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2.
J Am Heart Assoc ; 8(15): e010881, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31311438

RESUMO

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

3.
Eur Heart J ; 40(20): 1618-1619, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31086954
4.
Eur Heart J ; 40(26): 2142-2151, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31098611

RESUMO

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

6.
J Am Coll Cardiol ; 72(8): 874-882, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30115226

RESUMO

BACKGROUND: Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive. OBJECTIVES: This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. METHODS: Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. RESULTS: Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. CONCLUSIONS: Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621).

7.
Dermatol Online J ; 23(4)2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28541876

RESUMO

We present a rare case of acute febrile neutrophilic dermatosis, also known as Sweet syndrome, associated with recurrence of metastatic cervical cancer. This report highlights similar reports and serves as an important reminder of the relationship between Sweet syndrome and cervical cancer. Increasing awareness of Sweet syndrome assists clinicians in recognizing characteristic findings and encourages evaluation of patients for new-onset or recurrent neoplastic disease. Additionally, we discuss the typical presentation of the syndrome, the proper workup and treatment, and a common pitfall encountered in the diagnosis of Sweet syndrome.


Assuntos
Carcinoma de Células Escamosas/complicações , Recidiva Local de Neoplasia/complicações , Síndromes Paraneoplásicas/etiologia , Síndrome de Sweet/etiologia , Neoplasias do Colo do Útero/complicações , Doença Aguda , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/patologia , Síndrome de Sweet/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
8.
Eur J Heart Fail ; 19(8): 1036-1042, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27928880

RESUMO

AIMS: Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage. METHODS AND RESULTS: Patients with TTS were recruited from the International Takotsubo Registry ( www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93). CONCLUSION: The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity. TRIAL REGISTRATION: NCT0194762.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Eletrocardiografia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Sistema de Registros , Cardiomiopatia de Takotsubo/diagnóstico , Troponina/sangue , Síndrome Coronariana Aguda/sangue , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Curva ROC , Cardiomiopatia de Takotsubo/sangue
9.
JAMA Cardiol ; 1(3): 335-40, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27438117

RESUMO

IMPORTANCE: Apical ballooning is broadly recognized as the classic form of takotsubo syndrome (TTS). Atypical subtypes of TTS also exist, which constitute about 20% of all cases. To date, clinical profile and course of atypical TTS types have rarely been studied. OBJECTIVE: To characterize the clinical profile and outcomes of typical vs atypical types of TTS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: Records of 1750 patients from the International Takotsubo Registry, comprising 26 participating cardiovascular centers in 9 different countries, were reviewed and data on clinical profile and outcomes collected from January 1, 2011, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Clinical characteristics and in-hospital as well as long-term outcomes were assessed. RESULTS: Of 1750 patients diagnosed with TTS between 1998 and 2014, a total of 1430 (81.7%) presented with apical TTS (defined as typical TTS) and 320 (18.3%) with midventricular, basal, or focal TTS (all defined as atypical TTS). Patients with atypical TTS were younger than those with typical TTS (mean [SD], 62.5 [13.3] vs 67.3 [12.9] years; P < .001). Brain natriuretic peptide levels on admission were lower (median factor increase of the upper limit of normal, 4.18 vs 6.59; P = .02) and left ventricular ejection fraction was higher (mean [SD], 43.4% [10.7%] vs 40.6% [12.0%]; P < .001) in patients with atypical than those with typical forms of TTS. ST-segment depression was more prevalent in patients with atypical TTS (31 of 286 [10.8%] vs 90 of 1292 [7.0%]; P = .03), while ST-segment elevation was found more frequently in patients with typical TTS (593 of 1292 [45.9%] vs 97 of 286 [33.9%]; P < .001). Patients with atypical TTS more often had neurologic disorders than those with typical TTS (81 of 274 [29.6%] vs 286 of 1251 [22.9%]; P = .02). While in-hospital mortality was comparable between patients with atypical and typical TTS (10 of 320 [3.1%] vs 62 of 1430 [4.3%]; P = .32), the atypical forms showed a favorable outcome at 1 year (P = .01). However, after adjustment for confounders, only left ventricular ejection fraction less than 45%, atrial fibrillation, and neurologic disease, but not the type of TTS, were independent predictors. After 1 year, patients with both types of TTS showed a similar prognosis at long-term follow-up. CONCLUSIONS AND RELEVANCE: Atypical TTS has different characteristics than typical TTS, including younger age of onset, more frequent ST-segment depression, higher prevalence of neurologic diseases, less pronounced reduction in left ventricular ejection fraction, and lower brain natriuretic peptide values on admission. Outcomes are comparable between patients with both types after adjustment for confounders, suggesting that both should be equally monitored.


Assuntos
Cardiomiopatia de Takotsubo , Adolescente , Seguimentos , Humanos , Peptídeo Natriurético Encefálico/sangue , Sistema de Registros , Volume Sistólico , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/mortalidade , Cardiomiopatia de Takotsubo/fisiopatologia
10.
Eur Heart J ; 37(37): 2823-2829, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-26935270

RESUMO

AIMS: Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term 'broken heart syndrome'. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. METHODS AND RESULTS: Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with 'happy heart syndrome' was similar to those with the 'broken heart syndrome' including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in 'happy hearts' compared with 'broken hearts' (35.0 vs. 16.3%, P = 0.030). CONCLUSION: Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the 'happy hearts' than among the 'broken hearts'. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS.


Assuntos
Cardiomiopatia de Takotsubo , Eletrocardiografia , Coração , Humanos , Estresse Psicológico , Síndrome
11.
N Engl J Med ; 373(10): 929-38, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26332547

RESUMO

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).


Assuntos
Cardiomiopatia de Takotsubo , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/tratamento farmacológico , Cardiomiopatia de Takotsubo/mortalidade , Cardiomiopatia de Takotsubo/fisiopatologia , Função Ventricular Esquerda
12.
J Cardiovasc Med (Hagerstown) ; 16(5): 355-62, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25826477

RESUMO

AIMS: The aim of the present study was to analyze gender disparities in a large cohort of acute coronary syndrome (ACS) patients from the Zurich Acute Coronary Syndrome (Z-ACS) Registry. METHODS: Gender disparities in ACS were examined. The primary endpoint included in-hospital death rate, and the secondary endpoint major adverse cardiac and cerebrovascular events (MACCEs) at 30-day follow-up. Furthermore, independent predictors for MACCEs and death were identified. RESULTS: In total, 2612 patients with ACS were identified. Out of these, 23% were women. The mean age was higher in women (68.6 ± 12.2; P < 0.001). Troponin-T on admission (1.33 ± 4.64 vs. 1.19 ± 3.04 µg/l; P = 0.002) and N-terminal of the prohormone brain natriuretic peptide on admission (3456.2 ± 7286.7 vs. 1665.6 ± 4800.6 ng/l; P < 0.001) were higher in women compared with men. Single-vessel disease was more common in women (44.9 vs. 39.7%; P = 0.023) and, conversely, multivessel disease was more prevalent in male patients as compared with their female counterparts (59.4 vs. 54.4%; P = 0.029). At discharge, men were more likely prescribed statins (89.4 vs. 85.2%; P = 0.004). Overall mortality and MACCEs were similar for both genders. In women, peak creatine kinase and peak C-reactive protein emerged as independent predictors for MACCEs and SBP on admission, and maximal C-reactive protein and use of glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) as strong independent predictors for in-hospital death. CONCLUSION: The present results suggest a closing gap in short-term outcome and improvement in cardiac care between women and men. Nonetheless, differences in treatment strategies continue to exist, particularly pertaining to statin regimens at discharge, which might potentially have a powerful impact on long-term outcomes and gender disparities.


Assuntos
Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária , Feminino , Seguimentos , Hemodinâmica/fisiologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Sistema de Registros , Fatores Sexuais , Suíça/epidemiologia , Resultado do Tratamento
13.
Clin Res Cardiol ; 104(1): 51-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25142902

RESUMO

BACKGROUND: With increasing life expectancy in the western world, the aging population will compose a significant portion of the demographic. Notably, cardiovascular disease is particularly prevalent in the elderly population. The aim of the present study is to investigate the outcomes of octogenarians referred for urgent coronary angiography in the setting of acute coronary syndromes (ACS). METHODS: Between June 2007 and June 2012, consecutive patients with ACS were referred for evaluation and percutaneous intervention. Subsequently, the in-hospital death and major adverse cardiovascular events (MACE) at 30 days were analyzed. Multivariate analysis was performed to identify the predictors for death and MACE. RESULTS: In patients ≥80 years (n = 296) ST-segment elevation myocardial infarction (STEMI) occurred in 46.6%, non-ST-segment elevation myocardial infarction (NSTEMI) in 45.9%, and 7.4% had unstable angina. On the other hand, in patients <80 years (n = 2,316) STEMI was observed in 53.4%, NSTEMI in 37.8% and unstable angina in 9.0%. The primary end-point of total mortality was significantly higher in octogenarians (7.4 vs. 4.5%, p = 0.026). Similarly, the secondary end-point comprising overall MACE rate was significantly higher among the elderly (12.5 vs. 7.3%, p = 0.002). Within the group of octogenarians, no relation between age and outcomes was noted (for death: OR 0.99, 95% CI 0.84-1.16, p = 0.915; and for MACE: OR 1.10, 95% CI 0.88-1.36, p = 0.412); however, in patients <80 years, age was related to outcomes (for death: OR 1.05, 95% CI, 1.02-1.08, p = 0.003; and for MACE: OR 1.03, 95% CI, 1.01-1.05, p = 0.011). In a multivariate analysis, systolic blood pressure (OR 0.97 95% CI 0.94-0.99, p = 0.0058), maximal value of creatine kinase (OR 1.00, 95% CI 1.00-1.00, p = 0.033), and maximal value of NT-proBNP (OR 1.00, 95% CI 1.00-1.00, p = 0.0225) were independent predictors for death, while systolic blood pressure (OR 0.98, 95% CI 0.96-0.99, p = 0.0384) and maximal value of C-reactive protein (OR 1.01, 95% CI 1.00-1.01, p = 0.0265) were associated with overall MACE. CONCLUSIONS: Here we confirm that in-hospital death and MACE rate remain significantly elevated in octogenarians in spite of implementation of modern therapies. However, our real-world registry strongly suggests that early revascularization appears safe and effective in elderly patients. Furthermore, we have identified that systolic blood pressure, creatine kinase, NT-proBNP, and C-reactive protein are strong predictors for outcomes in octogenarians.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Angina Instável/diagnóstico por imagem , Angina Instável/terapia , Angiografia Coronária , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Encaminhamento e Consulta , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Idoso de 80 Anos ou mais , Angina Instável/sangue , Angina Instável/mortalidade , Angina Instável/fisiopatologia , Biomarcadores/sangue , Pressão Sanguínea , Proteína C-Reativa/análise , Distribuição de Qui-Quadrado , Creatina Quinase/sangue , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Razão de Chances , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
14.
J Investig Med High Impact Case Rep ; 3(4): 2324709615623298, 2015 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26788528

RESUMO

Background. Disseminated intravascular coagulopathy (DIC) is a complication of an underlying disease and not a primary illness. It is most commonly associated with sepsis, trauma, obstetrical complications, and malignancies. There are very few cases in the literature illustrating the association between DIC and congestive heart failure. Findings. In this report, we present a case of severe congestive heart failure, leading to biventricular thrombi and subsequently DIC. Conclusion. We suggest that the association between congestive heart failure and DIC is an underrecognized one. Congestive heart failure continues to remain a major cause of morbidity and mortality despite advances in medical therapies. Thus far, the precise role of coagulation factors in congestive heart failure is unknown. Further investigations are needed to elucidate the pathophysiology of congestive heart failure and coagulation factors.

15.
Vaccine ; 28(48): 7606-12, 2010 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-20920574

RESUMO

Two groups of 50 BALB/c male mice were immunized with live Chlamydia trachomatis mouse pneumonitis (MoPn) using the intranasal (i.n.) or the meatus urethra (intraurethral: i.u.) routes. As a control group, 100 male mice were sham-immunized in parallel. Both groups of animals vaccinated with live organisms developed strong Chlamydia-specific humoral and cell mediated immune responses. Based on the IgG2a/IgG1 ratio and the levels of IFN-γ both groups mounted a Th1 immune response. At six weeks following the immunization, all mice were challenged in the meatus urethra. The urethra, urinary bladder, testes and epididymides were harvested at weekly intervals and tested for the presence of C. trachomatis. Based on the culture results from these four organs both groups of Chlamydia-immunized mice showed significant protection. In the group immunized i.u., 10% (5/50) had positive cultures, while in the group immunized i.n. 28% (14/50) had positive cultures during the 5 weeks of observation. In contrast, in the sham-immunized animals 47% (47/100) had positive cultures (P<0.005) during the study period. In addition, the number of positive organs, the length of time that the animal had positive cultures, and the total number of inclusion forming units (IFU) recovered were overall significantly lower in the i.u. or i.n. groups in comparison with the sham-immunized animals. However, in relation to the i.u. immunized group, the protection elicited in the i.n. group was delayed and not as robust. In conclusion, immunization of mice in the meatus urethra may provide the gold standard for testing Chlamydia vaccines in a male model.


Assuntos
Formação de Anticorpos , Vacinas Bacterianas/imunologia , Infecções por Chlamydia/prevenção & controle , Chlamydia trachomatis/imunologia , Imunidade Celular , Animais , Anticorpos Antibacterianos/sangue , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/isolamento & purificação , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Imunoglobulina G/sangue , Interferon gama/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia , Uretra/microbiologia
16.
Blood ; 116(20): 4175-84, 2010 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-20733158

RESUMO

T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3(+)CD4(+)IL-17-producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4(+)CD25(high)FoxP3(+) regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4(+) and CD8(+) IL-17-producing T cells in a mouse model of lymph node infusion-induced BM failure. Although anti-IL-17 treatment did not abrogate BM failure, early treatment with the anti-IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression.


Assuntos
Anemia Aplástica/imunologia , Anemia Aplástica/fisiopatologia , Células Th17/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/sangue , Anemia Aplástica/diagnóstico , Animais , Anticorpos Neutralizantes/farmacologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Proliferação de Células/efeitos dos fármacos , Demografia , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Interferon gama/sangue , Interleucina-17/imunologia , Contagem de Linfócitos , Depleção Linfocítica , Masculino , Camundongos , Pessoa de Meia-Idade , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
17.
J Neurochem ; 114(3): 886-96, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20492353

RESUMO

How synaptic vesicles (SVs) are localized to the pre-active zone (5-200 nm beneath the active zone) in the nerve terminal, which may represent the slow response SV pool, is not fully understood. Electron microscopy revealed the number of SVs located in the pre-active zone, was significantly decreased in hypothalamic neurons of carboxypeptidase E knockout (CPE-KO) mice compared with wild-type mice. Additionally, we found K(+)-stimulated glutamate secretion from hypothalamic embryonic neurons was impaired in CPE-KO mice. Biochemical studies indicate that SVs from the hypothalamus of wild-type mice and synaptic-like microvesicles from PC12 cells contain a transmembrane form of CPE, with a cytoplasmic tail (CPE(C10)), maybe involved in synaptic function. Yeast two-hybrid and pull-down experiments showed that the CPE cytoplasmic tail interacted with gamma-adducin, which binds actin enriched at the nerve terminal. Total internal reflective fluorescence (TIRF) microscopy using PC12 cells as a model showed that expression of GFP-CPE(C15) reduced the steady-state level of synaptophysin-mRFP containing synaptic-like microvesicles accumulated in the area within 200 nm from the sub-plasma membrane (TIRF zone). Our findings identify the CPE cytoplasmic tail, as a new mediator for the localization of SVs in the actin-rich pre-active zone in hypothalamic neurons and the TIRF zone of PC12 cells.


Assuntos
Carboxipeptidase H/fisiologia , Hipotálamo/enzimologia , Terminações Pré-Sinápticas/enzimologia , Vesículas Sinápticas/enzimologia , Actinas/metabolismo , Animais , Carboxipeptidase H/química , Carboxipeptidase H/genética , Carboxipeptidase H/ultraestrutura , Células Cultivadas , Citoplasma/química , Citoplasma/metabolismo , Citoplasma/ultraestrutura , Hipotálamo/ultraestrutura , Camundongos , Camundongos Knockout , Células PC12 , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Ratos , Membranas Sinápticas/enzimologia , Membranas Sinápticas/ultraestrutura , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/ultraestrutura , Sinaptossomos
18.
Foot Ankle Spec ; 3(2): 76-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20400417

RESUMO

A 65-year-old man without significant comorbidities was referred to the senior author (EG) 9 months after an ankle arthrodesis procedure with complaints of pain, swelling, and progressive hindfoot valgus. The patient had elected to have the index surgery because of severe ankle arthritis due to longstanding lateral ankle instability. Physical examination revealed a well-healed anterior, midline ankle incision with normal pulses and sensation. Painful, limited ankle and subtalar range of motion was noted along with 20 degrees of hindfoot valgus and subfibular impingement. Radiographs of the ankle revealed an attempted ankle fusion using a knee arthroplasty trabecular metal augment placed vertically at the tibiotalar joint. There were no screws or other hardware present to provide compression and stability of the fusion. A computed tomography scan showed a tibiotalar nonunion, erosion of the talar body, and severe tibiotalar and subtalar arthritis. Inflammatory markers were within normal range. Based on the findings of a failed fusion and progressive painful hindfoot deformity, it was determined that the patient would benefit from removal of the hardware and revision fusion surgery. Tibiotalocalcaneal (TTC) hindfoot fusion was planned because of the patient's talar collapse and tibiotalar/ subtalar arthritis. The TTC procedure was performed with a retrograde intramedullary nail, femoral head allograft, and morselized fibular autograft enriched with platelet-rich plasma. The femoral head was used as a structural allograft to fill the large bone defect, prevent limb shortening, and assist in correction of the hindfoot deformity. Intraoperative findings revealed severe metallic synovitis of the ankle and subtalar joints, metal debris at the site of the trabecular implant, and segmental defects of the distal tibia and talus. Weight bearing was permitted after 16 weeks when evidence of successful ankle fusion was confirmed radiographically. At 24 months, the patient was pain free and ambulating without difficulty.


Assuntos
Artrodese/métodos , Artroplastia/efeitos adversos , Deformidades Adquiridas do Pé/etiologia , Deformidades Adquiridas do Pé/cirurgia , Articulação Talocalcânea/cirurgia , Idoso , Articulação do Tornozelo/cirurgia , Transplante Ósseo , Humanos , Masculino , Reoperação , Transplante Homólogo
19.
Infect Immun ; 77(12): 5602-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19805533

RESUMO

The pathogenesis of an infection of the male genitourinary tract of mice with a human serovar of Chlamydia trachomatis has not been characterized. To establish a new model, we inoculated C3H/HeN (H-2(k)) mice in the meatus urethra with C. trachomatis serovar D. To determine the 50% infectious dose (ID(50)), male mice were inoculated with doses ranging from 10(2) to 10(6) inclusion-forming units (IFU). The mice were euthanized 10 days post infection (p.i.), and the urethra, bladder, epididimydes, and testes were cultured for Chlamydia. Positive cultures were obtained from the urethra, urinary bladder, and epididimydes, and the ID(50) was determined to be 5 x 10(4) IFU/mouse. Subsequently, to characterize the course of the infection, wild-type (WT) and C3H animals with severe combined immunodeficiency (SCID animals) were inoculated with 10(6) IFU/mouse (20 times the ID(50)). In the WT mice, the infection peaked in the second week, and by 42 days p.i., it was cleared. In contrast, most of the SCID mice continued to have positive cultures at 60 days p.i. C. trachomatis-specific antibodies were first detected in WT animals' sera at 21 days p.i. and increased until 42 days p.i. The immunoglobulin G2a (IgG2a) titers were 32-fold higher than those of IgG1, indicative of a Th1-biased immune response. A lymphoproliferative assay using splenocytes showed a significant cell-mediated immune response in the WT mice. As expected, no humoral or cell-mediated immune responses were observed in the SCID animals. In conclusion, inoculation of WT male mice in the meatus urethra with a human serovar of C. trachomatis resulted in a limited infection mainly localized to the lower genitourinary tract. On the other hand, SCID animals could not clear the infection, suggesting that in male mice, the adaptive immune response is necessary to control an infection with a C. trachomatis human serovar.


Assuntos
Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/imunologia , Modelos Animais de Doenças , Uretra/imunologia , Uretra/microbiologia , Animais , Anticorpos Antibacterianos/sangue , Proliferação de Células , Epididimo/microbiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos SCID , Baço/imunologia , Testículo/microbiologia , Fatores de Tempo , Bexiga Urinária/microbiologia
20.
Exp Hematol ; 37(4): 477-86, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19216020

RESUMO

OBJECTIVE: To investigate the role of perforin-mediated cell apoptosis in murine models of immune-mediated bone marrow (BM) failure. MATERIALS AND METHODS: We compared C57BL/6J (B6) mice carrying a perforin gene deletion (Prf(-/-)) with wild-type (WT) controls for cellular composition in lymphohematopoietic tissues. Lymph node (LN) cells from Prf(-/-) mice were coincubated with BM cells from B10-H2(b)/LilMcdJ (C.B10) mice in an apoptosis assay in vitro. We then infused Prf(-/-) and WT B6 LN cells into sublethally irradiated C.B10 and CByB6F1 recipients with mismatches at the minor and major histocompatibility loci, respectively, in order to induce BM failure. Cellular composition was analyzed by flow cytometry. RESULTS: Prf(-/-) mice showed normal lymphoid cell composition, but Prf(-/-) LN cells had reduced ability to induce C.B10 BM cell apoptosis in vitro. Infusion of 5 to 10 x 10(6) Prf(-/-) LN cells produced obvious BM failure in C.B10 and CByB6F1 recipients; pancytopenia and BM hypocellularity were only slightly less severe than those caused by infusion of 5 x 10(6) WT B6 LN cells. Infused Prf(-/-) LN cells showed less T-cell expansion, normal T-cell activation, and higher proportions of T cells expressing gamma-interferon, tissue necrosis factor-alpha, and Fas ligand CD178, in comparison to infused WT B6 LN cells. Fas expression was equally high in residual BM cells in recipient of both Prf(-/-) and B6 LN cells. CONCLUSION: Perforin deficiency alters T-cell expansion but upregulates T-cell Fas ligand expression. Perforin-mediated cell death appears to play a minor role in mouse models of immune-mediated BM failure.


Assuntos
Apoptose , Doenças da Medula Óssea/imunologia , Perforina/metabolismo , Linfócitos T/imunologia , Animais , Doenças da Medula Óssea/fisiopatologia , Proteína Ligante Fas/imunologia , Citometria de Fluxo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Perforina/genética , Transdução de Sinais/imunologia
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