RESUMO
Listeria monocytogenes is a gram-positive bacterium that causes listeriosis. Brain abscess is a very uncommon manifestation of listeriosis and has not been reported to be associated with adalimumab (humira), one of the approved medications for treating Crohn's disease. A 45-year-old female with Crohn's disease presented with sudden onset of fever, headache, nausea, vomiting, and altered mental status for 1 day. She was on prednisone and 6-mercaptopurine. She had started taking adalimumab 17 days prior to admission. She had signs of toxicity, confusion, and nuchal rigidity, but showed neither central nervous system deficits nor focal deficits. The laboratory results revealed Gram-positive coccobacillus, positive blood and cerebrospinal fluid culture for Listeria monocytogenes, and a 5 × 5 mm ring-enhancing lesion of brain abscess on MRI. After holding off 6-mercaptopurine and adalimumab, her mental status improved on the next day. Finally, she was discharged on day 7 of hospitalization with ampicillin 2 g intravenously every 4 h for a total of 2 weeks. Two weeks later, the follow-up MRI showed a 2-mm area of residual enhancement in the left temporal lobe at the site of the previous brain abscess. Adalimumab, as a tumor necrosis factor (TNF)-alpha inhibitor, carries a risk of triggering opportunistic infection, such as listeriosis. With an altered mental status or neurological signs in patients receiving TNF-alpha antagonizing agent, physicians should suspect bacterial infection in the central nervous system and promptly initiate treatment for brain abscess if needed.
Assuntos
Abdome/parasitologia , Dor Abdominal/diagnóstico , Anisaquíase/diagnóstico , Abdome/patologia , Abdome/cirurgia , Dor Abdominal/parasitologia , Dor Abdominal/patologia , Dor Abdominal/cirurgia , Animais , Anisaquíase/parasitologia , Anisaquíase/patologia , Anisaquíase/cirurgia , Anisakis/anatomia & histologia , Anisakis/crescimento & desenvolvimento , Criança , Amarelo de Eosina-(YS) , Hematoxilina , Humanos , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Masculino , MicroscopiaRESUMO
NOD1 and NOD2 are members of the NOD-like receptor family of cytosolic pattern recognition receptors that recognize specific fragments of the bacterial cell wall component peptidoglycan. Neisseria species are unique amongst Gram-negative bacteria in that they turn over large amounts of peptidoglycan during growth. We examined the ability of NOD1 and NOD2 to recognize Neisseria gonorrhoeae, and determined the role of NOD-dependent signaling in regulating the immune response to gonococcal infection. Gonococci, as well as conditioned medium from mid-logarithmic phase grown bacteria, were capable of activating both human NOD1 and NOD2, as well as mouse NOD2, leading to the activation of the transcription factor NF-κB and polyubiquitination of the adaptor receptor-interacting serine-threonine kinase 2. We identified a number of cytokines and chemokines that were differentially expressed in wild type versus NOD2-deficient macrophages in response to gonococcal infection. Moreover, NOD2 signaling up-regulated complement pathway components and cytosolic nucleic acid sensors, suggesting a broad impact of NOD activation on innate immunity. Thus, NOD1 and NOD2 are important intracellular regulators of the immune response to infection with N. gonorrhoeae. Given the intracellular lifestyle of this pathogen, we believe these cytosolic receptors may provide a key innate immune defense mechanism for the host during gonococcal infection.
Assuntos
Gonorreia/imunologia , Macrófagos/fisiologia , Neisseria gonorrhoeae/imunologia , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Animais , Ativação do Complemento/genética , Células HEK293 , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/genética , Imunomodulação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD2/genética , Peptidoglicano/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genéticaRESUMO
Chlamydia pneumoniae is a common respiratory pathogen associated with atypical pneumonia, and it has been suggested as a trigger or promoter of several chronic inflammatory conditions, such as asthma and atherosclerosis. The beta form of IL-1 (IL-1beta) is a proinflammatory cytokine released by many cell types and is an important mediator of inflammation during infection. IL-1beta production is a tightly controlled process that includes regulation at multiple levels and typically requires two distinct signals for activation and release. In this study, we investigated the ability of C. pneumoniae to induce IL-1beta secretion. We found that C. pneumoniae was unique among the other Chlamydia species tested in its ability to potently induce secretion of mature IL-1beta from unprimed bone marrow-derived macrophages during a productive infection. TLR2 was required for induction of pro-IL-1beta, whereas the NLRP3/ASC was required for caspase-1 activation and pro-IL-1beta cleavage to produce mature IL-1beta. Caspase-1 cleavage was independent of endogenous ATP release, but required potassium flux, lysosomal acidification, and cathepsin B release. We further investigated the role of IL-1 in host defense against C. pneumoniae-induced pneumonia using mice deficient in the type I IL-1R. Although the IL-1R(-/-) mice developed an inflammatory infiltrate, the number of infiltrating neutrophils was lower, whereas there was evidence of increased infiltrating fibroblasts and mesenchymal cells and more lung fibrosis. We conclude that C. pneumoniae directly activates the NLRP3/ASC inflammasome, leading to the release of biologically active IL-1beta, and that concurrent IL-1 signaling is required for optimal host defense against acute bacterial pneumonia.
Assuntos
Proteínas de Transporte/fisiologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/patologia , Chlamydophila pneumoniae/imunologia , Proteínas do Citoesqueleto/fisiologia , Mediadores da Inflamação/fisiologia , Interleucina-1beta/fisiologia , Animais , Proteínas Reguladoras de Apoptose , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/microbiologia , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Infecções por Chlamydia/metabolismo , Proteínas do Citoesqueleto/deficiência , Proteínas do Citoesqueleto/metabolismo , Fibrose , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/microbiologia , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/patologia , Transdução de Sinais/imunologiaRESUMO
Voriconazole is a third generation triazole with improved activity against many fungal pathogens. We examined the efficacy of voriconazole in a murine infection model and evaluated the drug's effect on cellular characteristics and serum polysaccharide levels. The antifungal reduced serum polysaccharide and significantly prolonged the survival of lethally infected animals.
Assuntos
Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Pneumopatias Fúngicas/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Animais , Cryptococcus neoformans , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/sangue , VoriconazolRESUMO
BACKGROUND: The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the PURSUIT trial population for 30-day mortality prediction. METHODS: The PURSUIT risk score was calculated for 337 consecutive Olmsted County residents with non-ST-elevation acute myocardial infarction admitted to the coronary care unit of our institution from 1988 through 1998. Predischarge ejection fraction (EF) measurement was available for 246 patients (73%). After excluding patients with prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%. Among 30-day survivors, mortality at 1 year was 7.9%. RESULTS: Mean age was 70 +/- 13 years, and 37% of patients were women. Mean predischarge EF was 52% +/- 16%. Patients with higher PURSUIT risk score had lower EF (P <.001). Three-vessel (> or =70% stenosis in all 3 coronary arteries) or left main (> or =50% stenosis) coronary artery disease was present in 60 of 219 patients (27%) who had coronary angiography. Higher PURSUIT risk score was associated with greater likelihood of 3-vessel or left main disease (P <.001). The PURSUIT risk score had very good predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day to 1-year, C-statistic = 0.77) mortality. CONCLUSIONS: The PURSUIT risk score correlates with EF, angiographic severity of coronary artery disease, and short- and long-term mortality of nonselected patients with non-ST-elevation acute myocardial infarction.
Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Medição de Risco/métodos , Idoso , Comorbidade , Angiografia Coronária , Doença da Artéria Coronariana/tratamento farmacológico , Eptifibatida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Análise de Regressão , Projetos de Pesquisa , Volume Sistólico , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate epidemiologic trends, clinical features and outcome of esophageal candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. PATIENTS AND METHODS: The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of esophageal candidiasis. Proven esophageal candidiasis was defined as clinical plus radiographic and/or endoscopic findings of esophageal candidiasis. Probable esophageal candidiasis was defined as esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. RESULTS: Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) esophageal candidiasis. A history of prior mucosal candidiasis was present in 94% of all episodes. The median CD4+ count at the time of diagnosis was 7/microl (range, 0 to 550), and the median viral load was 98000 copies/ml (range, 22916 to 1278933). Concurrent oropharyngeal candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. CONCLUSION: Esophageal candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4+ counts.
Assuntos
Terapia Antirretroviral de Alta Atividade , Candidíase/epidemiologia , Doenças do Esôfago/epidemiologia , Infecções por HIV/complicações , Adolescente , Antifúngicos/uso terapêutico , Contagem de Linfócito CD4 , Candidíase/tratamento farmacológico , Candidíase/etiologia , Candidíase/patologia , Criança , Doenças do Esôfago/tratamento farmacológico , Doenças do Esôfago/etiologia , Doenças do Esôfago/patologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
To determine whether an increased QRS duration in the absence of bundle branch block (BBB) on the presenting electrocardiogram of patients with acute myocardial infarction (AMI) is associated with decreased survival, we retrospectively reviewed 781 consecutive patients admitted to the coronary care unit of our institution with AMI without BBB between 1988 and 1998. In patients with ST elevation AMI (n = 412), the groups with QRS duration > or =100 ms and <100 ms had similar survival. Conversely, in patients with non-ST elevation AMI (n = 369), in-hospital, 1-, 3-, and 5-year survival was 84.4%, 75.6%, 66.7%, and 52.2%, respectively, in the group with QRS > or =100 ms compared with 95.4%, 89.2%, 83.8%, and 74.3%, respectively, in the group with QRS <100 ms (p <0.01, log-rank test). In patients with non-ST elevation AMI, those with QRS duration > or =100 ms were more likely to be men, to have had a prior AMI that healed, to be in Killip class II, III, or IV, and to have lower ejection fraction than patients with QRS duration <100 ms. After adjusting for age, sex, prior AMI or stroke, heart rate, and Killip class on admission, QRS duration > or =100 ms was independently associated with in-hospital and overall mortality in patients with non-ST elevation AMI. QRS duration > or =100 ms in the absence of BBB is an independent predictor of increased mortality in patients with non-ST elevation AMI.