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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.
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Fibrilación Atrial/epidemiología , Embolia Pulmonar/epidemiología , Medición de Riesgo , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Comorbilidad , Femenino , Alemania/epidemiología , Mortalidad Hospitalaria , Humanos , Hipertiroidismo/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Sistema de Registros , Troponina/sangreRESUMEN
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.
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Desfibriladores Implantables , Cardioversión Eléctrica , Pautas de la Práctica en Medicina , Austria , Alemania , Encuestas y Cuestionarios , SuizaRESUMEN
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.
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Fibrilación Atrial/fisiopatología , Función del Atrio Izquierdo/fisiología , Remodelación Atrial/fisiología , Técnicas Electrofisiológicas Cardíacas/métodos , Volumen Sistólico/fisiología , Anciano , Fibrilación Atrial/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Fibrilación Atrial , Terapia de Resincronización Cardíaca/métodos , Ablación por Catéter/métodos , Atrios Cardíacos/fisiopatología , Insuficiencia Cardíaca , Volumen Sistólico/fisiología , Anticoagulantes/uso terapéutico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Salud Global , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Pronóstico , Tasa de Supervivencia/tendenciasRESUMEN
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.
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Amiodarona/uso terapéutico , Taquicardia Supraventricular/tratamiento farmacológico , Taquicardia Ventricular/tratamiento farmacológico , Amiodarona/efectos adversos , Amiodarona/farmacocinética , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Monitoreo de Drogas , Electrocardiografía/efectos de los fármacos , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Cuidados a Largo Plazo , Taquicardia Supraventricular/sangre , Taquicardia Ventricular/sangreAsunto(s)
Anticoagulantes/uso terapéutico , Desfibriladores Implantables , Marcapaso Artificial , Pautas de la Práctica en Medicina/estadística & datos numéricos , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Austria , Alemania , Hemorragia/inducido químicamente , Encuestas y Cuestionarios , Suiza , Tromboembolia/prevención & controlRESUMEN
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.
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Adenocarcinoma/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Médicos Forenses , Próstata/patología , Neoplasias de la Próstata/epidemiología , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Autopsia , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/patología , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
Epithelioid hemangioendothelioma is a rare vascular tumor with intermediate biologic behavior and metastatic potential. Primary renal epithelioid hemangioendothelioma is extremely rare and we present the second report of this rare tumor in an interesting clinical scenario. A 59-year-old male with established history of widely metastatic high grade esophageal adenocarcinoma was found to have an isolated renal nodule on a followup computed tomography (CT) scan. Surgical excision, with the suspicion of metastatic carcinoma, and subsequent pathologic examination revealed an epithelioid hemangioendothelioma. The various differential diagnoses and use of morphological clues and immunohistochemistry are discussed.
RESUMEN
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.
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Neoplasias Endometriales/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor de Crecimiento de Hepatocito/biosíntesis , Anciano , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , PronósticoRESUMEN
Only few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present here two cases of renal ES/PNET with an uncanny presentation. The first case was discovered after the patient presented clinically with irradiating flank pain, mimicking the pain related with kidney stones. The second case had clinical presentation of pulmonary thromboembolism after the patient was involved in an automobilist accident. The tumors were mainly composed of small blue cells which by immunohistochemical were positive for neural markers, and FISH revealed the translocation 22q12 for the EWSR1 gene. The diagnosis of renal primitive neuroectodermal tumor/EWING tumor is very rare and usually involves several different diagnostic techniques. The differential diagnosis is usually broad with frequent overlapping features between the entities. The cases presented in this paper illustrated the difficulties with which routine anatomical pathologist is faced when dealing with rare renal poorly differentiated neoplasm in adults.
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Enfermedades de las Válvulas Cardíacas/inducido químicamente , Agonistas alfa-Adrenérgicos/efectos adversos , Tumor Carcinoide/complicaciones , Agonistas de Dopamina/efectos adversos , Alcaloides de Claviceps/efectos adversos , Humanos , Serotonina/fisiología , Serotoninérgicos/efectos adversosAsunto(s)
Antipsicóticos/efectos adversos , Citalopram/efectos adversos , Risperidona/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Torsades de Pointes/inducido químicamente , Anciano , Antipsicóticos/uso terapéutico , Citalopram/uso terapéutico , Quimioterapia Combinada , Electrocardiografía Ambulatoria , Femenino , Humanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/fisiopatología , Risperidona/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Torsades de Pointes/fisiopatologíaRESUMEN
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.
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Curación de Fractura/fisiología , Marcha/fisiología , Monitoreo Fisiológico/instrumentación , Fracturas de la Tibia/fisiopatología , Análisis de Varianza , Animales , Fenómenos Biomecánicos , Femenino , Fijación Interna de Fracturas/métodos , Osteotomía , Presión , Ovinos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Patients with warm autoantibodies are at high risk for delayed hemolytic transfusion reactions due to the presence of alloantibodies. To provide blood safe for transfusion and to avoid adsorption studies in some cases, the provision of prophylactic antigen-matched donor blood where feasible for patients with warm autoantibodies is advocated. STUDY DESIGN AND METHODS: Twenty consecutive adult patients with warm autoantibodies (January 1999 to February 2000) received chronic RBC transfusions by use of this protocol: the serology consistent with warm autoantibodies was confirmed; the alloantibodies were identified; the complete phenotype was determined (i.e., C, E, c, e, K, Jk(a), Jk(b), Fy(a), Fy(b), S, and s); and prophylactic antigen-matched (i.e., donor RBCs matched with the patient's phenotype), WBC-reduced donor RBCs were provided for transfusion. On subsequent admissions, samples were evaluated by panel studies and DATs. If the serology remained consistent with previous findings, prophylactic antigen-matched, WBC-reduced RBCs were transfused without further testing. RESULTS: Eight of 20 (40%) patients had existing, clinically significant alloantibodies. In 12 of 20 (60%) patients, a phenotype was determined and the patients received transfusion of a total of 149 prophylactic antigen-matched RBC units (mean, 15 units per patient) precluding adsorption studies on 51 pretransfusion samples. In 8 of 20 (40%) cases (2 with alloantibodies), phenotypes were indeterminant, necessitating differential allogeneic adsorption studies on 39 samples before transfusion of 144 RBC units (mean, 18 units per patient). CONCLUSIONS: Determining complete phenotypes should be a routine component of the serologic evaluation of patients with warm autoantibodies. Our algorithm for providing prophylactic antigen-matched RBCs to these patients when a complete phenotype can be determined provides flexibility in their transfusion management while maintaining safety and circumvents or simplifies pretransfusion adsorption studies.
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Anemia Hemolítica Autoinmune/terapia , Autoanticuerpos/sangre , Enfermedades Autoinmunes/terapia , Antígenos de Grupos Sanguíneos/inmunología , Incompatibilidad de Grupos Sanguíneos/diagnóstico , Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión Sanguínea , Isoanticuerpos/sangre , Adolescente , Adsorción , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Anemia Hemolítica Autoinmune/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Incompatibilidad de Grupos Sanguíneos/sangre , Incompatibilidad de Grupos Sanguíneos/inmunología , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Reacciones Falso Negativas , Femenino , Humanos , Inmunización , Isoanticuerpos/inmunología , Masculino , Persona de Mediana Edad , Fenotipo , Seguridad , Reacción a la TransfusiónRESUMEN
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.
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Antagonistas de Aminoácidos Excitadores/farmacología , Ketamina/farmacología , Psicosis Inducidas por Sustancias/psicología , Esquizofrenia/inducido químicamente , Adulto , Conducta/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/sangre , Femenino , Humanos , Ketamina/sangre , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Psicología del EsquizofrénicoRESUMEN
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.
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Reflejo de Sobresalto/efectos de los fármacos , Fumar/psicología , Estimulación Acústica , Adulto , Estudios Cruzados , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Cese del Hábito de Fumar/psicologíaRESUMEN
Porcine enteric calicivirus (PEC/Cowden) causes diarrhea in pigs, grows in cell culture, and is morphologically and genetically similar to the Sapporo-like human caliciviruses. Genetic analysis revealed that the tissue culture-adapted (TC) Cowden PEC has one distant and three clustered amino acid substitutions in the capsid region and 2 amino acid changes in the RNA polymerase region compared to wild-type (WT) PEC (M. Guo, K.-O. Chang, M. E. Hardy, Q. Zhang, A. V. Parwani, and L. J. Saif, J. Virol. 73:9625-9631, 1999). In this study, the TC PEC, passaged in a porcine kidney cell line, and the WT PEC, passaged in gnotobiotic (Gn) pigs, were used to orally inoculate 13 4- to 6-day-old Gn pigs. No diarrhea developed in the TC-PEC-exposed pigs, whereas moderate diarrhea developed in the WT-PEC orally inoculated pigs, persisting for 2 to 5 days. Fecal virus shedding persisting for at least 7 days was detected by both reverse transcription (RT)-PCR and antigen-enzyme-linked immunosorbent assay (antigen-ELISA) in both TC-PEC and WT-PEC orally inoculated pigs but not in mock-inoculated pigs. The PEC particles were detected by immunoelectron microscopy (IEM) in intestinal contents from all the WT-PEC-inoculated pigs, but not from the TC-PEC-inoculated pigs. Mild (duodenum and jejunum) or no (ileum) villous atrophy was observed in histologic sections of the small intestines of TC-PEC-inoculated pigs, whereas WT PEC caused mild to severe (duodenum and jejunum) villous atrophy and fusion. Scanning electron microscopy confirmed mild shortening and blunting of villi in the duodenum and jejunum of the TC-PEC-inoculated pigs, in contrast to moderate to severe villous shortening and blunting in the duodenum and jejunum of WT-PEC-inoculated pigs. Higher numbers of PEC antigen-positive villous enterocytes were detected by immunofluorescent (IF) staining in the proximal small intestine of the WT-PEC-inoculated pigs, in contrast to low numbers of PEC antigen-positive enterocytes in only one of four TC-PEC-inoculated pigs. No PEC antigen-positive cells were observed in the colon or extraintestinal tissues of all inoculated pigs or in the small intestine of one mock-inoculated pig. Thus, the TC PEC was at least partially attenuated (no diarrhea, mild lesions) after serial passage in cell culture. In further experiments, three 4- to 6-day-old Gn pigs were intravenously (i.v.) inoculated with WT PEC, and all pigs developed diarrhea and villous atrophy in the small intestines resembling that observed in the orally inoculated pigs. Fecal viral shedding persisting for 8 days was detected by both RT-PCR and antigen-ELISA, and PEC was detected by IEM in feces or intestinal contents. The PEC RNA and antigens (at low titers) were detected in acute-phase sera from all the WT-PEC i.v.-inoculated pigs and also from seven of nine of the WT-PEC orally inoculated pigs. Oral or i.v. inoculation of four additional pigs with the PEC-positive acute-phase sera induced diarrhea, small intestinal lesions, PEC shedding in feces, and seroconversion to PEC, confirming the occurrence of viremia during PEC infection, with infectious PEC present in acute-phase sera. No diarrhea, histopathologic changes, or IF staining in the small intestine or fecal or serum detection of PEC was evident in two pigs i.v. mock-inoculated or a pig inoculated i.v. with inactivated WT PEC. To our knowledge, this is the first report of an attenuated enteric calicivirus, the induction of diarrhea, and intestinal lesions in Gn pigs caused by i.v. inoculation of WT PEC and the presence of viremia following PEC infection.
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Infecciones por Caliciviridae/virología , Caliciviridae/genética , Animales , Caliciviridae/patogenicidad , Infecciones por Caliciviridae/patología , Infecciones por Caliciviridae/fisiopatología , Técnicas de Cultivo , Genoma Viral , Humanos , Porcinos , Virulencia/genéticaRESUMEN
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."