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[PMID]: 26286334
[Au] Autor:Lee YC; Kim SB; Gang SJ; Park SY; Kim SR
[Ad] Address:Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea. leeyc@jbnu.ac.kr....
[Ti] Title:Acute necrotizing pneumonia combined with parapneumonic effusion caused by Mycobacterium lentiflavum: a case report.
[So] Source:BMC Infect Dis;15(1):354, 2015.
[Is] ISSN:1471-2334
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Mycobacterium lentiflavum (M. lentiflavum), a slow growing nontuberculous mycobacterium (NTM), has recently been described as an emerging human pathogen regardless of the immune status of the host. Previous reports have demonstrated that cervical lymphadenitis of children is the most frequent pathology of M. lentiflavum. However, there are little reports regarding pulmonary diseases by M. lentiflavum specifically in immunocompetent patients. CASE PRESENTATION: A 60-year-old man having prolonged productive cough and dyspnea with fever was initially diagnosed as pneumonia with parapneumonic effusion. Imaging studies showed that the radiologic abnormality was acute bronchopneumonic infiltration with abscess formation in the left lower lobe and parapneumonic pleural effusion. M. lentiflavum was identified in the cultured pleural tissues. On the basis of these findings, he was diagnosed as pulmonary infection and pleurisy caused by M. lentiflavum, which was treated with a combination of antibiotics covering NTM. His clinical manifestations were dramatically improved by the treatment targeting NTM, while those were refractory to empirical antibiotic therapy. CONCLUSION: In this report, we introduce the isolation of M. lentiflavum from pleural tissues associated with acute necrotizing pneumonia combined with parapneumonic effusion in an immunocompetent host, suggesting that the M. lentiflavum can be a human pathogen invovled in pulmonary infectious diseases and pleurisy with poor response to empirical antibiotic treatment.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150822
[Lr] Last revision date:150822
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s12879-015-1100-z

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[PMID]: 26250569
[Au] Autor:Kodali A; Khalighi K
[Ad] Address:Department of Internal Medicine, Easton Hospital, Easton, PA, USA.
[Ti] Title:A Case of Late Implantable Cardiac Device Infection with Aspergillus in an Immunocompetent Host.
[So] Source:Am J Case Rep;16:520-3, 2015.
[Is] ISSN:1941-5923
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND With the increasing use of cardiac implantable electronic devices (CIED), there has been an associated increase in rate of complications. Infection accounts for about 1% of these, of which only a handful were reported secondary to Aspergillus fumigatus. All of these were seen in chronically-ill patients with several co-morbid conditions within a few years of implantation. None have been reported in an otherwise immunocompetent patient at 7 years after CIED implantation. CASE REPORT A 67-year-old woman with symptomatic sick sinus syndrome required a pacemaker 15 years ago with subsequent revision 7 years prior due to battery depletion. She now presented with a left pectoral non-tender mass that developed over several weeks. She denied history of recent fever, trauma, or infection. An elective pacemaker revision and pocket exploration led to the drainage of 150 cc of serosanguineous discharge from the pocket. She received peri-procedural prophylaxis with Vancomycin, but later, wound cultures grew Aspergillus fumigatus. She underwent complete removal of the pacemaker system along with a 6-week course of voriconazole and is doing well. CONCLUSIONS Even though Staphylococcus aureus causes most CIED infections, there should be a suspicion for fungal organisms, especially in culture-negative infections, in immunocompromised states like diabetes mellitus or with minimal improvement on antibiotics. If not treated appropriately, aspergillosis may have catastrophic outcomes, including endocarditis, often leading to death. Appropriate treatment should include immediate initiation of antifungals and removal of the CIED. It is still unclear why an immunocompetent patient developed aspergillosis, but appropriate management helped avoid a grave outcome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Cu] Class update date: 150822
[Lr] Last revision date:150822
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.12659/AJCR.893413

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[PMID]: 25148516
[Au] Autor:Cross RM; Flanigan DL; Monastyrskyi A; LaCrue AN; Sáenz FE; Maignan JR; Mutka TS; White KL; Shackleford DM; Bathurst I; Fronczek FR; Wojtas L; Guida WC; Charman SA; Burrows JN; Kyle DE; Manetsch R
[Ad] Address:Department of Chemistry, University of South Florida , CHE 205, 4202 East Fowler Avenue, Tampa, Florida 33620, United States.
[Ti] Title:Orally bioavailable 6-chloro-7-methoxy-4(1H)-quinolones efficacious against multiple stages of Plasmodium.
[So] Source:J Med Chem;57(21):8860-79, 2014 Nov 13.
[Is] ISSN:1520-4804
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.
[Mh] MeSH terms primary: Antimalarials/chemical synthesis
Plasmodium/drug effects
Quinolones/chemical synthesis
[Mh] MeSH terms secundary: Animals
Antimalarials/chemistry
Antimalarials/pharmacology
Humans
Inhibitory Concentration 50
Malaria/drug therapy
Mice
Microsomes, Liver/metabolism
Parasitemia/drug therapy
Plasmodium berghei
Quinolones/chemistry
Quinolones/pharmacology
Structure-Activity Relationship
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antimalarials); 0 (Quinolones)
[Em] Entry month:1503
[Cu] Class update date: 150822
[Lr] Last revision date:150822
[Js] Journal subset:IM
[Da] Date of entry for processing:141113
[St] Status:MEDLINE
[do] DOI:10.1021/jm500942v

  4 / 247955 MEDLINE  
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[PMID]: 25006247
[Au] Autor:Vajjhala PR; Kaiser S; Smith SJ; Ong QR; Soh SL; Stacey KJ; Hill JM
[Ad] Address:From the School of Chemistry and Molecular Biosciences and p.vajjhala@uq.edu.au....
[Ti] Title:Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly.
[So] Source:J Biol Chem;289(34):23504-19, 2014 Aug 22.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Inflammasomes are macromolecular complexes that mediate inflammatory and cell death responses to pathogens and cellular stress signals. Dysregulated inflammasome activation is associated with autoinflammatory syndromes and several common diseases. During inflammasome assembly, oligomerized cytosolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC. Inflammasome assembly is mediated by pyrin domains (PYDs) and caspase recruitment domains, which are protein interaction domains of the death fold superfamily. However, the molecular details of their interactions are poorly understood. We have studied the interaction between ASC and pyrin PYDs that mediates ASC recruitment to the pyrin inflammasome, which is implicated in the pathogenesis of familial Mediterranean fever. We demonstrate that both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD. Molecular docking of pyrin-ASC PYD complexes showed that pyrin PYD can simultaneously interact with up to three ASC PYDs. Furthermore, ASC PYD can self-associate and interact with pyrin, consistent with previous reports that pyrin promotes ASC clustering to form a proinflammatory complex. Finally, the effects of familial Mediterranean fever-associated mutations, R42W and A89T, on structural and functional properties of pyrin PYD were investigated. The R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC, it also bound less to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active. Our data give new insights into the binding modes of PYDs and inflammasome architecture.
[Mh] MeSH terms primary: Cytoskeletal Proteins/metabolism
Inflammasomes/metabolism
[Mh] MeSH terms secundary: Amino Acid Sequence
Binding Sites
Cytoskeletal Proteins/genetics
Humans
Models, Molecular
Molecular Sequence Data
Mutagenesis
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Sequence Homology, Amino Acid
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Cytoskeletal Proteins); 0 (Inflammasomes); 0 (PYCARD protein, human); 0 (marenostrin)
[Em] Entry month:1412
[Cu] Class update date: 150822
[Lr] Last revision date:150822
[Js] Journal subset:IM
[Da] Date of entry for processing:140823
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M114.553305

  5 / 247955 MEDLINE  
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[PMID]: 25930117
[Au] Autor:Mattos DA; Silva MV; Gaspar LP; Castilho LR
[Ad] Address:Bio-Manguinhos-FIOCRUZ, Technological Development Vice-directory, Rio de Janeiro, RJ, Brazil....
[Ti] Title:Increasing Vero viable cell densities for yellow fever virus production in stirred-tank bioreactors using serum-free medium.
[So] Source:Vaccine;33(35):4288-91, 2015 Aug 20.
[Is] ISSN:1873-2518
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:In this work, changes in Vero cell cultivation methods have been employed in order to improve cell growth conditions to obtain higher viable cell densities and to increase viral titers. The propagation of the 17DD yellow fever virus (YFV) in Vero cells grown on Cytodex I microcarriers was evaluated in 3-L bioreactor vessels. Prior to the current changes, Vero cells were repeatedly displaying insufficient microcarrier colonization. A modified cultivation process with four changes has resulted in higher cell densities and higher virus titers than previously observed for 17DD YFV.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 25862300
[Au] Autor:Pereira RC; Silva AN; Souza MC; Silva MV; Neves PP; Silva AA; Matos DD; Herrera MA; Yamamura AM; Freire MS; Gaspar LP; Caride E
[Ad] Address:Oswaldo Cruz Foundation (FIOCRUZ), Bio-Manguinhos, Avenida Brasil 4365, 21045-900, Rio de Janeiro, RJ, Brazil....
[Ti] Title:An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.
[So] Source:Vaccine;33(35):4261-8, 2015 Aug 20.
[Is] ISSN:1873-2518
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with ß-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2µg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 247955 MEDLINE  
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[PMID]: 25982135
[Au] Autor:Fadoo Z; Nisar I; Yousuf F; Lakhani LS; Ashraf S; Imam U; Zaheer J; Naqvi A; Belgaumi A
[Ad] Address:Department of Pediatrics and Child Health and Department of Oncology, Aga Khan University, Karachi, Pakistan....
[Ti] Title:Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan.
[So] Source:Pediatr Blood Cancer;62(10):1700-8, 2015 Oct.
[Is] ISSN:1545-5017
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood. Some evidence suggests differences in clinical and cytogenetic characteristics of ALL based on geographic and ethnic variations. However, data on ALL characteristics and early outcome of therapy from low/middle-income countries such as Pakistan are scanty. PROCEDURE: A prospective, multi-institutional cohort study in Karachi enrolled 646 newly diagnosed children with ALL over 3 years. Standard forms were used to collect demographic, clinical, and laboratory data at presentation and at the end of induction. RESULTS: Of the total, 66.1% (n = 427) were males. Median age was 6 (mean ± SE 6.87 ± 0.16; range 0.16-18) years. The most common clinical presentation was fever (88.7%). BPC-ALL was diagnosed in 78.5%, while 17.5% had T-ALL; 28.8% had a WBC >50 × 10(9) /L. With 316 patients karyotyped, hypodiploidy and hyperdiploidy were seen in 5.1% and 10.7%, respectively. Of those tested, ETV6-RUNX1 translocation was detected in 13.2%, while BCR-ABL1 translocation and MLL gene rearrangements were seen in 7.3% and 4.6%, respectively. The cumulative loss to follow up before and during induction was 12.8% (n = 83) and 11.5% (n = 74) died before or during this phase. Induction was successfully completed by only 75.6% (n = 489) of the entire cohort and 69.6% (n = 450) achieved remission. CONCLUSION: These patients had ALL with higher risk features than that reported from developed countries. One quarter failed to complete induction chemotherapy. This suboptimal result requires further study and development of innovative interventions, particularly focusing on the causes and solutions for late referral, abandonment, and infections. Pediatr Blood Cancer 2015;62:1700-1708. © 2015 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/pbc.25583

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[PMID]: 25929242
[Au] Autor:Rao AD; Sugar EA; Barrett N; Mahesh M; Arceci RJ
[Ad] Address:Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland....
[Ti] Title:The utility of computed tomography in the management of fever and neutropenia in pediatric oncology.
[So] Source:Pediatr Blood Cancer;62(10):1761-7, 2015 Oct.
[Is] ISSN:1545-5017
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Despite the frequent use and radiation exposure of computed tomography (CT) scans, there is little information on patterns of CT use and their utility in the management of pediatric patients with fever and neutropenia (FN). We examined the contribution of either the commonly employed pan-CT (multiple anatomical locations) or targeted CT (single location) scanning to identify possible infectious etiologies in this challenging clinical scenario. Procedure Pediatric patients with an underlying malignancy admitted for fever (temperature ≥38.3°C) and an absolute neutrophil count <500 cells/µL from 2003-2009 were included. Risk factors associated with utilization, results, and effects on clinical management of CT scans were identified. Results Charts for 635 admissions for FN from 263 patients were reviewed. Overall, 139 (22%) admissions (93 individuals) had at least one scan. Of 188 scans, 103 (55%) were pan-scans. Changes in management were most strongly associated with the identification of evidence consistent with infection (OR = 12.64, 95% CI: 5.05-31.60, P < 0.001). Seventy-eight (41%) of all CT scans led to a change in clinical management, most commonly relating to use of antibiotic (N = 41, 53%) or antifungal/antiviral medications (N = 33, 42%). The odds of a change in clinical management did not differ for those receiving a pan-scan compared to those receiving a targeted scan (OR = 1.23; 95% CI, 0.61-2.46; P = 0.57). Conclusions When CT is clinically indicated, it is important for clinicians to strongly consider utilizing a targeted scan to reduce radiation exposure to patients as well as to decrease costs without compromising care. Pediatr Blood Cancer 2015;62:1761-1767. © 2015 Wiley Periodicals, Inc.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/pbc.25561

  9 / 247955 MEDLINE  
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[PMID]: 26035278
[Au] Autor:Varughese S; Read JG; Al-Khal A; Salah SA; El Deeb Y; Cameron PA
[Ad] Address:aEmergency Medicine bHealth Services Research cInfectious Diseases, Hamad Medical Corporation, Doha, Qatar dDepartment of Sociology and Global Health, Duke University, Durham, North Carolina, USA eDepartment of Emergency Medicine, Monash University, Melbourne, Victoria, Australia.
[Ti] Title:Effectiveness of the Middle East respiratory syndrome-coronavirus protocol in enhancing the function of an Emergency Department in Qatar.
[So] Source:Eur J Emerg Med;22(5):316-20, 2015 Oct.
[Is] ISSN:1473-5695
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: This study aimed to investigate the effectiveness of a Middle East respiratory syndrome coronavirs (MERS-CoV) surveillance protocol in the Emergency Department (ED) at Hamad General Hospital. Effectiveness was measured by: (a) reduction in the number of patients admitted into the MERS-CoV tracking system; (b) identification of positive MERS-CoV cases; (c) containment of cross infectivity; and (d) increased efficiency in ED functioning. METHODS: A retrospective chart review was carried out of all ED patients suspected of MERS-CoV during the height of the epidemic (August to October 2013). An algorithm was created on the basis of international guidelines to screen and triage suspected MERS-CoV patients. Once identified, patients were isolated, had a chest roentgenogram [chest radiography (CXR)] taken, and a nasopharyngeal swab for polymerase chain reaction (PCR) was sent with sputum samples for testing. Patients with normal CXR and mild respiratory symptoms were discharged with home isolation instructions until nasopharyngeal and sputum PCR results were available. Patients with fever and acute respiratory distress, with or without abnormal CXR, were treated in the hospital until tests proved negative for MERS-CoV. RESULTS: The protocol successfully reduced the number of patients who needed to be tested for MERS-CoV from 12 563 to 514, identified seven positive cases, and did not lead to apparent cross infectivity that resulted in serious illness or death. The protocol also increased the efficiency of ED and cut the turnaround time for nasopharyngeal swab and sputum results from 3 days to 1 day. CONCLUSION: A highly protocolized surveillance system limited the impact of MERS-CoV on ED functioning by identifying and prioritizing high-risk patients. The emergence of new infectious diseases requires constant monitoring of interventions to reduce the impact of epidemics on population health and health services.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/MEJ.0000000000000285

  10 / 247955 MEDLINE  
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[PMID]: 26166312
[Au] Autor:Veeraputhiran M; Jain T; Deol A; Ayash L; Kim S; Dyson G; Bhutani D; Lum LG; Ratanatharathorn V; Uberti JP; Abidi MH
[Ad] Address:Department of Oncology, Wayne State University, Detroit, MI. Electronic address: mkumaran.2006@gmail.com....
[Ti] Title:BEAM Conditioning Regimen Has Higher Toxicity Compared With High-Dose Melphalan for Salvage Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.
[So] Source:Clin Lymphoma Myeloma Leuk;15(9):531-5, 2015 Sep.
[Is] ISSN:2152-2669
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Salvage autologous stem cell transplantation (ASCT) is increasingly used for eligible patients with multiple myeloma (MM) for progress after conventional chemotherapy. We recently used BEAM (BCNU, etoposide, cytarabine, and melphalan) conditioning for patients with myeloma receiving salvage ASCT whose disease progressed after a first ASCT with high-dose melphalan (HDM). We report safety and efficacy of BEAM salvage ASCT in MM in comparison with HDM-based salvage ASCT. PATIENTS AND METHODS: Between 2008 and 2013, 43 consecutive patients received salvage ASCT for MM (19 with HDM; 24 with BEAM). RESULTS: The BEAM group had a higher incidence of infections, intensive level of care, and fever (19 vs. 13 patients; P = .02), whereas the melphalan group had a higher incidence of mucositis (7 vs. 2 patients; P = .03). Other toxicities were not different. There was no significant difference in disease status and response rate before and after salvage ASCT between the 2 groups. The median time of follow-up after salvage ASCT was 5 and 9 months and the median progression-free survival (PFS) times were 7.7 and 12.1 months (P = .82) for BEAM and melphalan, respectively. CONCLUSION: BEAM seemed to be associated with higher toxicity with comparable efficacy to HDM ASCT. Longer follow-up is needed to determine whether there is any significant difference in PFS between the 2 groups.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1508
[Js] Journal subset:IM
[St] Status:In-Data-Review


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