RESUMEN
Cutaneous squamous cell carcinoma (cSCC) numbers among the most common types of skin cancer and is known as one of the cancer entities with the highest mutational burden among all solid tumours. Due to the positive correlation between mutational burden and response rate to inhibitors of the programmed cell death 1 (PD-1), those inhibitors are considered promising candidates for the systemic therapy of cSCC. Recently, the PD-1 inhibitors pembrolizumab, nivolumab and cemiplimab demonstrated efficacy in the systemic treatment of locally advanced or metastatic cSCC leading to the approval of cemiplimab by the FDA (U.S. Food and Drug Administration) in 2018 and the EMA (European Medicines Agency) in 2019. Patients with haematological malignancies tend to develop skin cancers of high aggressiveness, enhanced cumulative recurrence rate and higher rates of metastases with subsequent death. Chronic lymphocytic leukaemia (CLL) is the most frequent type of leukaemia in the United States and Europe with the majority of patients older than 50 years of age. This neoplasm predominantly originates from B -cells leading to an impaired immune system of the patient. Although CLL is a B-cell malignancy, studies have also described the involvement of T cells in the pathogenesis and progression of the disease with contradictory findings on the effects of PD-1 inhibitors in CLL. Due to their underlying hematologic malignancy, these patients have commonly no access to PD-1 inhibitor trials for treatment of advanced cSCC. We report on two patients with locally advanced or metastatic cSCC. Both patients had been suffering from a CLL for many years without indication for treatment. Despite a potential immunosuppressive state of the patients due to their CLL, both were treated with the PD-1 inhibitor pembrolizumab resulting in different therapy outcomes.
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Carcinoma de Células Escamosas , Leucemia Linfocítica Crónica de Células B , Neoplasias Cutáneas , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Masculino , Neoplasias Cutáneas/tratamiento farmacológico , Estados UnidosRESUMEN
OBJECTIVES: To assess the impact of the scout view orientation on radiation exposure and image quality in thoracoabdominal CT, when automated tube voltage selection (ATVS) and automated tube current modulation (ATCM) are used in combination with scan planning on a single scout view. METHODS: Fifty patients underwent two thoracoabdominal CT examinations, one planned on an anteroposterior scout view, one planned on a lateral scout view. Both examinations included contrast-enhanced imaging of chest (CH) and abdomen (AB) and non-contrast-enhanced imaging of the liver (LI). For all examinations the same imaging protocol was used on the same dual-source CT scanner. The radiation exposure was recorded and objective as well as visual image quality was assessed for all examinations. RESULTS: The median dose-length product was significantly lower in scans planned on a lateral scout view (CH: 179 vs. 218 mGy*cm, LI: 148 vs. 178 mGy*cm, AB: 324 vs. 370 mGy*cm, p < 0.0001). Objective image quality was marginal lower in scans planned on a lateral scout view, whereas the visual image quality was rated as equal. CONCLUSION: At the tested radiation doses, the orientation of the scout view has a significant impact on the radiation exposure but no clinically relevant impact on the image quality. KEY POINTS: ⢠The scout view orientation has a significant impact on the radiation exposure. ⢠The scout view orientation has no clinically relevant impact on image quality. ⢠A lateral scout view should be preferred with regard to radiation exposure.
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Dosis de Radiación , Exposición a la Radiación/estadística & datos numéricos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiografía Abdominal/métodos , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Abdomen/diagnóstico por imagen , Femenino , Humanos , Hígado , Masculino , Persona de Mediana Edad , Radiografía Abdominal/normas , Radiografía Torácica/normas , Reproducibilidad de los Resultados , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos X/normasRESUMEN
Spinal muscular atrophy (SMA) is a common recessive disorder characterized by the loss of lower motor neurons in the spinal cord. The disease has been classified into three types based on age of onset and severity. SMA I-III all map to chromosome 5q13 (refs 2,3), and nearly all patients display deletions or gene conversions of the survival motor neuron (SMN1) gene. Some correlation has been established between SMN protein levels and disease course; nevertheless, the genetic basis for SMA phenotypic variability remains unclear, and it has been postulated that the loss of an additional modifying factor contributes to the severity of type I SMA. Using comparative genomics to screen for such a factor among evolutionarily conserved sequences between mouse and human, we have identified a novel transcript, H4F5, which lies closer to SMN1 than any previously identified gene in the region. A multi-copy microsatellite marker that is deleted in more than 90% of type I SMA chromosomes is embedded in an intron of this gene, indicating that H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.
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Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Cromosomas Humanos Par 5 , Clonación Molecular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Eliminación de Gen , Marcadores Genéticos , Homocigoto , Humanos , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Homología de Secuencia de Aminoácido , Proteína 1 para la Supervivencia de la Neurona MotoraRESUMEN
We have demonstrated a monolithic cladding-pumped ytterbium-doped single all-fiber laser oscillator generating 1 kW of CW signal power at 1080 nm with 71% slope efficiency and near diffraction-limited beam quality. Fiber components were highly integrated on "spliceless" passive fibers to promote laser efficiency and alleviate non-linear effects. The laser was pumped through a 7:1 pump combiner with seven 200-W 91x nm fiber-pigtailed wavelength-beam-combined diode-stack modules. The signal power of such a single all-fiber laser oscillator showed no evidence of roll-over, and the highest output was limited only by available pump power.
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Amplificadores Electrónicos , Láseres de Semiconductores , Oscilometría/instrumentación , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
BACKGROUND: The aim of the study was to ascertain the state of the art in x-ray assessment in an emergency surgical department. METHODS: From August 2008 to February 2009 a total of 1,588 plain x-rays of 658 patients from the emergency department were included in this study. The images were assessed by 3 experienced orthopedic surgeons and 1 experienced radiologist. The incidence of missed traumatic lesions and suspected lesions and the treatment of these patients were noted. RESULTS: A total of 136 pathological cases with 238 pathological x-ray findings were found. The mean rate of missed lesions was 13% of the assessed cases. Despite the fact that the rate of missed lesions varied from 9-25% depending on the level of experience, all patients were treated adequately. The quality of x-ray assessment improved with the level of training of the individual doctors. CONCLUSION: The present situation is in need of improvement but it is not critical. Junior medical staff should undergo a special training in x-ray assessment.
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Errores Diagnósticos/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Competencia Profesional/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Traumatología/estadística & datos numéricos , Heridas y Lesiones/diagnóstico por imagen , Heridas y Lesiones/epidemiología , Errores Diagnósticos/prevención & control , Reacciones Falso Negativas , Alemania/epidemiología , Humanos , Incidencia , Radiografía , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: The aim of this study was to evaluate the detection rate of [68Ga]prostate-specific membrane antigen ([68Ga]PSMA-11) positron emission tomography (PET)/magnetic resonance imaging (MRI) and to compare it with [68Ga]PSMA-11 PET/X-ray computed tomography (CT) in patients with recurrent prostate cancer (PC) after radical prostatectomy. PROCEDURES: A total of 93 patients with biochemically recurrent prostate cancer underwent [68Ga]PSMA-11 PET/CT and subsequently a whole-body integrated PET/MRI examination. Board certified nuclear medicine physicians and radiologists evaluated PET/CT and PET/MRI datasets regarding identification of tumor lesions ((i) lymph nodes, (ii) bone lesions, (iii) local recurrence, and (iv) parenchymal lesions) based on maximum [68Ga]PSMA-11 uptake as well as morphological changes. Quality of PET images for both PET/CT and PET/MRI were rated using a 5-point scoring system by evaluating lesion homogeneity, contrast, contour, and delineation. Wilcoxon signed-rank tests were used to determine statistical differences. RESULTS: PC relapse was detected in 62/93 patients. PET/MRI detected 148 out of 150 lesions described in PET/CT. In addition, PET/MRI detected 11 lesions not detected in PET/CT (5 lymph nodes, 6 local recurrences). The exact McNemar statistical test (one-sided) showed significant difference between PET/CT and PET/MRI for diagnosis of local recurrence (p value = 0.031). Diagnostic confidence for (iii) was higher in PET/MRI compared with PET/CT (PET/CT = 1.1; PET/MRI = 4.9). Diagnostic confidence for (i) (PET/CT = 4.9; PET/MRI = 4.6), (ii) (PET/CT = 4.9; PET/MRI = 4.6), and (iv) (PET/CT = 4.6; PET/MRI = 4.8) was equivalent between PET/MRI and PET/CT. CONCLUSIONS: Integrated [68Ga]PSMA-11 PET/MRI provides a similarly high diagnostic performance for localization of recurrent PC as PET/CT. For the detection of local recurrences [68Ga]PSMA-11 PET/MRI is superior compared with [68Ga]PSMA-11 PET/CT.
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Antígenos de Superficie/metabolismo , Ácido Edético/análogos & derivados , Glutamato Carboxipeptidasa II/metabolismo , Imagen por Resonancia Magnética/métodos , Oligopéptidos/farmacocinética , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/patología , Imagen de Cuerpo Entero/métodos , Anciano , Anciano de 80 o más Años , Ácido Edético/química , Ácido Edético/farmacocinética , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Oligopéptidos/química , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/cirugía , Radiofármacos/química , Radiofármacos/farmacocinética , Estándares de Referencia , Distribución TisularRESUMEN
PURPOSE: To evaluate the predictive value of MR imaging criteria, the biopsy Gleason score, and preoperative PSA levels for differentiating between T2 and T3 prostate carcinomas. MATERIALS AND METHODS: Endorectal MR images of 81 patients (median age: 65 years, range: 48 to 81 years) who had biopsy-proven prostate cancer and underwent a radical prostatectomy were analyzed retrospectively. The existence of different imaging features were recorded for each patient. A radiological analysis comprising all used imaging criteria was also performed for every patient. Optimal cut-off levels for the biopsy Gleason score and preoperative PSA levels were obtained using ROC analyses. Subsequently, a logistic regression analysis was performed to identify features which make a significant contribution to the prediction of the tumor stage. RESULTS: Histological examination showed that 24 patients (29.6 %) had a T3 tumor and 57 patients (70.4 %) had a T2 tumor. The mean preoperative PSA level was 9.4 ng/ml (+/- 7 ng/ml), and the median Gleason score was 6 with a range of 4 to 8. The radiological judgment comprising all imaging criteria led to a sensitivity of 54.2 % and specificity of 79 % for the detection of a T3 tumor. The obliteration of the rectoprostatic angle (regression coefficient B = 2.30; standard error (se) = 0.80; p = 0.002) and the biopsy Gleason score (B = 1.16; se = 0.3; p = 0.001) were the parameters with the highest independent predictive value for the diagnosis of an extracapsular tumor spread. The other radiological criteria and the preoperative PSA level were not statistically significant. A combination of the parameters "obliteration of the rectoprostatic angle" and "biopsy Gleason score" led to a sensitivity and specificity of 75 % and 79 %, respectively (existence of one parameter sufficient). The optimal cut-off value was a Gleason score of 7 for the differentiation between T2 and T3 prostate carcinomas. CONCLUSION: In our study, only the criteria "obliteration of the rectoprostatic angle" and "biopsy Gleason score" were of predictive value for the diagnosis of a T3 prostate carcinoma. The other MR imaging criteria and the preoperative PSA levels had no additional benefit.
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Biomarcadores de Tumor/sangre , Biopsia , Imagen por Resonancia Magnética/métodos , Proctoscopía/métodos , Antígeno Prostático Específico/sangre , Próstata/patología , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To evaluate the accuracy of software for computer-aided detection (CAD) of lung nodules using different reconstruction slice thickness protocols in multidetector CT. MATERIALS AND METHODS: Raw image data sets for 15 patients who had undergone 16-row multidetector CT (MDCT) for known pulmonary nodules were reconstructed at a reconstruction thickness of 5.0, 2.0 and 1.0 mm with a reconstruction increment of 1.5, 1.0 and 0.5 mm, respectively. The "Nodule Enhanced Viewing" (NEV) tool of LungCare for computer-aided detection of lung nodules was applied to the reconstructed images. The reconstructed images were also blinded and then evaluated by 2 radiologists (A and B). Data from the evaluating radiologists and CAD was then compared to an independent reference standard established using the consensus of 2 independent experienced chest radiologists. The eligible nodules were grouped according to their size (diameter > 10, 5 - 10, < 5 mm) for assessment. Statistical analysis was performed using the receiver operating characteristic (ROC) curve analysis, t-test and two-rater Cohen's Kappa co-efficient. RESULTS: A total of 103 nodules were included in the reference standard by the consensus panel. The performance of CAD was marginally lower than that of readers at a 5.0-mm reconstruction thickness (AUC = 0.522, 0.517 and 0.497 for A, B and CAD, respectively). In the case of 2.0-mm reconstruction slices, the performance of CAD was better than that of the readers (AUC = 0.524, 0.524 and 0.614 for A, B and CAD, respectively). CAD was found to be significantly superior to radiologists in the case of 1.0-mm reconstruction slices (AUC = 0.537, 0.531 and 0.675 for A, B and CAD, respectively). The sensitivity at a reconstruction thickness of 1.0 mm was determined to be 66.99 %, 68.93 % and 80.58 % for A, B and CAD, respectively. The time required for detection was shortest for CAD at reconstruction slices of 1.0 mm (mean t = 4 min). The performance of radiologists was greatly enhanced when using CAD: sensitivity 91.26 % and 94.17 % for CAD+A and CAD+B, respectively (AUC = 0.889 and 0.917). CAD was most advantageous in the detection of nodules < 10 mm. CONCLUSION: At a 1.0-mm reconstruction thickness, CAD's ability to detect nodules < 10 mm is superior to that of radiologists and its relatively short evaluation time makes it a viable second reader.
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Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Diagnóstico por Computador/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
PURPOSE: To evaluate the diagnostic quality and minimum required dose to obtain acceptable images for diagnostic purposes in the field of musculoskeletal radiology. MATERIALS AND METHODS: A critical comparison of the image quality produced by a novel flat panel detector and the conventional screen/film system using a contrast-detail phantom was performed in phase I. Images from both systems were obtained with the same dose and displayed with similar contrast and density. In phase II images of significant anatomical structures in cadaver extremities obtained using the digital detector system and the standard film/screen system were critically evaluated. After a successive reduction in the X-ray dose for 84 patients in phase III, eight independent radiologists compared the image quality of the screen/film system to that of the novel flat panel detector. RESULTS: Phases I and II revealed a difference in the image quality achieved by the standard screen/film system and the digital detector system to the advantage of the digital detector system. In 77 of 84 patients (91.7 %), phase III showed equal image quality after a 50 % reduction in the X-ray dose. In 3 cases (3.6 %) the image quality and the level of contrast were better. No unified statement could be made for 4 patients (4.7 %). CONCLUSION: Digital imaging of skeletal disorders using the novel flat panel detector makes it possible to reduce the X-ray dose by 50 % with equal or even better image quality.
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Enfermedades Óseas/diagnóstico por imagen , Sistema Musculoesquelético/diagnóstico por imagen , Dosis de Radiación , Intensificación de Imagen Radiográfica , Adulto , Preescolar , Femenino , Fracturas Óseas/diagnóstico por imagen , Humanos , Masculino , Fantasmas de Imagen , Valores de Referencia , SelenioRESUMEN
OBJECTIVE: For staging, follow-up and even screening (www.screening.info) an "all-in-one" imaging examination is desirable. In the concept of whole body MRI, lung imaging prevails as the weakest link. The purpose of our study was to determine the optimal MRI sequences for the detection of malignant lung nodules. PATIENTS AND METHODS: On the basis of 6 lung cancer, 46 metastases and one tuberculoma in 13 patients eight MRI sequences--HASTE, IR-HASTE, fat saturated TrueFISP, STIR, VIBEipat = 2, and contrast-enhanced (CE) VIBE (with ipat = 2, 0, 4) performed with parallel imaging and 12 matrix coil elements--were compared in terms of contrast-to-noise ratio (CNR) and quality in the visualization of the lung nodules using multidetector CT as standard of reference. The parameters of the sequences were pragmatically selected to minimize the imaging time to allow for imaging the entire lung within one breathold interval. RESULTS: The STIR sequence was found to be the best for detecting malignant lung nodules (p<0.01) followed by the FS TrueFISP, CE VIBE subsetipat = 0, CE VIBE subsetipat = 2, IR-HASTE, HASTE, CE VIBE subsetipat = 4, and VIBE. The STIR sequence visualized malignant nodules down to 2 mm in size and did not display the 19 mm tuberculoma. CONCLUSION: The STIR sequence should be included in future studies investigating if MRI can compete with CT in the early identification (detection and classification) of malignant lung nodules.
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Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética/métodos , Anciano , Carcinoma/diagnóstico , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Neoplasias del Colon/patología , Neoplasias del Colon/secundario , Femenino , Humanos , Masculino , Melanoma/patología , Melanoma/secundario , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/diagnóstico por imagen , Metástasis de la Neoplasia/patología , Estadificación de Neoplasias , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/secundario , Proyectos Piloto , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/secundario , Tomografía Computarizada por Rayos X/métodos , Tuberculoma/patologíaRESUMEN
More than other medical discipline, radiology is marked by technical innovation and continuous development, as well as the optimization of the underlying physical principles. In this respect, several trends that will crucially change and develop radiology over the next decade can be observed. Through the use of ever faster computer tomography, which also shows an ever-decreasing radiation exposure, the "workhorse" of radiology will have an even greater place and displace conventional Xray techniques further. In addition, hybrid imaging, which is based on a combination of nuclear medicine and radiological techniques (keywords: PET/CT, PET/MRI) will become much more established and, in particular, will improve oncological imaging further, allowing increasingly individualized imaging for specific tracers and techniques of functional magnetic resonance imaging for a particular tumour. Future radiology will be strongly characterized by innovations in the software and Internet industry, which will enable new image viewing and processing methods and open up new possibilities in the context of the organization of radiological work.
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Diagnóstico por Imagen/tendencias , Predicción , Radiología/tendencias , Neoplasias Urológicas/diagnóstico por imagen , Neoplasias Urológicas/patología , Alemania , Humanos , Estadificación de NeoplasiasRESUMEN
The survival motor neuron (SMN) protein and the SMN interacting protein 1 (SIP1) are part of a 300 kD protein complex with a crucial role in snRNP biogenesis and pre-mRNA splicing. Both proteins are colocalised in nuclear structures called gems and in the cytoplasm. Approximately 96% of patients with autosomal recessive spinal muscular atrophy (SMA) show mutations in the SMN1 gene, while about 4% fail to show any mutation, despite a typical SMA phenotype. Additionally, sibs with identical 5q13 homologs and homozygous absence of SMN1 can show variable phenotypes which suggest that SMA is modified by other, yet unknown factors. Since both genes, SMN1 and SIP1, belong to the same pathway and are part of the same protein complex, it is obvious to ask whether mutations within SIP1 are responsible for both the phenotypic variability and the appearance of non-SMN mutated SMA patients. First, we identified the chromosomal location of SIP1 and assigned it to chromosomal region 14q13-q21 by fluorescence in situ hybridisation. No SMA related disorder has yet been assigned to this chromosomal region. Next, we determined the exon-intron structure of the SIP1 gene which encompasses 10 exons and identified five transcription isoforms. We sequenced either RT-PCR products or genomic DNA covering the complete coding region from 23 typical SMA patients who had failed to show any SMN1 mutation. No mutation and no polymorphism was found within SIP1. Additionally, we sequenced RT-PCR products or genomic fragments of the entire SIP1 coding region from 26 sibs of 11 SMA families with identical genotypes (delta7SMN/delta7SMN or delta7SMN/other mutation) but different phenotypes and again no mutation was found. Finally, we performed quantitative analysis of RT-PCR products from the same 26 sibs. No difference in expression level of the five isoforms among phenotypically variable sibs was observed. Based on these data, we suggest that neither the phenotypic variability nor the 5q-unlinked SMA are caused by mutations within SIP1.
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Proteínas del Tejido Nervioso/genética , Fenotipo , Atrofias Musculares Espinales de la Infancia/genética , Empalme Alternativo , Preescolar , Cromosomas Humanos Par 14/genética , ADN/análisis , ADN/sangre , Análisis Mutacional de ADN , Cartilla de ADN/química , Exones , Pruebas Genéticas , Genotipo , Humanos , Hibridación Fluorescente in Situ , Lactante , Intrones , Datos de Secuencia Molecular , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Mutación , ARN Mensajero/análisis , Proteínas de Unión al ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Atrofias Musculares Espinales de la Infancia/patologíaRESUMEN
Two-site enzyme-linked immunosorbent assays (ELISA) have been established for the specific and sensitive determination of two membrane proteins of the small synaptic vesicles (SSV), namely: peripheral synapsin I and integral synaptophysin. The ELISA used highly specific capture monoclonal antibodies (mAB) and polyclonal antibodies (pAB) as detectors. For synapsin I, the mAB were newly generated, whereas for synaptophysin, the commercially available mAB SY38 was applied. In order to calibrate the ELISA and to raise pAB, both proteins were purified in the mg-range. Synapsin I was purified by conventional means from human and porcine brain and synaptophysin was purified by immunoaffinity chromatography from porcine brain. Using the ELISA, neither synapsin I nor synaptophysin could be determined in serum or cerebrospinal fluid (CSF) from healthy donors or patients suffering various neurological disorders or pheochromocytomas. For this reason, the degradation of both proteins in serum and CSF was investigated. With the exception of synaptophysin measured in serum, both proteins exhibited fast rates of degradation. Despite the negative results in human body fluids, the two ELISA are appropriate for the quantification of these membrane proteins in neuronal or neuroendocrine cell extracts or preparations of SSV.
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Ensayo de Inmunoadsorción Enzimática/métodos , Sinapsinas/sangre , Sinapsinas/líquido cefalorraquídeo , Sinaptofisina/sangre , Sinaptofisina/líquido cefalorraquídeo , Secuencia de Aminoácidos , Animales , Anticuerpos , Anticuerpos Monoclonales , Química Encefálica , Calibración , Cromatografía de Afinidad , Humanos , Ratones , Datos de Secuencia Molecular , Sensibilidad y Especificidad , Porcinos , Sinapsinas/aislamiento & purificación , Sinaptofisina/aislamiento & purificaciónRESUMEN
Effects of genetic selection for high wheel-running activity (17th generation) and access to running wheels on skeletal muscle glucose uptake were studied in mice with the following treatments for 8 wk: 1) access to unlocked wheels; 2) same as 1, but wheels locked 48 h before glucose uptake measurement; or 3) wheels always locked. Selected mice ran more than random-bred (nonselected) mice (8-wk mean +/- SE = 8,243 +/- 711 vs. 3,719 +/- 233 revolutions/day). Body weight was 5-13% lower for selected vs. nonselected groups. Fat pad/body weight was ~40% lower for selected vs. nonselected and unlocked vs. locked groups. Insulin-stimulated glucose uptake and fat pad/body weight were inversely correlated for isolated soleus (r = -0.333; P < 0.005) but not extensor digitorum longus (EDL) or epitrochlearis muscles. Insulin-stimulated glucose uptake was higher in EDL (P < 0.02) for selected vs. nonselected mice. Glucose uptake did not differ by wheel group, and amount of running did not correlate with glucose uptake for any muscle. Wheel running by mice did not enhance subsequent glucose uptake by isolated muscles.
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Glucosa/farmacocinética , Ratones Endogámicos ICR/genética , Músculo Esquelético/metabolismo , Esfuerzo Físico/fisiología , Animales , Antimetabolitos/farmacocinética , Glucemia/metabolismo , Cruzamiento , Desoxiglucosa/farmacocinética , Femenino , Glucógeno/metabolismo , Hematócrito , Hipoglucemiantes/sangre , Hipoglucemiantes/farmacología , Insulina/sangre , Insulina/farmacología , Hígado/anatomía & histología , Hígado/metabolismo , Masculino , Ratones , Actividad Motora/fisiología , Músculo Esquelético/anatomía & histología , Tamaño de los ÓrganosRESUMEN
Membrane-bound P2-receptors mediate the actions of extracellular nucleotides in cell-to-cell signalling. P2X-receptors are ligand-gated ion channels, whereas P2Y-receptors belong to the superfamily of G-protein-coupled receptors. So far, the P2Y family is composed of eight cloned and functionally defined subtypes. Five of them (P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11) are present in human tissues. The P2Y3-, p2y8- and tp2y-receptors may be species orthologues. The principal physiological agonists of the cloned human P2Y-receptors are ADP (P2Y1), UTP/ATP (P2Y2), UTP (P2Y4), UDP (P2Y6) and ATP (P2Y11). The rat P2Y4-receptor is activated by both UTP and ATP. Specific patterns of polar amino acid residues in the exofacial portions of transmembrane domains (TMs) 6 and 7 of the P2Y-receptors may account for the ligand specificity of the subtypes. Suramin acts as an antagonist at most P2Y-receptors with the exception of P2Y4- and tp2y-receptors. PPADS has been shown to block P2Y1-, the human P2Y4- and P2Y6-receptors. The nucleotide analogue 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate (MRS 2179), in contrast, seems to be a potent and selective antagonist at the P2Y1-receptor. All cloned and functionally expressed P2Y-receptors are able to couple to phospholipase C. The P2Y11-receptor mediates in addition a stimulation of adenylate cyclase and the tp2y-receptor an inhibition of this signal transduction pathway. Other functionally defined subtypes, e.g., the receptor mediating an inhibition of adenylate cyclase in blood platelets, are not yet cloned. The distribution of P2Y1 mRNA is widespread. The receptor plays a crucial role in blood platelet aggregation and mediates the adenine nucleotide-induced release of the endothelium-derived relaxing factor nitric oxide. P2Y1-receptors may also be involved in the modulation of neuro-neural signalling transmission. P2Y2 transcripts are abundantly distributed. One important example for its functional role is the control of chloride ion fluxes in airway epithelia. The P2Y4-receptor is highly expressed in the placenta. The distribution of the P2Y6-receptor is widespread including heart, blood vessels and brain. The P2Y11-receptor may play a role in the differentiation of immunocytes.
Asunto(s)
Receptores Purinérgicos P2/fisiología , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia Molecular , Receptores Purinérgicos P2/química , Receptores Purinérgicos P2/efectos de los fármacos , Receptores Purinérgicos P2Y1 , Receptores Purinérgicos P2Y2 , Transducción de Señal , Relación Estructura-ActividadRESUMEN
Symptomatic simple liver cysts should be treated. In this report we describe the results of a straightforward, well-tolerated laparoscopic operation for this condition. Between 1990 and 1996 we performed 19 laparoscopic liver cyst excisions. The exposed portion of the cyst wall was excised and a piece of omentum was secured into the remaining cyst cavity to prevent recurrence. The average age of the patients was 65 years (range 30 to 81 years). Eight patients (42%) had single simple cysts, nine patients (47%) had multiple simple cysts, and two patients (11%) had polycystic liver disease. Fifty-three percent of the patients had previous abdominal operations, 47% had undergone previous needle aspirations, and one had previously undergone unsuccessful laparoscopic cyst decompression elsewhere. The indications for surgery included abdominal pain, mass, early satiety, malaise, bloating, and shortness of breath. Two patients underwent concurrent cholecystectomies, and one patient underwent concurrent laparoscopic Nissen fundoplication. Follow-up, which averaged 32 months (range 3 to 68 months), is complete in all patients. There was one treatment failure among the patients with simple cysts. Both patients with polycystic liver disease have had recurrent symptoms. The laparoscopic approach to simple liver cysts is relatively straightforward, and if certain technical principles are adhered to, the success rate is very high.
Asunto(s)
Quistes/cirugía , Laparoscopía/métodos , Hepatopatías/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
We describe a case of combined mechanical thrombectomy of the right middle cerebral artery and stent angioplasty of the right internal carotid artery in a severe stroke caused by arterio-arterial embolism due to a traumatic dissection of the internal carotid artery. The patient was admitted with an NIHSS score of 19 and was discharged from hospital with a score of 2. Three months later neurological examination disclosed no pathological findings. The case demonstrates the crucial role of interventional procedures in the treatment of severe stroke where intravenous thrombolysis has little prospect of success.
Asunto(s)
Disección de la Arteria Carótida Interna/terapia , Infarto de la Arteria Cerebral Media/terapia , Stents , Trombectomía/métodos , Arteria Carótida Interna/patología , Disección de la Arteria Carótida Interna/complicaciones , Angiografía Cerebral , Angiografía Coronaria , Humanos , Infarto de la Arteria Cerebral Media/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The aim of this study was to show the different origins and courses of the extracranial VA on CTA with special emphasis on embryological considerations. The duplicated VA is an anomaly that has been assumed to predispose for dissection and to be associated with aneurysms. We report its frequency and clinical significance. METHODS: We retrospectively reviewed CTA of 539 patients by using a contrast-enhanced CTA protocol of the VA on CT. RESULTS: Ninety-four-point-two percent of left VA originated from left subclavian artery and entered the transverse foramen at C6 in nearly all cases. Six-point-three-percent of left VA (m = 4 %, f = 10 %) originated from the aortic arch and entered the transverse foramen either at C4, C5 or C7 but never at C6. One case of an aberrant retroesophageal right VA originated from the aortic arch distal to the left subclavian artery and entered at C7 (0.19 %). All other right VA originated from the right subclavian artery (99.8 %) and entered between C4 and C6. We diagnosed four cases of duplicated VA (0.74 %) with a female predominance (1.9 %) without any signs of dissection on CTA. Two cases with VA duplication had intracranial arterial aneurysms. CONCLUSIONS: The VA is a longitudinal anastomosis of segmental metameric arteries. The level of entrance into the transverse foramen indicates which metameric artery or arteries persist. Duplication corresponds to persistence of two segmental arteries and is a rare phenomenon. VA duplication might be associated with vascular lesions.