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1.
Br J Surg ; 108(7): 834-842, 2021 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-33661306

RESUMEN

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.


Asunto(s)
Embolización Terapéutica/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/terapia , Cuidados Preoperatorios/métodos , Anciano , Femenino , Estudios de Seguimiento , Venas Hepáticas , Humanos , Regeneración Hepática , Masculino , Persona de Mediana Edad , Vena Porta , Estudios Retrospectivos , Resultado del Tratamiento
3.
Radiologe ; 56(1): 70-6, 2016 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-26538135

RESUMEN

BACKGROUND: For resident doctors the acquisition of technical and professional competence is decisive for the successful practice of their activities. Competency and professional development of resident doctors benefit from regular self-reflection and assessment by peers. While often promoted and recommended by national educational authorities, the implementation of a robust evaluation process in the clinical routine is often counteracted by several factors. OBJECTIVE: The aim of the study was to test a self-developed digital evaluation system for the assessment of radiology residents at our institute for practicality and impact with regard to the radiological training. MATERIAL AND METHODS: The intranet-based evaluation system was implemented in January 2014, which allowed all Radiology consultants to submit a structured assessment of the Radiology residents according to standardized criteria. It included 7 areas of competency and 31 questions, as well as a self-assessment module, both of which were filled out electronically on a 3-month basis using a 10-point scale and the opportunity to make free text comments. The results of the mandatory self-evaluation by the residents were displayed beside the evaluation by the supervisor. Access to results was restricted and quarterly discussions with the residents were conducted confidentially and individually. RESULTS AND DISCUSSION: The system was considered to be practical to use and stable in its functionality. The centrally conducted anonymous national survey of residents revealed a noticeable improvement of satisfaction with the institute assessment for the criterion "regular feedback"compared to the national average. Since its implementation the system has been further developed and extended and is now available for other institutions.


Asunto(s)
Competencia Clínica , Instrucción por Computador/métodos , Evaluación Educacional/métodos , Internado y Residencia/organización & administración , Evaluación de Programas y Proyectos de Salud/métodos , Radiología/organización & administración , Curriculum , Alemania , Encuestas y Cuestionarios , Interfaz Usuario-Computador
4.
Eur Radiol ; 21(6): 1323-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21188594

RESUMEN

PURPOSE: The aim of this study was to compare ultrasound-guided access of the superficial femoral artery and the common femoral artery. MATERIAL AND METHODS: 100 patients were randomized to ultrasound-guided access either into the SFA or the CFA. The two groups were compared with respect to technical success, access time and complications. In addition, a subgroup analysis was performed to compare the complication rate using manual compression versus closure devices for haemostasis. RESULTS: In the SFA group 49/50 patients were successfully accessed in the assigned location, compared to 41/50 in the CFA group (p = 0.016). The median access time was significantly faster in the SFA group (3 min 25 s) compared to the CFA group (5 min 26 s) (p < 0.001). The most frequent complications in the SFA group were pseudoaneurysms (16.3%) whereas access site haematomas (14.6%) were the most common complication in the CFA group. However, when looking at subgroup with closure devices there was no difference between the SFA group compared to CFA group (p = 1.000). CONCLUSION: Accessing the SFA was more often successful and significantly faster than puncturing the CFA. The pseudoaneurysm rate was higher in the SFA group when using manual compression, but similar when using closure devices.


Asunto(s)
Arteria Femoral/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Anciano , Anciano de 80 o más Años , Cateterismo Periférico , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
5.
Eur Radiol ; 21(4): 807-15, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20890705

RESUMEN

OBJECTIVES: To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. METHODS: Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. RESULTS: Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. CONCLUSION: The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed.


Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Dolor/patología , Nervio Trigémino/patología , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Corteza Cerebral/patología , Electrodos , Femenino , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Humanos , Inositol/metabolismo , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Neurotransmisores/metabolismo , Estudios Prospectivos , Protones , Enfermedades Dentales/patología
6.
AJNR Am J Neuroradiol ; 42(11): 1962-1967, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34674994

RESUMEN

BACKGROUND AND PURPOSE: Spiral MR imaging may enable improved image quality and higher scan speeds than Cartesian trajectories. We sought to compare a novel spiral 2D T2-weighted TSE sequence with a conventional Cartesian and an artifact-robust, non-Cartesian sequence named MultiVane for routine clinical brain MR imaging. MATERIALS AND METHODS: Thirty-one patients were scanned with all 3 sequences (Cartesian, 4 minutes 14 seconds; MultiVane, 2 minutes 49 seconds; spiral, 2 minutes 12 seconds) on a standard clinical 1.5T MR scanner. Three readers described the presence and location of abnormalities and lesions and graded images qualitatively in terms of overall image quality, the presence of motion and pulsation artifacts, gray-white matter differentiation, lesion conspicuity, and subjective preference. Image quality was objectivized by measuring the SNR and the coefficients of variation for CSF, GM, and WM. RESULTS: Spiral achieved a scan time reduction of 51.9% and 21.9% compared with Cartesian and MultiVane, respectively. The number and location of lesions were identical among all sequences. As for the qualitative analysis, interreader agreement was high (Krippendorff α > .75). Spiral and MultiVane both outperformed the Cartesian sequence in terms of overall image quality, the presence of motion artifacts, and subjective preference (P < .001). In terms of the presence of pulsation artifacts, gray-white matter differentiation, and lesion conspicuity, all 3 sequences performed similarly well (P > .15). Spiral and MultiVane outperformed the Cartesian sequence in coefficient of variation WM and SNR (P < .01). CONCLUSIONS: Spiral 2D T2WI TSE is feasible for routine structural brain MR imaging and offers high-quality, artifact-robust brain imaging in short scan times.


Asunto(s)
Imagen por Resonancia Magnética , Sustancia Blanca , Artefactos , Encéfalo/diagnóstico por imagen , Sustancia Gris , Humanos
7.
Neuropeptides ; 42(4): 377-86, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18547640

RESUMEN

Neuromedin U (NMU), a neuropeptide implicated in feeding, inflammation, pain control and anxiety-related behaviours, is widely distributed in peripheral organs and the CNS. These effects are thought to be mediated by its receptors NMU(1) and NMU(2). Since its precise sites of interaction in the CNS were to date unknown, we studied the distribution of in vitro binding sites for (125)I-NMU-23 in the rat CNS by receptor autoradiography. High-density specific binding was found in discrete areas of the brain and spinal cord, namely in the limbic system (hippocampal formation, septohippocampal nucleus, indusium griseum, hypothalamus, amygdaloid nuclei), superior colliculus, dorsal raphé, and substantia gelatinosa of the spinal cord. Our findings provide further supportive evidence for a multifunctional role for the peptide in the brain and spinal cord.


Asunto(s)
Autorradiografía , Sistema Nervioso Central , Neuropéptidos/metabolismo , Receptores de Neurotransmisores/metabolismo , Animales , Sitios de Unión , Sistema Nervioso Central/anatomía & histología , Sistema Nervioso Central/metabolismo , Humanos , Masculino , Isoformas de Proteínas/metabolismo , Ratas , Ratas Wistar
8.
AJNR Am J Neuroradiol ; 39(7): 1255-1259, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29700045

RESUMEN

Diffusion restriction is the morphologic hallmark of acute ischemic infarcts and excitotoxic brain injury in various cerebral pathologies. Diffusion restriction is visible as hyperintensity on DWI and as hypointensity on ADC maps. Due to the vicinity of multiple anatomic structures in the brain stem and hippocampus, very small lesions with diffusion restriction may result in severe clinical symptomatology, but these small lesions easily go undetected on standard cerebral DWI due to insufficient spatial resolution, T2* blurring, and image artifacts caused by susceptibility-related image distortions. Diffusion-weighted zonal oblique multislice-EPI with reduced FOV acquisition permits a considerable increase in spatial resolution and enhances the visualization of very small pathologic lesions in the brain stem and hippocampus. Improved performance in the depiction of different pathologic lesions with diffusion restriction in the brain stem and hippocampus using this sequence compared with standard DWI in selected cases is presented.


Asunto(s)
Tronco Encefálico/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Hipocampo/diagnóstico por imagen , Neuroimagen/métodos , Adulto , Anciano , Anciano de 80 o más Años , Tronco Encefálico/patología , Femenino , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad
9.
Mol Cell Biol ; 16(9): 4665-72, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8756623

RESUMEN

The murine Sak gene encodes two isoforms of a putative serine/threonine kinase, Sak-a and Sak-b, with a common N-terminal kinase domain and different C-terminal sequences. Sak is expressed primarily at sites where cell division is most active in adult and embryonic tissues (C. Fode, B. Motro, S. Youseli, M. Heffernan, and J. W. Dennis, Proc. Natl. Acad. Sci. USA 91:6388-6392, 1994). In this study, we found that Sak-a transcripts were absent in growth-arrested NIH 3T3 cells, while in cycling cells, mRNA levels increased late in G1 phase and remained elevated through S phase and mitosis before declining early in G1. The half-life of hemagglutinin epitope-tagged Sak-a protein was determined to be approximately 2 to 3 h, and the protein was observed to be multiubiquitinated, a signal for rapid protein degradation. Overexpression of Sak-a protein inhibited colony-forming efficiency in CHO cells. Neither the Sak-b isoform nor Sak-a with a mutation in a strictly conserved residue in the kinase domain (Asp-154-->Asn) conferred growth inhibition, suggesting that both the kinase domain and the C-terminal portion of Sak-a are functional regions of the protein. Sak-a overexpression did not induce a block in the cell cycle. However, expression of HA-Sak-a, but not HA-Sak-b, from a constitutive promoter for 48 h in CHO cells increased the incidence of multinucleated cells. Our results show that Sak-a transcript levels are controlled in a cell cycle-dependent manner and that this precise regulation is necessary for cell growth and the maintenance of nuclear integrity during cell division.


Asunto(s)
Proteínas Serina-Treonina Quinasas/fisiología , Células 3T3 , Secuencia de Aminoácidos , Animales , Células CHO , Ciclo Celular , División Celular , Núcleo Celular/ultraestructura , Cricetinae , Inducción Enzimática , Ratones , Datos de Secuencia Molecular , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/inmunología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes de Fusión/inmunología
10.
Cardiovasc Intervent Radiol ; 40(8): 1141-1146, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28584945

RESUMEN

Interventional radiology provides a wide variety of vascular, nonvascular, musculoskeletal, and oncologic minimally invasive techniques aimed at therapy or palliation of a broad spectrum of pathologic conditions. Outcome data for these techniques are globally evaluated by hospitals, insurance companies, and government agencies targeting in a high-quality health care policy, including reimbursement strategies. To analyze effectively the outcome of a technique, accurate reporting of complications is necessary. Throughout the literature, numerous classification systems for complications grading and classification have been reported. Until now, there has been no method for uniform reporting of complications both in terms of definition and grading. The purpose of this CIRSE guideline is to provide a classification system of complications based on combining outcome and severity of sequelae. The ultimate challenge will be the adoption of this system by practitioners in different countries and health economies within the European Union and beyond.


Asunto(s)
Garantía de la Calidad de Atención de Salud/métodos , Radiología Intervencionista/normas , Europa (Continente) , Humanos , Sociedades Médicas
11.
AJNR Am J Neuroradiol ; 38(9): 1748-1753, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28663263

RESUMEN

BACKGROUND AND PURPOSE: In postmortem studies, subclinical optic nerve demyelination is very common in patients with MS but radiologic demonstration is difficult and mainly based on STIR T2WI. Our aim was to evaluate 3D double inversion recovery MR imaging for the detection of subclinical demyelinating lesions within optic nerve segments. MATERIALS AND METHODS: The signal intensities in 4 different optic nerve segments (ie, retrobulbar, canalicular, prechiasmatic, and chiasm) were evaluated on 3D double inversion recovery MR imaging in 95 patients with MS without visual symptoms within the past 3 years and in 50 patients without optic nerve pathology. We compared the signal intensities with those of the adjacent lateral rectus muscle. The evaluation was performed by a student group and an expert neuroradiologist. Statistical evaluation (the Cohen κ test) was performed. RESULTS: On the 3D double inversion recovery sequence, optic nerve segments in the comparison group were all hypointense, and an isointense nerve sheath surrounded the retrobulbar nerve segment. At least 1 optic nerve segment was isointense or hyperintense in 68 patients (72%) in the group with MS on the basis of the results of the expert neuroradiologist. Student raters were able to correctly identify optic nerve hypersignal in 97%. CONCLUSIONS: A hypersignal in at least 1 optic nerve segment on the 3D double inversion recovery sequence compared with hyposignal in optic nerve segments in the comparison group was very common in visually asymptomatic patients with MS. The signal-intensity rating of optic nerve segments could also be performed by inexperienced student readers.


Asunto(s)
Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Neuroimagen/métodos , Nervio Óptico/diagnóstico por imagen , Adolescente , Adulto , Anciano , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Nervio Óptico/patología , Adulto Joven
12.
Mol Endocrinol ; 6(5): 826-36, 1992 May.
Artículo en Inglés | MEDLINE | ID: mdl-1376411

RESUMEN

Insulin-like growth factors (IGFs) are polypeptide hormones with structural homology to proinsulin. IGFs circulate in blood bound to specific IGF binding proteins (IGFBPs). cDNA sequences of six members of a family of human and rat IGFBPs have been published. Here we present a partial characterization of the human IGFBP-2 gene. This single copy gene is located on chromosome 2 and spans a total of more than 32 kilobases (kb) of genomic sequence. It is organized in four exons with sizes of more than 568, 220, 141, and 496 nucleotides. The intron between exon one and exon two contributes 27 kb to the size of the IGFBP-2 gene. The second and the third introns comprise 1.1 kb and 1.95 kb, respectively. When the structure of the IGFBP-2 gene is compared to that of the IGFBP-1 and IGFBP-3 genes, the exon boundaries are found to be conserved in these three genes. A single transcriptional start site was localized to 113 +/- 2 nucleotides 5' of the ATG start codon of IGFBP-2 translation. Furthermore, the region between nucleotides -635 and -2 upstream of the ATG was demonstrated to exhibit promoter activity in human Jurkat K16 cells. This region is devoid of TATA or CAAT consensus sequence motifs and has a high content of dC and dG nucleotides. In this respect the putative IGFBP-2 promoter region resembles the promoters which are often associated with housekeeping genes.


Asunto(s)
Proteínas Portadoras/genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Biblioteca Genómica , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Datos de Secuencia Molecular , Secuencias Reguladoras de Ácidos Nucleicos , Homología de Secuencia de Ácido Nucleico
13.
Mol Endocrinol ; 3(7): 1053-60, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2477691

RESUMEN

Rat serum contains two major forms of insulin-like growth factor (IGF) binding proteins (BPs) that have apparent mol wts of about 35,000 and 150,000. We have isolated a cDNA clone encoding an IGF-BP whose N-terminal sequence is completely homologous to the NH2-terminal of the Buffalo rat liver cells-3A BP. The 270 amino acid mature protein has a predicted mol wt of 29,500. It contains a cysteine rich domain at each end of the molecule and an Arg-Gly-Asp (RGD) tripeptide motif near its C-terminus which suggests that this BP might associate with integrin cell surface receptors. The mature protein shares only partial homology with two published human IGF-BPs. Northern blot analysis shows that its mRNA is abundant in several fetal tissues, in adult brain, testes, ovaries, and kidney. Expression in the liver is high in fetal life but decreases to a barely detectable level in adulthood. However, upon hypophysectomy, the mRNA level increases at least 20-fold which suggests a hormonal regulation for the hepatic production of this small IGF-BP.


Asunto(s)
Proteínas Portadoras/genética , Clonación Molecular , ARN Mensajero/análisis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Southern Blotting , Hipofisectomía , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Hígado/análisis , Masculino , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas
14.
Endocrinology ; 138(8): 3269-75, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9231777

RESUMEN

Tamoxifen is a synthetic estrogen analog which may regulate osteogenesis in vivo by virtue of its antiglucocorticoid properties. We have examined tamoxifen regulation of glucocorticoid-induced osteogenesis in two different in vitro bone systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell line, ROS 17/2.8. In the CPO model, alkaline phosphatase (AP) activity and collagen synthesis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1 microM). These Dex-mediated effects were inhibited by increasing concentrations of tamoxifen (10-100 microM). Similarly, in the RBMC model, Dex-dependent (0.01 microM Dex) mineralized tissue formation and AP activity were blocked by tamoxifen (0.1 microM). Although tamoxifen inhibited Dex-mediated increases of AP activity in ROS 17/2.8 cells, it did not inhibit uptake of 3H-Dex or of 3H-estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, osteopontin, and osteocalcin. Dex-induced increases for all proteins mRNAs in the RBMC model were not reduced by tamoxifen. Similarly, tamoxifen had no effects on cellular proliferation. We conclude that tamoxifen has no direct effect on gene expression of bone-related proteins of osteoblastic cells. Further, in the ROS 17/2.8 cell line, the antiglucocorticoid properties of tamoxifen do not appear to be mediated through either Dex or estrogen receptors.


Asunto(s)
Antagonistas de Estrógenos/farmacología , Glucocorticoides/farmacología , Osteogénesis/efectos de los fármacos , Tamoxifeno/farmacología , Fosfatasa Alcalina/análisis , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Médula Ósea/metabolismo , Médula Ósea/fisiología , Células de la Médula Ósea , Huesos/citología , Huesos/metabolismo , Huesos/fisiología , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Células Cultivadas , Pollos , Colágeno/análisis , Colágeno/genética , Colágeno/metabolismo , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Fémur/citología , Fémur/metabolismo , Fémur/fisiología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Técnicas In Vitro , Masculino , Osteocalcina/análisis , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/fisiología , Osteopontina , Periostio/citología , Periostio/metabolismo , Periostio/fisiología , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Sialoglicoproteínas/análisis , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo
15.
Gene ; 241(1): 65-73, 2000 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-10607900

RESUMEN

The Sak gene encodes a serine/threonine kinase, which is a member of the Polo family of mitotic regulators. Sak transcripts are present in S/G2/M phase cells, and in proliferating cell layers of the mouse embryo and adult tissues. In this report, we have characterized the murine Sak gene structure, the Sak chromosomal location, and identified the promoter. The murine Sak gene is located on the proximal arm of mouse chromosome 13, as determined by RFLP analysis. The murine gene comprises 15 coding exons spanning 16kb of genomic sequence, and encodes two alternately spliced transcripts. Sak-a, the predominant transcript, is encoded by 15 exons, while early termination of transcription and alternative splicing at exons 5 and 6 results in Sak-b. This truncated transcript encodes the complete kinase domain and a carboxyl end translated from 147bp of sequence contiguous with exon 5. Human Sak-a (Stk18) cDNA is reported to contain an insertion of sequence corresponding to the mouse Sak-b tail. Primer extension analysis of murine Sak revealed one major transcription start site at position -303bp relative to the start of translation. A genomic fragment of 3.5kb located 5' of the Sak transcriptional start drives expression of a luciferase-reporter gene in CHO and GC1-SPG cells in an orientation-dependent fashion. Using various Sak promoter/luciferase constructs, the core promoter region required for expression was located within 400bp of the message Cap site, and sequence further 5' strongly suppressed transcription.


Asunto(s)
Genes Reguladores/genética , Proteínas Serina-Treonina Quinasas/genética , Animales , Secuencia de Bases , Células CHO , Mapeo Cromosómico , Cricetinae , Exones , Eliminación de Gen , Intrones , Ratones , Modelos Genéticos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Transcripción Genética
16.
Curr Med Chem ; 10(11): 883-907, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12678679

RESUMEN

Malaria is a very serious infectious disease against which the currently available drugs are loosing effectiveness. The main problem is the emergence and the spreading of resistant parasite strains. New treatments are needed in order to regain control over the disease. Drug discovery efforts towards this goal are likely to be more successful, if they focus towards novel mechanisms of action. Such efforts will result in drugs that are functionally and structurally different from the existing drugs and therefore will overcome existing resistances. Here we focus on the aspartic protease plasmepsin II, which is a promising new drug target. We review the drug discovery efforts that were published in the literature on this enzyme, and we present the compounds synthesized at Actelion Pharmaceuticals Ltd.


Asunto(s)
Antimaláricos/farmacología , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Plasmodium falciparum/efectos de los fármacos , Inhibidores de Proteasas/farmacología , Animales , Técnicas Químicas Combinatorias , Etilaminas/síntesis química , Etilaminas/farmacología , Humanos , Imitación Molecular , Fenilbutiratos/síntesis química , Fenilbutiratos/química , Fenilbutiratos/farmacología , Piperidinas/síntesis química , Piperidinas/farmacología , Inhibidores de Proteasas/síntesis química , Proteínas Protozoarias , Relación Estructura-Actividad
17.
AJNR Am J Neuroradiol ; 20(10): 1785-93, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10588098

RESUMEN

BACKGROUND AND PURPOSE: Noninvasive characterization of spinal vascular lesions is essential for guiding clinical management, and several MR angiographic techniques have been applied in the past with variable results. The purpose of our study was to assess the potential of a dynamic 3D contrast-enhanced MR angiographic sequence to characterize spinal vascular lesions and to identify their arterial feeders and venous drainage. METHODS: A contrast-enhanced gradient-echo 3D pulse sequence providing angiographic information within 24 seconds was applied prospectively in 12 consecutive patients with a presumed spinal vascular lesion. The images were evaluated for visibility of the arterial feeder, and the results were compared with those of conventional angiography performed the next day. RESULTS: The MR angiographic findings proved that the lesions were correctly characterized as spinal arteriovenous malformations (AVMs) (n = 6), spinal dural arteriovenous fistulas (AVFs) (n = 3), a hemangioblastoma (n = 1), a teratoma (n = 1), and a vertebral hemangioma (n = 1). The arterial feeder was visible in all six AVMs and in the hemangioblastoma, corresponding to conventional angiographic findings. In two of three spinal dural AVFs, an enlarged draining medullary vein was seen within the neural foramen, providing correct localization. The third fistula could not be seen owing to reduced image quality from motion artifacts. CONCLUSION: Fast 3D contrast-enhanced MR angiography is a noninvasive technique with high accuracy in the characterization of spinal vascular disease. Visibility of the arterial pedicles corresponds well with that of digital subtraction angiography, facilitating the management of these patients.


Asunto(s)
Fístula Arteriovenosa/diagnóstico , Malformaciones Arteriovenosas/diagnóstico , Procesamiento de Imagen Asistido por Computador , Angiografía por Resonancia Magnética , Neovascularización Patológica/diagnóstico , Neoplasias de la Médula Espinal/irrigación sanguínea , Médula Espinal/irrigación sanguínea , Adulto , Anciano , Angiografía de Substracción Digital , Arterias/patología , Preescolar , Diagnóstico Diferencial , Femenino , Hemangioblastoma/irrigación sanguínea , Hemangioblastoma/diagnóstico , Hemangioma/irrigación sanguínea , Hemangioma/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Enfermedades de la Médula Espinal/diagnóstico , Neoplasias de la Médula Espinal/diagnóstico , Teratoma/irrigación sanguínea , Teratoma/diagnóstico , Venas/patología
18.
Praxis (Bern 1994) ; 101(13): 865-7, 2012 Jun 20.
Artículo en Alemán | MEDLINE | ID: mdl-22715079

RESUMEN

We report the case of a 30-year-old female patient who underwent unilateral transverse sinus stenosis stenting due to a newly diagnosed idiopathic intracranial hypertension (Pseudotumor cerebri) with symptoms of papilledema, decreased visual acuity and headache. Resolution of the symptoms and improvement of magnetic resonance and ophthalmiologic findings could be documented.


Asunto(s)
Discectomía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Microcirugia/métodos , Complicaciones Posoperatorias/diagnóstico , Seudotumor Cerebral/diagnóstico , Radiculopatía/cirugía , Adulto , Femenino , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Papiledema/diagnóstico , Papiledema/terapia , Complicaciones Posoperatorias/terapia , Seudotumor Cerebral/terapia , Stents
19.
Dtsch Med Wochenschr ; 136(28-29): 1472-5, 2011 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-21732261

RESUMEN

HISTORY AND FINDINGS: A previously healthy 43-year-old woman was admitted because of pain in the lower abdomen. Abdominal and transvaginal ultrasound revealed a cystic structure in the right ovary, providing the indication for an exploratory laparoscopy. A hemorrhagic corpus luteum was enucleated. Laboratory tests had merely shown a raised C-reactive protein level and marginally elevated leukocytes. A family history of thrombotic episodes had been elicited. FURTHER COURSE, DIAGNOSIS AND TREATMENT: Although heparin had been applied increasing swelling developed in both thighs and lower legs at day six, indicating thrombosis of the inferior vena cava. Laboratory tests revealed a mutation in factor V (Leiden). Computed tomography showed complete thrombotic IVC occlusion. Thrombolytic treatment with recombinant tissue plasminogen was initiated, direct thrombus aspiration attempted and a filter inserted in the IVC. Low molecular heparin was infused, replaced by oral anticoagulation with phenprocoumon. Subsequent Doppler ultrasound examination demonstrated almost complete resolution of the thrombus, except for a few small residual thrombi. CONCLUSION: This case demonstrates that even minor laparoscopic interventions carry the risk of an IVC thrombosis as a late complication, indicating appropriate measures to prevent thrombosis.


Asunto(s)
Cuerpo Lúteo/cirugía , Laparoscopía/efectos adversos , Quistes Ováricos/diagnóstico , Quistes Ováricos/cirugía , Complicaciones Posoperatorias/diagnóstico , Trombosis/diagnóstico , Vena Cava Inferior , Adulto , Factor V/genética , Femenino , Humanos , Mutación , Complicaciones Posoperatorias/tratamiento farmacológico , Trombectomía , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Trombosis/genética , Filtros de Vena Cava
20.
Cardiovasc Intervent Radiol ; 34(3): 542-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20593287

RESUMEN

Venous stenting has been shown to effectively treat iliofemoral venous obstruction with good short- and mid-term results. The aim of this study was to investigate long-term clinical outcome and stent patency. Twenty patients were treated with venous stenting for benign disease at our institution between 1987 and 2005. Fifteen of 20 patients (15 female, mean age at time of stent implantation 38 years [range 18-66]) returned for a clinical visit, a plain X-ray of the stent, and a Duplex ultrasound. Four patients were lost to follow-up, and one patient died 277 months after stent placement although a good clinical result was documented 267 months after stent placement. Mean follow-up after stent placement was 167.8 months (13.9 years) (range 71 (6 years) to 267 months [22 years]). No patient needed an additional venous intervention after stent implantation. No significant difference between the circumference of the thigh on the stented side (mean 55.1 cm [range 47.0-70.0]) compared with the contralateral thigh (mean 54.9 cm [range 47.0-70.0]) (p=0.684) was seen. There was a nonsignificant trend toward higher flow velocities within the stent (mean 30.8 cm/s [range 10.0-48.0]) and the corresponding vein segment on the contralateral side (mean 25.2 cm/s [range 12.0-47.0]) (p=0.065). Stent integrity was confirmed in 14 of 15 cases. Only one stent showed a fracture, as documented on x-ray, without any impairment of flow. Venous stenting using Wallstents showed excellent long-term clinical outcome and primary patency rate.


Asunto(s)
Vena Femoral , Vena Ilíaca , Enfermedades Vasculares Periféricas/terapia , Stents , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Radiografía , Estadísticas no Paramétricas , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex
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