RESUMO
BACKGROUND: Although prior studies indicate a high prevalence of atrial fibrillation (AF) in patients with pulmonary embolism (PE), the exact prevalence and prognostic impact are unknown. METHODS: We aimed to investigate the prevalence, risk factors and prognostic impact of AF on risk stratification, in-hospital adverse outcomes and mortality in 528 consecutive PE patients enrolled in a single-centre registry between 09/2008 and 09/2017. RESULTS: Overall, 52 patients (9.8%) had known AF and 57 (10.8%) presented with AF on admission; of those, 34 (59.6%) were newly diagnosed with AF. Compared to patients with no AF, overt hyperthyroidism was associated with newly diagnosed AF (OR 7.89 [2.99-20.86]), whilst cardiovascular risk comorbidities were more frequently observed in patients with known AF. Patients with AF on admission had more comorbidities, presented more frequently with tachycardia and elevated cardiac biomarkers and were hence stratified to higher risk classes. However, AF on admission had no impact on in-hospital adverse outcome (8.3%) and in-hospital mortality (4.5%). In multivariate logistic regression analyses corrected for AF on admission, NT-proBNP and troponin elevation as well as higher risk classes in risk assessment models remained independent predictors of an in-hospital adverse outcome. CONCLUSION: Atrial fibrillation is a frequent finding in PE, affecting more than 10% of patients. However, AF was not associated with a higher risk of in-hospital adverse outcomes and did not affect the prognostic performance of risk assessment strategies. Thus, our data support the use of risk stratification tools for patients with acute PE irrespective of the heart rhythm on admission.
Assuntos
Fibrilação Atrial/epidemiologia , Embolia Pulmonar/epidemiologia , Medição de Risco , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Comorbidade , Feminino , Alemanha/epidemiologia , Mortalidade Hospitalar , Humanos , Hipertireoidismo/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Sistema de Registros , Troponina/sangueRESUMO
BACKGROUND: The possible treatment strategies for defects of the pace-sense (P/S) part of a defibrillation lead are either implantation of a new high-voltage (HV)-P/S lead, with or without extraction of the malfunctioning lead, or implantation of a P/S lead. METHODS: We conducted a Web-based survey across cardiac implantable electronic device (CIED) centers to investigate their procedural practice and decision-making process in cases of failure of the P/S portion of defibrillation leads. In particular, we focused on the question of whether the integrity of the HV circuit is confirmed by a test shock before decision-making. The questionnaire included 14 questions and was sent to 951 German, 341 Austrian, and 120 Swiss centers. RESULTS: The survey was completed by 183 of the 1412 centers surveyed (12.7% response rate). Most centers (90.2%) do not conduct a test shock to confirm the integrity of the HV circuit before decision-making. Procedural practice in lead management varies depending on the presentation of lead failure and whether the center applies a test shock. In centers that do not conduct a test shock, the majority (69.9%) implant a new HV-P/S lead. Most centers (61.7%) that test the integrity of the HV system implant a P/S lead. The majority of centers favor DF-4 connectors (74.1%) over DF-1 connectors (25.9%) at first CIED implantation. CONCLUSION: Either implanting a new HV-P/S lead or placing an additional P/S lead are selected strategies if the implantable cardioverter-defibrillator lead failure is localized to the P/S portion. However, conducting a test shock to confirm the integrity of the HV component is rarely performed.
Assuntos
Desfibriladores Implantáveis , Cardioversão Elétrica , Padrões de Prática Médica , Áustria , Alemanha , Inquéritos e Questionários , SuíçaRESUMO
Heart failure and atrial fibrillation are common and responsible for significant mortality of patients. Both share the same risk factors like hypertension, ischemic heart disease, diabetes, obesity, arteriosclerosis, and age. A variety of microscopic and macroscopic changes favor the genesis of atrial fibrillation in patients with preexisting heart failure, altered subcellular Ca2+ homeostasis leading to increased cellular automaticity as well as concomitant fibrosis that are induced by pressure/volume overload and altered neurohumoral states. Atrial fibrillation itself promotes clinical deterioration of patients with preexisting heart failure as atrial contraction significantly contributes to ventricular filling. In addition, atrial fibrillation induced tachycardia can even further compromise ventricular function by inducing tachycardiomyopathy. Even though evidence has been provided that atrial functions significantly and independently of confounding ventricular pathologies, correlate with mortality of heart failure patients, rate and rhythm controls have been shown to be of equal effectiveness in improving mortality. Yet, it also has been shown that cohorts of patients with heart failure benefit from a rhythm control concept regarding symptom control and hospitalization. To date, amiodarone is the most feasible approach to restore sinus rhythm, yet its use is limited by its extensive side-effect profile. In addition, other therapies like catheter-based pulmonary vein isolation are of increasing importance. A wide range of heart failure-specific therapies are available with mixed impact on new onset or perpetuation of atrial fibrillation. This review highlights pathophysiological concepts and possible therapeutic approaches to treat patients with heart failure at risk for or with atrial fibrillation.
Assuntos
Fibrilação Atrial , Terapia de Ressincronização Cardíaca/métodos , Ablação por Cateter/métodos , Átrios do Coração/fisiopatologia , Insuficiência Cardíaca , Volume Sistólico/fisiologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Saúde Global , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Prognóstico , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and cancers have common pathoetiologic and pathogenetic cascades, both diseases will co-occur and patients may represent a potential target group for cancer screening interventions. MATERIALS AND METHODS: Prostates and coronary vessels were examined from 37 deceased men, aged 50 years and older, who died unexpectedly and suddenly from traumatic causes. Tissue sections of the entire prostate were examined for benign and malignant lesions. Analysis of Variance was used to compare mean coronary artery atherosclerosis scores among groups of men with diagnosis of adenocarcinoma, intraepithelial neoplasm, benign hyperplasia and normal prostate glands. RESULTS: Twelve prostates (32.5%) showed adenocarcinoma of the prostate, four with Gleason score 7 and eight with Gleason score 6. After adjustment for age and race, there remained no statistical difference between prostate pathology groups and atherosclerosis score (F = 0.72; P = 0.55). CONCLUSIONS: To our knowledge, ours is the first study to use direct pathological examination of tissues for definitive identification of atherosclerosis and prostate cancer. In our case series, the occurrence and progression of coronary atherosclerotic disease and cancer of the prostate were not associated.
Assuntos
Adenocarcinoma/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Médicos Legistas , Próstata/patologia , Neoplasias da Próstata/epidemiologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Autopsia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Hepatocyte growth factor (HGF), c-Met, and basic fibroblast growth factor (bFGF) are molecular markers that contribute to angiogenesis and proliferation in numerous cancers. We assessed the prognostic significance of these factors in tumour and stroma of endometrial cancer (EC) patients (n=211). METHODS: Immunohistochemistry (IHC) was used to detect tumour and stromal protein expression of the biomarkers. Associations between expression and clinicopathological factors were assessed using Chi-square tests. Kaplan-Meier curves, log-rank tests, and Cox regression were used to summarise associations between biomarker expression and overall survival (OS) and recurrence-free survival (RFS). RESULTS: Tumour bFGF was significantly associated with high-grade endometrioid and clear cell histology (P<0.001), advanced stage (P=0.008), positive lymph-node involvement (P=0.002), poor OS (log-rank test, P=0.009), and poor RFS (P<0.001). In multivariable analyses, cases with HGF-positive, stromal bFGF-positive tumours had a lower risk of death compared with cases with HGF-positive, stromal bFGF-negative tumours (hazard ratio (HR): 0.14, 95% CI: 0.03, 0.60). Cases with HGF-positive, bFGF-positive tumours had a higher risk of recurrence compared with cases with negative expression of both markers (HR: 9.88, 95% CI: 2.63, 37.16). CONCLUSION: These IHC data show that tumour and stromal bFGF expression have opposite associations with survival outcomes in EC patients. If confirmed in larger studies, tumour-derived bFGF could be an attractive target in EC therapy.
Assuntos
Neoplasias do Endométrio/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento de Hepatócito/biossíntese , Idoso , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , PrognósticoAssuntos
Anticoagulantes/uso terapêutico , Desfibriladores Implantáveis , Marca-Passo Artificial , Padrões de Prática Médica/estatística & dados numéricos , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Áustria , Alemanha , Hemorragia/induzido quimicamente , Inquéritos e Questionários , Suíça , Tromboembolia/prevenção & controleRESUMO
INTRODUCTION: The extent of left atrial (LA) adverse remodeling as a cardiac disease marker has become increasingly important. In patients with atrial fibrillation (AF), atrial remodeling (AR) is accompanied by increased mortality. The relation between LA function and the extent of low-voltage areas (LVAs) has not yet been systematically investigated. METHODS: In patients with AF undergoing catheter-ablation, LA was studied using echocardiography and ultra-high-density mapping (Rhythmia®). Fibrosis (i.e. extent of LVAs) was estimated by quantifying areas with bipolar electrogram amplitudes of ≤0.5, ≤0.4, ≤0.3, ≤0.2 or ≤0.1â¯mV. RESULTS: A total of 22 patients with a mean LVEF of 53⯱â¯2% was studied. Mean LA volume index (LAVI) was significantly increased at 39⯱â¯3â¯ml/m2 indicating AR. Size of LVAs was 57⯱â¯7â¯cm2 representing 47⯱â¯5% of the total LA area (low-voltage set to ≤0.5â¯mV). With low-voltage set to ≤0.4, ≤0.3, ≤0.2 and ≤0.1, total area decreased to 34⯱â¯6, 28⯱â¯6, 22⯱â¯5 and 12⯱â¯3â¯cm2. LAVI positively correlated with the extent of LVAs at all cut-offs. Mean LA emptying fraction was 42⯱â¯3% and showed a negative correlation with LVAs with low-voltage set to ≤0.4â¯mV. Moreover, mean LA strain was 13⯱â¯2% and correlated with LVAs with low-voltage at all cut-offs further supporting the notion that the extent of LVAs impacts LA function. Notably, with low-voltage set to ≤0.2, ≤0.3 and ≤0.4â¯mV impaired LA strain was detected with an accuracy of >76% (pâ¯<â¯0.05). CONCLUSION: Structural (i.e. LAVI) and functional (i.e. LA emptying fraction and LA strain) parameters of the LA correlate with the extent of LVAs.
Assuntos
Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo/fisiologia , Remodelamento Atrial/fisiologia , Técnicas Eletrofisiológicas Cardíacas/métodos , Volume Sistólico/fisiologia , Idoso , Fibrilação Atrial/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Amiodarone has multiple and complex electrophysiological effects that render it a very effective antiarrhythmic drug for the treatment of both, supraventricular and ventricular arrhythmias. Proarrhythmic effects of amiodarone in patients with structural heart disease are rare. However, extracardiac adverse effects occurring in association with amiodarone treatment are frequent and feared. These adverse effects have usually been related to total amiodarone exposure (i. e., dose and duration of treatment). Parallel to a more frequent use of lower amiodarone maintenance doses (100-200 mg/day), the incidence of severe unwanted extracardiac side effects has decreased. High-dose maintenance regiments (daily dose ≥300 mg) are usually obsolete. This paper discusses recommendations regarding the monitoring of cardiac and extracardiac side effects of amiodarone. They need to be regarded by physicians using amiodarone to ensure long-term safety of amiodarone therapy.
Assuntos
Amiodarona/uso terapêutico , Taquicardia Supraventricular/tratamento farmacológico , Taquicardia Ventricular/tratamento farmacológico , Amiodarona/efeitos adversos , Amiodarona/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos , Eletrocardiografia/efeitos dos fármacos , Sistema de Condução Cardíaco/efeitos dos fármacos , Humanos , Assistência de Longa Duração , Taquicardia Supraventricular/sangue , Taquicardia Ventricular/sangueRESUMO
BACKGROUND: Current clinical methods for monitoring fracture healing are often invasive and inaccurate. This paper evaluates the use of a pressure sensitive platform to improve monitoring. METHODS: Standardised 3 mm diaphyseal bone defects were created in the right tibia of 64 female sheep and stabilised with either a rigid monolateral external fixator or a more flexible variant. Over a nine week healing period gait parameters were measured using a pressure sensitive platform and interfragmentary movements at the fracture site were monitored. Frequency spectra were calculated for the ground reaction forces. The tibiae were tested biomechanically after sacrifice and callus sections were analysed histomorphometrically. FINDINGS: All animals unloaded the operated and overloaded the contralateral hindlimb. Callus mineralisation and stiffness, as well as limb loading increased during healing whilst interfragmentary movements were reduced. Larger interfragmentary movements resulted in a slower fracture healing rate as documented histologically and biomechanically. Frequency analysis showed upto 14 dB loss of power at frequencies associated with bone mechanotransduction at four weeks postoperatively, reducing to a 3 dB loss at nine weeks. INTERPRETATION: Gait analysis is a valuable tool for monitoring the course of fracture healing. Different fixation stiffnesses caused different initial interfragmentary movements leading to different healing rates. Ground reaction forces were strongly related to the course of callus mineralisation and thus directly reflected the recovery of stiffness at the fracture site. Reduced levels of loading frequencies that may affect bone healing persist to nine weeks postoperatively.
Assuntos
Consolidação da Fratura/fisiologia , Marcha/fisiologia , Monitorização Fisiológica/instrumentação , Fraturas da Tíbia/fisiopatologia , Análise de Variância , Animais , Fenômenos Biomecânicos , Feminino , Fixação Interna de Fraturas/métodos , Osteotomia , Pressão , Ovinos , Estatísticas não ParamétricasRESUMO
BACKGROUND: Schizophrenics show deficits in sensorimotor gating, as measured by prepulse inhibition of acoustic startle (PPI). The goal of this investigation is to further characterize PPI and habituation deficits in schizophrenia, and to examine whether differing subgroups of schizophrenics would show comparable PPI deficits. METHODS: PPI was measured in 24 male schizophrenic subjects (9 acutely decompensated inpatients and 15 stable outpatients) and in 20 age-matched normal control subjects. Schizophrenic subjects were rated for positive and negative symptoms at the time of testing. RESULTS: Schizophrenic subjects showed deficits in prepulse inhibition and habituation as compared to normal subjects. Similar latency facilitation was produced by the prepulse in both groups. Acutely decompensated inpatients and stable outpatients did not differ in percent PPI. PPI did not correlate with severity of positive or negative symptoms. CONCLUSIONS: These results suggest that schizophrenic subjects have impaired central inhibitory mechanisms as measured by PPI, and support the hypothesis that periods of relative clinical remission are not accompanied by normalization of sensorimotor gating.
Assuntos
Estimulação Acústica , Habituação Psicofisiológica , Reflexo de Sobressalto , Esquizofrenia/fisiopatologia , Doença Aguda , Adulto , Análise de Variância , Biomarcadores , Estudos de Casos e Controles , Doença Crônica , Eletromiografia , Humanos , Masculino , Pessoa de Meia-Idade , Inibição Proativa , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p =.0001) and the BPRS withdrawal subscale (p =.0001), whereas SVs experienced an increase only in positive symptoms (p =.0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.
Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Psicoses Induzidas por Substâncias/psicologia , Esquizofrenia/induzido quimicamente , Adulto , Comportamento/efeitos dos fármacos , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/sangue , Feminino , Humanos , Ketamina/sangue , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicologia do EsquizofrênicoRESUMO
The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.
Assuntos
Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Ketamina/efeitos adversos , Inibição Neural/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Ácido Glutâmico/metabolismo , Alucinações/induzido quimicamente , Alucinações/fisiopatologia , Humanos , Ketamina/administração & dosagem , Masculino , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Valores de Referência , Reflexo de Sobressalto/fisiologiaRESUMO
We report 4 distinctive renal epithelial neoplasms that are essentially identical at the morphologic and immunohistochemical levels and do not fit an accepted category in the existing classification of these lesions. The patients were all females, with ages ranging from 32 to 79 years (mean, 50 years). The tumors were well circumscribed and were composed of uniform, predominantly low cuboidal cells with eosinophilic, focally vacuolated cytoplasm. Tumor cells generally formed interconnecting tubules, with smaller areas of cordlike growth and spindling in a bubbly, myxoid stroma. All tumors were confined to the kidney, and all were immunoreactive for high-molecular-weight cytokeratin 34betaE12, cytokeratin 7, epithelial membrane antigen, and cytokeratin cocktail AE1/3. Only 1 tumor was focally immunoreactive for Ulex europaeus agglutinin. Ultrastructural study showed tumor cells forming tubular structures reminiscent of the loop of Henle or distal convoluted tubule. Follow-up in all 4 cases was benign. These distinctive tumors may be confused with aggressive sarcomatoid renal cell carcinomas because of their spindled morphology. The morphologic, immunohistochemical, and ultrastructural features of these lesions indicate differentiation toward distal nephron segments. Similar tumors probably have been reported among low-grade collecting duct carcinomas or tumors "possibly related to the loop of Henle."
Assuntos
Neoplasias Renais/patologia , Néfrons/patologia , Lectinas de Plantas , Adulto , Idoso , Diferenciação Celular , Citoplasma/patologia , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Neoplasias Renais/química , Túbulos Renais Distais/patologia , Lectinas/análise , Alça do Néfron/patologia , Microscopia Eletrônica , Pessoa de Meia-Idade , Mucina-1/análise , Vacúolos/patologiaRESUMO
RATIONALE: Prepulse inhibition of the acoustic startle response (PPI) is a paradigm in which a startle response to an auditory stimulus is reduced when that stimulus is preceded by a lower intensity, non-startling stimulus (prepulse). PPI is used as an operational measure of sensorimotor gating in both humans and other mammals. Acute administration of nicotine enhances PPI in rats, an effect that has been recently demonstrated in humans. OBJECTIVES: We compared PPI in 12 male smokers and 14 male non-smokers tested in four repeat startle sessions across 2 test days in order to examine further the effects of smoking and smoking withdrawal on acoustic startle and PPI. METHODS: In a crossover design, the smokers smoked ad lib or abstained from smoking overnight prior to 9 a.m. testing. These 2 test days were in randomized order. On both days, smokers were immediately retested after smoking three cigarettes. Non-smokers were tested twice on each of 2 separate days. RESULTS: Across sessions, the smokers had reduced startle to pulse alone stimuli in the first block of each session when compared to the non-smokers. The non-smokers had no change in gating across their four test sessions. For the smokers, the abstinence condition produced a non-significant reduction in PPI compared to that of the ad lib smoking day. During the smoking abstinence session, smokers had comparable gating to non-smokers. Smoking immediately after washout produced a significant improvement in PPI such that gating in the smokers exceeded that of the non-smokers. CONCLUSION: Smoking after overnight washout from cigarettes enhanced sensorimotor gating compared to pre-smoking values and compared to gating in non-smokers.
Assuntos
Reflexo de Sobressalto/efeitos dos fármacos , Fumar/psicologia , Estimulação Acústica , Adulto , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Abandono do Hábito de Fumar/psicologiaRESUMO
We evaluated rotavirus subunit vaccines for use in humans and animals. Insect cells were co-infected with combinations of individual baculovirus recombinants expressing human, bovine or simian rotavirus VP2, VP4, VP6 or VP7 to produce virus-like particles (VLPs). To determine whether immunization with VLPs could induce active protective immunity, VLPs were administered parenterally to rabbits, and the immune response and protection from rabbit ALA rotavirus challenge were evaluated. Complete or partial protection was attained, showing that parenteral immunization with VLPs induces active protective immunity. We also examined whether heterotypic immune responses could be induced with a limited number of broadly reactive VP7 proteins or with chimeric particles (multiple VP7 types on individual particles). The feasibility of this approach was determined by immunizing mice with VLPs containing a G3 VP7 or G1 VP7 and chimeric G1/G3 VLPs. Broadly reactive neutralizing antibody was induced by the G1 VLPs. VLPs also have been successfully used to boost lactogenic (colostral and milk) immunity in dairy cows. Taken together, these results show that VLPs can be effective immunogens in rabbits, mice and dairy cattle when administered parenterally, a limited number of VLPs may be sufficient to produce a broadly protective vaccine, and G3 VLPs may serve as an effective subunit vaccine for use in bovines.
Assuntos
Antígenos Virais , Infecções por Rotavirus/prevenção & controle , Rotavirus/imunologia , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Capsídeo/genética , Capsídeo/imunologia , Proteínas do Capsídeo , Bovinos , Humanos , Imunização Passiva , Camundongos , CoelhosRESUMO
Transmissible gastroenteritis virus (TGEV), a coronavirus, replicates in intestinal enterocytes and causes diarrhea in young pigs. Porcine respiratory coronavirus (PRCV), a spike (S) gene natural deletion mutant of TGEV, has a respiratory tissue tropism and causes mild or subclinical respiratory infections. Conventional antigen-based diagnostic tests fail to differentiate TGEV and PRCV, and a blocking ELISA test to serologically differentiate TGEV/PRCV-infected pigs is conducted on convalescent serum retrospectively after disease outbreaks. A reverse transcription (RT)-nested polymerase chain reaction (PCR) with primers targeted to the S gene deletion region to differentiate TGEV/PRCV was developed. The specificity of the RT-nested PCR was confirmed with reference and recent field strains of TGEV/PRCV, and its sensitivity was analyzed by testing nasal and fecal samples collected from pigs at various days postinoculation (DPI) with TGEV or PRCV. Specific PCR products for TGEV/PRCV were detected only with the homologous reference or field coronaviruses and for 10-14 DPI of pigs with TGEV (feces) or PRCV (nasal samples). The RT-nested PCR assay was more sensitive than antigen-based assays on the basis of duration of virus detection in experimentally infected pigs and was directly applicable to nasal as well as fecal specimens from the field.
Assuntos
Infecções por Coronavirus/veterinária , Gastroenterite Suína Transmissível/diagnóstico , Infecções Respiratórias/veterinária , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Animais , Infecções por Coronavirus/diagnóstico , Diagnóstico Diferencial , Fezes/virologia , Líquido da Lavagem Nasal , Infecções Respiratórias/diagnóstico , Sensibilidade e Especificidade , Suínos , Vírus da Gastroenterite TransmissívelRESUMO
Dot and Northern blot hybridization assays were developed to detect and differentiate group A bovine rotavirus serotypes using radiolabeled serotype 6 (Nebraska calf diarrhea virus [NCDV] and United Kingdom [UK] strains) or serotype 10 (Crocker [Cr] strain) VP7 gene probes. Partial length VP7-specific cDNA encompassing areas of major sequence diversity were generated by the polymerase chain reaction (PCR) using either cloned VP7 genes (NCDV and UK strains) or reverse transcribed mRNA (Cr strain) as templates. Radiolabeled probes prepared from the PCR-generated cDNA were tested at various stringency conditions to optimize the hybridization assays. At high stringency conditions (52 C, 50% formamide, 5 x standard saline citrate), the NCDV, UK, and Cr probes serotypically differentiated bovine rotavirus isolates in RNA samples prepared from cell culture propagated viruses or in fecal specimens from infected gnotobiotic calves. The sensitivity and specificity of NCDV and Cr VP7 probes were characterized in dot blot hybridization assays, and the probes were estimated to detect at least 1 ng of viral RNA. The serotyping results obtained using VP7 probes were similar to those obtained using serologic assays. Further development of these assays may provide a useful means for the rapid detection and differentiation of bovine rotavirus serotypes in fecal samples from calves in the field.
Assuntos
Antígenos Virais/genética , Proteínas do Capsídeo , Capsídeo/genética , Sondas de DNA , RNA Viral/análise , Rotavirus/isolamento & purificação , Animais , Sequência de Bases , Northern Blotting , Bovinos , Doenças dos Bovinos/microbiologia , Immunoblotting , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Oligodesoxirribonucleotídeos , Reação em Cadeia da Polimerase , RNA de Cadeia Dupla/análise , Rotavirus/classificação , Rotavirus/genética , Infecções por Rotavirus/microbiologia , Infecções por Rotavirus/veterinária , Sensibilidade e Especificidade , SorotipagemRESUMO
Group A bovine rotaviruses (BRV) have been identified worldwide as a major cause of diarrhea in the young of many species, including humans. Group A rotaviruses are classified into serotypes on the basis of the outer capsid proteins, VP7 (G types) and VP4 (P types). To date, there are 14 G types of group A rotaviruses, with G1, G6, G8, and G10 described for BRV isolates. In this study, G6- and G10-specific monoclonal antibodies (MAbs) were used in an enzyme-linked immunosorbent assay (ELISA) for the G typing of BRV-positive stool samples from diarrheic beef and dairy calves from South Dakota, Ohio, Michigan, Nebraska, and Washington, USA, and Ontario, Canada. ELISA plates were coated using a broadly reactive VP7 MAb (Common 60) or with G6- or G10-specific MAbs. BRV-positive fecal samples were diluted and added to duplicate wells, followed by the addition of polyclonal guinea pig anti-group A rotavirus serum as the secondary antibody. Several reference G6 and G10 BRV strains as well as other G types previously reported in cattle (G1, G2, G3, G8) and BRV-negative samples were included as G type specificity and negative controls. From a total of 308 field samples analyzed, 79% (244/308) tested positive by the broadly reactive VP7 MAb; of these, 54% (131/244) were G6 positive, 14% (35/244) were G10 positive, 4% (9/244) were both G6 and G10 positive, and 28% (69/244) were G6 and G10 negative.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doenças dos Bovinos/microbiologia , Diarreia/veterinária , Infecções por Rotavirus/veterinária , Rotavirus/classificação , Animais , Anticorpos Monoclonais , Anticorpos Antivirais/análise , Bovinos , Doenças dos Bovinos/imunologia , Diarreia/microbiologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização/veterinária , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Sensibilidade e Especificidade , Sorotipagem/veterináriaRESUMO
Previously, we described a disease syndrome in young turkeys caused by an enterovirus-like virus. The virus was designated an enterovirus-like virus based on size, morphology, and intracytoplasmic crystalline arrays of virus. In the present study, further characterization of the virus was performed to ascertain its classification. The virus has a buoyant density of 1.33 g/ml in CsCl and single-stranded RNA genome of approximately 7.5 kilobases. These combined characteristics indicate that this agent is an enterovirus.