.6%). Significant independent variables associated with the development of intra-abdominal sepsis were diagnoses of trauma or cholangiocarcinoma, and the need for reoperation to control hemorrhage during the postoperative period. Before 1984, infected fluid collections were treated predominantly by operative drainage, but this has largely been replaced by percutaneous methods, which have proven effective in most cases. Eighteen (50%) of the infections were caused by a mixed bacterial culture, with Streptococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus and Escherichia coli being the most common isolates. Six patients with clinical signs of sepsis had a sterile fluid collection drained with complete relief of symptoms. This review suggests that intra-abdominal sepsis is a frequent complication after hepatic resection, and can often be managed successfully by nonoperative percutaneous drainage. PMID:2493775

  17. Relationship Between Blood Concentrations of Hepcidin and Anemia Severity, Mycobacterial Burden, and Mortality Among Patients With HIV-Associated Tuberculosis

    PubMed Central

    Kerkhoff, Andrew D.; Meintjes, Graeme; Burton, Rosie; Vogt, Monica; Wood, Robin; Lawn, Stephen D.

    2016-01-01

    Background Anemia is very common in patients with human immunodeficiency virus (HIV)–associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. Methods Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, “hospitalized patients”), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, “ambulatory patients with tuberculosis”), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, “ambulatory patients without tuberculosis”). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified. Results Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality. Conclusions High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients. PMID:26136467

  18. A mycobacterial phosphoribosyltransferase promotes bacillary survival by inhibiting oxidative stress and autophagy pathways in macrophages and zebrafish.

    PubMed

    Mohanty, Soumitra; Jagannathan, Lakshmanan; Ganguli, Geetanjali; Padhi, Avinash; Roy, Debasish; Alaridah, Nader; Saha, Pratip; Nongthomba, Upendra; Godaly, Gabriela; Gopal, Ramesh Kumar; Banerjee, Sulagna; Sonawane, Avinash

    2015-05-22

    Mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. The M. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. Here, by using Concanavalin A and LC-MS analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by Rv3242c from M. tuberculosis cell walls. Homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activity in Mycobacterium smegmatis expressing recombinant Rv3242c (MsmRv3242c) confirmed the mass spectrometry data. Using Mycobacterium marinum-zebrafish and the surrogate MsmRv3242c infection models, we proved that phosphoribosyltransferase is involved in mycobacterial virulence. Histological and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebrafish and also survived less in macrophages. In contrast, infection with wild type and the complemented ΔmimG:Rv3242c M. marinum strains showed prominent pathological features, such as severe emaciation, skin lesions, hemorrhaging, and more zebrafish death. Similarly, recombinant MsmRv3242c bacteria showed increased invasion in non-phagocytic epithelial cells and longer intracellular survival in macrophages as compared with wild type and vector control M. smegmatis strains. Further mechanistic studies revealed that the Rv3242c- and mimG-mediated enhancement of intramacrophagic survival was due to inhibition of autophagy, reactive oxygen species, and reduced activities of superoxide dismutase and catalase enzymes. Infection with MsmRv3242c also activated the MAPK pathway, NF-κB, and inflammatory cytokines. In summary, we show that a novel mycobacterial mannosylated phosphoribosyltransferase acts as a virulence and immunomodulatory factor, suggesting that it may constitute a novel target for antimycobacterial drugs. PMID:25825498

  19. A Mycobacterial Phosphoribosyltransferase Promotes Bacillary Survival by Inhibiting Oxidative Stress and Autophagy Pathways in Macrophages and Zebrafish*

    PubMed Central

    Mohanty, Soumitra; Jagannathan, Lakshmanan; Ganguli, Geetanjali; Padhi, Avinash; Roy, Debasish; Alaridah, Nader; Saha, Pratip; Nongthomba, Upendra; Godaly, Gabriela; Gopal, Ramesh Kumar; Banerjee, Sulagna; Sonawane, Avinash

    2015-01-01

    Mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. The M. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. Here, by using Concanavalin A and LC-MS analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by Rv3242c from M. tuberculosis cell walls. Homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activity in Mycobacterium smegmatis expressing recombinant Rv3242c (MsmRv3242c) confirmed the mass spectrometry data. Using Mycobacterium marinum-zebrafish and the surrogate MsmRv3242c infection models, we proved that phosphoribosyltransferase is involved in mycobacterial virulence. Histological and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebrafish and also survived less in macrophages. In contrast, infection with wild type and the complemented ΔmimG:Rv3242c M. marinum strains showed prominent pathological features, such as severe emaciation, skin lesions, hemorrhaging, and more zebrafish death. Similarly, recombinant MsmRv3242c bacteria showed increased invasion in non-phagocytic epithelial cells and longer intracellular survival in macrophages as compared with wild type and vector control M. smegmatis strains. Further mechanistic studies revealed that the Rv3242c- and mimG-mediated enhancement of intramacrophagic survival was due to inhibition of autophagy, reactive oxygen species, and reduced activities of superoxide dismutase and catalase enzymes. Infection with MsmRv3242c also activated the MAPK pathway, NF-κB, and inflammatory cytokines. In summary, we show that a novel mycobacterial mannosylated phosphoribosyltransferase acts as a virulence and immunomodulatory factor, suggesting that it may constitute a novel target for antimycobacterial drugs. PMID:25825498

  20. Particle exposures and infections.

    PubMed

    Ghio, A J

    2014-06-01

    Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Cigarette smoking, burning of biomass, dust storms, mining, agricultural work, environmental tobacco smoke (ETS), wood stoves, traffic-related emissions, gas stoves, and ambient air pollution are all particle-related exposures associated with an increased risk for respiratory infections. In addition, cigarette smoking, burning of biomass, dust storms, mining, and ETS can result in an elevated risk for tuberculosis, atypical mycobacterial infections, and meningitis. One of the mechanisms for particle-related infections includes an accumulation of iron by surface functional groups of particulate matter (PM). Since elevations in metal availability are common to every particle exposure, all PM potentially contributes to these infections. Therefore, exposures to wood stove emissions, diesel exhaust, and air pollution particles are predicted to increase the incidence and prevalence of tuberculosis, atypical mycobacterial infections, and meningitis, albeit these elevations are likely to be small and detectable only in large population studies. Since iron accumulation correlates with the presence of surface functional groups and dependent metal coordination by the PM, the risk for infection continues as long as the particle is retained. Subsequently, it is expected that the cessation of exposure will diminish, but not totally reverse, the elevated risk for infection. PMID:24488331

  1. Antibiotic penetration of experimental intra-abdominal abscesses.

    PubMed

    Galandiuk, S; Lamos, J; Montgomery, W; Young, S; Polk, H C

    1995-06-01

    Intra-abdominal abscess is seldom adequately treated by systemic antibiotics alone and often requires surgical or computed tomography-guided drainage for resolution. Abscess penetration of six currently used antibiotics was examined in a murine intra-abdominal abscess model. Ampicillin/sulbactam, cefmetazole, clindamycin, and trospectomycin penetrated intra-abdominal abscesses to a greater degree than cefoxitin and ceftriaxone. Abscess pus antibiotic levels were not significantly higher after multiple doses than after a single dose. Pus antibiotic levels below the MIC90 for Bacteroides and E. coli within intra-abdominal abscess were observed for most antibiotics with the doses used in this study. Selection of antibiotics with a greater ability to penetrate abscess may be important in optimally treating patients with abdominal infection. PMID:7762902

  2. Effect of intestinal resection on serum antibodies to the mycobacterial 45/48 kilodalton doublet antigen in Crohn's disease.

    PubMed Central

    Kreuzpaintner, G; Das, P K; Stronkhorst, A; Slob, A W; Strohmeyer, G

    1995-01-01

    Interest in the role of mycobacterial infection in Crohn's disease has been revived by the cultural detection of Mycobacterium paratuberculosis in patients with Crohn's disease. This hypothesis was examined serologically using assays with high specificity for Crohn's disease. The effect of intestinal resection on serum antibodies specific for Crohn's disease was investigated with an immunoblot assay and an enzyme linked immunosorbent assay using the 45/48 kilodalton doublet antigen of Mycobacterium tuberculosis. Antibodies were detected in 64.7% of patients with Crohn's disease (n = 17), 10% of patients with ulcerative colitis (n = 10), 5% of patients with carcinoma of the colon (n = 20), and none of 10 healthy subjects with the immunoblot assay. Statistical comparison of the Crohn's disease patients with each control group resulted in p = 0.0000236. Immunoglobulin G was essentially unchanged 75 days (mean) after surgery. After more than 180 days, however, the antibody response was reduced in all of five patients studied, and was no longer demonstrable in two of them (40%). Simultaneously, the Crohn's disease activity index (CDAI) decreased. Both the high specificity of this assay for Crohn's disease and the diminished antibody response after intestinal resection in parallel with decreased CDAI support a mycobacterial aetiology of Crohn's disease. Images Figure 1 Figure 2 Figure 3 PMID:7590431

  3. Abdominal Dual Energy Imaging

    NASA Astrophysics Data System (ADS)

    Sommer, F. Graham; Brody, William R.; Cassel, Douglas M.; Macovski, Albert

    1981-11-01

    Dual energy scanned projection radiography of the abdomen has been performed using an experimental line-scanned radiographic system. Digital images simultaneously obtained at 85 and 135 kVp are combined, using photoelectric/Compton decomposition algorithms to create images from which selected materials are cancelled. Soft tissue cancellation images have proved most useful in various abdominal imaging applications, largely due to the elimination of obscuring high-contrast bowel gas shadows. These techniques have been successfully applied to intravenous pyelography, oral cholecystography, intravenous abdominal arteriog-raphy and the imaging of renal calculi.

  4. The Acute Abdominal Aorta.

    PubMed

    Mellnick, Vincent M; Heiken, Jay P

    2015-11-01

    Acute disorders of the abdominal aorta are potentially lethal conditions that require prompt evaluation and treatment. Computed tomography (CT) is the primary imaging method for evaluating these conditions because of its availability and speed. Volumetric CT acquisition with multiplanar reconstruction and three-dimensional analysis is now the standard technique for evaluating the aorta. MR imaging may be useful for select applications in stable patients in whom rupture has been excluded. Imaging is indispensable for diagnosis and treatment planning, because management has shifted toward endoluminal repair. Acute abdominal aortic conditions most commonly are complications of aneurysms and atherosclerosis. PMID:26526434

  5. Abdominal Vascular Catastrophes.

    PubMed

    Singh, Manpreet; Koyfman, Alex; Martinez, Joseph P

    2016-05-01

    Abdominal vascular catastrophes are among the most challenging and time sensitive for emergency practitioners to recognize. Mesenteric ischemia remains a highly lethal entity for which the history and physical examination can be misleading. Laboratory tests are often unhelpful, and appropriate imaging must be quickly obtained. A multidisciplinary approach is required to have a positive impact on mortality rates. Ruptured abdominal aortic aneurysm likewise may present in a cryptic fashion. A specific type of ruptured aneurysm, the aortoenteric fistula, often masquerades as the more common routine gastrointestinal bleed. The astute clinician recognizes that this is a more lethal variant of gastrointestinal hemorrhage. PMID:27133247

  6. Abdominal Aortic Aneurysms

    PubMed Central

    Fortner, George; Johansen, Kaj

    1984-01-01

    Aneurysms are common in our increasingly elderly population, and are a major threat to life and limb. Until the advent of vascular reconstructive techniques, aneurysm patients were subject to an overwhelming risk of death from exsanguination. The first successful repair of an abdominal aortic aneurysm using an interposed arterial homograft was reported by Dubost in 1952. A milestone in the evolution of vascular surgery, this event and subsequent diagnostic, operative and prosthetic graft refinements have permitted patients with an unruptured abdominal aortic aneurysm to enjoy a better prognosis than patients with almost any other form of major systemic illness. Images PMID:6702193

  7. Activation of human neutrophils by mycobacterial phenolic glycolipids

    PubMed Central

    Fäldt, J; Dahlgren, C; Karlsson, A; Ahmed, A M S; Minnikin, D E; Ridell, M

    1999-01-01

    The interaction between mycobacterial phenolic glycolipids (PGLs) and phagocytes was studied. Human neutrophils were allowed to interact with each of four purified mycobacterial PGLs and the neutrophil production of reactive oxygen metabolites was followed kinetically by luminol-/isoluminol-amplified chemiluminescence. The PGLs from Mycobacterium tuberculosis and Mycobacterium kansasii, respectively, were shown to stimulate the production of oxygen metabolites, while PGLs from Mycobacterium marinum and Mycobacterium bovis BCG, respectively, were unable to induce an oxidative response. Periodate treatment of the M. tuberculosis PGL decreased the production of oxygen radicals, showing the importance of the PGL carbohydrate moiety for the interaction. The activation, however, could not be inhibited by rhamnose or fucose, indicating a complex interaction which probably involves more than one saccharide unit. This is in line with the fact that the activating PGLs from M. tuberculosis and M. kansasii contain tri- and tetrasaccharides, respectively, while the nonactivating PGLs from M. marinum and M. bovis BCG each contain a monosaccharide. The complement receptor 3 (CR3) has earlier been shown to be of importance for the phagocyte binding of mycobacteria, but did not appear to be involved in the activation of neutrophils by PGLs. The subcellular localization of the reactive oxygen metabolites formed was related to the way in which the glycolipids were presented to the cells. PMID:10540187

  8. Osteopontin Immunoreactivity in the Ileum and Ileoceccal Lymph Node of Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopontin (Opn), a highly acidic glycoprotein, promotes cellular adhesion and recruitment and has been shown to be upregulated in the granulomas of mycobacterial infections. Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is associated with granulomatous enteritis. ...

  9. 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

  10. Clinical Evaluation of Hepatic Portal Venous Gas after Abdominal Surgery

    PubMed Central

    Okada, Satomi; Azuma, Takashi; Kawashita, Yujo; Matsuo, Shigetoshi; Eguchi, Susumu

    2016-01-01

    Hepatic portal venous gas (HPVG) is induced by various abdominal diseases. Since HPVG is accompanied by bowel ischemia, intestinal infection and hypovolemia, various modes of critical management are needed to treat the underlying conditions. HPVG associated with abdominal complications after surgery has rarely been reported. We present 4 patients with HPVG after abdominal surgery: 2 of the 4 patients died of multiple organ failure, and the other 2 recovered with solely conservative therapy. Although postoperative HPVG is a severe and life-threatening condition, early detection and systemic treatment lead to a better patient outcome. PMID:27403110

  11. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  12. Screening for Abdominal Aortic Aneurysm

    MedlinePlus

    Understanding Task Force Recommendations Screening for Abdominal Aortic Aneurysm The U.S. Preventive Services Task Force (Task Force) ... final recommendation statement on Screening for Abdominal Aortic Aneurysm. This final recommendation statement applies to adults ages ...

  13. Practical Approaches to Definitive Reconstruction of Complex Abdominal Wall Defects.

    PubMed

    Latifi, Rifat

    2016-04-01

    With advances in abdominal surgery and the management of major trauma, complex abdominal wall defects have become the new surgical disease, and the need for abdominal wall reconstruction has increased dramatically. Subsequently, how to reconstruct these large defects has become a new surgical question. While most surgeons use native abdominal wall whenever possible, evidence suggests that synthetic or biologic mesh needs to be added to large ventral hernia repairs. One particular group of patients who exemplify "complex" are those with contaminated wounds, enterocutaneous fistulas, enteroatmospheric fistulas, and/or stoma(s), where synthetic mesh is to be avoided if at all possible. Most recently, biologic mesh has become the new standard in high-risk patients with contaminated and dirty-infected wounds. While biologic mesh is the most common tissue engineered used in this field of surgery, level I evidence is needed on its indication and long-term outcomes. Various techniques for reconstructing the abdominal wall have been described, however the long-term outcomes for most of these studies, are rarely reported. In this article, I outline current practical approaches to perioperative management and definitive abdominal reconstruction in patients with complex abdominal wall defects, with or without fistulas, as well as those who have lost abdominal domain. PMID:26585951

  14. Distribution of extended-spectrum β-lactamases, AmpC β-lactamases, and carbapenemases among Enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: results of the study for Monitoring Antimicrobial Resistance Trends (SMART).

    PubMed

    Sheng, Wang-Huei; Badal, Robert E; Hsueh, Po-Ren

    2013-07-01

    The increasing trend of β-lactam resistance among Enterobacteriaceae is a worldwide threat. Enterobacteriaceae isolates causing intra-abdominal infections (IAI) from the Study for Monitoring Antimicrobial Resistance Trends (SMART) collected in 2008 and 2009 from the Asia-Pacific region were investigated. Detection of extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases was performed by multiplex PCR. A total of 699 Enterobacteriaceae isolates with positive genotypic results, included Escherichia coli (n = 443), Klebsiella pneumoniae (n = 187), Enterobacter cloacae (n = 45), Klebsiella oxytoca (n = 9), Citrobacter freundii (n = 5), Proteus mirabilis (n = 3), Enterobacter aerogenes (n = 2), Morganella morganii (n = 2), and one each of Enterobacter asburiae, Proteus vulgaris, and Providencia rettgeri were analyzed. Nearly 20% of these β-lactamase-producing Enterobacteriaceae isolates were from community-associated IAI. CTX-M (588 isolates, including 428 [72.8%] with CTX-M-15) was the most common ESBL, followed by SHV (n = 59) and TEM (n = 4). CMY (n = 110, including 102 [92.7%] with CMY-2) was the most common AmpC β-lactamase, followed by DHA (n = 46) and ACT/MIR (n = 40). NDM (n = 65, including 62 [95.4%] with NDM-1) was the most common carbapenemase, followed by IMP (n = 7) and OXA (n = 7). Isolates from hospital-associated IAI had more complicated β-lactamase combinations than isolates from the community. Carbapenemases were all exclusively detected in Enterobacteriaceae isolates from India, except that IMP β-lactamases were also detected in Philippines and Australia. CTX-M β-lactamases were the predominant ESBLs produced by Enterobacteriaceae causing IAI in the Asia-Pacific region. Emergence of CTX-M-15-, CMY-2-, and NDM-1-producing Enterobacteriaceae isolates is of major concern and highlights the need for further surveillance in this area. PMID:23587958

  15. Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART).

    PubMed

    Yang, Qiwen; Wang, Hui; Chen, Minjun; Ni, Yuxing; Yu, Yunsong; Hu, Bijie; Sun, Ziyong; Huang, Wenxiang; Hu, Yunjian; Ye, Huifen; Badal, Robert E; Xu, Yingchun

    2010-12-01

    The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum β-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China. PMID:21036547

  16. Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections

    PubMed Central

    Ramesh, Mayakonda Krishnamurthy; Cesnauskas, Gintaras; Novikovs, Nikolajs; Stefanova, Penka; Sutcliffe, Joyce A.; Walpole, Susannah M.

    2014-01-01

    Eravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogens in vitro, including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.) PMID:24342651

  17. A novel quinoline derivative that inhibits mycobacterial FtsZ.

    PubMed

    Mathew, Bini; Ross, Larry; Reynolds, Robert C

    2013-07-01

    High throughput phenotypic screening of large commercially available libraries through two NIH programs has produced thousands of potentially interesting hits for further development as antitubercular agents. Unfortunately, these screens do not supply target information, and further follow up target identification is required to allow optimal rational design and development of highly active and selective clinical candidates. Cheminformatic analysis of the quinoline and quinazoline hits from these HTS screens suggested a hypothesis that certain compounds in these two classes may target the mycobacterial tubulin homolog, FtsZ. In this brief communication, activity of a lead quinoline against the target FtsZ from Mycobacterium tuberculosis (Mtb) is confirmed as well as good in vitro whole cell antibacterial activity against Mtb H37Rv. The identification of a putative target of this highly tractable pharmacophore should help medicinal chemists interested in targeting FtsZ and cell division develop a rational design program to optimize this activity toward a novel drug candidate. PMID:23647650

  18. Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides

    PubMed Central

    Maranha, Ana; Moynihan, Patrick J.; Miranda, Vanessa; Correia Lourenço, Eva; Nunes-Costa, Daniela; Fraga, Joana S.; José Barbosa Pereira, Pedro; Macedo-Ribeiro, Sandra; Ventura, M. Rita; Clarke, Anthony J.; Empadinhas, Nuno

    2015-01-01

    Mycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition to the partial esterification of glucose or methylglucose units with short-chain fatty acids, octanoate was invariably detected on the MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers octanoate to glucosylglycerate (GG) and diglucosylglycerate (DGG), the earliest intermediates in MGLP biosynthesis. Enzymatic studies, synthetic chemistry, NMR spectroscopy and mass spectrometry approaches suggest that, in contrast to the prevailing consensus, octanoate is not esterified to the primary hydroxyl group of glycerate but instead to the C6 OH of the second glucose in DGG. These observations raise important new questions about the MGLP reducing end architecture and about subsequent biosynthetic steps. Functional characterization of this unique octanoyltransferase, whose gene has been proposed to be essential for M. tuberculosis growth, adds new insights into a vital mycobacterial pathway, which may inspire new drug discovery strategies. PMID:26324178

  19. Component separation in abdominal trauma.

    PubMed

    Rawstorne, Edward; Smart, Christopher J; Fallis, Simon A; Suggett, Nigel

    2014-01-01

    Component separation is established for complex hernia repairs. This case presents early component separation and release of the anterior and posterior sheath to facilitate closure of the abdominal wall following emergency laparotomy, reinforcing the repair with a biological mesh. On Day 11 following an emergency laparotomy for penetrating trauma, this patient underwent component separation and release of the anterior and posterior sheath. An intra-abdominal biological mesh was secured, and the fascia and skin closed successfully. Primary abdominal closure can be achieved in patients with penetrating abdominal trauma with the use of component separation and insertion of intra-abdominal biological mesh, where standard closure is not possible. PMID:24876334

  20. Induction of mycobacterial proteins during phagocytosis and heat shock: a time interval analysis.

    PubMed

    Alavi, M R; Affronti, L F

    1994-05-01

    Mycobacterium tuberculosis survives macrophage bactericidal activities by mechanisms that may include induction of stress proteins. We sought to determine whether the synthesis of any mycobacterial proteins is increased during phagocytosis and whether any of these proteins are also up-regulated during heat shock. Protein synthesis by M. tuberculosis H37Ra during phagocytosis by the mouse macrophage cell line IC-21, and during heat shock at 45 and 48 degrees C, was monitored at various time intervals using 35S-labeled methionine/cysteine and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our data suggest the existence of certain common elements in the stress response of mycobacteria to the three stress stimuli. This apparent similarity was best characterized by the up-regulation of a 25-kDa protein after exposure to each of the stress conditions. Furthermore, this 25-kDa protein and a 37-kDa protein that was also synthesized during phagocytosis appeared to be extracellular because they were preferentially solubilized when infected macrophages were lysed with 0.5% NP-40. PMID:8182341

  1. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy.

    PubMed

    Pule, Caroline M; Sampson, Samantha L; Warren, Robin M; Black, Philippa A; van Helden, Paul D; Victor, Tommie C; Louw, Gail E

    2016-01-01

    The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy. PMID:26472768

  2. Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis.

    PubMed

    Mougous, Joseph D; Petzold, Christopher J; Senaratne, Ryan H; Lee, Dong H; Akey, David L; Lin, Fiona L; Munchel, Sarah E; Pratt, Matthew R; Riley, Lee W; Leary, Julie A; Berger, James M; Bertozzi, Carolyn R

    2004-08-01

    Sulfolipid-1 (SL-1) is an abundant sulfated glycolipid and potential virulence factor found in Mycobacterium tuberculosis. SL-1 consists of a trehalose-2-sulfate (T2S) disaccharide elaborated with four lipids. We identified and characterized a conserved mycobacterial sulfotransferase, Stf0, which generates the T2S moiety of SL-1. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. The structure of Stf0 at a resolution of 2.6 A reveals the molecular basis of trehalose recognition and a unique dimer configuration that encloses the substrate into a bipartite active site. These data provide strong evidence that Stf0 carries out the first committed step in the biosynthesis of SL-1 and establish a system for probing the role of SL-1 in M. tuberculosis infection. PMID:15258569

  3. Abdominal trauma by ostrich

    PubMed Central

    Usurelu, Sergiu; Bettencourt, Vanessa; Melo, Gina

    2015-01-01

    Introduction Ostriches typically avoid humans in the wild, since they correctly assess humans as potential predators, and, if approached, often run away. However, ostriches may turn aggressive rather than run when threatened, especially when cornered, and may also attack when they feel the need to defend their offspring or territories. Presentation of case A 71-year-old male patient presented with intra abdominal injury sustained from being kicked in the abdominal wall by an ostrich. During laparotomy, were found free peritoneal effusion and perforation of the small intestine. Discussion The clinical history and physical examination are extremely important for diagnostic and therapeutic decision making. CT-scan is the most accurate exam for making diagnosis. Surgery is the treatment of choice, and is always indicated when there is injury to the hollow viscera. In general it is possible to suture the defect. Conclusion In cases of blunt abdominal trauma by animals is necessary to have a low threshold of suspicion for acute abdomen. PMID:25685344

  4. Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis

    PubMed Central

    Shiryaev, Sergey A.; Cieplak, Piotr; Aleshin, Alexander E.; Sun, Qing; Zhu, Wenhong; Motamedchaboki, Khatereh; Sloutsky, Alexander; Strongin, Alex Y.

    2011-01-01

    Mycobacterium tuberculosis is the causative agent of human tuberculosis (TB). Mycobacterial secretory protein ESAT-6 induces MMP-9 in epithelial cells neighboring infected macrophages. MMP-9 then enhances recruitment of uninfected macrophages, which contribute to nascent granuloma maturation and bacterial growth. Disruption of MMP-9 function attenuates granuloma formation and bacterial growth. The abundant mycobacterial HSP65 chaperone is the major target for immune response and a critical component in M. tuberculosis adhesion to macrophages. We hypothesized that HSP65 is susceptible to MMP-9 proteolysis and that the resulting HSP65 immunogenic peptides affect host adaptive immunity. To identify MMPs which cleave HSP65, we used the MMP-2 and MMP-9 gelatinases, the simple hemopexin domain MMP-8, the membrane associated MMP-14, MMP-15, MMP-16 and MMP-24, and the glycosylphosphatidylinositol-linked MMP-17 and MMP-25 in our studies. We determined both the relative cleavage efficiency of MMPs against the HSP65 substrate and the peptide sequence of the cleavage sites. Cleavage of the unstructured PAGHG474L C-terminal region initiates the degradation of HSP65 by MMPs. This initial cleavage destroys the substrate-binding capacity of the HSP65 chaperone. Multiple additional cleavages of the unfolded HSP65 then follows. MMP-2, MMP-8, MMP-14, MMP-15 and MMP-16, in addition to MMP-9, generate the known highly immunogenic N-terminal peptide of HSP65. Based on our biochemical data, we now suspect that MMP proteolysis of HSP65 in vivo, including MMP-9 proteolysis, also results in the abundant generation of the N-terminal immunogenic peptide and that this peptide, in addition to intact HSP65, contributes to the complex immunomodulatory interplay in the course of TB infection. PMID:21752195

  5. Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis.

    PubMed

    Shiryaev, Sergey A; Cieplak, Piotr; Aleshin, Alexander E; Sun, Qing; Zhu, Wenhong; Motamedchaboki, Khatereh; Sloutsky, Alexander; Strongin, Alex Y

    2011-09-01

    Mycobacterium tuberculosis is the causative agent of human tuberculosis (TB). Mycobacterial secretory protein ESAT-6 induces matrix metalloproteinase (MMP)-9 in epithelial cells neighboring infected macrophages. MMP-9 then enhances recruitment of uninfected macrophages, which contribute to nascent granuloma maturation and bacterial growth. Disruption of MMP-9 function attenuates granuloma formation and bacterial growth. The abundant mycobacterial 65 kDa heat shock protein (HSP65) chaperone is the major target for the immune response and a critical component in M. tuberculosis adhesion to macrophages. We hypothesized that HSP65 is susceptible to MMP-9 proteolysis and that the resulting HSP65 immunogenic peptides affect host adaptive immunity. To identify MMPs that cleave HSP65, we used MMP-2 and MMP-9 gelatinases, the simple hemopexin domain MMP-8, membrane-associated MMP-14, MMP-15, MMP-16 and MMP-24, and glycosylphosphatidylinositol-linked MMP-17 and MMP-25. We determined both the relative cleavage efficiency of MMPs against the HSP65 substrate and the peptide sequence of the cleavage sites. Cleavage of the unstructured PAGHG474L C-terminal region initiates the degradation of HSP65 by MMPs. This initial cleavage destroys the substrate-binding capacity of the HSP65 chaperone. Multiple additional cleavages of the unfolded HSP65 then follow. MMP-2, MMP-8, MMP-14, MMP-15 and MMP-16, in addition to MMP-9, generate the known highly immunogenic N-terminal peptide of HSP65. Based on our biochemical data, we now suspect that MMP proteolysis of HSP65 in vivo, including MMP-9 proteolysis, also results in the abundant generation of the N-terminal immunogenic peptide and that this peptide, in addition to intact HSP65, contributes to the complex immunomodulatory interplay in the course of TB infection. PMID:21752195

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

    SciTech Connect

    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.

  7. Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge

    PubMed Central

    Kerscher, Bernhard; Wilson, Gillian J.; Reid, Delyth M.; Mori, Daiki; Taylor, Julie A.; Besra, Gurdyal S.; Yamasaki, Sho; Brown, Gordon D.

    2015-01-01

    The C‐type lectin receptor (CTLR), Clec4d (MCL, CLECSF8), is a member of the Dectin‐2 cluster of CTLRs, which also includes the related receptors Mincle and Dectin‐2. Like Mincle, Clec4d recognizes mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti‐mycobacterial immunity in mouse and man. Here, we characterized receptor expression in naïve mice, under inflammatory conditions, and during Mycobacterium bovis BCG infection using newly generated monoclonal antibodies. In naïve mice, Clec4d was predominantly expressed on myeloid cells within the peritoneal cavity, blood, and bone marrow. Unexpectedly, basal expression of Clec4d was very low on leukocytes in the lung. However, receptor expression was significantly upregulated on pulmonary myeloid cells during M. bovis BCG infection. Moreover, Clec4d expression could be strongly induced in vitro and in vivo by various microbial stimuli, including TLR agonists, but not exogenous cytokines. Notably, we show that Clec4d requires association with the signaling adaptor FcRγ and Mincle, but not Dectin‐2, for surface expression. In addition, we provide evidence that Clec4d and Mincle, but not Dectin‐2, are interdependently coregulated during inflammation and infection. These data show that Clec4d is an inducible myeloid‐expressed CTLR in mice, whose expression is tightly linked to that of Mincle. PMID:26558717

  8. Use of synthetic mesh for the entire abdominal wall after TRAM flap transfer.

    PubMed

    Moscona, R A; Ramon, Y; Toledano, H; Barzilay, G

    1998-03-01

    Abdominal wall competence is a major concern of all plastic surgeons using the TRAM flap for breast reconstruction. Low hernia rates and adequate abdominal stability are standard expectations in abdominal wall closure. Described here is this institution's experience with the use of a large piece of synthetic mesh as a supplementary reinforcement for the entire abdominal wall in an attempt to stabilize it and achieve a superior abdominal aesthetic result. Twenty-five consecutive patients had routine reinforcement with the extended mesh technique. Mean patient follow-up was 24 months with a minimum of 1 year. No hernia or mesh-related infection were encountered and only one patient had a lower abdominal bulge. We recommend the use of a large synthetic mesh for improved strength and aesthetic quality of the abdominal wall after TRAM flap breast reconstruction. PMID:9500387

  9. A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744

    PubMed Central

    Oliva, María E; Rekha, Arcot; Yellin, Albert; Pasternak, Jacyr; Campos, Maria; Rose, Gilbert M; Babinchak, Timothy; Ellis-Grosse, Evelyn J; Loh, Evan

    2005-01-01

    Background Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. Methods A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14–35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations. Results A total of 825 patients received ≥ 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events. Conclusion This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI. PMID:16236177

  10. [Differential diagnosis of abdominal pain].

    PubMed

    Frei, Pascal

    2015-09-01

    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. PMID:26331201

  11. Abdominal imaging: An introduction

    SciTech Connect

    Frick, M.P.; Feinberg, S.B.

    1986-01-01

    This nine-chapter book gives an overview of the integrated approach to abdominal imaging. Chapter 1 provides an introduction to the physics used in medical imaging; chapter 2 is on the selection of imaging modalities. These are followed by four chapters that deal, respectively, with plain radiography, computed tomographic scanning, sonography, and nuclear imaging, as applied to the abdomen. Two chapters then cover contrast material-enhanced studies of the gastrointestinal (GI) tract: one focusing on technical considerations; the other, on radiologic study of disease processes. The final chapter is a brief account of different interventional procedures.

  12. Lower Abdominal Pain.

    PubMed

    Carlberg, David J; Lee, Stephen D; Dubin, Jeffrey S

    2016-05-01

    Although most frequently presenting with lower abdominal pain, appendicitis, colitis, and diverticulitis can cause pain throughout the abdomen and can cause peritoneal and retroperitoneal symptoms. Evaluation and management of lower intestinal disease requires a nuanced approach by the emergency physician, sometimes requiring computed tomography, ultrasonography, MRI, layered imaging, shared decision making, serial examination, and/or close follow-up. Once a presumed or confirmed diagnosis is made, appropriate treatment is initiated, and may include surgery, antibiotics, and/or steroids. Appendicitis patients should be admitted. Diverticulitis and inflammatory bowel disease can frequently be managed on an outpatient basis, but may require admission and surgical consultation. PMID:27133242

  13. 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

  14. Hypnosis for functional abdominal pain.

    PubMed

    Gottsegen, David

    2011-07-01

    Chronic abdominal pain is a common pediatric condition affecting 20% of the pediatric population worldwide. Most children with this disorder are found to have no specific organic etiology and are given the diagnosis of functional abdominal pain. Well-designed clinical trials have found hypnotherapy and guided imagery to be the most efficacious treatments for this condition. Hypnotic techniques used for other somatic symptoms are easily adaptable for use with functional abdominal pain. The author discusses 2 contrasting hypnotic approaches to functional abdominal pain and provides implications for further research. These approaches may provide new insights into this common and complex disorder. PMID:21922712

  15. 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. PMID:26536359

  16. 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

  17. Abdominal actinomycosis with multiple myeloma: A case report

    PubMed Central

    ERCOLAK, VEHBI; PAYDAS, SEMRA; ERGIN, MELEK; ATES, BERNA T.; DUMAN, BERNA B.; GUNALDI, MERAL; AFSAR, CIGDEM U.

    2014-01-01

    Actinomycosis is a chronic suppurative infection, for which immune suppression is a predisposing factor. In unusual cases, this disease may present as an abdominal wall involvement simulating a soft tissue tumor as seen in the present case. The presented patient had no signs of trauma or surgical approach and the pathology was considered to be a primary abdominal wall actinomycosis. Preoperative diagnosis is difficult due to the nonspecific nature of clinical presentation, radiographic and laboratory findings. Surgery combined with antibiotic treatment is a curative approach for this relatively rare infection. Surgeons must be aware of this disease in order to ensure correct diagnosis and to prevent performing any unnecessary procedures. The present study describes a case of abdominal actinomycosis with multiple myeloma, together with a review of important points related to this disease. PMID:25202429

  18. Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorithm: Application to Mycobacterial Zinc Hydrolases.

    PubMed

    Romero, Juan Manuel; Martin, Mariano; Ramirez, Claudia Lilián; Dumas, Victoria Gisel; Marti, Marcelo Adrián

    2015-01-01

    Determination of the free energy profile for an enzyme reaction mechanism is of primordial relevance, paving the way for our understanding of the enzyme's catalytic power at the molecular level. Although hybrid, mostly DFT-based, QM/MM methods have been extensively applied to this type of studies, achieving accurate and statistically converged results at a moderate computational cost is still an open challenge. Recently, we have shown that accurate results can be achieved in less computational time, combining Jarzynski's relationship with a hybrid differential relaxation algorithm (HyDRA), which allows partial relaxation of the solvent during the nonequilibrium steering of the reaction. In this work, we have applied this strategy to study two mycobacterial zinc hydrolases. Mycobacterium tuberculosis infections are still a worldwide problem and thus characterization and validation of new drug targets is an intense field of research. Among possible drug targets, recently two essential zinc hydrolases, MshB (Rv1170) and MA-amidase (Rv3717), have been proposed and structurally characterized. Although possible mechanisms have been proposed by analogy to the widely studied human Zn hydrolases, several key issues, particularly those related to Zn coordination sphere and its role in catalysis, remained unanswered. Our results show that mycobacterial Zn hydrolases share a basic two-step mechanism. First, the attacking water becomes deprotonated by the conserved base and establishes the new C-O bond leading to a tetrahedral intermediate. The intermediate requires moderate reorganization to allow for proton transfer to the amide N and C-N bond breaking to occur in the second step. Zn ion plays a key role in stabilizing the tetrahedral intermediate and balancing the negative charge of the substrate during hydroxide ion attack. Finally, comparative analysis of other Zn hydrolases points to a convergent mechanistic evolution. PMID:26415840

  19. ADULT ABDOMINAL WALL HERNIA IN IBADAN

    PubMed Central

    Ayandipo, O.O; Afuwape, O.O; Irabor, D.O; Abdurrazzaaq, A.I.

    2015-01-01

    Background: Abdominal wall hernias are very common diseases encountered in surgical practice. Groin hernia is the commonest type of abdominal wall hernias. There are several methods of hernia repair but tension-free repair (usually with mesh) offers the least recurrent rate. Aim: To describe the clinical profile of anterior abdominal wall hernias and our experience in the surgical management of identified hernias Method: The project was a retrospective study of all patients with abdominal wall hernia presenting into surgical divisions of University College Hospital Ibadan during a 6 year period (January 2008 to December 2013). Relevant information was retrieved from their case notes and analysed. Results: The case records of 1215 (84.7%) patients out of 1435 were retrieved. Elective surgery was done in 981(80.7%) patients while 234 (19.3%) patients had emergency surgery. There were 922 (84.8%) groin hernias and post-operative incisional hernia accounted for 9.1% (111) of the patients. About half (49.1%) of those with incisional hernia were post obstetric and gynaecologic procedure followed by post laparotomy incisional hernias 16 (14%) and others (23.5%). The ratio of inguinal hernia to other types in this study is 3:1. Hollow viscus resection and emergency surgery were predictors of wound infection statistically significant in predicting wound infection (P < 0.001). Peri-operative morbidity/mortality at 28 days post operation was documented in 113 patients (12.1%). One year recurrence rate of groin hernia was 2.1%. Conclusion: The pattern of presentation and management of anterior wall hernias are still the same compared with the earlier study in this hospital. New modality of treatment should be adopted as the standard choice of care. Abdominal wall hernias are very common clinical presentation. Modified Bassini repair was the preferred method of repair due to its simplicity. Mesh repair is becoming more common in recent time but high cost and initial non

  20. How I Manage Abdominal Injuries.

    ERIC Educational Resources Information Center

    Haycock, Christine E.

    1986-01-01

    In sports, abdominal injuries occur most frequently in cycling, horseback riding, and skiing. Most involve children, not adults. Any athlete sustaining a severe blow to the abdomen should be examined. Guidelines are provided for recognizing and treating injuries to the abdominal muscles, kidneys, spleen, and liver. (Author/MT)

  1. Functional Abdominal Pain in Children

    MedlinePlus

    ... dominalPa in inCh ildre n What is functional abdominal pain, and why does it happen? Most otherwise-healthy ... stomachaches for two months or more have functional abdominal pain. The term “functional” refers to the fact that ...

  2. Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity

    PubMed Central

    2014-01-01

    Background Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discovery of new drug targets. Results We conducted an in silico analysis of 19 mycobacterial species/clinical strains for the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L-alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing for classification of mycobacterial species into three main categories, primarily based on their rpf gene complement. These include the M. tuberculosis Complex (MTBC), other pathogenic mycobacteria and environmental species. The complement of these genes within the MTBC and other mycobacterial pathogens is highly conserved. In contrast, environmental strains display significant genetic expansion in most of these gene families. Mycobacterium leprae retains more than one functional gene from each enzyme family, underscoring the importance of genetic multiplicity for PG remodelling. Notably, the highest degree of conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that these enzymes are essential for growth and survival. Conclusion PG remodelling enzymes in a range of mycobacterial species are associated with extensive genetic multiplicity, suggesting functional diversification within these families of enzymes to allow organisms to adapt. PMID:24661741

  3. Mycobacterial RNA polymerase forms unstable open promoter complexes that are stabilized by CarD

    PubMed Central

    Davis, Elizabeth; Chen, James; Leon, Katherine; Darst, Seth A.; Campbell, Elizabeth A.

    2015-01-01

    Escherichia coli has served as the archetypal organism on which the overwhelming majority of biochemical characterizations of bacterial RNA polymerase (RNAP) have been focused; the properties of E. coli RNAP have been accepted as generally representative for all bacterial RNAPs. Here, we directly compare the initiation properties of a mycobacterial transcription system with E. coli RNAP on two different promoters. The detailed characterizations include abortive transcription assays, RNAP/promoter complex stability assays and DNAse I and KMnO4 footprinting. Based on footprinting, we find that promoter complexes formed by E. coli and mycobacterial RNAPs use very similar protein/DNA interactions and generate the same transcription bubbles. However, we find that the open promoter complexes formed by E. coli RNAP on the two promoters tested are highly stable and essentially irreversible (with lifetimes much greater than 1 h), while the open promoter complexes on the same two promoters formed by mycobacterial RNAP are very unstable (lifetimes of about 2 min or less) and readily reversible. We show here that CarD, an essential mycobacterial transcription activator that is not found in E. coli, stabilizes the mycobacterial RNAP/open promoter complexes considerably by preventing transcription bubble collapse. PMID:25510492

  4. Diagnosis of abdominal abscesses in patients with major trauma: the use of computed tomography

    SciTech Connect

    Whitley, N.O.; Shatney, C.H.

    1983-04-01

    The usefulness of computed tomography (CT) in diagnosing abdominal abscesses was evaluated prospectively in 69 septic patients who had suffered massive trauma. For the 82 abdominal CT scans obtained, the accuracy rate was 84%, the sensitivity was 92%, and the specificity was 79%. With the use of abdominal CT, 32 patients were spared a ''blind'' laparotomy in the search for the focus of infection. It is concluded that CT is of significant value in the diagnosis of abdominal abscess in the septic trauma patient.

  5. Rapid Rebound of the Treg Compartment in DEREG Mice Limits the Impact of Treg Depletion on Mycobacterial Burden, but Prevents Autoimmunity

    PubMed Central

    Varela, Filipa; Behrends, Jochen; Swallow, Maxine; Kruse, Friederike; Krull, Freyja; Ghorbani, Peyman; Mayer, Christian T.

    2014-01-01

    The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3+ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity

  6. Rapid rebound of the Treg compartment in DEREG mice limits the impact of Treg depletion on mycobacterial burden, but prevents autoimmunity.

    PubMed

    Berod, Luciana; Stüve, Philipp; Varela, Filipa; Behrends, Jochen; Swallow, Maxine; Kruse, Friederike; Krull, Freyja; Ghorbani, Peyman; Mayer, Christian T; Hölscher, Christoph; Sparwasser, Tim

    2014-01-01

    The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3+ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity

  7. Abdominal migraine in the differential diagnosis of acute abdominal pain.

    PubMed

    Cervellin, Gianfranco; Lippi, Giuseppe

    2015-06-01

    Although traditionally regarded as a specific pediatric disease, abdominal migraine may also be observed in adults. Unfortunately, however, this condition is frequently overlooked in the differential diagnosis of abdominal pain in the emergency department (ED). A 30-year-old woman presented to our ED complaining of abdominal pain and vomiting, lasting for 12 hours. The pain was periumbilical, continuous, and not associated with fever or diarrhea. The physical examination and the results of conventional blood tests were normal. The patient was treated with intravenous ketoprofen, metoclopramide, and ranitidine, obtaining a prompt relief of symptoms. She had a history of similar episodes in the last 15 years, with several ED visits, blood test examinations, ultrasonography of the abdomen, and upper gastrointestinal endoscopies. Celiac disease, porphyry, sickle cell disease, and inflammatory bowel disease were all excluded. In July 2012, she became pregnant, and she delivered a healthy baby on April 2013. Until November 2014, she has remained asymptomatic. Based on the clinical characteristics of the abdominal pain episodes, the exclusion of any alternative diagnosis, and the relief of symptoms during and after pregnancy, a final diagnosis of abdominal migraine could be established. A skilled emergency physician should always consider abdominal migraine in the differential diagnosis of patients admitted to the ED with abdominal pain, especially when the attacks are recurrent and no alternative diagnosis can be clearly established. PMID:25616589

  8. Ascariasis as a cause of recurrent abdominal pain.

    PubMed

    Guzman, Gerly Edson; Teves, Pedro Montes; Monge, Eduardo

    2010-04-01

    Ascariasis is the most common helminthic infection in developing countries. It may cause chronic abdominal pain, tenderness and bloating. Our aim is to report a case of acute episodic abdominal pain and pancreatitis associated with ascariasis. We report a 59-year-old female patient who was admitted for acute abdominal pain, having had several previous similar events before one of them was diagnosed as acute idiopathic pancreatitis. On admission, her physical exam was normal. Laboratory results showed hemoglobin 12.2 g/dL, white blood cell count 11 900 cells/mm(3), eosinophils 420 cells/mm(3), serum amylase 84 IU/mL, lipase 22 IU/mL and normal liver function tests. Abdominal ultrasound and a plain abdominal X-ray were also normal. An upper endoscopy showed round white worms in the duodenum and the stomach, some of them with bile in their intestines. The intestinal parasites were diagnosed as Ascaris lumbricoides, and the patient was started on albendazole, with full recovery within a week. We believe that ascariasis should be considered in patients with recurrent abdominal pain and idiopathic pancreatitis. PMID:20447214

  9. [Abdominal wall closure by incisional hernia and herniation after laparostoma].

    PubMed

    Mischinger, H-J; Kornprat, P; Werkgartner, G; El Shabrawi, A; Spendel, S

    2010-03-01

    As hernias and abdominal wall defects have a variety of etiologies each with its own complications and comorbidities in various constellations, efficient treatment requires patient-oriented management. There is no recommended standard treatment and the very different clinical pictures demand an individualized interdisciplinary approach. Particularly in the case of complicated hernias, the planning of the operation should focus on the problems posed by the individual patient. Treatment mainly depends on the etiology of the hernia, immediate or long-term complications and the efficiency of individual repair techniques. Abdominal wall repair for recurrent herniation requires direct closure of the fascia generally using the sublay technique with a lightweight mesh. It is still unclear whether persistent inflammation, mesh dislocation, fistula formation or other long-term complications are due to certain materials or to the surgical technique. With mesh infections it has been shown to be advantageous to remove a polytetrafluoroethylene (PTFE) mesh, while the combination of systemic and local treatment appears to suffice for a polypropylene or polyester mesh. Heavier meshes in the sublay position or plastic reconstruction with autologous tissue are indicated as substitutes for the abdominal wall for giant hernias, repeated recurrences and large abdominal wall defects. A laparostoma is increasingly more often created to treat septic intra-abdominal processes but is very often responsible for a complicated hernia. If primary repair of the abdominal wall is not an option, resorbable material or split skin is used for coverage under the auspices of a planned hernia repair. PMID:20145901

  10. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients.

    PubMed

    Vemula, Mani H; Ganji, Rakesh; Sivangala, Ramya; Jakkala, Kiran; Gaddam, Sumanlatha; Penmetsa, Sitaramaraju; Banerjee, Sharmistha

    2016-01-01

    Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4(+) T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins

  11. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    PubMed Central

    Vemula, Mani H.; Ganji, Rakesh; Sivangala, Ramya; Jakkala, Kiran; Gaddam, Sumanlatha; Penmetsa, Sitaramaraju; Banerjee, Sharmistha

    2016-01-01

    Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can

  12. [BIOLOGICAL IMPLANTS IN ABDOMINAL WALL HERNIA REPAIR (REVIEW)].

    PubMed

    Abatov, N; Badyrov, R; Abatova, A; Assamidanov, E; Kaukenov, B

    2016-02-01

    The use of synthetic meshes as a material for abdominal wall hernia repair does not always ensure a recurrence-free treatment outcome and full recovery of the abdominal wall functional activity. There are well-known disadvantages such as poor resistance to infection, the infiltrate formation in the place of implantation, expressed adhesive process in cases of introperitoneal fixation, to create certain restrictions on the using of these implants for abdominal wall reconstruction. The search for alternative materials that could minimize the risk of complications, has led to the study of biological grafts. It is known that various methods for the manufacturing biological implants determine endogenous properties for each material separately, and may be cause a variety of biological responses in vivo after implantation. The question has not been resolved, what the fresh raw material is better to use for derive biological implants. In this review we investigated the interaction of different types of biological implants between the abdominal wall and the organs of abdominal cavity of the recipient, their ability to resist infection and the development of relapses, as a leading indicator of the effectiveness of hernioplasty. PMID:27001778

  13. Treatment options for traumatic pseudoaneurysms of the paravisceral abdominal aorta.

    PubMed

    Tucker, Sonny; Rowe, Vincent L; Rao, Rajeev; Hood, Douglas B; Harrell, Donald; Weaver, Fred A

    2005-09-01

    Penetrating gunshot wounds (GSWs) to the abdominal aorta are frequently lethal. Alternative management options for treatment of traumatic pseudoaneurysms of the abdominal aorta are illustrated by three patient case histories. Patient A sustained two GSWs to the abdomen (midepigastrium, right subcostal region). He was hypotensive in the field. Emergent laparotomy was undertaken with suture ligature of a celiac injury and distal pancreatectomy/splenectomy for a pancreatic injury. Postoperative abdominal CT for an intraabdominal infection with leukocytosis revealed a 4 cm traumatic pseudoaneurysm of the abdominal aorta that extended from the suprarenal aorta to the level of the renal arteries. Six weeks later, he underwent an open repair. Patient B sustained multiple GSWs to his right arm and right upper quadrant. He was hemodynamically stable. He underwent abdominal exploration for a grade 3 liver laceration. Postoperative abdominal CT revealed a supraceliac abdominal aortic pseudoaneurysm. An aortogram demonstrated a 1.5 cm defect in the aortic wall above the celiac trunk communicating with the inferior vena cava (IVC). He underwent endovascular repair with covered aortic stent graft. Patient C sustained multiple thoracoabdominal GSWs. He was hemodynamically stable. Emergent laparotomy revealed multiple left colonic perforations, two duodenal lacerations, and an unsalvageable left kidney laceration. Postoperatively, he developed a duodenal-cutaneous fistula with multiple intraabdominal abscesses. Serial CT scans revealed an enlarging infrarenal aortic pseudoaneurysm. He underwent angiographic coil embolization and intraarterial injection of thrombin into the pseudoaneurysm sac. The average time from injury to surgical treatment was 46 days (range 29-67). Postoperatively, none of the patients developed paraplegia. Advances in endovascular techniques have provided options to deal with traumatic pseudoaneurysms of the abdominal aorta. In a hemodynamically stable

  14. Perioperative complications in abdominal sacrocolpopexy and vaginal sacrospinous ligament fixation procedures.

    PubMed

    Demirci, Fuat; Ozdemir, Ismail; Somunkiran, Asli; Topuz, Samet; Iyibozkurt, Cem; Duras Doyran, Gonul; Kemik Gul, Ozlem; Gul, Baris

    2007-03-01

    This study assessed perioperative complications in abdominal sacrocolpopexy and vaginal sacrospinous ligament fixation procedures. Perioperative complications were defined as any complication occurring during surgery or the first 6 weeks postoperatively. Forty-five patients underwent abdominal procedures (20 sacrohysteropexy and 25 sacrocolpopexy) and 60 patients underwent vaginal sacrospinous fixation. Of the 105 patients, 13 had vaginal vault prolapse. In the abdominal group, one bladder injury, four hemorrhages, and three wound dehiscences occurred. In the vaginal group, one rectal injury and one postoperative vaginal vault infection occurred. Major and minor complications were more frequent in the abdominal group than in the vaginal group. Blood loss was not significantly different. The operating time and hospital stay in the abdominal group were significantly longer than in the vaginal group. In conclusion, abdominal sacrocolpopexy had a higher rate of perioperative complications and longer hospital stay and operating time. PMID:16688396

  15. Ultrastructural morphologic changes in mycobacterial biofilm in different extreme condition.

    PubMed

    Kumar, Virendra; Sachan, Tarun Kumar; Sharma, Pragya; Rawat, Krishna Dutta

    2015-02-01

    The aim of this study was to investigate the morphologic and ultrastructural features of biofilms of slow and fast-growing mycobacteria in different stress conditions, presence and absence of oleic acid albumin dextrose catalase (OADC) enrichment and at different temperatures: 30, 37 and 42 °C. Four hundred mycobacterial isolates were taken. The biomass of each biofilm was quantified using a modified microtiter plate assay method. Isolates were divided into those that formed fully established biofilms, moderately attached biofilms and weakly adherent biofilms by comparison with a known biofilm-forming strain. The large quantity of biofilm was produced by Mycobacterium smegmatis at temperature 37 and 42 °C as compared to 30 °C. Mycobacterium fortuitum and M. avium developed large amount of biofilm at 30 °C as compared to 37 and 42 °C. Mycobacterium tuberculosis developed strong biofilm at 37 °C and no biofilm at 30 and 42 °C in Sauton's media. The selected non-tuberculous mycobacteria and H37Rv developed strong biofilm in the presence of OADC enrichment in Sauton's medium. Microscopic examination of biofilms by scanning electron microscopy revealed that poorly adherent biofilm formers failed to colonize the entire surface of the microtiter well. While moderately adherent biofilm formers grew in uniform monolayers but failed to develop a mature three-dimensional structure. SEM analysis of an isolate representative of the group formed fully established biofilms with a textured, multi-layered, three-dimensional structure. PMID:25192360

  16. Who Has Mycobacterial Disease? A Cross Sectional Study in Agropastoral Communities in Tanzania

    PubMed Central

    Kilale, Andrew Martin; Ngadaya, Esther; Muhumuza, Julius; Kagaruki, Gibson Benard; Lema, Yakobo Leonard; Ngowi, Bernard James; Mfinanga, Sayoki Godfrey; Hinderaker, Sven Gudmund

    2016-01-01

    Objective To determine and describe clinical symptoms, demographic characteristics and environmental exposures as determinants of pulmonary mycobacterial diseases among patients examined for tuberculosis in agropastoral communities in Northern Tanzania. Methods This was a cross sectional study. Sputum samples were collected from patients attending three hospitals in Tanzania, and were investigated for pulmonary tuberculosis by microscopy between November 2010 and June 2012. The patients were interviewed about background information, and potential exposure to mycobacteria. Results We examined 1,711 presumptive tuberculosis cases where 936 (54.2%) were males and 775 (45.3%) females. Of all the study participants, 277 (16%) were found to have sputum samples positive for mycobacteria; 228 (13%) were smear positive, 123 (7%) were culture positive and 74 (4%) were positive by both smear microscopy and culture. Of the 123 mycobacterial culture positive, 15 (12.2%) had non-tuberculous mycobacteria. Males were more likely than females to be positive for mycobacteria. Factors associated with mycobacterial disease were loss of appetite, age groups below 41 years, and being a male. Among HIV negative patients, loss of appetite, age below 20 years and being a male were associated with being mycobacterial positive. Among HIV positive patients, males and those patients with a persistently coughing family member were more likely to harbor mycobacteria. Conclusion The findings in this study show that both M. tuberculosis and non-tuberculous mycobacterial strains were prevalent in the study community. Some risk factors were identified. Although the reported predictors may improve screening for mycobacterial diseases, their use requires some precaution. PMID:27213532

  17. 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

  18. Penetrating abdominal trauma.

    PubMed

    Henneman, P L

    1989-08-01

    The management of patients with penetrating abdominal trauma is outlined in Figure 1. Patients with hemodynamic instability, evisceration, significant gastrointestinal bleeding, peritoneal signs, gunshot wounds with peritoneal violation, and type 2 and 3 shotgun wounds should undergo emergency laparotomy. The initial ED management of these patients includes airway management, monitoring of cardiac rhythm and vital signs, history, physical examination, and placement of intravenous lines. Blood should be obtained for initial hematocrit, type and cross-matching, electrolytes, and an alcohol level or drug screen as needed. Initial resuscitation should utilize crystalloid fluid replacement. If more than 2 liters of crystalloid are needed to stabilize an adult (less in a child), blood should be given. Group O Rh-negative packed red blood cells should be immediately available for a patient in impending arrest or massive hemorrhage. Type-specific blood should be available within 15 minutes. A patient with penetrating thoracic and high abdominal trauma should receive a portable chest x-ray, and a hemo- or pneumothorax should be treated with tube thoracostomy. An unstable patient with clinical signs consistent with a pneumothorax, however, should receive a tube thoracostomy prior to obtaining roentgenographic confirmation. If time permits, a nasogastric tube and Foley catheter should be placed, and the urine evaluated for blood (these procedures can be performed in the operating room). If kidney involvement is suspected because of hematuria or penetrating trauma in the area of a kidney or ureter in a patient requiring surgery, a single-shot IVP should be performed either in the ED or the operating room. An ECG is important in patients with possible cardiac involvement and in patients over the age of 40 going to the operating room. Tetanus status should be updated, and appropriate antibiotics covering bowel flora should be given. Operative management should rarely be delayed

  19. Economics of abdominal wall reconstruction.

    PubMed

    Bower, Curtis; Roth, J Scott

    2013-10-01

    The economic aspects of abdominal wall reconstruction are frequently overlooked, although understandings of the financial implications are essential in providing cost-efficient health care. Ventral hernia repairs are frequently performed surgical procedures with significant economic ramifications for employers, insurers, providers, and patients because of the volume of procedures, complication rates, the significant rate of recurrence, and escalating costs. Because biological mesh materials add significant expense to the costs of treating complex abdominal wall hernias, the role of such costly materials needs to be better defined to ensure the most cost-efficient and effective treatments for ventral abdominal wall hernias. PMID:24035086

  20. Acute incarcerated external abdominal hernia

    PubMed Central

    Yang, Xue-Fei

    2014-01-01

    External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surgery in some cases to achieve minimally invasive treatment. However, strict adherence to the indications and contraindications is still required. PMID:25489584

  1. Shifts in Mycobacterial Populations and Emerging Drug-Resistance in West and Central Africa

    PubMed Central

    Fissette, Kristina; de Rijk, Pim; Uwizeye, Cécile; Nduwamahoro, Elie; Goovaerts, Odin; Affolabi, Dissou; Gninafon, Martin; Lingoupou, Fanny M.; Barry, Mamadou Dian; Sow, Oumou; Merle, Corinne; Olliaro, Piero; Ba, Fatoumata; Sarr, Marie; Piubello, Alberto; Noeske, Juergen; Antonio, Martin; Rigouts, Leen; de Jong, Bouke C

    2014-01-01

    In this study, we retrospectively analysed a total of 605 clinical isolates from six West or Central African countries (Benin, Cameroon, Central African Republic, Guinea-Conakry, Niger and Senegal). Besides spoligotyping to assign isolates to ancient and modern mycobacterial lineages, we conducted phenotypic drug-susceptibility-testing for each isolate for the four first-line drugs. We showed that phylogenetically modern Mycobacterium tuberculosis strains are more likely associated with drug resistance than ancient strains and predict that the currently ongoing replacement of the endemic ancient by a modern mycobacterial population in West/Central Africa might result in increased drug resistance in the sub-region. PMID:25493429

  2. Abdominal actinomycosis presenting as appendicitis: two case reports and review.

    PubMed

    Liu, Ken; Joseph, David; Lai, Ken; Kench, James; Ngu, Meng Chong

    2016-01-01

    Abdominal actinomycosis (AA) is a rare infection caused by filamentous Gram-positive anaerobic bacteria Actinomyces. We report two cases of adults with AA who initially presented with clinical and radiological features of appendicitis. Both patients underwent appendicectomy with histopathology diagnostic for actinomycosis of the appendix and subsequently completed prolonged courses of oral penicillin. AA is a rare differential diagnosis for appendicitis and should be considered especially in patients with a chronic, indolent course and nonspecific abdominal symptoms. A high index of suspicion may avoid unnecessary surgery, as treatment with prolonged antibiotic therapy is very effective. PMID:27147718

  3. Abdominal actinomycosis presenting as appendicitis: two case reports and review

    PubMed Central

    Liu, Ken; Joseph, David; Lai, Ken; Kench, James; Ngu, Meng Chong

    2016-01-01

    Abdominal actinomycosis (AA) is a rare infection caused by filamentous Gram-positive anaerobic bacteria Actinomyces. We report two cases of adults with AA who initially presented with clinical and radiological features of appendicitis. Both patients underwent appendicectomy with histopathology diagnostic for actinomycosis of the appendix and subsequently completed prolonged courses of oral penicillin. AA is a rare differential diagnosis for appendicitis and should be considered especially in patients with a chronic, indolent course and nonspecific abdominal symptoms. A high index of suspicion may avoid unnecessary surgery, as treatment with prolonged antibiotic therapy is very effective. PMID:27147718

  4. Micromanaging abdominal aortic aneurysms.

    PubMed

    Maegdefessel, Lars; Spin, Joshua M; Adam, Matti; Raaz, Uwe; Toh, Ryuji; Nakagami, Futoshi; Tsao, Philip S

    2013-01-01

    The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to "fine tune" the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility. PMID:23852016

  5. Abdominal aortic feminism.

    PubMed

    Mortimer, Alice Emily

    2014-01-01

    A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. PMID:25398912

  6. Platelets Direct Monocyte Differentiation Into Epithelioid-Like Multinucleated Giant Foam Cells With Suppressive Capacity Upon Mycobacterial Stimulation

    PubMed Central

    Feng, Yonghong; Dorhoi, Anca; Mollenkopf, Hans-Joachim; Yin, Hongyun; Dong, Zhengwei; Mao, Ling; Zhou, Jun; Bi, Aixiao; Weber, Stephan; Maertzdorf, Jeroen; Chen, Gang; Chen, Yang; Kaufmann, Stefan H. E.

    2014-01-01

    Background. Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection. Methods. We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection. Results. Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN. Conclusions. Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis. PMID:24987031

  7. Elevated expression of T-bet in mycobacterial antigen-specific CD4(+) T cells from patients with tuberculosis.

    PubMed

    Yang, Bingfen; Zhai, Fei; Jiang, Jing; Wang, Xinjing; Cao, Zhihong; Cheng, Xiaoxing

    2015-01-01

    T-bet is a T-box transcriptional factor that controls the differentiation and effector functions of CD4 T cells. In this study, we studied the role of T-bet in regulating CD4(+) T cell immunity against tuberculosis (TB). T-bet expression in Mycobacterium tuberculosis antigen-specific CD4(+) T cells was significantly higher in patients with active TB than in individuals with latent TB infection (p<0.0001). Comparison of T-bet expression in TCM and TEM subsets showed that CD4(+)T-bet(+)M. tuberculosis antigen-specific CD4(+) T cells had significantly lower frequency of TCM (p=0.003) and higher frequency of TEM (p=0.003) than CD4(+)T-bet(-) cells. The expression of PD-1 in antigen-specific CD4(+) T cells was significantly higher in patients with TB than in individuals with latent TB infection (p=0.006). CD4(+)CD154(+)T-bet(+) T cells had significantly higher expression of PD-1 than CD4(+)CD154(+)T-bet(-) T cells (p=0.0028). It is concluded that T-bet expression might be associated with differentiation into effector memory cells and PD-1 expression in mycobacterial antigen-specific CD4(+) T cells. PMID:26302932

  8. JAMA Patient Page: Abdominal Hernia

    MedlinePlus

    ... an operation. Umbilical hernia Abdominal wall Intestinal loop Peritoneum Skin Peritoneum Umbilical annulus SYMPTOMS The first symptom of a ... vomiting, or constipation. Inguinal hernia Indirect inguinal hernia Peritoneum Deep inguinal ring Inguinal canal Superficial inguinal ring ...

  9. Functional Abdominal Pain in Children

    MedlinePlus

    ... At low doses, these medicines can be excellent pain relievers for some children. A fearful, anxious, or depressed child however should be fully assessed by a psychiatrist or psychologist. Some psychological treatments that help children cope with functional abdominal pain ...

  10. Mycobacterial HBHA induces endoplasmic reticulum stress-mediated apoptosis through the generation of reactive oxygen species and cytosolic Ca2+ in murine macrophage RAW 264.7 cells

    PubMed Central

    Choi, J-A; Lim, Y-J; Cho, S-N; Lee, J-H; Jeong, J A; Kim, E J; Park, J B; Kim, S H; Park, H S; Kim, H-J; Song, C-H

    2013-01-01

    Mycobacterial heparin-binding haemagglutinin antigen (HBHA) is a virulence factor that induces apoptosis of macrophages. Endoplasmic reticulum (ER) stress-mediated apoptosis is an important regulatory response that can be utilised to study the pathogenesis of tuberculosis. In the present study, HBHA stimulation induced ER stress sensor molecules in a caspase-dependent manner. Pre-treatment of RAW 264.7 cells with an IκB kinase 2 inhibitor reduced not only C/EBP homology protein expression but also IL-6 and monocyte chemotactic protein-1 (MCP-1) production. BAPTA-AM reduced both ER stress responses and caspase activation and strongly suppressed HBHA-induced IL-6 and MCP-1 production in RAW 264.7 cells. Enhanced reactive oxygen species (ROS) production and elevated cytosolic [Ca2+]i levels were essential for HBHA-induced ER stress responses. Collectively, our data suggest that HBHA induces cytosolic [Ca2+]i, which influences the generation of ROS associated with the production of proinflammatory cytokines. These concerted and complex cellular responses induce ER stress-associated apoptosis during HBHA stimulation in macrophages. These results indicate that the ER stress pathway has an important role in the HBHA-induced apoptosis during mycobacterial infection. PMID:24336077

  11. EsxA membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5

    PubMed Central

    Zhang, Qi; Wang, Decheng; Jiang, Guozhong; Liu, Wei; Deng, Qing; Li, Xiujun; Qian, Wei; Ouellet, Hugues; Sun, Jianjun

    2016-01-01

    EsxA is required for virulence of Mycobacterium tuberculosis (Mtb) and plays an essential role in phagosome rupture and translocation to the cytosol of macrophages. Recent biochemical studies have demonstrated that EsxA is a membrane-permeabilizing protein. However, evidence that link EsxA membrane-permeabilizing activity to Mtb cytosolic translocation and virulence is lacking. Here we found that mutations at glutamine 5 (Q5) could up or down regulate EsxA membrane-permeabilizing activity. The mutation Q5K significantly diminished the membrane-permeabilizing activity, while Q5V enhanced the activity. By taking advantage of the single-residue mutations, we tested the effects of EsxA membrane-permeabilizing activity on mycobacterial virulence and cytosolic translocation using the esxA/esxB knockout strains of Mycobacterium marinum (Mm) and Mtb. Compared to wild type (WT), the Q5K mutant exhibited significantly attenuated virulence, evidenced by intracellular survival and cytotoxicity in mouse macrophages as well as infection of zebra fish embryos. The attenuated virulence of the Q5K mutant was correlated to the impaired cytosolic translocation. On the contrary, the Q5V mutant had a significantly increased cytosolic translocation and showed an overall increased virulence. This study provides convincing evidence that EsxA contributes to mycobacterial virulence with its membrane-permeabilizing activity that is required for cytosolic translocation. PMID:27600772

  12. EsxA membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5.

    PubMed

    Zhang, Qi; Wang, Decheng; Jiang, Guozhong; Liu, Wei; Deng, Qing; Li, Xiujun; Qian, Wei; Ouellet, Hugues; Sun, Jianjun

    2016-01-01

    EsxA is required for virulence of Mycobacterium tuberculosis (Mtb) and plays an essential role in phagosome rupture and translocation to the cytosol of macrophages. Recent biochemical studies have demonstrated that EsxA is a membrane-permeabilizing protein. However, evidence that link EsxA membrane-permeabilizing activity to Mtb cytosolic translocation and virulence is lacking. Here we found that mutations at glutamine 5 (Q5) could up or down regulate EsxA membrane-permeabilizing activity. The mutation Q5K significantly diminished the membrane-permeabilizing activity, while Q5V enhanced the activity. By taking advantage of the single-residue mutations, we tested the effects of EsxA membrane-permeabilizing activity on mycobacterial virulence and cytosolic translocation using the esxA/esxB knockout strains of Mycobacterium marinum (Mm) and Mtb. Compared to wild type (WT), the Q5K mutant exhibited significantly attenuated virulence, evidenced by intracellular survival and cytotoxicity in mouse macrophages as well as infection of zebra fish embryos. The attenuated virulence of the Q5K mutant was correlated to the impaired cytosolic translocation. On the contrary, the Q5V mutant had a significantly increased cytosolic translocation and showed an overall increased virulence. This study provides convincing evidence that EsxA contributes to mycobacterial virulence with its membrane-permeabilizing activity that is required for cytosolic translocation. PMID:27600772

  13. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1

    PubMed Central

    Nusbaum, Rebecca J.; Calderon, Veronica E.; Huante, Matthew B.; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L.; Hunter, Robert L.; Actor, Jeffrey K.; Cirillo, Jeffrey D.; Aronson, Judith; Gelman, Benjamin B.; Lisinicchia, Joshua G.; Valbuena, Gustavo; Endsley, Janice J.

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  14. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1.

    PubMed

    Nusbaum, Rebecca J; Calderon, Veronica E; Huante, Matthew B; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L; Hunter, Robert L; Actor, Jeffrey K; Cirillo, Jeffrey D; Aronson, Judith; Gelman, Benjamin B; Lisinicchia, Joshua G; Valbuena, Gustavo; Endsley, Janice J

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  15. Osteopontin Expression During the Periparturient Period in Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Investigation of the role of osteopontin (Opn) in Johne’s disease is of interest based upon its ability to influence cytokine expression and to improve host defense against mycobacterial infections. The objective of this study was to characterize Opn expression and secretion by peripheral blood mono...

  16. Abdominal emergencies in the geriatric patient

    PubMed Central

    2014-01-01

    Abdominal pain is one of the most frequent reasons that elderly people visit the emergency department (ED). In this article, we review the deadliest causes of abdominal pain in this population, including mesenteric ischemia, abdominal aortic aneurysm, and appendicitis and potentially lethal non-abdominal causes. We also highlight the pitfalls in diagnosing, or rather misdiagnosing, these clinical entities. PMID:25635203

  17. Abdominal intrauterine vacuum aspiration.

    PubMed

    Tjalma, W A A

    2014-01-01

    Evaluating and "cleaning" of the uterine cavity is probably the most performed operation in women. It is done for several reasons: abortion, evaluation of irregular bleeding in premenopausal period, and postmenopausal bleeding. Abortion is undoubtedly the number one procedure with more than 44 million pregnancies terminated every year. This procedure should not be underestimated and a careful preoperative evaluation is needed. Ideally a sensitive pregnancy test should be done together with an ultrasound in order to confirm a uterine pregnancy, excluding extra-uterine pregnancy, and to detect genital and/or uterine malformations. Three out of four abortions are performed by surgical methods. Surgical methods include a sharp, blunt, and suction curettage. Suction curettage or vacuum aspiration is the preferred method. Despite the fact that it is a relative safe procedure with major complications in less than one percent of cases, it is still responsible for 13% of all maternal deaths. All the figures have not declined in the last decade. Trauma, perforation, and bleeding are a danger triage. When there is a perforation, a laparoscopy should be performed immediately, in order to detect intra-abdominal lacerations and bleeding. The bleeding should be stopped as soon as possible in order to not destabilize the patient. When there is a perforation in the uterus, this "entrance" can be used to perform the curettage. This is particularly useful if there is trauma of the isthmus and uterine wall, and it is difficult to identify the uterine canal. A curettage is a frequent performed procedure, which should not be underestimated. If there is a perforation in the uterus, then this opening can safely be used for vacuum aspiration. PMID:25134300

  18. Novel nicotine analogues with potential anti-mycobacterial activity.

    PubMed

    Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

    2016-04-15

    Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1μg/mL (2.86nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24h and Volume of distribution (Vd) of 27.36L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37μg/mL, Tmax of 0.05h, T1/2 of 24h and Vd equivalent to 23.18L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations. PMID:26951892

  19. Mycobacteria as a cause of infective exacerbation in bronchiectasis.

    PubMed Central

    Chan, C. H.; Ho, A. K.; Chan, R. C.; Cheung, H.; Cheng, A. F.

    1992-01-01

    In 91 patients with bronchiectasis seen over 6 years, a positive mycobacterial culture was obtained in 12 cases (13%). The organisms isolated were Mycobacterium tuberculosis in nine cases, Mycobacterium avium in two cases and Mycobacterium tuberculosis and chelonei were obtained on separate occasions in one case. Computed tomography and/or bronchography showed that the bronchiectatic changes commonly involved the lower lobes and to a lesser extent, the middle and lingula lobes. In none of these 12 cases was tuberculosis strongly suspected on clinical or radiological grounds. We conclude that mycobacterial infections are common in patients with bronchiectasis and sputum should be cultured for mycobacteria periodically in these patients. In doubtful cases, bronchoscopy may be helpful to obtain a positive mycobacterial culture. PMID:1494510

  20. The use of a biological graft for the closure of large abdominal wall defects following excision of soft tissue tumours

    PubMed Central

    Illingworth, Emma; Rooney, Paul S.; Heath, Richard; Chandrasekar, Coonoor R.

    2015-01-01

    Primary soft tissue tumours arising from the abdominal wall are uncommon and surgical excision of such tumours can result in large abdominal wall defects. There are many techniques available for abdominal wall repair following tumour excision, each having its own advantages and disadvantages. The options range from direct closure to the use of tissue flap reconstructions and/or prosthetic meshes. Currently, synthetic material such as polypropylene mesh is a common choice for closure of abdominal wall defects after tumour excision. Biological meshes are an alternative option for repair, and this report outlines two cases of abdominal wall repair using the porcine intestinal submucosa biological graft following excision of abdominal wall tumours. There was no evidence of infection, recurrence, seroma or hernias at 2-year follow-up. Following excision of soft tissue tumours of the abdominal wall, biological reconstructions can be successfully used to bridge the defect with minimal morbidity. PMID:26109681

  1. Acanthamoeba Encephalitis: Isolation of Genotype T1 in Mycobacterial Liquid Culture Medium

    PubMed Central

    Azzam, Rula; Badenoch, Paul R.; Francis, Michelle J.; Fernandez, Charles; Adamson, Penelope J.; Dendle, Claire; Woolley, Ian; Robson, Jenny; Korman, Tony M.

    2014-01-01

    We report a case of Acanthamoeba encephalitis diagnosed from an antemortem brain biopsy specimen, where the organism was first isolated in mycobacterial liquid medium and first identified by using a sequence generated by a commercial panfungal sequencing assay. We correlate susceptibility results with clinical outcome. PMID:25502534

  2. Mycobacterial antigen 85 complex (Ag85) as a target for ficolins and mannose-binding lectin.

    PubMed

    Świerzko, Anna S; Bartłomiejczyk, Marcin A; Brzostek, Anna; Łukasiewicz, Jolanta; Michalski, Mateusz; Dziadek, Jarosław; Cedzyński, Maciej

    2016-06-01

    The pattern recognition molecules (PRMs) able to activate complement via the lectin pathway are suspected to be involved in the interaction between pathogenic Mycobacteria and the host immune response. Recently, we have found strong interactions between 25 and 35kDa mycobacterial cell fractions and mannose-binding lectin (MBL) and ficolins. Here we demonstrate that two biologically important mycobacterial structures, mannosylated lipoarabinomannan (ManLAM) and the antigen 85 (Ag85) complex, induce activation of the lectin pathway of complement. The strong interaction of recombinant MBL with purified ManLAM was confirmed, but no binding of recombinant ficolins (ficolin-1, -2, -3) with this structure was observed. Interestingly, all PRMs tested reacted with the mycobacterial antigen 85 (Ag85) complex. Based on the use of specific inhibitors (mannan for MBL, acetylated bovine serum albumin for ficolin-1 and -2, Hafnia alvei PCM 1200 lipopolysaccharide for ficolin-3), we concluded that carbohydrate-recognition (MBL) and fibrinogen-like domains (ficolins) were involved in these interactions. Our results indicate that the mycobacterial antigen 85 complex is a target for ficolins and MBL. Furthermore, those PRMs also bound to fibronectin and therefore might influence the Ag85 complex-dependent interaction of Mycobacterium with the extracellular matrix. PMID:27141819

  3. Mycobacterial DNA extraction for whole-genome sequencing from early positive liquid (MGIT) cultures.

    PubMed

    Votintseva, Antonina A; Pankhurst, Louise J; Anson, Luke W; Morgan, Marcus R; Gascoyne-Binzi, Deborah; Walker, Timothy M; Quan, T Phuong; Wyllie, David H; Del Ojo Elias, Carlos; Wilcox, Mark; Walker, A Sarah; Peto, Tim E A; Crook, Derrick W

    2015-04-01

    We developed a low-cost and reliable method of DNA extraction from as little as 1 ml of early positive mycobacterial growth indicator tube (MGIT) cultures that is suitable for whole-genome sequencing to identify mycobacterial species and predict antibiotic resistance in clinical samples. The DNA extraction method is based on ethanol precipitation supplemented by pretreatment steps with a MolYsis kit or saline wash for the removal of human DNA and a final DNA cleanup step with solid-phase reversible immobilization beads. The protocol yielded ≥0.2 ng/μl of DNA for 90% (MolYsis kit) and 83% (saline wash) of positive MGIT cultures. A total of 144 (94%) of the 154 samples sequenced on the MiSeq platform (Illumina) achieved the target of 1 million reads, with <5% of reads derived from human or nasopharyngeal flora for 88% and 91% of samples, respectively. A total of 59 (98%) of 60 samples that were identified by the national mycobacterial reference laboratory (NMRL) as Mycobacterium tuberculosis were successfully mapped to the H37Rv reference, with >90% coverage achieved. The DNA extraction protocol, therefore, will facilitate fast and accurate identification of mycobacterial species and resistance using a range of bioinformatics tools. PMID:25631807

  4. Dissecting the membrane cholesterol requirement for mycobacterial entry into host cells.

    PubMed

    Viswanathan, Gopinath; Jafurulla, Md; Kumar, G Aditya; Raghunand, Tirumalai R; Chattopadhyay, Amitabha

    2015-07-01

    Mycobacteria are intracellular pathogens that can invade and survive within host macrophages, and are a major cause of mortality and morbidity worldwide. The molecular mechanism involved in the internalization of mycobacteria is poorly understood. In this work, we have explored the role of host membrane cholesterol in the entry of the avirulent surrogate mycobacterial strain Mycobacterium smegmatis into THP-1 macrophages. Our results show that depletion of host membrane cholesterol using methyl-β-cyclodextrin results in a significant reduction in the entry of M. smegmatis into host cells. More importantly, we show that the inhibition in the ability of M. smegmatis to enter host macrophages could be reversed upon replenishment of membrane cholesterol. To the best of our knowledge, these results constitute the first report showing that membrane cholesterol replenishment can reverse the inhibition in the entry of mycobacteria into host cells. In addition, we demonstrate that cholesterol complexation using amphotericin B (without physical depletion) is sufficient to inhibit mycobacterial entry. Importantly, we observed a significant reduction in mycobacterial entry upon enrichment of host membrane cholesterol. Taken together, our results demonstrate, for the first time, that an optimum host plasma membrane cholesterol is necessary for the entry of mycobacteria. These results assume relevance in the context of developing novel therapeutic strategies targeting cholesterol-mediated mycobacterial host cell entry. PMID:26021693

  5. Differential Immune Responses and Protective Effects in Avirulent Mycobacterial Strains Vaccinated BALB/c Mice.

    PubMed

    Liu, Laicheng; Fu, Ruiling; Yuan, Xuefeng; Shi, Chunwei; Wang, Shuling; Lu, Xianyu; Ma, Zhao; Zhang, Xiaoming; Qin, Weiyan; Fan, Xionglin

    2015-07-01

    Screening live mycobacterial vaccine candidates is the important strategy to develop new vaccines against adult tuberculosis (TB). In this study, the immunogenicity and protective efficacy of several avirulent mycobacterial strains including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial, and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our results demonstrated that differential immune responses were induced in different mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae immunization resulted in Th1-type responses in the lung, as well as splenocytes secreting IFN-γ against a highly conserved mycobacterial antigen Ag85A. M. smegmatis also induced the same splenocytes secreting IFN-γ as BCG and M. terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly increased expression of IL-10 and TGF-β in the lung. Most importantly, mice vaccinated with H37Ra and M. vaccae could provide the same protection in the lung against virulent M. tuberculosis challenge as BCG. The result may have important implications in developing adult TB vaccine. PMID:25995039

  6. Evaluation of Oral Antiseptic Rinsing before Sputum Collection To Reduce Contamination of Mycobacterial Cultures▿

    PubMed Central

    Peres, Renata L.; Palaci, Moisés; Loureiro, Rafaela B.; Dietze, Reynaldo; Johnson, John L.; Golub, Jonathan E.; Ruffino-Netto, A.; Maciel, Ethel L.

    2011-01-01

    To assess whether rinsing with oral antiseptics before sputum collection would reduce contamination of mycobacterial cultures, 120 patients with suspected tuberculosis were randomly assigned to rinse with chlorhexidine or cetylpyridinium mouthwash before collection. The culture contamination rate was significantly lower after rinsing with chlorhexidine before collection, especially for cultures grown in MGIT medium. PMID:21677070

  7. Role of tissue expanders in patients with loss of abdominal domain awaiting intestinal transplantation.

    PubMed

    Watson, Melissa J; Kundu, Neilendu; Coppa, Christopher; Djohan, Risal; Hashimoto, Koji; Eghtesad, Bijan; Fujiki, Masato; Diago Uso, Teresa; Gandhi, Namita; Nassar, Ahmed; Abu-Elmagd, Kareem; Quintini, Cristiano

    2013-12-01

    Abdominal closure is a complex surgical problem in intestinal transplant recipients with loss of abdominal domain, as graft exposure results in profound morbidity. Although intraoperative coverage techniques have been described, this is the first report of preoperative abdominal wall augmentation using tissue expanders in patients awaiting intestinal transplantation. We report on five patients who received a total of twelve tissue expanders as a means to increase abdominal surface area. Each patient had a compromised abdominal wall (multiple prior operations, enterocutaneous fistulae, subcutaneous abscesses, stomas) with loss of domain and was identified as high risk for an open abdomen post-transplant. Cross-sectional imaging and dimensional analysis were performed to quantify the effect of the expanders on total abdominal and intraperitoneal cavity volumes. The overall mean increase in total abdominal volume was 958 cm(3) with a mean expander volume of 896.5 cc. Two expanders were removed in the first patient due to infection, but after protocol modification, there were no further infections. Three patients eventually underwent small bowel transplantation with complete graft coverage. In our preliminary experience, abdominal tissue expander placement is a safe, feasible, and well-tolerated method to increase subcutaneous domain and facilitate graft coverage in patients undergoing intestinal transplantation. PMID:24118196

  8. Closely Related Mycobacterial Strains Demonstrate Contrasting Levels of Efficacy as Antitumor Vaccines and Are Processed for Major Histocompatibility Complex Class I Presentation by Multiple Routes in Dendritic Cells

    PubMed Central

    Cheadle, Eleanor J.; O'Donnell, Dearbhaile; Selby, Peter J.; Jackson, Andrew M.

    2005-01-01

    Mycobacteria expressing recombinant antigens are already being developed as vaccines against both infections and tumors. Little is known about how dendritic cells might process such antigens. Two different mycobacterial species, the fast-growing Mycobacterium smegmatis and the slow-growing M. bovis M. bovis BCG, were engineered to express a model tumor antigen, the Kb-restricted dominant cytotoxic T-lymphocyte epitope OVA257-264. Recombinant M. bovis BCG but not recombinant M. smegmatis conferred protection to mice challenged with the B16-OVA tumor cell line. We went on to investigate whether the contrast in antitumor efficacy could be due to differences in how dendritic cells process antigen from the two mycobacterial strains for class I presentation. Both strains of mycobacteria caused phenotypic maturation of dendritic cells, but recombinant M. smegmatis infection led to a greater degree of dendritic cell maturation than recombinant M. bovis BCG infection. Antigen from recombinant M. smegmatis was processed and presented as OVA257-264 on Kb molecules by the dendritic cell line DC2.4 but not by bone marrow-derived dendritic cells (BMDC) or splenic dendritic cells. In contrast, antigen from recombinant M. bovis BCG was presented by all three dendritic cell types as long as the mycobacteria were viable. Such presentation was dependent on proteasome function and nascent major histocompatibility complex (MHC) class I molecules in DC2.4 cells but independent of the proteasome and transporter associated with antigen processings (TAP) in BMDC and splenic dendritic cells. These data demonstrate for the first time that antigen vectored by the slow-growing M. bovis BCG but not that vectored by fast-growing, readily destroyed M. smegmatis is processed and presented on MHC class I by in vitro-generated dendritic cells, which has implications for recombinant microbial vaccine development. PMID:15664917

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

    PubMed Central

    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

  10. 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

  11. Multidetector computed tomography in the evaluation of pediatric acute abdominal pain in the emergency department.

    PubMed

    Lin, Wei-Ching; Lin, Chien-Heng

    2016-06-01

    The accurate diagnosis of pediatric acute abdominal pain is one of the most challenging tasks in the emergency department (ED) due to its unclear clinical presentation and non-specific findings in physical examinations, laboratory data, and plain radiographs. The objective of this study was to evaluate the impact of abdominal multidetector computed tomography (MDCT) performed in the ED on pediatric patients presenting with acute abdominal pain. A retrospective chart review of children aged <18 years with acute abdominal pain who visited the emergency department and underwent MDCT between September 2004 and June 2007 was conducted. Patients with a history of trauma were excluded. A total of 156 patients with acute abdominal pain (85 males and 71 females, age 1-17 years; mean age 10.9 ± 4.6 years) who underwent abdominal MDCT in the pediatric ED during this 3-year period were enrolled in the study. One hundred and eighteen patients with suspected appendicitis underwent abdominal MDCT. Sixty four (54.2%) of them had appendicitis, which was proven by histopathology. The sensitivity of abdominal MDCT for appendicitis was found to be 98.5% and the specificity was 84.9%. In this study, the other two common causes of nontraumatic abdominal emergencies were gastrointestinal tract (GI) infections and ovarian cysts. The most common etiology of abdominal pain in children that requires imaging with abdominal MDCT is appendicitis. MDCT has become a preferred and invaluable imaging modality in evaluating uncertain cases of pediatric acute abdominal pain in ED, in particular for suspected appendicitis, neoplasms, and gastrointestinal abnormalities. PMID:27154197

  12. A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components.

    PubMed

    Xia, Mei; Hesser, Danny C; De, Prithwiraj; Sakala, Isaac G; Spencer, Charles T; Kirkwood, Jay S; Abate, Getahun; Chatterjee, Delphi; Dobos, Karen M; Hoft, Daniel F

    2016-09-01

    γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2 T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2 T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2 T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ9δ2 T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ9δ2 T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB. PMID:27297390

  13. A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components

    PubMed Central

    Xia, Mei; Hesser, Danny C.; De, Prithwiraj; Sakala, Isaac G.; Spencer, Charles T.; Kirkwood, Jay S.; Abate, Getahun; Chatterjee, Delphi

    2016-01-01

    γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2 T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2 T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2 T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ9δ2 T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ9δ2 T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB. PMID:27297390

  14. Abdominal radiation causes bacterial translocation

    SciTech Connect

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-02-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa.

  15. Ubiquitin-fusion degradation pathway: A new strategy for inducing CD8 cells specific for mycobacterial HSP65

    SciTech Connect

    Shen Jianying; Hisaeda, Hajime; Chou Bin; Yu Qingsheng; Tu Liping; Himeno, Kunisuke

    2008-01-25

    The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8{sup +} T cells. In this study, we exploited UPS to induce CD8{sup +} T cells specific for mycobacterial HSP65 (mHSP65), one of the leading vaccine candidates against infection with Mycobacterium tuberculosis. A chimeric DNA termed pU-HSP65 encoding a fusion protein between murine ubiquitin and mHSP65 was constructed, and C57BL/6 (B6) mice were immunized with the DNA using gene gun bombardment. Mice immunized with the chimeric DNA acquired potent resistance against challenge with the syngeneic B16F1 melanoma cells transfected with the mHSP65 gene (HSP65/B16F1), compared with those immunized with DNA encoding only mHSP65. Splenocytes from the former group of mice showed a higher grade of cytotoxic activity against HSP65/B16F1 cells and contained a larger number of granzyme B- or IFN-{gamma}-producing CD8{sup +} T cells compared with those from the latter group of mice.

  16. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity.

    PubMed

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-12-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, and CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  17. Menaquinone Synthesis is Critical for Maintaining Mycobacterial Viability During Exponential Growth and Recovery from Non-Replicating Persistence

    PubMed Central

    Dhiman, Rakesh K.; Mahapatra, Sebabrata; Slayden, Richard A.; Boyne, Melissa E.; Lenaerts, Anne; Hinshaw, Jerald C.; Angala, Shiva K.; Chatterjee, Delphi; Biswas, Kallolmay; Narayanasamy, Prabagaran; Kurosu, Michio; Crick, Dean C.

    2016-01-01

    Summary Understanding the basis of bacterial persistence in latent infections is critical for eradication of tuberculosis. Analysis of Mycobacterium tuberculosis mRNA expression in an in vitro model of non-replicating persistence indicated that the bacilli require electron transport chain components and ATP synthesis for survival. Additionally, low μM concentrations of aminoalkoxydiphenylmethane derivatives inhibited both the aerobic growth and survival of non-replicating, persistent M. tuberculosis. Metabolic labeling studies and quantitation of cellular menaquinone levels suggested that menaquinone synthesis, and consequently electron transport, is the target of the aminoalkoxydiphenylmethane derivatives. This hypothesis is strongly supported by the observations that treatment with these compounds inhibits oxygen consumption and that supplementation of growth medium with exogenous menaquinone rescued both growth and oxygen consumption of treated bacilli. In vitro assays indicate that the aminoalkoxydiphenylmethane derivatives specifically inhibit MenA, an enzyme involved in the synthesis of menaquinone. Thus, the results provide insight into the physiology of mycobacterial persistence and a basis for the development of novel drugs that enhance eradication of persistent bacilli and latent tuberculosis. PMID:19220750

  18. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    PubMed Central

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  19. Interleukin-1β triggers the differentiation of macrophages with enhanced capacity to present mycobacterial antigen to T cells

    PubMed Central

    Schenk, Mirjam; Fabri, Mario; Krutzik, Stephan R; Lee, Delphine J; Vu, David M; Sieling, Peter A; Montoya, Dennis; Liu, Philip T; Modlin, Robert L

    2014-01-01

    The rapid differentiation of monocytes into macrophages (MΦ) and dendritic cells is a pivotal aspect of the innate immune response. Differentiation is triggered following recognition of microbial ligands that activate pattern recognition receptors or directly by pro-inflammatory cytokines. We demonstrate that interleukin-1β (IL-1β) induces the rapid differentiation of monocytes into CD209+ MΦ, similar to activation via Toll-like receptor 2/1, but with distinct phenotypic and functional characteristics. The IL-1β induced MΦ express higher levels of key markers of phagocytosis, including the Fc-receptors CD16 and CD64, as well as CD36, CD163 and CD206. In addition, IL-1β-induced MΦ exert potent phagocytic activity towards inert particles, oxidized low-density lipoprotein and mycobacteria. Furthermore, IL-1β-induced MΦ express higher levels of HLA-DR and effectively present mycobacterial antigens to T cells. Therefore, the ability of IL-1β to induce monocyte differentiation into MΦ with both phagocytosis and antigen-presenting function is a distinct part of the innate immune response in host defence against microbial infection. PMID:24032597

  20. Abdominal bloating: pathophysiology and treatment.

    PubMed

    Seo, A Young; Kim, Nayoung; Oh, Dong Hyun

    2013-10-01

    Abdominal bloating is a very common and troublesome symptom of all ages, but it has not been fully understood to date. Bloating is usually associated with functional gastrointestinal disorders or organic diseases, but it may also appear alone. The pathophysiology of bloating remains ambiguous, although some evidences support the potential mechanisms, including gut hypersensitivity, impaired gas handling, altered gut microbiota, and abnormal abdominal-phrenic reflexes. Owing to the insufficient understanding of these mechanisms, the available therapeutic options are limited. However, medical treatment with some prokinetics, rifaximin, lubiprostone and linaclotide could be considered in the treatment of bloating. In addition, dietary intervention is important in relieving symptom in patients with bloating. PMID:24199004

  1. Abdominal pain with a twist

    PubMed Central

    2011-01-01

    Malrotation in children is due to either an incomplete or non-rotation of the foetal mid-gut during perinatal development. Presentation is usually in the first few weeks of life, often with life-threatening volvulus and ischaemia. However, it can be a rare cause of abdominal pain in older children and young adults. We present such a case, as a reminder to emergency physicians that malrotation should be considered in the differential diagnosis of recurrent or chronic abdominal pain not only in children but also in adolescents. PMID:21635723

  2. Ultrasonographic diagnosis in abdominal tuberculosis.

    PubMed

    Sheikh, M; Moosa, I; Hussein, F M; Qurttom, M A; Behbehani, A I

    1999-05-01

    Sonographic findings were retrospectively analysed in 39 patients with proven abdominal tuberculosis (TB). The patients were treated over 15 years at a major teaching hospital, Mubarak Al-Kabber Hospital, in Kuwait. The findings included clear or complex ascites with fine strands, loculations and debris. The other findings were lymphadenopathy, bowel wall thickening, omental mass, focal lesions in the liver and spleen and psoas abscess. The sonographic findings in abdominal TB are not specific but may give valuable information to prevent unnecessary laparotomy. PMID:10901897

  3. Secondary abdominal appendicular ectopic pregnancy.

    PubMed

    Nama, Vivek; Gyampoh, Bright; Karoshi, Mahantesh; McRae, Reynold; Opemuyi, Isaac

    2007-01-01

    Although the case fatality rate for ectopic pregnancies has decreased to 0.08% in industrialized countries, it still represents 3.8% of maternal mortality in the United States alone. In developing countries, the case fatality rate varies from 3% to 27%. Laparoscopic management of tubal pregnancies is now the standard form of treatment where this technology is available. Abdominal pregnancies are rare, and secondary implantation of tubal ectopic pregnancies is the most common cause of abdominal gestations. We present an interesting case of secondary implantation of a tubal ectopic pregnancy to highlight the appendix as a possible secondary implantation site after a tubal ectopic pregnancy. PMID:17630175

  4. Rare presentation of multi-organ abdominal echinococcosis: report of a case and review of literature

    PubMed Central

    Zheng, Xiaoyan; Zou, Yang; Yin, Chenghong

    2015-01-01

    Hydatid disease, which is also known as cystic echinococcosis, is a zoonotic infection caused by the cestode tapeworm Echinococcus granulosus and rarely by Echinococcus multilocularis. In this report we describe an unusual case of a 19-year-old woman who was admitted to our hospital for abdominal pain, nausea, and vomiting. Computed tomography revealed multi-organ abdominal echinococcosis. The patient recovered after undergoing surgery to excise the cyst. The diagnosis, clinical features, treatment, and prevention in this case of multi-organ abdominal echinococcosis are discussed, in light of the relevant literature. PMID:26617932

  5. Abdominal pain - children under age 12

    MedlinePlus

    Stomach pain in children; Pain - abdomen - children; Abdominal cramps in children; Belly ache in children ... When your child complains of abdominal pain, see if they can describe it to you. Here are different kinds of pain: ...

  6. Mycobacterium chelonae infection under adalimumab therapy for spondylarthritis.

    PubMed

    Kluger, N; Cohen, P; Fallet-Bianco, C; Guillevin, L

    2010-01-01

    Tumour necrosis factor (TNF)-alpha antagonists have been prescribed increasingly over the past few years to manage various inflammatory diseases. This widespread use was quickly followed by the heightened frequency of opportunistic mycobacterial infections including environmental non-tuberculous mycobacterial infections (ENTM). We describe a 66-year-old man taking adalimumab for spondyloarthropathy who developed an inflammatory infiltration in his right index finger. A non-necrotising granuloma with epitheloid and giant cells in the dermis and eosinophilic acid-fast bacilli, identified by using Ziehl-Neelsen staining suggested a mycobacterial infection. Cultures for mycobacteria grew positive on Loewenstein-Jensen medium and molecular identification confirmed M. chelonae infection. The outcome was favourable after five months of clarythromycin. In this context of more frequent ENTM infections, chronic non-specific cutaneous lesions of the extremities should evoke systematically cutaneous ENTM infections. Skin biopsy with histological examination and oriented microbiological cultures and molecular identification are mandatory to confirm the diagnosis. PMID:20346249

  7. 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

  8. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency.

    PubMed

    Bogunovic, Dusan; Byun, Minji; Durfee, Larissa A; Abhyankar, Avinash; Sanal, Ozden; Mansouri, Davood; Salem, Sandra; Radovanovic, Irena; Grant, Audrey V; Adimi, Parisa; Mansouri, Nahal; Okada, Satoshi; Bryant, Vanessa L; Kong, Xiao-Fei; Kreins, Alexandra; Velez, Marcela Moncada; Boisson, Bertrand; Khalilzadeh, Soheila; Ozcelik, Ugur; Darazam, Ilad Alavi; Schoggins, John W; Rice, Charles M; Al-Muhsen, Saleh; Behr, Marcel; Vogt, Guillaume; Puel, Anne; Bustamante, Jacinta; Gros, Philippe; Huibregtse, Jon M; Abel, Laurent; Boisson-Dupuis, Stéphanie; Casanova, Jean-Laurent

    2012-09-28

    ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity. PMID:22859821

  9. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency

    PubMed Central

    Bogunovic, Dusan; Byun, Minji; Durfee, Larissa A.; Abhyankar, Avinash; Sanal, Ozden; Mansouri, Davood; Salem, Sandra; Radovanovic, Irena; Grant, Audrey V.; Adimi, Parisa; Mansouri, Nahal; Okada, Satoshi; Bryant, Vanessa L.; Kong, Xiao-Fei; Kreins, Alexandra; Velez, Marcela Moncada; Boisson, Bertrand; Khalilzadeh, Soheila; Ozcelik, Ugur; Darazam, Ilad Alavi; Schoggins, John W.; Rice, Charles M.; Al-Muhsen, Saleh; Behr, Marcel; Vogt, Guillaume; Puel, Anne; Bustamante, Jacinta; Gros, Philippe; Huibregtse, Jon M.; Abel, Laurent; Boisson-Dupuis, Stéphanie; Casanova, Jean-Laurent

    2012-01-01

    ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. We describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes — granulocytes in particular — reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of Nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity. PMID:22859821

  10. Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells

    PubMed Central

    Fischer, Karsten; Scotet, Emmanuel; Niemeyer, Marcus; Koebernick, Heidrun; Zerrahn, Jens; Maillet, Sophie; Hurwitz, Robert; Kursar, Mischo; Bonneville, Marc; Kaufmann, Stefan H. E.; Schaible, Ulrich E.

    2004-01-01

    A group of T cells recognizes glycolipids presented by molecules of the CD1 family. The CD1d-restricted natural killer T cells (NKT cells) are primarily considered to be self-reactive. By employing CD1d-binding and T cell assays, the following structural parameters for presentation by CD1d were defined for a number of mycobacterial and mammalian lipids: two acyl chains facilitated binding, and a polar head group was essential for T cell recognition. Of the mycobacterial lipids tested, only a phosphatidylinositol mannoside (PIM) fulfilled the requirements for CD1d binding and NKT cell stimulation. This PIM activated human and murine NKT cells via CD1d, thereby triggering antigen-specific IFN-γ production and cell-mediated cytotoxicity, and PIM-loaded CD1d tetramers identified a subpopulation of murine and human NKT cells. This phospholipid, therefore, represents a mycobacterial antigen recognized by T cells in the context of CD1d. PMID:15243159

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

    SciTech Connect

    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

    2010-09-17

    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 coincidently 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.

  12. Mycobacterial cell walls. I. Methods of preparation and treatment with various chemicals.

    PubMed

    TAKEYA, K; HISATSUNE, K

    1963-01-01

    Takeya, Kenji (Kyushu University, Fukuoka, Japan) and Kazuhito Hisatsune. Mycobacterial cell walls. I. Methods of preparation and treatment with various chemicals. J. Bacteriol. 85:16-23. 1963.-Several methods of preparation of mycobacterial cell walls were examined, and the grinding method with glass powder, using Dry Ice, was found to give fairly good cell-wall preparations. "Paired fibrous structures" were clearly seen on the purified cell wall. The appearance of the cell wall as revealed by the electron microscope was not altered by digestion with trypsin, pronase, or pronase in 5% alcoholic solution, nor by treatment with 95% alcohol, acetone-alcohol mixture, or ether-alcohol mixture. By treatment with alcoholic KOH solution, the fibrous structure was removed. The remaining thin layer of the cell wall was tentatively designated the "basal layer" of the mycobacterial cell wall. The fibers appeared also to be removed by chloroform treatment. Nagarse digestion seemed to solubilize some constituents of the cell wall. The cell wall lost its shape and rigidity after lysozyme digestion. PMID:13984703

  13. Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins.

    PubMed Central

    Andersen, P

    1994-01-01

    An experimental vaccine that was based on secreted proteins of Mycobacterium tuberculosis was investigated in a mouse model of tuberculosis. I used a short-term culture filtrate (ST-CF) containing proteins secreted from actively replicating bacteria grown under defined culture conditions. The immunogenicity of the ST-CF was investigated in combination with different adjuvants, and peak proliferative responses were observed when ST-CF was administered with the surface-active agent dimethyldioctadecylammonium chloride. The immunity induced by this vaccine was dose dependent, and, in the optimal concentration, the vaccine induced a potent T-helper 1 response which efficiently protected the animals against a subsequent challenge with virulent M. tuberculosis. Antigenic targets for the T cells generated were mapped by employing narrow-molecular-weight fractions of ST-CF. The experimental vaccine primed a broadly defined T-cell repertoire directed to multiple secreted antigens present in ST-CF. A vaccination with viable Mycobacterium bovis bacillus Calmette-Guérin (BCG), in contrast, induced a restricted T-cell reactivity directed to two secreted protein fractions with molecular masses of 5 to 12 and 25 to 35 kDa. The protective efficacy of the ST-CF vaccine was compared with that of a BCG standard vaccine, and both induced a highly significant protection of equal magnitude. The vaccination with ST-CF gave rise to a population of long-lived CD4 cells which could be isolated 22 weeks after the vaccination and could adoptively transfer acquired resistance to T-cell-deficient recipients. My results confirm the hypothesis that M. tuberculosis cells release protective antigens during growth. The high efficacy of a subunit vaccine observed in the present study is discussed as a possible alternative to a live recombinant vaccine carrier. Images PMID:7910595

  14. Host responses to mycobacterial infections: Spotlight on biomarker discovery to predict vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The global spread of tuberculosis (TB) in animals and humans result in enormous economic. social and public health burdens. TB vaccine development in both humans and animals has produced a growing portfolio of candidates with potential applicability across species. However, the lack of understandin...

  15. The therapeutic approach to non-tuberculous mycobacterial infection of the lung.

    PubMed

    McGrath, Emmet E; Anderson, Paul B

    2010-10-01

    Non-tuberculous mycobacteria (NTM) are a group of alcohol fast, aerobic, nonmotile bacteria that are found in the environment. Recent reports indicate that their incidence and prevalence is increasing and guidelines have been developed laying down criteria for diagnosis. The treatment of these mycobacteria may be difficult, in many cases involving complex regimens containing multiple drugs. While traditional anti-tuberculosis medications are frequently used, specific therapeutic regimens depend on the organism isolated, in vitro susceptibility testing, drug tolerance and toxicity and concomitant medical disorders. In this review, we describe the diagnosis and treatment of the more important lung pathogens, describing complexities and controversies surrounding treatment with traditional, adjunctive and the newer and more experimental agents. PMID:20542128

  16. [Laparoscopic repair of abdominal wall hernias].

    PubMed

    Bezsilla, János

    2010-10-01

    Repair of abdominal wall defects is a challenge for all general surgeons and a variety of methods have been described in the past. Traditionally, primary suture repair was shown to have a high recurrence rate in long-term follow-up studies. Herniorrhaphies that apply a large prosthetic mesh are appear to have a lower failure rate, but extensive dissection of soft tissue contributes to an increased incidence of wound infections and wound-related complications. The method of laparoscopic incisional hernia repair was developed in the early 1990s. This technique is based on the same physical and surgical principles as the open underlay procedure. The laparoscopic intraperitoneal onlay mesh (IPOM) technique and mesh materials were developed further in subsequent years, and there have been numerous reports on successful use of the IPOM technique even for extremely large hernia openings in obese and elderly patients. Reduced surgical trauma and lower infection and recurrence rates are key advantages of the minimally invasive repair. Therefore, this operation has increased in popularity promising shorter hospital stay, improved outcome, and fewer complications than traditional open procedures. PMID:20965866

  17. Update in tuberculosis and nontuberculous mycobacterial disease 2012.

    PubMed

    Menzies, Dick; Nahid, Payam

    2013-10-15

    In 2012, new publications in the Journal described both the predictive value of the new IFN-γ release assays for diagnosis of latent tuberculosis (TB), but also provided evidence that these new tests cannot be interpreted simply as positive or negative, as initially hoped. Surgical masks can reduce transmission of TB infection, but other measures such as state-wide implementation of targeted testing and treatment of latent TB or active case finding require substantial and sustained effort to successfully reduce TB morbidity and mortality. A quasiexperimental study revealed that a package of social interventions could substantially reduce risk of TB disease in heavily exposed (and infected) children in the preantibiotic era. A study in a high-TB burden setting suggested that a new rapid drug-susceptibility test for TB may be more practical for implementation than traditional culture-based phenotypic tests. And two studies of TB vaccines revealed that currently used bacillus Calmette-Guérin strains vary in their ability to affect correlates of immunogenicity, whereas a new candidate vaccine, MVA85A, was safe and immunogenic in adults. Studies of nontuberculous mycobacteria (NTM) described a rapid rise in the prevalence and spatial clustering of NTM in the United States over the past decade. Although risk factors for pulmonary NTM such as advanced age and low BMI are known, the mechanisms underlying infection and disease remain mysterious. Four studies of therapy of NTM disease highlighted the pressing need for well-designed international randomized controlled trials to improve our management of NTM disease. PMID:24127799

  18. Abdominal Distension and Vascular Collapse.

    PubMed

    Cosentino, Gina; Uwaifo, Gabriel I

    2016-04-01

    We present the case of a 43-year-old gentleman who presented to the emergency room with acute abdominal distension, confusion and vascular collapse. The emergent radiologic imaging obtained showed massive bilateral adrenal enlargement, but despite the initial clinical suspicion of possible overwhelming sepsis and/or massive abdominal/intralesional hemorrhage, lab tests based obtained rapidly confirmed the diagnosis of acute Addisonian crisis which responded dramatically to adrenocorticoid hormone replacement therapy and aggressive fluid resuscitation. The patient's established history of metastatic lung cancer confirmed this as a case of metastatic massive bilateral adrenal metastases with an initial presentation of acute adrenal insufficiency which is uncommon in the setting of metastatic carcinomatosis but more typically associated with lymphomas. Recognition of this clinical possibility is vital to enable rapid diagnosis and consequent life saving therapy. PMID:27328473

  19. [Abdominal bruit associated with hypertension].

    PubMed

    Fontseré, N; Bonet, J; Bonal, J; Romero, R

    2004-01-01

    First cause of secondary hypertension is renovascular hypertension which presents abdominal bruit in 16 to 20% of cases. This clinical sign is also associated with other vascular disease of the abdomen such as celiac trunk stenosis and/or aneurysms located on the pancreaticoduodenal or gastroduodenal arcs level, with little representation among aneurysm. They usually appear on a context of digestive complications like neoplasias, chronic pancreatitis or gastric obstructions possibly with obstructive icterus, hemorrhage and acute abdomen episodes. Its presentation in other contexts is rare and constitutes a diagnostic challenge. Diagnosis is made by abdominal arteriography which is the best method because you can locate the problem as well as intervene therapeutically with embolization of the aneurysme. We would like to emphasize the importance of a quick diagnosis due to the risk of rupture and the high morbi-mortality associated. PMID:15219082

  20. Management of voluminous abdominal incisional hernia.

    PubMed

    Bouillot, J-L; Poghosyan, T; Pogoshian, T; Corigliano, N; Canard, G; Veyrie, N

    2012-10-01

    Incisional hernia is one of the classic complications after abdominal surgery. The chronic, gradual increase in size of some of these hernias is such that the hernia ring widens to a point where there is a loss of substance in the abdominal wall, herniated organs can become incarcerated or strangulated while poor abdominal motility can alter respiratory function. The surgical treatment of small (<5 cm) incisional hernias is safe and straightforward, by either laparotomy or laparoscopy. For large hernias, surgical repair is often difficult. After reintegration of herniated viscera into the abdominal cavity, the abdominal wall defect must be closed anatomically in order to restore the function to the abdominal wall. Prosthetic reinforcement of the abdominal wall is mandatory for long-term successful repair. There are multiple techniques for prosthetic hernia repair, but placement of Dacron mesh in the retromuscular plane is our preference. PMID:23137643

  1. A case of guilt by association: Water bug bite incriminated in M. ulcerans infection.

    PubMed

    Marion, Estelle; Chauty, Annick; Yeramian, Edouard; Babonneau, Jérèmie; Kempf, Marie; Marsollier, Laurent

    2014-06-01

    Buruli ulcer is a cutaneous mycobacterial disease caused by Mycobacterium ulcerans, whose incidence is increasing steadily, especially in West Africa. This study reports a first documented case of M. ulcerans infection which can be attributed to a water bug bite at the site of the primary lesion. PMID:26786340

  2. A Comparison Between Non-Descent Vaginal Hysterectomy and Total Abdominal Hysterectomy

    PubMed Central

    Dibyajyoti, Gharphalia

    2016-01-01

    Introduction Hysterectomy is one of the most common gyneacological surgeries performed worldwide. The vaginal technique has been introduced and performed centuries back, but has been less successful due to lack of experience and enthusiasm among Gynaecologists, due to a misconception that the abdominal route is safer and easier. Aim To evaluate the most efficient route of hysterectomy in women with mobile nonprolapsed uteri of 12 weeks or lesser by comparing the intra and postoperative complications of vaginal and abdominal hysterectomies. Materials and Methods A prospective, randomized controlled trial was performed wherein, 300 consecutive patients requiring hysterectomy for benign diseases were analysed over a period of 2 years (December 2012–November 2014). Group A (n = 150) underwent vaginal hysterectomy (non descent vaginal hysterectomy, NDVH) which was compared with group B (n = 150) who had abdominal hysterectomy. The primary outcome measures were operative time, intraoperative blood loss, postoperative analgesia, hospital stay, postoperative mobility, blood transfusion, wound infection, febrile morbidity and postoperative systemic infections. Secondary outcome measures were conversion of vaginal to abdominal route and re-laparotomy. Results Baseline characteristics were similar between the two groups. There were no intraoperative complications in either group. Regarding operation duration, intraoperative blood loss, postoperative pain, postoperative blood transfusion, mobilization in post operative ward, postoperative wound infection, febrile morbidity, duration of hospital stay, p-value was significant in vaginal hysterectomy compared to abdominal hysterectomy. Regarding postoperative systemic infections, p-value was not significant. None of the cases in the vaginal group were converted to abdominal route and none of the cases in the whole study group underwent re-laparotomy. Conclusion The present study concludes that patients requiring hysterectomy

  3. Systems biology approaches to understanding mycobacterial survival mechanisms

    PubMed Central

    Boshoff, Helena I.M.; Lun, Desmond S.

    2010-01-01

    The advent of high-throughput platforms for the interrogation of biological systems at the cellular and molecular level have allowed living cells to be observed and understood at a hitherto unprecedented level of detail and have enabled the construction of comprehensive, predictive in silico models. Here, we review the application of such high-throughput, systems-biological techniques to mycobacteria—specifically to the pernicious human pathogen Mycobacterium tuberculosis (MTb) and its ability to survive in human hosts. We discuss the development and application of transcriptomic, proteomic, regulomic, and metabolomic techniques for MTb as well as the development and application of genome-scale in silico models. Thus far, systems-biological approaches have largely focused on in vitro models of MTb growth; reliably extending these approaches to in vivo conditions relevant to infection is a significant challenge for the future that holds the ultimate promise of novel chemotherapeutic interventions. PMID:21072257

  4. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  5. Primary aortoenteric fistula to the sigmoid colon in association with intra-abdominal abscess.

    PubMed

    Lee, Wonho; Jung, Chul Min; Cho, Eun-Hee; Ryu, Dong Ryeol; Choi, Daehee; Kim, Jaihwan

    2014-04-01

    Primary aortoenteric fistula (PAEF) is a rare but catastrophic cause of massive gastrointestinal bleeding. Diagnosis of PAEF is difficult to make and is frequently delayed without strong clinical suspicion. Timely surgical intervention is essential for patient's survival. We report on a case of an 86-year-old woman with no history of abdominal surgery, who presented with abdominal pain. Initially, computed tomography scan showed an intra-abdominal abscess, located anterior to the aortic bifurcation. However, she was discharged without treatment because of spontaneous improvement on a follow-up computed tomography scan, which showed a newly developed right common iliac artery aneurysm. One week later, she was readmitted due to recurrent abdominal pain. On the second day of admission, sudden onset of gastrointestinal bleeding occurred for the first time. After several endoscopic examinations, an aortoenteric fistula bleeding site was found in the sigmoid colon, and aortography showed progression of a right common iliac artery aneurysm. We finally concluded that intra-abdominal abscess induced an infected aortic aneurysm and enteric fistula to the sigmoid colon. This case demonstrated an extremely rare type of PAEF to the sigmoid colon caused by an infected abdominal aortic aneurysm, which has rarely been reported. PMID:24755749

  6. Intra-abdominal sepsis: the role of surgery.

    PubMed

    Gallinaro, R N; Polk, H C

    1991-09-01

    The role of the surgeon in intra-abdominal sepsis is multifactorial. A comprehensive understanding of the incidence and pathophysiology of diseases which cause intra-abdominal sepsis is the key to the diagnosis and treatment of such ailments. In simplest terms, the aetiology has two basic mechanisms: (a) violation of the 'bug-body barrier' and (b) obstruction to the flow of a body fluid with subsequent bacterial overgrowth. Either of these mechanisms may affect any of the organs within the abdomen, leading to sepsis. The peritoneal cavity is a dynamic structure which responds to insults in certain predictable manners which notify the alert physician that danger is present. Recognition of these signs through history and physical examination are the most important aspects of diagnosis. Confirmation of suspicions can be obtained with radiological modalities, but they are not a substitute for clinical judgement. Treatment of intra-abdominal sepsis should always begin with resuscitation and systemic antibiotics. Alleviation of the septic source is mandatory, and this may be achieved either operatively or non-operatively (i.e. percutaneous or endoscopic procedures). When the patient does not improve after the initial procedure, then a missed focus of infection must be investigated. In some cases, a planned or staged second operation may be needed to further debride necrotic tissue. Antibiotics should be of adequate spectrum and bioavailability to kill the species of bacteria most likely to cause the infection. This regimen may be altered when culture and sensitivity reports are completed. Finally, patients whose immune system function has been altered by disease or treatment must be assumed very ill until proven otherwise. These are general guidelines in the management of patients with intra-abdominal sepsis. Individual cases may necessitate slight modifications, but all require a high level of vigilance and expertise in order to combat a very lethal disease. PMID

  7. Necrotizing Soft Tissue Infection Caused by Spilled Gallstones

    PubMed Central

    Pandit, Narendra; Kumar, Hemanth; Verma, GR

    2016-01-01

    We report a case of a 57-year-old woman who presented with a necrotizing soft tissue infection of the right anterior abdominal wall, 1 year after open cholecystectomy for gallbladder perforation. Surgical exploration revealed pigmented gallstones along with pus in the abdominal wall and gallbladder fossa. Intraoperative spillage of gallstones is common during both open and laparoscopic cholecystectomy, but, in rare cases, can lead to serious complications including necrotizing infection of the abdominal wall. PMID:27144208

  8. Pituitary dysfunction in infective brain diseases

    PubMed Central

    Beatrice, Anne M.; Selvan, Chitra; Mukhopadhyay, Satinath

    2013-01-01

    Infectious diseases of the central nervous system (CNS) are increasingly being recognized as important causes of hypopituitarism. Although tuberculosis is the most common agent involved, non-mycobacterial agents like viruses, bacteria, fungus, and protozoa are important causes in our country. Involvement post infections could be due to a strategically located tuberculoma, or pituitary abscess, or meningoencephalitis. Although it might not be reasonable to screen all patients with CNS infections for hypopituitarism, awareness of the possibility and clinical follow-up for suggestive symptoms is required. PMID:24910821

  9. Triazaspirodimethoxybenzoyls as Selective Inhibitors of Mycobacterial Lipoamide Dehydrogenase

    SciTech Connect

    Bryk, Ruslana; Arango, Nancy; Venugopal, Aditya; Warren, J. David; Park, Yun-Hee; Patel, Mulchand S.; Lima, Christopher D.; Nathan, Carl

    2010-06-25

    Mycobacterium tuberculosis (Mtb) remains the leading single cause of death from bacterial infection. Here we explored the possibility of species-selective inhibition of lipoamide dehydrogenase (Lpd), an enzyme central to Mtb's intermediary metabolism and antioxidant defense. High-throughput screening of combinatorial chemical libraries identified triazaspirodimethoxybenzoyls as high-nanomolar inhibitors of Mtb's Lpd that were noncompetitive versus NADH, NAD{sup +}, and lipoamide and >100-fold selective compared to human Lpd. Efficacy required the dimethoxy and dichlorophenyl groups. The structure of an Lpd-inhibitor complex was resolved to 2.42 {angstrom} by X-ray crystallography, revealing that the inhibitor occupied a pocket adjacent to the Lpd NADH/NAD{sup +} binding site. The inhibitor did not overlap with the adenosine moiety of NADH/NAD{sup +} but did overlap with positions predicted to bind the nicotinamide rings in NADH and NAD{sup +} complexes. The dimethoxy ring occupied a deep pocket adjacent to the FAD flavin ring where it would block coordination of the NADH nicotinamide ring, while the dichlorophenyl group occupied a more exposed pocket predicted to coordinate the NAD{sup +} nicotinamide. Several residues that are not conserved between the bacterial enzyme and its human homologue were predicted to contribute both to inhibitor binding and to species selectivity, as confirmed for three residues by analysis of the corresponding mutant Mtb Lpd proteins. Thus, nonconservation of residues lining the electron-transfer tunnel in Mtb Lpd can be exploited for development of species-selective Lpd inhibitors.

  10. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

    PubMed Central

    2016-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  11. Agents of newly recognized or infrequently encountered mycobacterial diseases.

    PubMed Central

    Wayne, L G; Sramek, H A

    1992-01-01

    This paper reviews recent information on the systematics and clinical significance of potentially pathogenic environmental mycobacteria. A short history of these mycobacteria is given. Information on species for which clinical and systematic aspects have already been well documented, i.e., Mycobacterium kansasii, M. marinum, M. scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi, and members of the M. fortuitum complex, is updated. Although the M. avium complex was extensively reviewed in earlier literature, major new systematic and clinical information is presented in some detail. Species that have received very limited prior coverage, i.e., M. asiaticum, M. haemophilum, M. malmoense, and M. shimoidei, are the main subjects of this review and are discussed in detail. The rare infections attributed to species that are normally considered nonpathogenic, i.e., M. gastri, M. gordonae, the M. terrae complex, and most of the rapidly growing mycobacteria outside of the M. fortuitum complex, are critically reviewed. Finally, suggestions are offered for practical measures that can minimize the risk of failing to isolate or misidentifying some of the more obscure potentially pathogenic environmental mycobacteria that are only infrequently recognized. PMID:1735092

  12. Molecular and physiological effects of mycobacterial oxyR inactivation.

    PubMed

    Pagán-Ramos, Eileen; Master, Sharon S; Pritchett, Christopher L; Reimschuessel, Renate; Trucksis, Michele; Timmins, Graham S; Deretic, Vojo

    2006-04-01

    The majority of slow-growing mycobacteria have a functional oxyR, the central regulator of the bacterial oxidative stress response. In contrast, this gene has been inactivated during the evolution of Mycobacterium tuberculosis. Here we inactivated the oxyR gene in Mycobacterium marinum, an organism used to model M. tuberculosis pathogenesis. Inactivation of oxyR abrogated induction of ahpC, a gene encoding alkylhydroperoxide reductase, normally activated upon peroxide challenge. The absence of oxyR also resulted in increased sensitivity to the front-line antituberculosis drug isoniazid. Inactivation of oxyR in M. marinum did not affect either virulence in a fish infection model or survival in human macrophages. Our findings demonstrate, at the genetic and molecular levels, a direct role for OxyR in ahpC regulation in response to oxidative stress. Our study also indicates that oxyR is not critical for virulence in M. marinum. However, oxyR inactivation confers increased sensitivity to isonicotinic acid hydrazide, suggesting that the natural loss of oxyR in the tubercle bacillus contributes to the unusually high sensitivity of M. tuberculosis to isoniazid. PMID:16547055

  13. Lipoamide channel-binding sulfonamides selectively inhibit mycobacterial lipoamide dehydrogenase†,#

    PubMed Central

    Bryk, Ruslana; Arango, Nancy; Maksymiuk, Christina; Balakrishnan, Anand; Wu, Ying-Ta; Wong, Chi-Huey; Masquelin, Thierry; Hipskind, Philip; Lima, Christopher D.; Nathan, Carl

    2014-01-01

    Tuberculosis remains a global health emergency that calls for treatment regimens directed at new targets. Here we explored lipoamide dehydrogenase, a metabolic and detoxifying enzyme in Mycobacterium tuberculosis whose deletion drastically impairs Mtb's ability to establish infection in the mouse. Upon screening over 1,600,000 compounds, we identified N-methylpyridine 3-sulfonamides as potent and species-selective inhibitors of Mtb Lpd, affording over 1,000-fold selectivity versus the human homolog. The sulfonamides demonstrated low nanomolar affinity and bound at the lipoamide channel in an Lpd-inhibitor co-crystal. Their selectivity could be attributed, at least partially, to hydrogen bonding of the sulfonamide amide oxygen with the species-variant Arg93 in the lipoamide channel. Although potent and selective, the sulfonamides did not enter mycobacteria, as determined by their inability to accumulate in Mtb to effective levels and produce changes in intracellular metabolites. This work demonstrates that high potency and selectivity can be achieved at the lipoamide binding site of Mtb Lpd, a site different from the NAD+/NADH pocket targeted by previously reported species-selective triazaspirodimethoxybenzoyl inhibitors. PMID:24251446

  14. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

    PubMed

    Kwon, Yong-Soo; Koh, Won-Jung

    2016-05-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  15. Large Abdominal Wall Endometrioma Following Laparoscopic Hysterectomy

    PubMed Central

    Borncamp, Erik; Mehaffey, Philip; Rotman, Carlos

    2011-01-01

    Background: Endometriosis is a common condition in women that affects up to 45% of patients in the reproductive age group by causing pelvic pain. It is characterized by the presence of endometrial tissue outside the uterine cavity and is rarely found subcutaneously or in abdominal incisions, causing it to be overlooked in patients with abdominal pain. Methods: A 45-year-old woman presented with lower abdominal pain 2 years following a laparoscopic supracervical hysterectomy. She was found to have incidental cholelithiasis and a large abdominal mass suggestive of a significant ventral hernia on CT scan. Results: Due to the peculiar presentation, surgical intervention took place that revealed a large 9cm×7.6cm×6.2cm abdominal wall endometrioma. Conclusion: Although extrapelvic endometriosis is rare, it should be entertained in the differential diagnosis for the female patient who presents with an abdominal mass and pain and has a previous surgical history. PMID:21902990

  16. Blunt abdominal trauma in children.

    PubMed

    Tepas, J J

    1993-06-01

    The growing popularity of nonoperative treatment of children with splenic injuries has seduced some physicians into a false sense of security regarding care of the injured child. Although it has been established that hemodynamically stable children with splenic, hepatic, and even renal injuries can safely be treated "expectantly," this concept cannot be applied indiscriminately. Accurate diagnosis and effective care of the child with blunt abdominal trauma is an exercise of clinical precision that demands attention to detail and thorough evaluation. This review addresses this process in light of recent advances in diagnostic imaging and in consideration of recent reports analyzing different protocols for therapeutic decision making. PMID:8374651

  17. BIOMECHANICS OF ABDOMINAL AORTIC ANEURYSM

    PubMed Central

    Vorp, David A.

    2009-01-01

    Abdominal aortic aneurysm (AAA) is a condition whereby the terminal aorta permanently dilates to dangerous proportions, risking rupture. The biomechanics of AAA has been studied with great interest since aneurysm rupture is a mechanical failure of the degenerated aortic wall and is a significant cause of death in developed countries. In this review article, the importance of considering the biomechanics of AAA is discussed, and then the history and the state-of-the-art of this field is reviewed - including investigations into the biomechanical behavior of AAA tissues, modeling AAA wall stress and factors which influence it, and the potential clinical utility of these estimates in predicting AAA rupture. PMID:17254589

  18. [Abdominal pain, constipation and anemia].

    PubMed

    Barresi, Fabio; Kunz Caflish, Isabel; Bayly-Schinzel, Leena; Dressel, Holger

    2016-03-30

    We present the case of a 42-year old man who went to the emergency department because of spasmodic abdominal pain. The abdomen was soft. A gastroscopy and a colonoscopy were without pathological findings. The laboratory analyses indicated anemia. The differential blood count showed basophilic granules in the red blood cells. The blood lead level was elevated. A lead poisoning was diagnosed. The cause was the oral intake of an ayurvedic medication which the patient had received in Bangladesh to treat his vitiligo. PMID:27005735

  19. Frequency, causes and pattern of abdominal trauma: A 4-year descriptive analysis

    PubMed Central

    Arumugam, Suresh; Al-Hassani, Ammar; El-Menyar, Ayman; Abdelrahman, Husham; Parchani, Ashok; Peralta, Ruben; Zarour, Ahmad; Al-Thani, Hassan

    2015-01-01

    Background: The incidence of abdominal trauma is still underreported from the Arab Middle-East. We aimed to evaluate the incidence, causes, clinical presentation, and outcome of the abdominal trauma patients in a newly established trauma center. Materials and Methods: A retrospective analysis was conducted at the only level I trauma center in Qatar for the patients admitted with abdominal trauma (2008-2011). Patients demographics, mechanism of injury, pattern of organ injuries, associated extra-abdominal injuries, Injury Severity Score (ISS), Abbreviated Injury Scale, complications, length of Intensive Care Unit, and hospital stay, and mortality were reviewed. Results: A total of 6888 trauma patients were admitted to the hospital, of which 1036 (15%) had abdominal trauma. The mean age was 30.6 ± 13 years and the majority was males (93%). Road traffic accidents (61%) were the most frequent mechanism of injury followed by fall from height (25%) and fall of heavy object (7%). The mean ISS was 17.9 ± 10. Liver (36%), spleen (32%) and kidney (18%) were most common injured organs. The common associated extra-abdominal injuries included chest (35%), musculoskeletal (32%), and head injury (24%). Wound infection (3.8%), pneumonia (3%), and urinary tract infection (1.4%) were the frequently observed complications. The overall mortality was 8.3% and late mortality was observed in 2.3% cases mainly due to severe head injury and sepsis. The predictors of mortality were head injury, ISS, need for blood transfusion, and serum lactate. Conclusion: Abdominal trauma is a frequent diagnosis in multiple trauma and the presence of extra-abdominal injuries and sepsis has a significant impact on the outcome. PMID:26604524

  20. [Improvement of routine works and quality control in mycobacterial laboratory].

    PubMed

    Suzuki, Katsuhiro; Higuchi, Takeshi

    2007-03-01

    Many new methods have been introduced into routine laboratory works in microbiology since 1990. Molecular biology, in particular, opened a new era and promoted a technician's skill much. PCR and hybridization technique have been ordinary one in many laboratories. Since old techniques such as smear and culture are still needed, amount of routine works is increasing gradually. Thus, improving efficiency and keeping quality of routine works are becoming more and more important issues. This symposium focused on such points, and four skilled technicians around Japan presented their own tips. 1. Coexistence of M. tuberculosis and M. avium complex (MAC) in the MGIT culture system: Yasushi WATANABE (Clinical Laboratory Division, NHO Nishi-Niigata Chuo National Hospital). Sputum samples of some tuberculosis patients yielded only MAC in the MGIT culture system. Such co-infected cases presented problems to mislead proper treatment and infection control. The detection rate of MAC was significantly high, and the growth speed of MAC was significantly rapid in the MGIT culture system, compared to those of M. tuberculosis. Additionally, M. tuberculosis was not detected with even more quantity than MAC in the small amount of mixed samples. Higher sensitivity and growth speed of MAC are the important characteristics of the MGIT system. 2. Internal quality control with ordinary examination results: Akio AONO (Department of Clinical Examination, Double-Barred Cross Hospital, Japan Anti-Tuberculosis Association). Our laboratory utilizes ordinary examination results as the internal quality control for specimen pretreatment, culture, and drug susceptibility testing. The contamination rate of MGIT culture system is useful for the evaluation of the decontamination process. It was 6.3% on average in our laboratory in 2005. The number of drug resistant strains is also useful to assess the performance of drug susceptibility testing. The incidence of each anti-tuberculosis drug resistance

  1. Domain requirements for DNA unwinding by mycobacterial UvrD2, an essential DNA helicase.

    PubMed

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

    2008-09-01

    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

  2. Characterization and comparison of mycobacterial antigens by two-dimensional immunoelectrophoresis.

    PubMed

    Roberts, D B; Wright, G L; Affronti, L F; Reich, M

    1972-10-01

    Two-dimensional immunoelectrophoresis (2D-IEP), in which a complex of antigens is subjected to electrophoresis first through an agarose matrix in one direction and secondly through an antiserum-agarose matrix at right angles to the first direction, was evaluated as a tool for analysis of mycobacterial antigens. Cell extracts from four species of mycobacteria, Mycobacterium tuberculosis (four strains), M. bovis strain BCG, M. scrofulaceum, and M. phlei, were assayed by 2D-IEP with four anti-mycobacterial antisera. Besides displaying the precipitin curves in a more easily interpreted format than did conventional immunoelectrophoresis (IEP), 2D-IEP offered greater sensitivity in terms of numbers of precipitin curves when like reactions were compared with IEP patterns. As many as 60 immunoprecipitates were observed on 2D-IEP slides compared to 18 on comparable IEP plates. Technical reproducibility of patterns from run to run was excellent. Other parameters, such as the influence of using different batches of antigen on the pattern, are discussed. Each of the cell extract antigens gave a unique pattern of precipitin peaks which could be easily differentiated from the patterns given by the other mycobacterial cell extracts when reacted with any of the antisera in 2D-IEP. Since both the species and strains of mycobacteria could be easily and reproducibly differentiated solely on the basis of two-dimensional immunoelectrophoretic patterns obtained with any of the antisera employed in this study, it may be possible, by using IEP, to differentiate and identify all species and strains of mycobacteria with one standard, highly sensitive antiserum, rather than a battery of antisera. PMID:4628899

  3. Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG.

    PubMed

    Zahrt, T C; Song, J; Siple, J; Deretic, V

    2001-03-01

    In several bacteria, the catalase-peroxidase gene katG is under positive control by oxyR, a transcriptional regulator of the peroxide stress response. The Mycobacterium tuberculosis genome also contains sequences corresponding to oxyR, but this gene has been inactivated in the tubercle bacillus because of the presence of multiple mutations and deletions. Thus, M. tuberculosis katG and possibly other parts of the oxidative stress response in this organism are either not regulated or are controlled by a factor different from OxyR. The mycobacterial FurA is a homologue of the ferric uptake regulator Fur and is encoded by a gene located immediately upstream of katG. Here, we examine the possibility that FurA regulates katG expression. Inactivation of furA on the Mycobacterium smegmatis chromosome, a mycobacterial species that also lacks an oxyR homologue, resulted in derepression of katG, concomitant with increased resistance of the furA mutant to H2O2. In addition, M. smegmatis furA::Km(r) was more sensitive to the front-line antituberculosis agent isonicotinic acid hydrazide (INH) compared with the parental furA+ strain. The phenotypic manifestations were specific, as the mutant strain did not show altered sensitivity to organic peroxides, and both H2O2 and INH susceptibility profiles were complemented by the wild-type furA+ gene. We conclude that FurA is a second regulator of oxidative stress response in mycobacteria and that it negatively controls katG. In species lacking a functional oxyR, such as M. tuberculosis and M. smegmatis, FurA appears to be a dominant regulator affecting mycobacterial physiology and intracellular survival. PMID:11251835

  4. Abdominal wall reconstruction with implantable meshes.

    PubMed

    Masden, Derek; Felder, John M; Iorio, Matthew L; Bhanot, Parag; Attinger, Christopher E

    2011-01-01

    Abdominal wall defects present a difficult problem for the reconstructive surgeon. Over the years, numerous implantable materials have becomes available to aid the surgeon in recreating the abdominal wall. This spectrum of implants includes permanent synthetic meshes, absorbable meshes, composite meshes and biomaterials. This review includes the pros and cons for the commercially available abdominal wall implants as well as a review of the literature regarding outcomes for each material. This review will provide the surgeon with current evidence-based information on implantable abdominal materials to be able to make a more informed decision about which implant to use. PMID:21663579

  5. Mycobacterial Pan-Genome Analysis Suggests Important Role of Plasmids in the Radiation of Type VII Secretion Systems

    PubMed Central

    Dumas, Emilie; Christina Boritsch, Eva; Vandenbogaert, Mathias; Rodríguez de la Vega, Ricardo C.; Thiberge, Jean-Michel; Caro, Valerie; Gaillard, Jean-Louis; Heym, Beate; Girard-Misguich, Fabienne; Brosch, Roland; Sapriel, Guillaume

    2016-01-01

    In mycobacteria, various type VII secretion systems corresponding to different ESX (ESAT-6 secretory) types, are contributing to pathogenicity, iron acquisition, and/or conjugation. In addition to the known chromosomal ESX loci, the existence of plasmid-encoded ESX systems was recently reported. To investigate the potential role of ESX-encoding plasmids on mycobacterial evolution, we analyzed a large representative collection of mycobacterial genomes, including both chromosomal and plasmid-borne sequences. Data obtained for chromosomal ESX loci confirmed the previous five classical ESX types and identified a novel mycobacterial ESX-4-like type, termed ESX-4-bis. Moreover, analysis of the plasmid-encoded ESX loci showed extensive diversification, with at least seven new ESX profiles, identified. Three of them (ESX-P clusters 1–3) were found in multiple plasmids, while four corresponded to singletons. Our phylogenetic and gene-order-analyses revealed two main groups of ESX types: 1) ancestral types, including ESX-4 and ESX-4-like systems from mycobacterial and non-mycobacterial actinobacteria and 2) mycobacteria-specific ESX systems, including ESX-1-2-3-5 systems and the plasmid-encoded ESX types. Synteny analysis revealed that ESX-P systems are part of phylogenetic groups that derived from a common ancestor, which diversified and resulted in the different ESX types through extensive gene rearrangements. A converging body of evidence, derived from composition bias-, phylogenetic-, and synteny analyses points to a scenario in which ESX-encoding plasmids have been a major driving force for acquisition and diversification of type VII systems in mycobacteria, which likely played (and possibly still play) important roles in the adaptation to new environments and hosts during evolution of mycobacterial pathogenesis. PMID:26748339

  6. Mycobacterial Pan-Genome Analysis Suggests Important Role of Plasmids in the Radiation of Type VII Secretion Systems.

    PubMed

    Dumas, Emilie; Christina Boritsch, Eva; Vandenbogaert, Mathias; Rodríguez de la Vega, Ricardo C; Thiberge, Jean-Michel; Caro, Valerie; Gaillard, Jean-Louis; Heym, Beate; Girard-Misguich, Fabienne; Brosch, Roland; Sapriel, Guillaume

    2016-02-01

    In mycobacteria, various type VII secretion systems corresponding to different ESX (ESAT-6 secretory) types, are contributing to pathogenicity, iron acquisition, and/or conjugation. In addition to the known chromosomal ESX loci, the existence of plasmid-encoded ESX systems was recently reported. To investigate the potential role of ESX-encoding plasmids on mycobacterial evolution, we analyzed a large representative collection of mycobacterial genomes, including both chromosomal and plasmid-borne sequences. Data obtained for chromosomal ESX loci confirmed the previous five classical ESX types and identified a novel mycobacterial ESX-4-like type, termed ESX-4-bis. Moreover, analysis of the plasmid-encoded ESX loci showed extensive diversification, with at least seven new ESX profiles, identified. Three of them (ESX-P clusters 1-3) were found in multiple plasmids, while four corresponded to singletons. Our phylogenetic and gene-order-analyses revealed two main groups of ESX types: 1) ancestral types, including ESX-4 and ESX-4-like systems from mycobacterial and non-mycobacterial actinobacteria and 2) mycobacteria-specific ESX systems, including ESX-1-2-3-5 systems and the plasmid-encoded ESX types. Synteny analysis revealed that ESX-P systems are part of phylogenetic groups that derived from a common ancestor, which diversified and resulted in the different ESX types through extensive gene rearrangements. A converging body of evidence, derived from composition bias-, phylogenetic-, and synteny analyses points to a scenario in which ESX-encoding plasmids have been a major driving force for acquisition and diversification of type VII systems in mycobacteria, which likely played (and possibly still play) important roles in the adaptation to new environments and hosts during evolution of mycobacterial pathogenesis. PMID:26748339

  7. Rapid synthesis of linear homologous oligoarabinofuranosides related to mycobacterial lipoarabinomannan and a neoglycoconjugate thereof.

    PubMed

    Podvalnyy, Nikita M; Chizhov, Alexander O; Zinin, Alexander I; Kononov, Leonid O

    2016-08-01

    Rapid and simple synthesis of oligosaccharides related to one of the terminal motifs of mycobacterial lipoarabinomannan is described. An array of homologous linear α(1 → 5)-linked oligoarabinofuranosides with 4-(2-chloroethoxy)phenyl aglycon and selectively unprotected 5-OH group at the non-reducing end was obtained by oligomerization of 3-O-benzoyl β-D-arabinofuranose 1,2,5-orthobenzoate. Subsequent introduction of β(1 → 2)-linked arabinofuranose disaccharide moiety by step-wise glycosylation furnished the target oligosaccharides which were conjugated with bovine serum albumin. PMID:27267065

  8. Giant horseshoe intra-abdominal abscess.

    PubMed Central

    Altemeier, W A; Culbertson, W R; Fidler, J P

    1975-01-01

    A study of 12 patients with giant horseshoe abscess of the abdominal and pelvic cavities seen at the Surgical Services of the University of Cincinnati Medical Center has emphasized the complexity and bizarre nature of these lesions. These infections represented a huge abscess or series of communicating abscesses extending from one subphrenic space along the corresponding paracolic gutter into the pelvis, up and along the opposite paracolic space, and into the other subphrenic space. Since these lesions occurred infrequently, they were often not recognized until they had become far advanced and had produced profound effects on the patients. The diagnosis was difficult and obscured by various factors including the postoperative state after laparotomy for complex diseases or serious injuries of the biliary tract, the genitourinary tract, or the alimentary tract. An important etiologic component of the formation of these giant abscesses was the continuing escape and collection of large volumes of fluid resulting from lesions of the biliary tract, postoperative hemorrhage, or an unrecognized large perforated peptic ulcer. Nine patients were treated successfully and 3 died. The many diagnostic and therapeutic problems presented by the patients with this interesting and complex lesion have emphasized the importance of earlier and more accurate diagnosis, early and adequate surgical drainage, intelligently applied antibiotic therapy and appropriate supportive treatment. Failure to recognize and drain effectively each of the component sections of this lesion led to continuing sepsis with prolonged morbidity, progressive debility, and death. Images Fig. 1. Fig. 2. PMID:1079447

  9. Bilateral endogenous endophthalmitis in disseminated NTM infection: a case report.

    PubMed

    Sinawat, Supat; Yospaiboon, Yosanan; Sinawat, Suthasinee

    2011-05-01

    A 47-year-old Thai female with underlying Sweet's syndrome and disseminated non-tuberculous mycobacterial infection presented with a history of blurred vision on both eyes after being lost to follow-up for eight months. The visual acuity was hand motion on the right eye and counting finger on the left eye. There was moderate inflammation in the anterior chamber and vitreous cavity. Multiple foci of round chorioretinitis were found throughout the fundus on both eyes. The patient denied intravitreous tapping and antibiotic injection. Nevertheless, specimens from several sites were collected for culture and sensitivity test. The result of the culture and sensitivity test revealed rapidly growing mycobacteria on specimens taken from the right inguinal lymph node. The presented case may demonstrate the rare event of bilateral endogenous endophthalmitis with chorioretinitis arising from non-tuberculous mycobacterial infection. The pattern of chorioretinitis demonstrated by the presented report may provide useful clinical information for this rare condition. PMID:21675456

  10. Necrotizing Fasciitis of the Abdominal Wall Caused by Serratia Marcescens.

    PubMed

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

    2015-04-15

    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

  11. Septic arthritis of the pubic symphysis: an atypical abdominal pain.

    PubMed

    Ghislain, L; Heylen, A; Alexis, F; Tintillier, M

    2015-02-01

    Septic arthritis of the pubic symphysis is a rare infection mostly caused by Staphylococcus aureus, and is traditionally associated with risk factors (sports, female incontinence surgery). Typical features of pubic symphysis infection include abdominal, pelvic, or groin pain that increases upon standing and walking, causing limping to occur. Acute onset of fever is often associated. It is important to distinguish septic arthritis of the pubic symphysis from its aseptic homologue, improperly called 'osteitis pubis' in English literature. This general term is mostly used to designate a mechanical pubic pain and has several aetiological meanings (joint stress, postoperative pain, rheumatic diseases). However, some authors consider the infection of the pubic symphysis as a variant of osteitis pubis, placing the two diseases in the continuum of the same entity. This confusion in pubic pathology related to its rarity and its atypical presentation, may in some cases lead to diagnostic and therapeutic delay. In this article, we would like to make practitioners aware of this uncommon and often ignored anatomical site, so that it can recover its place in the differential diagnosis of abdominal pain. PMID:25227947

  12. The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding

    PubMed Central

    Sharma, Garima; Upadhyay, Sandeep; Srilalitha, M.; Nandicoori, Vinay K.; Khosla, Sanjeev

    2015-01-01

    To effectively modulate the gene expression within an infected mammalian cell, the pathogen Mycobacterium tuberculosis would need to bring about epigenetic modifications at appropriate genomic loci. Working on this hypothesis, we show in this study that the mycobacterial protein Rv2966c is a 5-methylcytosine-specific DNA methyltransferase that is secreted out from the mycobacterium and gets localized to the nucleus in addition to the cytoplasm inside the host cell. Importantly, Rv2966c binds to specific DNA sequences, methylates cytosines predominantly in a non-CpG context and its methylation activity is positively influenced by phosphorylation. Interestingly, like the mammalian DNA methyltransferase, DNMT3L, Rv2966c can also interact with histone proteins. Ours is the first study that identifies a protein from a pathogenic bacteria with potential to influence host DNA methylation in a non-canonical manner providing the pathogen with a novel mechanism to alter the host epigenetic machinery. This contention is supported by repression of host genes upon M. tuberculosis infection correlated with Rv2966c binding and non-CpG methylation. PMID:25824946

  13. A user's guide to intra-abdominal pressure measurement.

    PubMed

    Sugrue, Michael; De Waele, Jan J; De Keulenaer, Bart L; Roberts, Derek J; Malbrain, Manu L N G

    2015-01-01

    The intra-abdominal pressure (IAP) measurement is a key to diagnosing and managing critically ill medical and surgical patients. There are an increasing number of techniques that allow us to measure the IAP at the bedside. This paper reviews these techniques. IAP should be measured at end-expiration, with the patient in the supine position and ensuring that there is no abdominal muscle activity. The intravesicular IAP measurement is convenient and considered the gold standard. The level where the mid-axillary line crosses the iliac crest is the recommended zero reference for the transvesicular IAP measurement; moreover, marking this level on the patient increases reproducibility. Protocols for IAP measurement should be developed for each ICU based on the locally available tools and equipment. IAP measurement techniques are safe, reproducible and accurate and do not increase the risk of urinary tract infection. Continuous IAP measurement may offer benefits in specific situations in the future. In conclusion, the IAP measurement is a reliable and essential adjunct to the management of patients at risk of intra-abdominal hypertension. PMID:25973661

  14. Outcome of abdominal wall hernia repair with Permacol™ biologic mesh.

    PubMed

    Cheng, Amy W; Abbas, Maher A; Tejirian, Talar

    2013-10-01

    The use of biologic mesh in abdominal wall operations has gained popularity despite a paucity of outcome data. We aimed to review the experience of a large healthcare organization with Permacol™. A retrospective study was conducted of patients who underwent abdominal hernia repair with Permacol™ in 14 Southern California hospitals. One hundred ninety-five patients were analyzed over a 4-year period. Operations included ventral/incisional hernia repairs, ostomy closures, parastomal hernia repairs, and inguinal hernia repairs. In 50 per cent of the patients, Permacol™ was used to reinforce a primary fascial repair and in 50 per cent as a fascial bridge. The overall complication rate was 39.5 per cent. The complication rate was higher in patients with infected versus clean wounds, body mass index (BMI) 40 kg/m(2) or greater versus BMI less than 40 kg/m(2), in patients with prior mesh repair, and when mesh was used as a fascial bridge. With a mean follow-up of 2.1 years, morbid obesity was associated with a higher recurrence. To date this is the largest study on the use of Permacol™ in abdominal wall hernia repair. In our patient population undergoing heterogeneous operations with a majority of wounds as Class II or higher, use of Permacol™ did not eliminate wound morbidity or prevent recurrence, especially in morbidly obese patients. PMID:24160785

  15. A Redox Regulatory System Critical for Mycobacterial Survival in Macrophages and Biofilm Development

    PubMed Central

    Wolff, Kerstin A.; de la Peña, Andres H.; Nguyen, Hoa T.; Pham, Thanh H.; Amzel, L. Mario; Gabelli, Sandra B.; Nguyen, Liem

    2015-01-01

    Survival of M. tuberculosis in host macrophages requires the eukaryotic-type protein kinase G, PknG, but the underlying mechanism has remained unknown. Here, we show that PknG is an integral component of a novel redox homeostatic system, RHOCS, which includes the ribosomal protein L13 and RenU, a Nudix hydrolase encoded by a gene adjacent to pknG. Studies in M. smegmatis showed that PknG expression is uniquely induced by NADH, which plays a key role in metabolism and redox homeostasis. In vitro, RenU hydrolyses FAD, ADP-ribose and NADH, but not NAD+. Absence of RHOCS activities in vivo causes NADH and FAD accumulation, and increased susceptibility to oxidative stress. We show that PknG phosphorylates L13 and promotes its cytoplasmic association with RenU, and the phosphorylated L13 accelerates the RenU-catalyzed NADH hydrolysis. Importantly, interruption of RHOCS leads to impaired mycobacterial biofilms and reduced survival of M. tuberculosis in macrophages. Thus, RHOCS represents a checkpoint in the developmental program required for mycobacterial growth in these environments. PMID:25884716

  16. 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. PMID:18261937

  17. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle

    PubMed Central

    Ishikawa, Eri; Ishikawa, Tetsuaki; Morita, Yasu S.; Toyonaga, Kenji; Yamada, Hisakata; Takeuchi, Osamu; Kinoshita, Taroh; Akira, Shizuo; Yoshikai, Yasunobu

    2009-01-01

    Tuberculosis remains a fatal disease caused by Mycobacterium tuberculosis, which contains various unique components that affect the host immune system. Trehalose-6,6′-dimycolate (TDM; also called cord factor) is a mycobacterial cell wall glycolipid that is the most studied immunostimulatory component of M. tuberculosis. Despite five decades of research on TDM, its host receptor has not been clearly identified. Here, we demonstrate that macrophage inducible C-type lectin (Mincle) is an essential receptor for TDM. Heat-killed mycobacteria activated Mincle-expressing cells, but the activity was lost upon delipidation of the bacteria; analysis of the lipid extracts identified TDM as a Mincle ligand. TDM activated macrophages to produce inflammatory cytokines and nitric oxide, which are completely suppressed in Mincle-deficient macrophages. In vivo TDM administration induced a robust elevation of inflammatory cytokines in sera and characteristic lung inflammation, such as granuloma formation. However, no TDM-induced lung granuloma was formed in Mincle-deficient mice. Whole mycobacteria were able to activate macrophages even in MyD88-deficient background, but the activation was significantly diminished in Mincle/MyD88 double-deficient macrophages. These results demonstrate that Mincle is an essential receptor for the mycobacterial glycolipid, TDM. PMID:20008526

  18. Crystal structures of Mycobacterial MeaB and MMAA-like GTPases.

    PubMed

    Edwards, Thomas E; Baugh, Loren; Bullen, Jameson; Baydo, Ruth O; Witte, Pam; Thompkins, Kaitlin; Phan, Isabelle Q H; Abendroth, Jan; Clifton, Matthew C; Sankaran, Banumathi; Van Voorhis, Wesley C; Myler, Peter J; Staker, Bart L; Grundner, Christoph; Lorimer, Donald D

    2015-06-01

    The methylmalonyl Co-A mutase-associated GTPase M