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1.
Artigo em Inglês | MEDLINE | ID: mdl-38626903

RESUMO

BACKGROUND: To ensure safe and optimal surgical conditions in thoracic surgery, one-lung ventilation is crucial. Various techniques exist to achieve one-lung ventilation. Tracheotomized patients who require one-lung ventilation represent a unique and rare subgroup that demands specialized knowledge and skills. The very limited literature has discussed alternative methods, no randomized controlled trials have addressed this issue yet. METHODS: We performed a retrospective analysis of patients who underwent one-lung ventilation in the Department of Thoracic Surgery of a German University Hospital between 2016 and 2021. The study assessed patient demographics, airway management techniques, ventilation parameters, and adverse events. RESULTS: In 3,197 anesthesia procedures during the observation period, 152 patients had an existing tracheostomy, of which 56 required one-lung ventilation. Among others in 42 cases, a tracheostomy tube was combined with a bronchial blocker, and in 10 cases, a double-lumen tracheostomy tube was used. There were no severe complications. Intraoperative dislocations that required repositioning of the device occurred in six patients (13.3%) with bronchial blockers and one patient with double-lumen tracheostomy tube (10%). CONCLUSION: The management of one-lung ventilation in tracheotomized patients presents unique challenges. While double-lumen tracheostomy tubes have specific advantages, we recommend considering their use carefully. For most tracheotomized patients, bronchial blockers in conjunction with a tracheostomy tube are used, which offers safety and practicality, irrespective of the tracheostomy's age or type. Further research and randomized controlled trials are warranted to establish best practices for one-lung ventilation in this unique patient population.

2.
J Cardiothorac Vasc Anesth ; 29(6): 1537-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26321122

RESUMO

OBJECTIVES: Former analyses reported an increased rate of poor direct laryngoscopy view in cardiac surgery patients; however, these findings frequently could be attributed to confounding patient characteristics. In most of the reported cardiac surgery cohorts, the rate of well-known risk factors for poor direct laryngoscopy view such as male sex, obesity, or older age, were increased compared with the control groups. Especially in the ongoing debate on anesthesia staff qualification for cardiac interventions outside the operating room a detailed and stratified risk analysis seems necessary. DESIGN: Retrospective, anonymous, propensity score-based, matched-pair analysis. SETTING: Single-center study in a university hospital. PARTICIPANTS: No active participants. Retrospective, anonymous chart analysis. INTERVENTIONS: The anesthesia records of patients undergoing cardiac surgery in a period of 6 consecutive years were analyzed retrospectively. The results were compared with those of a control group of patients who underwent general surgery. Poor laryngoscopic view was defined as Cormack and Lehane classification grade 3 or 4. MEASUREMENTS AND MAIN RESULTS: The records of 21,561 general anesthesia procedures were reviewed for the study. The incidence of poor direct laryngoscopic views in patients scheduled for cardiac surgery was significantly increased compared with those of the general surgery cohort (7% v 4.2%). Using propensity score-based matched-pair analysis, equal subgroups were generated of each surgical department, with 2,946 patients showing identical demographic characteristics. After stratifying for demographic characteristics, the rate of poor direct laryngoscopy view remained statistically significantly higher in the cardiac surgery group (7.5% v 5.7%). CONCLUSIONS: Even with stratification for demographic risk factors, cardiac surgery patients showed a significantly higher rate of poor direct laryngoscopic view compared with general surgery patients. These results should be taken into account for human resource management and distribution of difficult airway equipment, especially when cardiac interventional programs are implemented in remote hospital locations.


Assuntos
Anestesia Geral/tendências , Agendamento de Consultas , Procedimentos Cirúrgicos Cardíacos/tendências , Laringoscopia/tendências , Pontuação de Propensão , Idoso , Anestesia Geral/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Humanos , Laringoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/tendências
3.
J Obstet Gynaecol Res ; 41(7): 1032-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25772267

RESUMO

AIM: The fear of airway problems often leads to prolonged attempts to obtain neuroaxial (spinal anesthesia or epidural anesthesia) anesthesia in obstetric anesthesia. The aim of this institutional quality management study was to revisit existing anesthesia care in the obstetric department, focusing on the frequency of delayed or failed neuroaxial anesthesia as well as the risk of airway problems in parturient and non-obstetric patients. METHODS: The clinical records from 8 consecutive years (2005-2013) were analyzed retrospectively. Cases of cesarean delivery with general anesthesia were analyzed and compared with an age-matched group of female patients undergoing non-obstetric abdominal or gynecological surgery with rapid sequence induction. Poor laryngeal visualization (Cormack-Lehane grade III or IV) and failed intubation were recorded. RESULTS: The records of 6393 cesarean deliveries including 851 with general anesthesia were analyzed. In 175 cases insufficient or delayed onset of regional anesthesia led to requirement for general anesthesia. The rate of poor laryngoscopic view in parturient women undergoing cesarean delivery was 14/851, and 4/814 in the reference group (P = 0.023). Failed intubation occurred in three patients undergoing cesarean delivery (0.4%) and in one non-obstetric patient (0.1%; P = 0.339). CONCLUSION: The rate of failed intubations in patients undergoing cesarean delivery may be equivalent to non-obstetric patients. In time-challenging cesarean deliveries, delay of conversion from non-successful neuroaxial anesthesia to general anesthesia in order to avoid adverse airway events does not appear to be justified.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Anestesia Geral/efeitos adversos , Cesárea/efeitos adversos , Complicações Intraoperatórias/etiologia , Intubação Intratraqueal/efeitos adversos , Qualidade da Assistência à Saúde , Sistema Respiratório/lesões , Adulto , Obstrução das Vias Respiratórias/epidemiologia , Anonimização de Dados , Registros Eletrônicos de Saúde , Feminino , Alemanha/epidemiologia , Hospitais Universitários , Humanos , Incidência , Complicações Intraoperatórias/epidemiologia , Gravidez , Sistema Respiratório/fisiopatologia , Estudos Retrospectivos , Risco
4.
Crit Care ; 18(4): R150, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-25015112

RESUMO

INTRODUCTION: It is well known that etomidate may cause adrenal insufficiency. However, the clinical relevance of adrenal suppression after a single dose of etomidate remains vague. The aim of this study was to investigate the association between the administration of a single dose of etomidate or an alternative induction regime ahead of major cardiac surgery and clinical outcome parameters associated with adrenal suppression and onset of sepsis. METHODS: The anesthesia and intensive care unit (ICU) records from patients undergoing cardiac surgery over five consecutive years (2008 to 2012) were retrospectively analyzed. The focus of the analysis was on clinical parameters like mortality, ventilation hours, renal failure, and sepsis-linked serum parameters. Multivariate analysis and Cox regression were applied to derive the results. RESULTS: In total, 3,054 patient records were analyzed. A group of 1,775 (58%) patients received a single dose of etomidate; 1,279 (42%) patients did not receive etomidate at any time. There was no difference in distribution of age, American Society of Anesthesiologists physical score, duration of surgery, and Acute Physiology and Chronic Health Evaluation II score. Postoperative data showed no significant differences between the two groups in regard to mortality (6.8% versus 6.4%), mean of mechanical ventilation hours (21.2 versus 19.7), days in the ICU (2.6 versus 2.5), hospital days (18.7 versus 17.4), sepsis-associated parameters, Sequential Organ Failure Assessment score, and incidence of renal failure. Administration of etomidate showed no significant influence (P = 0.6) on hospital mortality in the multivariate Cox analysis. CONCLUSIONS: This study found no evidence for differences in key clinical outcome parameters based on anesthesia induction with or without administration of a single dose of etomidate. In consequence, etomidate might remain an acceptable option for single-dose anesthesia induction.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/tendências , Etomidato/administração & dosagem , Cuidados Pré-Operatórios/métodos , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento
5.
J Cardiothorac Vasc Anesth ; 27(3): 516-21, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23083795

RESUMO

OBJECTIVE: Previous investigations reported a higher incidence of poor laryngoscopic views in pediatric patients undergoing cardiac surgery. The objective of this study was to analyze why children undergoing cardiac surgery have such an increased incidence of poor laryngoscopic views during anesthesia induction. DESIGN: This study was designed as a retrospective analysis. SETTING: This analysis was based on a single-center cohort of a university hospital. PARTICIPANTS: One thousand one hundred seventy-seven general anesthesia procedures, including a direct laryngoscopic view over a period of 6 consecutive years, in pediatric patients undergoing cardiac surgery. INTERVENTIONS: Because of the retrospective character of this study, there were no study-related interventions. MEASUREMENTS AND MAIN RESULTS: Poor laryngoscopic views were defined as Cormack and Lehane (CML) grade III and IV. The overall incidence of poor laryngoscopic views was 3.5%. In patients younger than 1 year of age, the incidence of CML III or IV was significantly higher than in the older patients (5.6% v 1.7%). None of the patients with CML III/IV findings had Down syndrome; whereas in 9 of 41 patients with CML grade III/IV, a concomitant congenital syndrome like DiGeorge syndrome or CHARGE syndrome was found. CONCLUSIONS: The general incidence of CML III/IV findings during the induction of anesthesia for pediatric cardiac surgery is more than twice as high as reported in unselected pediatric cohorts. In patients below 1 year of age and in male patients, difficult laryngoscopy is more frequent. Concomitant Down syndrome was not associated with difficult laryngoscopy.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Laringoscopia/métodos , Adolescente , Fatores Etários , Índice de Massa Corporal , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Criança , Pré-Escolar , Estudos de Coortes , Interpretação Estatística de Dados , Feminino , Previsões , Humanos , Lactente , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/estatística & dados numéricos , Masculino , Bloqueadores Neuromusculares , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
6.
Paediatr Anaesth ; 22(8): 729-36, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22340664

RESUMO

OBJECTIVE: Difficult laryngoscopy in pediatric patients undergoing anesthesia. AIM: This retrospective analysis was conducted to investigate incidence and predictors of difficult laryngoscopy in a large cohort of pediatric patients receiving general anesthesia with endotracheal intubation. BACKGROUND: Young age and craniofacial dysmorphy are predictors for the difficult pediatric airway and difficult laryngoscopy. For difficult laryngoscopy, other general predictors are not yet described. METHODS: Retrospectively, from a 5-year period, data from 11.219 general anesthesia procedures in pediatric patients with endotracheal intubation using age-adapted Macintosh blades in a single center (university hospital) were analyzed statistically. RESULTS: The overall incidence of difficult laryngoscopy [Cormack and Lehane (CML) grade III and IV] was 1.35%. In patients younger than 1 year, the incidence of CML III or IV was significantly higher than in the older patients (4.7% vs 0.7%). ASA Physical Status III and IV, a higher Mallampati Score (III and IV) and a low BMI were all associated (P < 0.05) with difficult laryngoscopy. Patients undergoing oromaxillofacial surgery and cardiac surgery showed a significantly higher rate of CML III/IV findings. CONCLUSION: The general incidence of difficult laryngoscopy in pediatric anesthesia is lower than in adults. Our results show that the risk of difficult laryngoscopy is much higher in patients below 1 year of age, in underweight patients and in ASA III and IV patients. The underlying disease might also contribute to the risk. If the Mallampati score could be obtained, prediction of difficult laryngoscopy seems to be reliable. Our data support the existing recommendations for a specialized anesthesiological team to provide safe anesthesia for infants and neonates.


Assuntos
Anestesia , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Adolescente , Fatores Etários , Índice de Massa Corporal , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Registros Eletrônicos de Saúde , Feminino , Previsões , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Risco , Fatores Sexuais
7.
J Virol ; 84(10): 5438-42, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20219925

RESUMO

Borna disease virus (BDV) frequently persists in the brain of infected animals. To analyze viral dissemination in the mouse nervous system, we generated a mouse-adapted virus that expresses green fluorescent protein (GFP). This viral vector supported GFP expression for up to 150 days and possessed an extraordinary staining capacity, visualizing complete dendritic arbors as well as individual axonal fibers of infected neurons. GFP-positive cells were first detected in cortical areas from where the virus disseminated through the entire central nervous system (CNS). Late in infection, GFP expression was found in the sciatic nerve, demonstrating viral spread from the central to the peripheral nervous system.


Assuntos
Doença de Borna/virologia , Vírus da Doença de Borna/patogenicidade , Sistema Nervoso/virologia , Animais , Vírus da Doença de Borna/genética , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Coloração e Rotulagem/métodos
8.
J Virol ; 83(11): 5401-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19297496

RESUMO

Avian bornaviruses (ABV), representing a new genus within the family Bornaviridae, were recently discovered in parrots from North America and Israel with proventricular dilatation disease (PDD). We show here that closely related viruses are also present in captive European parrots of various species with PDD. The six ABV strains that we identified in clinically diseased birds are new members of the previously defined ABV genotypes 2 and 4. Viruses of both genotypes readily established persistent, noncytolytic infections in quail and chicken cell lines but did not grow in cultured mammalian cells in which classical Borna disease virus strains replicate very efficiently. ABV antigens were present in both the cytoplasm and nucleus of infected cells, suggesting nuclear replication of ABV. The genome organization of avian and mammalian bornaviruses is highly conserved except that ABV lacks a distinct control element in the 5' noncoding region of the bicistronic mRNA encoding the viral proteins X and P. Reverse transcription-PCR analysis demonstrated the presence of virus in many, if not all, organs of birds with PDD. Viral nucleic acid was also found in feces of diseased birds, suggesting virus transmission by the fecal-oronasal route. Immunohistochemical analysis of organs from birds with PDD revealed that infection with ABV is not restricted to cells of the nervous system. Thus, ABV exhibits a broad tissue and cell tropism that is strikingly different from classical Borna disease virus.


Assuntos
Doenças das Aves/virologia , Bornaviridae/fisiologia , Infecções por Mononegavirales/veterinária , Proventrículo , Gastropatias/veterinária , Animais , Bornaviridae/genética , Bornaviridae/isolamento & purificação , Linhagem Celular , Feminino , Genoma Viral/genética , Masculino , Infecções por Mononegavirales/complicações , Infecções por Mononegavirales/patologia , Infecções por Mononegavirales/virologia , Ácidos Nucleicos/genética , Ácidos Nucleicos/metabolismo , Especificidade de Órgãos , Papagaios , Filogenia , RNA Viral/genética , Gastropatias/complicações , Especificidade por Substrato , Replicação Viral
9.
Clin Pharmacokinet ; 46(12): 1039-49, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18027988

RESUMO

OBJECTIVES: We determined in vitro the potency of macrolides as P-glycoprotein inhibitors and tested in hospitalised patients whether coadministration of P-glycoprotein inhibitors leads to increased serum concentrations of the P-glycoprotein substrates digoxin and digitoxin. METHODS: In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transport was investigated in Caco-2 cells. In a pharmacoepidemiological study, we analysed the serum digoxin and digitoxin concentrations with and without coadministration of P-glycoprotein inhibitors in hospitalised patients. RESULTS: All macrolides inhibited P-glycoprotein-mediated digoxin transport, with concentrations producing 50% inhibition (IC(50)) values of 1.8, 4.1, 15.4, 21.8 and 22.7 micromol/L for telithromycin, clarithromycin, roxithromycin, azithromycin and erythromycin, respectively. Coadministration of P-glycoprotein inhibitors was associated with increased serum concentrations of digoxin (1.3 +/- 0.6 vs 0.9 +/- 0.5 ng/mL, p < 0.01). Moreover, patients receiving macrolides had higher serum concentrations of cardiac glycosides (p < 0.05). CONCLUSION: Macrolides are potent inhibitors of P-glycoprotein. Drug interactions between P-glycoprotein inhibitors and substrates are likely to occur during hospitalisation.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Cardiopatias/metabolismo , Macrolídeos/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Transporte Biológico , Células CACO-2 , Creatinina/sangue , Digitoxina/administração & dosagem , Digitoxina/sangue , Digitoxina/farmacocinética , Digoxina/administração & dosagem , Digoxina/sangue , Digoxina/farmacocinética , Interações Medicamentosas , Eritromicina/administração & dosagem , Eritromicina/farmacocinética , Feminino , Cardiopatias/sangue , Cardiopatias/fisiopatologia , Humanos , Pacientes Internados , Inulina/administração & dosagem , Inulina/sangue , Inulina/farmacocinética , Cetolídeos/administração & dosagem , Cetolídeos/farmacocinética , Macrolídeos/administração & dosagem , Masculino , Farmacoepidemiologia/métodos
10.
Viruses ; 2(4): 927-938, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21994661

RESUMO

Like other pathogens that readily persist in animal hosts, members of the Bornaviridae family have evolved effective mechanisms to evade the innate immune response. The prototype of this virus family, Borna disease virus employs an unusual replication strategy that removes the triphosphates from the 5' termini of the viral RNA genome. This strategy allows the virus to avoid activation of RIG-I and other innate immune response receptors in infected cells. Here we determined whether the newly discovered avian bornaviruses (ABV) might use a similar strategy to evade the interferon response. We found that de novo infection of QM7 and CEC32 quail cells with two different ABV strains was efficiently inhibited by exogenous chicken IFN-α. IFN-α also reduced the viral load in QM7 and CEC32 cells persistently infected with both ABV strains, suggesting that ABV is highly sensitive to type I IFN. Although quail cells persistently infected with ABV contained high levels of viral RNA, the supernatants of infected cultures did not contain detectable levels of biologically active type I IFN. RNA from cells infected with ABV failed to induce IFN-ß synthesis if transfected into human cells. Furthermore, genomic RNA of ABV was susceptible to 5'-monophosphate-specific RNase, suggesting that it lacks 5'-triphospates like BDV. These results indicate that bornaviruses of mammals and birds use similar strategies to evade the host immune response.

11.
J Virol ; 81(15): 7933-40, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17522214

RESUMO

Borna disease virus (BDV) can persistently infect the central nervous system of a broad range of mammalian species. Mice are resistant to infections with primary BDV isolates, but certain laboratory strains can be adapted to replicate in mice. We determined the molecular basis of adaptation by studying mutations acquired by a cDNA-derived BDV strain during one brain passage in rats and three passages in mice. The adapted virus propagated efficiently in mouse brains and induced neurological disease. Its genome contained seven point mutations, three of which caused amino acid changes in the L polymerase (L1116R and N1398D) and in the polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either alone or in combination all showed enhanced multiplication speed in Vero cells, indicating improved intrinsic viral polymerase activity rather than adaptation to a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred replication competence of recombinant BDV in mice if introduced individually. Virus propagation in mouse brains was substantially enhanced if both L mutations were present simultaneously, but infection remained mostly nonsymptomatic. Only if all three amino acid substitutions were combined did BDV replicate vigorously and induce early disease in mice. Interestingly, the virulence-enhancing effect of the R66K mutation in P could be attributed to reduced negative regulation of polymerase activity by the viral X protein. Our data demonstrate that BDV replication competence in mice is mediated by the polymerase complex rather than the viral envelope and suggest that altered regulation of viral gene expression can favor adaptation to new host species.


Assuntos
Adaptação Biológica , Vírus da Doença de Borna/enzimologia , Vírus da Doença de Borna/fisiologia , RNA Polimerases Dirigidas por DNA/metabolismo , Proteínas Virais/metabolismo , Animais , Doença de Borna , Vírus da Doença de Borna/genética , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/virologia , RNA Polimerases Dirigidas por DNA/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Ratos , Transcrição Gênica , Proteínas Virais/genética , Replicação Viral
12.
J Virol ; 81(13): 7293-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17428876

RESUMO

An expression cassette for green fluorescent protein was successfully inserted at a site near the 5' end of the genome of Borna disease virus (BDV). When introduced into a mutant virus with highly active polymerase, the foreign gene was strongly expressed in neurons of infected rats. Since BDV can establish long-term persistence in the central nervous system of rodents, it may be used to engineer efficient vectors for specific delivery of foreign genes into highly differentiated neurons.


Assuntos
Vírus da Doença de Borna , Encéfalo , Expressão Gênica , Vetores Genéticos , Neurônios , Animais , Vírus da Doença de Borna/genética , Vírus da Doença de Borna/metabolismo , Encéfalo/metabolismo , Engenharia Genética , Mutação , Neurônios/metabolismo , Neurônios/virologia , RNA Polimerase Dependente de RNA/genética , Ratos , Ratos Endogâmicos Lew , Proteínas Virais/genética
13.
J Virol ; 81(13): 7297-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17428855

RESUMO

The X gene of Borna disease virus (BDV) encodes a nonstructural 10-kDa protein that can interact with viral polymerase cofactor P, thus regulating polymerase activity. It remained unknown whether X is essential for virus multiplication. All our attempts to generate mutant BDV with a nonfunctional X gene proved unsuccessful. However, a mutant virus with an inactive X gene was able to replicate in Vero cells if an artificial gene cassette encoding X was inserted at a site near the 5' end of the viral genome. These results indicate that X performs essential viral functions.


Assuntos
Região 5'-Flanqueadora , Vírus da Doença de Borna/genética , Genoma Viral , Proteínas não Estruturais Virais/genética , Replicação Viral/genética , Animais , Vírus da Doença de Borna/metabolismo , Chlorocebus aethiops , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Células Vero , Proteínas não Estruturais Virais/metabolismo
14.
J Gen Virol ; 88(Pt 11): 3130-3132, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17947539

RESUMO

We previously showed that mouse adaptation of cDNA-derived Borna disease virus (BDV) strain He/80(FR) was associated exclusively with mutations in the viral polymerase complex. Interestingly, independent mouse adaptation of non-recombinant He/80 was correlated with different alterations in the polymerase and mutations in the viral glycoprotein. We used reverse genetics to demonstrate that changes in the polymerase which improve enzymatic activity represent the decisive host range mutations. The glycoprotein mutations did not confer replication competence in mice, although they slightly improved viral performance if combined with polymerase mutations. Our findings suggest that the viral polymerase restricts the host range of BDV.


Assuntos
Vírus da Doença de Borna/genética , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Replicação Viral , Animais , Doença de Borna/mortalidade , Doença de Borna/virologia , Vírus da Doença de Borna/enzimologia , Vírus da Doença de Borna/metabolismo , Linhagem Celular , Camundongos , Mutação , Proteínas Virais/genética , Proteínas Virais/metabolismo
15.
J Virol ; 81(20): 11187-94, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17686872

RESUMO

Borna disease virus (BDV) is a highly neurotropic, noncytolytic virus. Experimentally infected B10.BR mice remain healthy unless specific antiviral T cells that infiltrate the infected brain are triggered by immunization. In contrast, infected MRL mice spontaneously mount an antiviral T-cell response that can result in meningoencephalitis and neurological disease. The antiviral T cells may, alternatively, eliminate the virus without inducing disease if they are present in sufficient numbers before the virus replicates to high titers. Since the immune response of H-2(k) mice is directed mainly against the epitope TELEISSI located in the viral nucleoprotein N, we generated BDV mutants that feature TQLEISSI in place of TELEISSI. We show that adoptive transfer of BDV N-specific CD8 T cells induced neurological disease in B10.BR mice persistently infected with wild-type BDV but not with the mutant virus expressing TQLEISSI. Surprisingly, the mutant virus replicated less well in adult MRL wild-type mice than in mutant mice lacking mature CD8 T cells. Furthermore, when MRL mice were infected with the TQLEISSI-expressing BDV mutant as newborns, neurological disease was observed, although at a lower rate and with slower kinetics than in mice infected with wild-type virus. These results confirm that TELEISSI is the major CD8 T-cell epitope in H-2(k) mice and suggest that unidentified minor epitopes are present in the BDV proteome which are recognized rather efficiently by antiviral T cells if the dominant epitope is absent.


Assuntos
Doença de Borna/terapia , Vírus da Doença de Borna/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T , Epitopos Imunodominantes , Transferência Adotiva , Sequência de Aminoácidos , Animais , Vírus da Doença de Borna/patogenicidade , Linfócitos T CD8-Positivos/transplante , Imunidade , Camundongos , Camundongos Endogâmicos , Doenças do Sistema Nervoso/etiologia , Nucleoproteínas/imunologia
16.
Ann Thorac Surg ; 84(5): 1515-20; discussion 1521, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17954055

RESUMO

BACKGROUND: Minimal extracorporeal circulation (MECC) is a promising perfusion technology, taking the advantage of an ECC while having a significantly reduced priming volume. We analyzed the actual possible benefits of using MECC in patients undergoing CABG procedures and compared the results with conventional extracorporeal circulation (CECC). METHODS: One thousand fifty-three consecutive patients underwent CABG surgery using the MECC perfusion technique. Subgroup analyses focused on perioperative myocardial markers (cardiac troponin I [cTnI]), incidence of atrial fibrillation (AF), and perioperative evaluation of inflammatory markers and data were compared with those of patients who underwent CABG using CECC. A propensity score analysis was performed. RESULTS: Patient characteristics and distribution of EuroSCORE risk were similar in both groups. Severity of coronary artery disease and extent of revascularization were also comparable in both groups (number of distal anastomoses: 3.2 +/- 1.1 in CECC vs 3.2 +/- 0.9 in MECC; p = not significant [ns]). The cTnI was significantly lower in the MECC group (11.0 +/- 10.8 microg/L in MECC vs 24.7 +/- 25.3 microg/L in CECC; p < 0.05). Incidence of AF was 11.1% in MECC and 39.0% in CECC (p < 0.05). Inflammatory markers (interleukin-6, SC5b-9) were lower in MECC patients (p < 0.05). Propensity score analysis confirmed faster recovery in MECC patients and lower incidence of AF. CONCLUSIONS: Minimal extracorporeal circulation is a safe perfusion technique for CABG and may therefore concurrence OPCAB and traditional CABG under CECC.


Assuntos
Ponte de Artéria Coronária/métodos , Circulação Extracorpórea/métodos , Adulto , Idoso , Fibrilação Atrial/etiologia , Ponte Cardiopulmonar , Complexo de Ataque à Membrana do Sistema Complemento , Proteínas do Sistema Complemento/análise , Ponte de Artéria Coronária/efeitos adversos , Circulação Extracorpórea/efeitos adversos , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
17.
Eur J Clin Pharmacol ; 62(11): 959-65, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17021890

RESUMO

OBJECTIVE: The aim of the present study was to evaluate a computerised monitoring system (CMS) based on laboratory test results for the detection of adverse drug reactions (ADRs) on a paediatric ward. METHODS: A prospective, 6-month pharmacoepidemiological survey was performed on a 22-bed paediatric isolation ward. ADRs were identified by intensive chart review. In addition to spontaneous reporting by the treating physician, automatic laboratory signals generated by a CMS were evaluated for their association with ADRs. ADRs were classified by the affected target organs according to the WHO-ART system organ classes. RESULTS: A total of 73 ADRs were identified in 439 admissions (396 patients) by chart review. The CMS alerted 31 (42.4%) ADRs while 23 (31.5%) ADRs were found solely by treating physicians. Eight ADRs were detected by both approaches resulting in a total detection rate of 74% (compared with intensive pharmacovigilance). Out of a total of 27,434 laboratory tests performed routinely, 1,563 were classified as abnormal by the predefined CMS and used as the basis of alerts. The sensitivity of the system with respect to patients alerted was 90.3% and the specificity only 19.6%. CONCLUSION: This study demonstrates that, using CMS, a different kind of mild adverse events were detected compared to the observation by the treating physician. The system presented appears to be sufficiently sensitive, but the specificity is too low to make it acceptable for physicians in daily practice. In children, clinically important ADRs can be detected best by intensified surveillance.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Adolescente , Criança , Pré-Escolar , Coleta de Dados , Feminino , Alemanha , Hospitais com menos de 100 Leitos , Sistemas de Informação Hospitalar , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Pediatria , Farmacoepidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade
18.
J Gen Virol ; 85(Pt 8): 2379-2387, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15269380

RESUMO

Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2(k) mice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.


Assuntos
Vírus da Doença de Borna/imunologia , Encéfalo/virologia , Células Dendríticas/imunologia , Animais , Imunização , Memória Imunológica , Camundongos , Proteínas do Nucleocapsídeo/imunologia , Fragmentos de Peptídeos/imunologia
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