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1.
Eur Phys J A Hadron Nucl ; 59(11): 253, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37927902

RESUMEN

We present the complete next-to-next-to-leading order (NNLO) pure pointlike QED corrections to lepton-proton scattering, including three-photon-exchange contributions, and investigate their impact in the case of the MUSE experiment. These corrections are computed with no approximation regarding the energy of the emitted photons and taking into account lepton-mass effects. We contrast the NNLO QED corrections to known next-to-leading order corrections, where we include the elastic two-photon exchange (TPE) through a simple hadronic model calculation with a dipole ansatz for the proton electromagnetic form factors. We show that, in the low-momentum-transfer region accessed by the MUSE experiment, the improvement due to more sophisticated treatments of the TPE, including inelastic TPE, is of similar if not smaller size than some of the NNLO QED corrections. Hence, the latter have to be included in a precision determination of the low-energy proton structure from scattering data, in particular for electron-proton scattering. For muon-proton scattering, the NNLO QED corrections are considerably smaller.

2.
Br J Dermatol ; 182(1): 202-207, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31049936

RESUMEN

The proteinase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), which forms part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, plays a direct role in nuclear factor kappa B activation. Here, we describe the case of a female infant with severe immune dysregulation leading to recurrent systemic infections, failure to thrive and severe crises of ichthyosiform erythroderma with high levels of serum IgE. Hence, initial symptoms indicated Netherton syndrome or Omenn syndrome. Surprisingly, sequence analyses of SPINK5 and RAG1/RAG2, respectively, excluded these diseases. During the hospital stay the patient's health deteriorated, despite intensive care therapy, and she died. In order to delineate the diagnosis, whole-exome sequencing was performed. Two compound heterozygous mutations in MALT1 were found and verified by Sanger sequencing (exon 2 c.245T>C, exon 2 c.310dup), which led to a MALT1 deficiency at the protein level. Based on these results, an immunological analysis was performed, as was immunofluorescence staining of key skin proteins, to confirm a diagnosis of MALT1 deficiency. This case report provides a closer description of the clinical and histological skin phenotype of MALT1 deficiency, and we conclude that MALT1 deficiency must be considered a possible differential diagnosis of Netherton and Omenn syndromes. What's already known about this topic? Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) deficiency is a combined immunodeficiency. MALT1 is part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, which is essential for nuclear factor kappa B activation. Current publications describe a phenotype of recurrent systemic infections; only in a few cases has an inflammatory involvement of the integument been described. What does this study add? A closer description of the cutaneous phenotype of MALT1 deficiency in a patient with two novel MALT1 mutations. Immune mapping of follicular epidermis shows lympho-epithelial Kazal-type-related inhibitor is reduced in MALT1 deficiency and absent on interfollicular staining. Clinically, MALT1 deficiency mimics Netherton syndrome and Omenn syndrome, and should be considered a differential diagnosis.


Asunto(s)
Linfoma de Células B de la Zona Marginal , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Inmunodeficiencia Combinada Grave , Femenino , Humanos , Lactante , Linfoma de Células B de la Zona Marginal/genética , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/genética , Mutación , Inhibidor de Serinpeptidasas Tipo Kazal-5
3.
Med Mycol ; 58(7): 859-866, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32030418

RESUMEN

An increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is mostly unclear. The aim of this study was to investigate the clinical relevance of Scedosporium spp. and Exophiala dermatitidis from sputum samples of patients with CF in the Netherlands. In this cross-sectional study, all CF patients of the Dutch national CF registry who were treated at five of the seven recognized CF centers during a 3-year period were included. We linked clinical data of the national CF registry with the national Dutch filamentous fungal database. We investigated the association between clinical characteristics and a positive sputum sample for Scedosporium spp. and E. dermatitidis, using logistic regression. Positive cultures for fungi were obtained from 3787 sputum samples from 699 of the 1312 patients with CF. Scedosporium spp. was associated with severe genotype, CF-related diabetes, several microorganisms, and inhaled antibiotics. E. dermatitidis was associated with older age, female sex, and Aspergillus spp. CF patients with and without Scedosporium spp. or E. dermatitidis seemed comparable in body mass index and lung function. This study suggests that Scedosporium spp. and E. dermatitidis are probably no major pathogens in CF patients in the Netherlands. Greater understanding of epidemiologic trends, risk factors, and pathogenicity of filamentous fungi in the respiratory tracts of patients with CF is needed.


Asunto(s)
Fibrosis Quística/complicaciones , Fibrosis Quística/microbiología , Exophiala/aislamiento & purificación , Infecciones Fúngicas Invasoras/diagnóstico , Feohifomicosis/diagnóstico , Scedosporium/aislamiento & purificación , Esputo/microbiología , Adolescente , Adulto , Niño , Estudios Transversales , Fibrosis Quística/epidemiología , Femenino , Humanos , Infecciones Fúngicas Invasoras/etiología , Masculino , Países Bajos/epidemiología , Feohifomicosis/etiología , Prevalencia , Adulto Joven
4.
Int J Sports Med ; 36(14): 1134-41, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26332903

RESUMEN

Subcutaneous adipose tissue (SAT) measurements with ultrasound have recently been introduced to assess body fat in elite athletes. However, appropriate protocols and data on various groups of athletes are missing. We investigated intra-rater reliability of SAT measurements using ultrasound in elite canoe athletes. 25 international level canoeists (18 male, 7 female; 23±4 years; 81±11 kg; 1.83±0.09 m; 20±3 training h/wk) were measured on 2 consecutive days. SAT was assessed with B-mode ultrasound at 8 sites (ISAK): triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, front thigh, medial calf, and quantified using image analysis software. Data was analyzed descriptively (mean±SD, [range]). Coefficient of variation (CV%), intraclass correlation coefficient (ICC, 2.1) and absolute (LoA) and ratio limits of agreement (RLoA) were calculated for day-to-day reliability. Mean sum of SAT thickness was 30.0±19.4 mm [8.0, 80.1 mm], with 3.9±1.8 mm [1.2 mm subscapular, 8.0 mm abdominal] for individual sites. CV for the sum of sites was 4.7%, ICC 0.99, LoA 1.7±3.6 mm, RLoA 0.940 ( * /÷1.155). Measuring SAT with ultrasound has proved to have excellent day-to-day reliability in elite canoe athletes. Recommendations for standardization of the method will further increase accuracy and reproducibility.


Asunto(s)
Deportes/fisiología , Grasa Subcutánea/anatomía & histología , Grasa Subcutánea/diagnóstico por imagen , Adulto , Composición Corporal , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Grosor de los Pliegues Cutáneos , Ultrasonografía , Adulto Joven
5.
Environ Sci Technol ; 46(7): 3964-72, 2012 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-22390718

RESUMEN

In the past, different slag materials were often used for landscaping and construction purposes or simply dumped. Nowadays German environmental laws strictly control the use of slags, but there is still a remaining part of 35% which is uncontrolled dumped in landfills. Since some slags have high heavy metal contents and different slag types have typical chemical and physical properties that will influence the risk potential and other characteristics of the deposits, an identification of the slag types is needed. We developed a FT-IR-based statistical method to identify different slags classes. Slags samples were collected at different sites throughout various cities within the industrial Ruhr area. Then, spectra of 35 samples from four different slags classes, ladle furnace (LF), blast furnace (BF), oxygen furnace steel (OF), and zinc furnace slags (ZF), were determined in the mid-infrared region (4000-400 cm(-1)). The spectra data sets were subject to statistical classification methods for the separation of separate spectral data of different slag classes. Principal component analysis (PCA) models for each slag class were developed and further used for soft independent modeling of class analogy (SIMCA). Precise classification of slag samples into four different slag classes were achieved using two different SIMCA models stepwise. At first, SIMCA 1 was used for classification of ZF as well as OF slags over the total spectral range. If no correct classification was found, then the spectrum was analyzed with SIMCA 2 at reduced wavenumbers for the classification of LF as well as BF spectra. As a result, we provide a time- and cost-efficient method based on FT-IR spectroscopy for processing and identifying large numbers of environmental slag samples.


Asunto(s)
Contaminantes Ambientales/análisis , Residuos Industriales/análisis , Metalurgia , Modelos Estadísticos , Análisis de Componente Principal/métodos , Minerales/análisis , Espectroscopía Infrarroja por Transformada de Fourier
6.
J Fish Biol ; 80(5): 1141-58, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22497376

RESUMEN

This review highlights the potential role that post-copulatory sexual selection plays in elasmobranch reproductive systems and the utility of this group to further understanding of evolutionary responses to the post-copulatory processes of sperm competition and cryptic female choice. The growing genetic evidence for female multiple mating (polyandry) in elasmobranchs is summarized. While polyandry appears to be common in this group, rates of multiple paternity are highly variable between species suggesting that there is large variance in the strength of post-copulatory sexual selection among elasmobranchs. Possible adaptations of traits important for post-copulatory sexual selection are then considered. Particular emphasis is devoted to explore the potential for sperm competition and cryptic female choice to influence the evolution of testes size, sperm morphology, genital morphology and sperm storage organs. Finally, it is argued that future work should take advantage of the wealth of information on these reproductive traits already available in elasmobranchs to gain a better understanding of how post-copulatory sexual selection operates in this group.


Asunto(s)
Elasmobranquios/fisiología , Reproducción , Conducta Sexual Animal/fisiología , Animales , Evolución Biológica , Femenino , Masculino
7.
Sci Adv ; 6(36)2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32917608

RESUMEN

Immunosuppressive cells in the tumor microenvironment allow cancer cells to escape immune recognition and support cancer progression and dissemination. To improve therapeutic efficacy, we designed a liposomal oxaliplatin formulation (PCL8-U75) that elicits cytotoxic effects toward both cancer and immunosuppressive cells via protease-mediated, intratumoral liposome activation. The PCL8-U75 liposomes displayed superior therapeutic efficacy across all syngeneic cancer models in comparison to free-drug and liposomal controls. The PCL8-U75 depleted myeloid-derived suppressor cells and tumor-associated macrophages in the tumor microenvironment. The combination of improved cancer cell cytotoxicity and depletion of immunosuppressive populations of immune cells is attractive for combination with immune-activating therapy. Combining the PCL8-U75 liposomes with a TLR7 agonist induced immunological rejection of established tumors. This combination therapy increased intratumoral numbers of cancer antigen-specific cytotoxic T cells and Foxp3- T helper cells. These results are encouraging toward advancing liposomal drug delivery systems with anticancer and immune-modulating properties into clinical cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Factores Inmunológicos , Inmunoterapia/métodos , Liposomas , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
8.
Science ; 234(4774): 327-33, 1986 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-17834530

RESUMEN

Experiments in which low-energy atoms are scattered from surfaces represent an important new method for structural analysis of the topmost atomic layers of a surface. The method and its application in a number of areas in surface science, such as detecting surface defects and studying lattice dynamics, are discussed.

9.
Unfallchirurg ; 112(3): 327-31, 2009 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-19212733

RESUMEN

The case of a 51-year-old patient is presented, with a humeral shaft fracture in combination with an ipsilateral reverse Hill-Sachs lesion, presumably after posterior shoulder dislocation as a result of an electrical accident followed by a fall from a ladder. After corresponding diagnostics, osteosynthesis of the shaft fracture was performed with a locked antegrade intramedullary nail. Simultaneously the reverse Hill-Sachs lesion was elevated und supplemented with the bone core that accrues during drilling of the nail entrance. In the follow-up period good fragment alignment, persistent joint stability and freedom of pain could be observed. On the basis of this case and the current literature the injury mechanism and potential therapy alternatives are discussed.


Asunto(s)
Artroplastia/instrumentación , Trasplante Óseo/instrumentación , Fijación Intramedular de Fracturas/instrumentación , Fracturas Óseas/cirugía , Húmero/lesiones , Procedimientos de Cirugía Plástica/instrumentación , Luxación del Hombro/cirugía , Fijación Intramedular de Fracturas/métodos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
10.
Neuroscience ; 157(4): 772-80, 2008 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-18951953

RESUMEN

Glycogen synthase kinase-3beta (GSK-3beta) has been proposed as the main kinase able to phosphorylate tau aberrantly in Alzheimer's disease and in related tauopathies. We have previously generated a double transgenic mouse line overexpressing the enzyme GSK-3beta and tau protein carrying a triple frontotemporal dementia and parkinsonism linked to chromosome 17 mutation whose expression patterns overlap in CA1 (pyramidal neurons) and dentate gyrus (granular neurons). Here, we have used this transgenic model to analyze how axonal and somatodendritic neuronal compartments are affected in the hippocampus. Our data demonstrate that neuronal subpopulations respond differentially to increased GSK-3 activity. Thus, dentate gyrus granular neurons undergo apoptotic death with subsequent degeneration of the mossy fibers, while CA1 pyramidal neurons accumulate hyperphosphorylated tau both in the axonal and in the somatodendritic compartments. These studies also allow us to propose a model of spreading of pathology through the hippocampus as a consequence of GSK-3 and tau dysregulation.


Asunto(s)
Diferenciación Celular/genética , Glucógeno Sintasa Quinasa 3/genética , Hipocampo/citología , Neuronas/clasificación , Neuronas/fisiología , Proteínas tau/genética , Factores de Edad , Animales , Anticuerpos Monoclonales/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Caspasa 3/metabolismo , Cromosomas Humanos Par 17/genética , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Indoles , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Mutación/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Neuronas/ultraestructura , Proteínas tau/metabolismo
11.
Neurodegener Dis ; 5(3-4): 247-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18322403

RESUMEN

Alzheimer's disease is characterized by the presence of two histopathological aberrant structures, the senile plaques and the neurofibrillary tangles. The main component of these tangles is the cytoskeletal protein tau in hyperphosphorylated form. Since a main tau kinase is glycogen synthase kinase 3 (GSK-3), the use of specific GSK-3 inhibitors, like lithium, could be a potential therapy in Alzheimer's disease. In this short article, we have done a review on tau phosphorylation in Alzheimer's disease and other tauopathies, and on the inhibition of kinases like GSK-3, involved in tau modification.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Compuestos de Litio/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Animales , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Compuestos de Litio/farmacología , Fármacos Neuroprotectores/farmacología
12.
Unfallchirurg ; 111(8): 628-31, 2008 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-18270680

RESUMEN

Isolated fractures of the greater tuberosity represent 14-21% of all proximal humeral fractures. Lesser tuberosity fractures have mainly been mentioned in case reports. We report a rare case of a combination of a lesser tuberosity avulsion with a multifragment fracture of the greater tuberosity of the proximal humerus in a young man. The injury mechanism might be a complex interaction between abduction and external rotation with impaction and shearing against the glenoid and acromion.


Asunto(s)
Fracturas del Hombro/diagnóstico por imagen , Fracturas del Hombro/cirugía , Heridas y Lesiones/diagnóstico por imagen , Heridas y Lesiones/cirugía , Adulto , Humanos , Masculino , Radiografía , Enfermedades Raras/diagnóstico por imagen , Enfermedades Raras/cirugía , Resultado del Tratamiento
13.
Rev Sci Instrum ; 89(12): 124706, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30599610

RESUMEN

The performance of a reversible helical electromagnetic launcher (RHEML) is reported and discussed. The results demonstrate the feasibility of using the RHEML as an electrically programmable shock tester (EPST). The data show that the reversible helical electromagnetic launcher can be operated with parallel-connected armatures that share current and force. This report is also the first-ever successful demonstration of iron-cored HEML stators. The electrical programmability of the EPST has been demonstrated by varying the shock pulse width in approximately 30 ms increments. The armature assembly has a total mass of approximately 25 kg (55 lbs). The stators are approximately 100 mm (4 in.) in diameter and 2.3 m (90 in.) long. The large mass reversible helical electromagnetic launcher is powered by a 1 MJ capacitive pulse forming network. The armature assembly has a measured minimum velocity of 0.4 m/s and a maximum velocity of 8.3 m/s. The minimum acceleration/deceleration force is 4.3 gees, while the maximum acceleration/deceleration force is 30.7 gees. The minimum shock pulse width is 16 ms, and the maximum shock pulse width is 150 ms.

14.
J Hosp Infect ; 97(3): 247-253, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28743503

RESUMEN

OBJECTIVE: A multiplex extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) quantitative polymerase chain reaction (qPCR), performed directly on rectal swabs, was compared with a culture-based protocol to study the discrepancies between the two methods, and identify existing challenges to apply this assay in routine clinical practice. The secondary objective was to assess the performance of the qPCR. MATERIALS AND METHODS: In two Dutch teaching hospitals, 573 rectal swabs were collected prospectively. Culture with additional testing with the Check-MDR CT103XL (Check-Points) was compared with the Check-Direct ESBL Screen for BD MAX (Check-Points), which detects the presence of the ESBL gene families CTX-M1, CTX-M2, CTX-M9 and SHV2/5-ESBL. The culture-based protocol (with Brilliance agar) was considered as the gold standard to assess the performance of the qPCR. RESULTS: Of the 573 rectal swabs, 74 (12.9%) were culture-positive. Eighty-four (14.7%) were qPCR-positive. There were eight culture-positive/qPCR-negative discrepancies and 18 culture-negative/qPCR-positive discrepancies. Sensitivity and specificity of qPCR vs culture were 87.7% [95% confidence interval (CI) 79.7-95.7] and 96.3% (95% CI 94.6-98.0), respectively. CONCLUSION: The Check-Direct ESBL Screen for the BD MAX is an easy-to-perform, quick molecular diagnostic test with the potential to significantly speed up screening for rectal ESBL-E carriage. Discrepancies were observed between the culture-based protocol and the qPCR in 4.5% of tested samples. Existing challenges for implementing qPCR are its limited sensitivity, the need for thorough knowledge of the local ESBL-E genes, and interpretation of culture-negative but qPCR-positive samples. It is believed that the limited sensitivity of qPCR could be optimized by including blaTEM as a molecular target, and improving the limit of detection.


Asunto(s)
Técnicas Bacteriológicas/métodos , Portador Sano/diagnóstico , Infecciones por Enterobacteriaceae/diagnóstico , Tamizaje Masivo/métodos , Técnicas de Diagnóstico Molecular/métodos , Recto/microbiología , beta-Lactamasas/genética , Portador Sano/microbiología , Infecciones por Enterobacteriaceae/microbiología , Hospitales , Humanos , Países Bajos , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de Tiempo
15.
United European Gastroenterol J ; 5(6): 880-886, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29026602

RESUMEN

BACKGROUND: Non-adherence to medication in patients with inflammatory bowel disease (IBD) is a challenging problem which is often overlooked or under-estimated by the physician or denied by the patient. We aimed to examine if re-phrasing the wording of the question used by the physician could help in revealing more patients who are non-adherent, and for whom appropriate counseling may be instituted. METHODS: A cross-sectional questionnaire-based study of IBD patients treated in a tertiary center was conducted. Patients received a questionnaire detailing their treatments and disease course, as well as their perceptions about disease. Two forms of questions about adherence were deliberately placed in two separate parts of the questionnaire: One was 'are you taking your medications regularly as prescribed?' (Standard question), and the second, more emphatic question, was 'how often does it happen that you miss a drug dosing?' (Re-phrased question). The rate of non-adherence disclosed by each of these questions was compared. Sensitivity, specificity and predicative values were computed for each question against the conventional definition of non-adherence as taking of less than 80% of prescribed medication doses disclosed by any of the methods. Predictors of non-compliance and of denying non-compliance were also explored. RESULTS: Overall, 165 patients were included (49% female, mean age 33.7 ± 12.7 SD, median age 30 years, 29.6% with ulcerative colitis, 62.4% with Crohn's disease). Upon questioning, 50 (30.3%) of the patients admitted to non-adherence in the last month when asked by the emphatic re-phrased question format, compared with only 10 patients (6%) reporting non-adherence when asked directly by the standard question (OR 7.4, 95%CI 3.6-15.2, p < 0.001). Thus, a 'Do you take your medicine regularly' question format disclosed only 20% of genuinely non-compliant patients and had 16% sensitivity and 98.2% specificity for revealing non-adherence (PPV 80%, NPV 72.9%) compared with the reference re-phrased question. The leading cause for non-adherence was skepticism about drug efficacy or safety (20.5%), followed by vacation or weekend (15%), problems with prescription or pharmacy (13.5%) and forgetfulness (10%). No single demographic or clinical factor correlated with non-adherence. The only factor which correlated with higher probability for non-adherence was biological and combination treatment. CONCLUSION: Non-compliance with treatment is much more common than patients admit. Asking patients how often does it happen that they miss a drug dosing is a simple, practical tool which performs significantly better in disclosing non-adherence compared with asking patients if they take their medication as they should.

16.
Aliment Pharmacol Ther ; 45(2): 276-282, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27862102

RESUMEN

BACKGROUND: Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking. AIM: To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients. METHODS: The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as 'sero-reversal', elevation of drug levels and regained clinical response were the sought outcomes. RESULTS: Twenty-three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero-reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero-reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics. CONCLUSIONS: In almost half of inflammatory bowel disease patients developing anti-adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico-biological response. However, these observations need to be confirmed with larger studies.


Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Formación de Anticuerpos/efectos de los fármacos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Adalimumab/efectos adversos , Adulto , Antiinflamatorios/efectos adversos , Anticuerpos/sangre , Azatioprina/uso terapéutico , Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Femenino , Humanos , Masculino , Mercaptopurina/uso terapéutico , Metotrexato/uso terapéutico , Resultado del Tratamiento , Adulto Joven
17.
Cancer Res ; 52(8): 2167-73, 1992 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-1559220

RESUMEN

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.


Asunto(s)
Linfotoxina-alfa/farmacología , Sarcoma Experimental/irrigación sanguínea , Neoplasias Cutáneas/irrigación sanguínea , Factor de Necrosis Tumoral alfa/farmacología , Adenosina Trifosfato/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Rayos Láser , Espectroscopía de Resonancia Magnética , Metilcolantreno , Ratones , Ratones Desnudos , Fosfocreatina/metabolismo , Fósforo , Ratas , Ratas Endogámicas , Flujo Sanguíneo Regional/efectos de los fármacos , Sarcoma Experimental/metabolismo , Neoplasias Cutáneas/metabolismo , Resistencia Vascular/efectos de los fármacos
18.
Appl Ergon ; 54: 196-204, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26851479

RESUMEN

Innovative in-car applications provided on smartphones can deliver real-time alternative mobility choices and subsequently generate visual-manual demand. Prior studies have found that multi-touch gestures such as kinetic scrolling are problematic in this respect. In this study we evaluate three prototype tasks which can be found in common mobile interaction use-cases. In a repeated-measures design, 29 participants interacted with the prototypes in a car-following task within a driving simulator environment. Task completion, driving performance and eye gaze have been analysed. We found that the slider widget used in the filtering task was too demanding and led to poor performance, while kinetic scrolling generated a comparable amount of visual distraction despite it requiring a lower degree of finger pointing accuracy. We discuss how to improve continuous list browsing in a dual-task context.


Asunto(s)
Atención , Conducción de Automóvil , Aplicaciones Móviles , Teléfono Inteligente , Interfaz Usuario-Computador , Adulto , Conducta de Elección , Presentación de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis y Desempeño de Tareas , Adulto Joven
19.
J Am Coll Cardiol ; 1(3): 816-8, 1983 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6826972

RESUMEN

Vulnerability to atrial fibrillation and flutter was examined in 11 alcohol abusers who did not have cardiomyopathy or manifest heart failure. Atrial extrastimulation was done with rapid pacing (drive cycle length 500 ms) to facilitate induction of atrial vulnerability, seen in four alcohol abusers. The remaining seven were retested 30 minutes after drinking 60 to 120 ml of 86 proof whiskey (ethanol blood levels were 49 to 101 mg/100 ml but pulmonary capillary wedge pressure remained normal in all) and atrial fibrillation or flutter was induced in three of the drinkers. Three nondrinkers, symptomatic with sinus bradycardia but not in heart failure, were found not to be vulnerable to atrial fibrillation or flutter, but flutter was induced in two of the three after drinking whiskey. Whiskey did not alter atrial functional refractory periods (mean +/- standard error of the mean 297 +/- 14 to 290 +/- 12 ms) or widen the dispersion among three disparate right atrial sites (57 +/- 13 to 47 +/- 12 ms). Thus, whiskey enhanced vulnerability to atrial fibrillation and flutter in patients without heart failure or cardiomyopathy, substantiating the "holiday heart" syndrome.


Asunto(s)
Fibrilación Atrial/etiología , Cardiomiopatía Alcohólica/fisiopatología , Adulto , Anciano , Cardiomiopatía Alcohólica/complicaciones , Etanol/sangre , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Presión Esfenoidal Pulmonar
20.
J Am Coll Cardiol ; 14(7): 1731-40, 1989 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2584563

RESUMEN

Signal-averaged electrocardiograms (X, Y and Z leads) were acquired from 24 patients with coronary artery disease and recurrent ventricular tachycardia, 24 control patients with coronary artery disease and 23 normal subjects to assess the discriminant value of fast Fourier transformation of the entire late potential period of the QRS complex. Analysis of the vector magnitude in the temporal domain (25 to 250 Hz bandpass filters) measured high frequency QRS duration, the duration of terminal signals less than 40 microV and the root mean square voltage of the last 40 ms. Late potentials were defined as terminal signals greater than 25 Hz that were less than 40 microV. Analysis in the frequency domain used a 120 ms window that encompassed (had onset with) all of the late potential, but the mean value was first subtracted to eliminate a direct current component. High frequency spectral areas (60 to 120 Hz) and the percent high frequency (100 x [60 to 120 Hz/0 to 120 Hz]) were calculated. Results in both temporal and frequency domains were similar in control patients with coronary artery disease and normal subjects. Patients with ventricular tachycardia had a longer high frequency QRS complex (p less than 0.0001) and longer high frequency terminal signals less than 40 microV (p less than 0.0004), but not significantly lower voltage in the last 40 ms. The most useful temporal domain measurement was high frequency QRS duration (if greater than or equal to 120 ms, odds ratio = 8.2). Patients with ventricular tachycardia had increased high frequency spectral areas (p less than 0.0002) in the late potential, and the percent high frequency was especially increased (p = 0.0000; if percent high frequency greater than 3.1%, odds ratio = 18.4). The odds ratio and the area under the receiver operating characteristic curve were both greater for percent high frequency than for high frequency QRS duration (p less than 0.03). All patients with ventricular tachycardia had a high frequency QRS complex greater than or equal to 107 ms or percent high frequency greater than or equal to 3.1% (sensitivity 100%). For a high frequency QRS complex greater than or equal to 107 ms and percent high frequency greater than or equal to 3.1%, specificity was 96%. Therefore, high frequencies in late potentials, not their duration or reduced voltage, most usefully identify patients with coronary artery disease who are prone to ventricular tachycardia.


Asunto(s)
Electrocardiografía , Taquicardia/fisiopatología , Adulto , Anciano , Enfermedad Coronaria/fisiopatología , Femenino , Análisis de Fourier , Humanos , Masculino , Persona de Mediana Edad , Reconocimiento de Normas Patrones Automatizadas
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