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1.
Int J Biometeorol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869702

RESUMEN

This paper provides an overview of the HEAT (Healthy Environments for AthleTes) project, which aims to understand the impact of environmental conditions on athlete health and performance during major sporting events such as long-distance running, cycling, and triathlons. In collaboration with the SAFER (Strategies to reduce Adverse medical events For the ExerciseR) initiative, the HEAT project carried out a field campaign at the 2022 Comrades Marathon in the KwaZulu-Natal province of South Africa. The measurement campaign deployed seven weather stations, seven PM2.5 monitors and one spore trap along the 90 km route to capture spatially representative measurements of complex micro-climates, allergenic aerospora, and particulate matter exposure. The results indicate that runners were exposed to moderate risk heat stress conditions. Novel findings from this initial campaign shows elevated and potentially harmful PM2.5 levels at spectator areas, possibly coinciding with small fire events around the race day festivities. Our findings show values PM2.5 levels over the WHO 24-h guidelines at all stations, while 2000 µg/m3 at two stations. However, the lack of an acute exposure standard means direct health impacts cannot be quantified in the context of a sport event. The HEAT project highlights important aspects of race day monitoring; regional scale climatology has an impact on the race day conditions, the microclimatic conditions (pollution and meteorology) are not necessarily captured by proximity instruments and direct environmental measurements are required to accurately capture conditions along the route.

2.
Rev. esp. cardiol. (Ed. impr.) ; 75(9): 748-756, sept. 2022. tab
Artículo en Español | IBECS | ID: ibc-208227

RESUMEN

Introducción y objetivos Siguen sin estudio la eficacia y la seguridad del ticagrelor frente al prasugrel en pacientes con síndrome coronario agudo (SCA) según el índice de masa corporal (IMC). Se evaluaron la eficacia y la seguridad del ticagrelor frente a prasugrel en pacientes con SCA según el IMC. Métodos Se agrupó a los pacientes (n=3.987) en 3 categorías: con peso normal (IMC <25; n=1.084), sobrepeso (IMC ≥ 25 <30; n=1.890) y obesidad (IMC ≥ 30; n=1.013). El objetivo primario de eficacia fue la incidencia de muerte por cualquier causa, infarto de miocardio o accidente cerebrovascular a 1 año. El objetivo secundario de seguridad fue la incidencia de hemorragias de tipo 3-5 de la Bleeding Academic Research Consortium a 1 año. Resultados El objetivo primario se produjo en 63 pacientes asignados a ticagrelor y 39 asignados a prasugrel en el grupo de peso normal (el 11,7 frente al 7,5%; HR=1,62; IC95%, 1,09-2,42; p=0,018), 78 pacientes asignados a ticagrelor y 58 asignados a prasugrel en el grupo de sobrepeso (el 8,3 frente al 6,2%; HR=1,36; IC95%, 0,97-1,91; p=0,076) y 43 pacientes asignados a ticagrelor y 37 asignados a prasugrel en el grupo de obesidad (el 8,6 frente al 7,3%; HR=1,18; IC95%, 0,76-1,84; p=0,451). La incidencia de eventos hemorrágicos a 1 año en los pacientes con peso normal (el 6,5 frente al 6,6%; p=0,990), sobrepeso (el 5,6 frente al 5,0%; p=0,566) u obesidad (el 4,4 frente al 2,8%; p=0,219) no difirió entre el ticagrelor y el prasugrel. No hubo una interacción significativa entre el brazo de tratamiento y el IMC en relación con el objetivo primario (pinteracción=0,578) o el secundario (pinteracción=0,596). Conclusiones En pacientes con SCA, el IMC no influyó significativamente en el efecto del tratamiento con ticagrelor en términos de eficacia o seguridad frente al prasugrel (AU)


Introduction and objectives The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI. Methods Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m2; n=1084), overweight (BMI ≥ 25 to <30kg/m2; n=1890), and obesity (BMI ≥ 30kg/m2; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding. Results The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=.578) or secondary endpoint (Pint=.596). Conclusions In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety (AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticagrelor/administración & dosificación , Clorhidrato de Prasugrel/análogos & derivados , Síndrome Coronario Agudo/tratamiento farmacológico , Índice de Masa Corporal , Resultado del Tratamiento
3.
J Med Case Rep ; 15(1): 90, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608053

RESUMEN

BACKGROUND: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. CASE PRESENTATION: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. CONCLUSION: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).


Asunto(s)
Antígeno de Maduración de Linfocitos B/inmunología , COVID-19/fisiopatología , Inmunoterapia Adoptiva/métodos , Mieloma Múltiple/terapia , Receptores Quiméricos de Antígenos/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/inmunología , Prueba de Ácido Nucleico para COVID-19 , Prueba Serológica para COVID-19 , Tos , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Fiebre , Hospitalización , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , SARS-CoV-2 , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
5.
Psychiatry Res Neuroimaging ; 303: 111131, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32585577

RESUMEN

In adults, trauma imagery has proven to be a useful tool to assess the neural mechanisms of psychological trauma processing. In adolescents, heterogeneous results could be found for other tasks, however, a trauma imagery paradigm has not been evaluated. For this purpose, we investigated a trauma imagery paradigm with control scripts to assess neural correlates of traumatic experiences in youth. 15 adolescents, who had experienced a traumatic interpersonal event in the past and have developed clinically relevant symptoms, underwent an fMRI scan while listening to their individual trauma- versus two control scripts (positive/negative). We analysed a parametric contrast of the imagery phases (trauma > negative > positive) which revealed activity in the thalamus, dorsal anterior cingulate cortex, cuneus, dorsomedial prefrontal cortex and amygdala. Additionally, amygdala-activity correlated positively with depression-symptom-severity. Our data provide evidence for the feasibility of fMRI during a trauma imagery task in adolescents to investigate networks previously related to hyperarousal in adults with PTSD. Further, we demonstrate the specificity of the activated networks for trauma imagery as compared to imagery of other emotional situations. The task might be particularly useful to evaluate neural correlates of treatment in adolescents when hyperarousal is a target symptom.


Asunto(s)
Conducta del Adolescente/psicología , Encéfalo/diagnóstico por imagen , Imaginación/fisiología , Red Nerviosa/diagnóstico por imagen , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/psicología , Adolescente , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiología , Encéfalo/fisiología , Emociones/fisiología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Red Nerviosa/fisiología , Proyectos Piloto , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Adulto Joven
6.
J Intern Med ; 285(1): 19-39, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30079527

RESUMEN

Recent advancements in bioanalytical techniques have led to the development of novel and robust diagnostic approaches that hold promise for providing optimal patient treatment, guiding prevention programs and widening the scope of personalized medicine. However, these advanced diagnostic techniques are still complex, expensive and limited to centralized healthcare facilities or research laboratories. This significantly hinders the use of evidence-based diagnostics for resource-limited settings and the primary care, thus creating a gap between healthcare providers and patients, leaving these populations without access to precision and quality medicine. Smartphone-based imaging and sensing platforms are emerging as promising alternatives for bridging this gap and decentralizing diagnostic tests offering practical features such as portability, cost-effectiveness and connectivity. Moreover, towards simplifying and automating bioanalytical techniques, biosensors and lab-on-a-chip technologies have become essential to interface and integrate these assays, bringing together the high precision and sensitivity of diagnostic techniques with the connectivity and computational power of smartphones. Here, we provide an overview of the emerging field of clinical smartphone diagnostics and its contributing technologies, as well as their wide range of areas of application, which span from haematology to digital pathology and rapid infectious disease diagnostics.


Asunto(s)
Práctica Clínica Basada en la Evidencia , Teléfono Inteligente , Técnicas Biosensibles , Técnicas Citológicas , Humanos , Dispositivos Laboratorio en un Chip , Microfluídica , Aplicaciones Móviles , Patología Molecular , Sistemas de Atención de Punto , Impresión Tridimensional
7.
Herz ; 43(8): 689-694, 2018 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-30456630

RESUMEN

The guidelines on myocardial revascularization published in 2018 are a joint initiative of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. To establish indications for myocardial revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), evidence of the functional relevance of coronary artery stenoses is needed either by non-invasive imaging function tests or intravascular hemodynamic measurements. The prognostic and symptomatic benefits of myocardial revascularization depend on whether complete revascularization can be achieved. This needs to be considered when choosing the most appropriate revascularization strategy. In addition, the individual operative risk, the technical feasibility, the presence of diabetes mellitus and the anatomical complexity of coronary artery disease, as assessed by the SYNTAX score, are key criteria when choosing the optimal method of revascularization. For PCI radial artery access and the general use of drug-eluting stents are recommended. For CABG multiple arterial grafts should be strived for including the radial artery for treatment of high-grade coronary stenosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Revascularización Miocárdica , Intervención Coronaria Percutánea , Guías de Práctica Clínica como Asunto , Puente de Arteria Coronaria , Humanos , Revascularización Miocárdica/métodos , Resultado del Tratamiento
8.
Leukemia ; 32(2): 510-519, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28663580

RESUMEN

The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 ß2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Médula Ósea/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Animales , Médula Ósea/efectos de los fármacos , Citocinas/metabolismo , Humanos , Inmunohistoquímica/métodos , Masculino , Ratas , Ratas Endogámicas BN
9.
Leukemia ; 31(10): 2011-2019, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28074068

RESUMEN

Genetic changes are infrequent in acute myeloid leukemia (AML) compared with other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CGI methylator phenotype (CIMP) (A-CIMP+). A-CIMP was associated with longer overall survival (OS) in this data set (median OS, years: A-CIMP+=not reached, CIMP-=1.17; P=0.08). For validation we used 194 samples from The Cancer Genome Atlas interrogated with Illumina 450k methylation arrays where we confirmed longer OS in A-CIMP (median OS, years: A-CIMP+=2.34, A-CIMP-=1.00; P=0.01). Hypermethylation in A-CIMP+ favored CGIs (OR: CGI/non-CGI=5.21), and while A-CIMP+ was enriched in CEBPA (P=0.002) and WT1 mutations (P=0.02), 70% of cases lacked either mutation. Hypermethylated genes in A-CIMP+ function in pluripotency maintenance, and a gene expression signature of A-CIMP was associated with outcomes in multiple data sets. We conclude that CIMP in AML cannot be explained solely by gene mutations (for example, IDH1/2, TET2), and that curability in A-CIMP+ AML should be validated prospectively.


Asunto(s)
Islas de CpG , Metilación de ADN , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Anciano , ADN de Neoplasias/genética , Conjuntos de Datos como Asunto , Femenino , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Proyectos Piloto , Pronóstico , Estudios Retrospectivos , Riesgo , Análisis de Supervivencia , Adulto Joven
10.
Rozhl Chir ; 93(4): 216-9, 2014 Apr.
Artículo en Checo | MEDLINE | ID: mdl-24881479

RESUMEN

In this case report, we describe the case of a 30-year-old obese patient with severe acute pancreatitis complicated during hospitalization by the development of infected necrosis, a pseudocyst and an abscess. We demonstrate a possible solution to these complications using a combination of minimally invasive approaches. The contribution of this case report resides in that it presents a combination of the percutaneous approach and the endosonographic approach in the treatment of pancreatic necrosis. We believe that in such an extensive necrosis of the pancreas as is described in our case, this combined approach is optimal. The condition for implementing such a procedure is a well-staffed and technically equipped workplace.


Asunto(s)
Absceso/etiología , Absceso/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Seudoquiste Pancreático/etiología , Seudoquiste Pancreático/cirugía , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/cirugía , Cirugía Asistida por Video , Absceso/diagnóstico , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Endosonografía , Humanos , Masculino , Páncreas/patología , Páncreas/cirugía , Seudoquiste Pancreático/diagnóstico , Pancreatitis Aguda Necrotizante/diagnóstico
11.
Thromb Haemost ; 109(5): 834-45, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23238773

RESUMEN

Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.


Asunto(s)
Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Receptores Purinérgicos P2Y12/efectos de los fármacos , Ticlopidina/análogos & derivados , Plaquetas/metabolismo , Ensayos Clínicos como Asunto , Clopidogrel , Interacciones Farmacológicas , Medicina Basada en la Evidencia , Humanos , Farmacogenética , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacocinética , Pruebas de Función Plaquetaria , Polimorfismo Genético , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/farmacocinética , Receptores Purinérgicos P2Y12/sangre , Medición de Riesgo , Ticlopidina/efectos adversos , Ticlopidina/farmacocinética , Ticlopidina/uso terapéutico , Resultado del Tratamiento
12.
Clin Pharmacol Ther ; 92(4): 476-85, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22948893

RESUMEN

Dual antiplatelet therapy with aspirin and clopidogrel is the accepted standard for prevention of ischemic complications after percutaneous coronary intervention and has been shown to reduce cardiovascular events in patients with acute coronary syndromes (ACSs). There is substantial interindividual variability in antiplatelet response to clopidogrel. Various clinical studies have demonstrated that patients with high on-clopidogrel platelet reactivity incur an increased risk for ischemic events. In recent years, several clinical and demographic variables as well as multiple genetic factors contributing to the variability in antiplatelet response to clopidogrel have been identified. We discuss strategies based on platelet function testing or genotyping for improvement of antiplatelet effects of clopidogrel and thereby clinical outcome.


Asunto(s)
Inhibidores de Agregación Plaquetaria/administración & dosificación , Medicina de Precisión/métodos , Ticlopidina/análogos & derivados , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Clopidogrel , Genotipo , Humanos , Fenotipo , Medicina de Precisión/tendencias , Ticlopidina/administración & dosificación , Resultado del Tratamiento
13.
Thromb Haemost ; 107(4): 634-41, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22371016

RESUMEN

Platelets play an important role in haemostasis and thrombus formation. Latest research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited data exist on inter-individual variability of platelet miRNA profile while no data are available on intra-individual variability. We assessed platelet miRNA profile in five volunteers at five time points over a time course of 10 days; 24 hours prior to the last blood sampling, subjects took 500 mg acetylsalicylic acid (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA array-analysis was performed. Temporal patterns and ASA effect were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, target gene search was performed and an annotation network was created. MiRNA expression profiling of 1,281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant to other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. After 24 hours, no significant effect of ASA was found. Concerning functional implications of the 20 most abundantly expressed miRNAs, we found six functional themes. In conclusion, platelet miRNA profile is remarkably stable over the time period studied. Single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward extra-platelet effects of platelet miRNAs.


Asunto(s)
Plaquetas/citología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , MicroARNs/metabolismo , Adulto , Aspirina/farmacología , Biología Computacional/métodos , Humanos , Leucocitos/citología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Análisis de Secuencia por Matrices de Oligonucleótidos , Agregación Plaquetaria , Reproducibilidad de los Resultados , Manejo de Especímenes/métodos , Factores de Tiempo
14.
Int J Obes (Lond) ; 35(3): 364-72, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20733585

RESUMEN

CONTEXT: Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects. OBJECTIVE: We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I. DESIGN AND SETTING: Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used. PARTICIPANTS: For the final analyses, 3882 subjects aged 20-79 years were available. MAIN OUTCOME MEASURES: Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures. RESULTS: Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:-8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m(-2) by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (-2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels). CONCLUSION: We propose that the GH-IGF-I axis is a mediator for the relationship between FTO and BMI.


Asunto(s)
Índice de Masa Corporal , Hormona de Crecimiento Humana/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Obesidad/genética , Proteínas/genética , Adulto , Anciano , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Estudios Transversales , Femenino , Variación Genética , Genotipo , Alemania , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Adulto Joven
15.
Vasa ; 39(3): 229-36, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20737381

RESUMEN

BACKGROUND: Directional atherectomy (DA) has become popular in some centers to remove atherosclerotic plaques in femoro-popliteal lesions. Although immediate and also short - term outcome data are promising, solid long-term data are warranted to justify the widespread use in daily practice. PATIENTS AND METHODS: In this prospective study de novo and restenotic lesions of the femoro-popliteal segments were treated with the Silverhawk device. 161 consecutive patients (164 lesions) with peripheral artery disease (PAD) Rutherford classes 2 to 5 were included from June 2002 to October 2004 and October 2006 to June 2007 (59 % male, mean age 67 +/- 11 years, range 40 to 88) and the outcome analyzed according to the TASC II classification. RESULTS: DA alone was performed successfully in 28 % (n = 46), adjunctive balloon angioplasty in 65 % (n = 107) and stenting in 7 % (n = 11). The overall technical success rate was 76 % (124 / 164) and the procedural success rate 95 % (154 / 164). At 12 months primary patency rate was 61 % (85 / 140) and the secondary patency rate was 75 % (105 / 140) in the entire cohort, being less favourable in TASC D compared to TASC A to C lesions (p = 0.034 and p < 0.001, respectively). Furthermore the restenosis rate differed trendwise (p = 0.06) between de novo and restenotic lesions. Changes in the ABI and the Rutherford classes were significantly in favour of TASC A to C lesions compared to TASC D after 12 months (p = 0.004). The event free survival (MI, TIA, or restenosis) was 48 % at 12 months and 38.5 % at 24 months. Predictor for restenosis in the multivariable analysis was only male gender (p=0.04). CONCLUSIONS: The results in TASC D lesions are inferior to those in the lesser stages. DA of femoro-popliteal arteries leads shows a trend to better long-term technical and clinical outcome in de novo lesions compared to restenotic lesions.


Asunto(s)
Arteriopatías Oclusivas/terapia , Aterectomía/instrumentación , Arteria Femoral , Arteria Poplítea , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/instrumentación , Arteriopatías Oclusivas/fisiopatología , Arteriopatías Oclusivas/cirugía , Aterectomía/efectos adversos , Constricción Patológica , Supervivencia sin Enfermedad , Diseño de Equipo , Femenino , Arteria Femoral/fisiopatología , Arteria Femoral/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Arteria Poplítea/fisiopatología , Arteria Poplítea/cirugía , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Stents , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Procedimientos Quirúrgicos Vasculares
16.
Eur J Med Res ; 15(1): 13-9, 2010 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-20159666

RESUMEN

OBJECTIVE: In patients with multiple myeloma, bendamustine monotherapy is effective as 1st and 2nd line therapy. However, data for patients with advanced multiple myeloma is rare. METHODS: In this retrospective analysis we have identified 39 patients with relapsed or refractory multiple myeloma by means of case research, who have been treated at our institution with bendamustine as salvage therapy. After in median 2 lines of prior therapy (range: 1-5) patients received in median 3 (range: 1-10) cycles of bendamustine. Bendamustine dosage was 80-150 mg on day 1+2 of a monthly cycle. Bendamustine was administered as monotherapy in 39% of patients, whereas 61% received concomitant steroids. RESULTS: Toxicity was mild to moderate. Response rates were as follows: 3% vgPR, 33% PR, 18% MR, 26% SD and 20% PD. The median event-free and overall survival were 7 and 17 months, respectively. CONCLUSIONS: In conclusion, in patients with advanced multiple myeloma bendamustine is effective and associated with mild toxicity. Therefore, the role of bendamustine in patients with multiple myeloma should be investigated in further clinical trials.


Asunto(s)
Antineoplásicos/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Clorhidrato de Bendamustina , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Compuestos de Mostaza Nitrogenada/efectos adversos , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
17.
Endoscopy ; 42(1): 28-33, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20066590

RESUMEN

BACKGROUND AND STUDY AIMS: To compare the rate of detection of colorectal neoplastic lesions using the selective photosensitizer precursor hexaminolevulinate (HAL) combined with a new fluorescence video endoscope system against that of standard white light endoscopy, and secondarily, to evaluate the safety profile of HAL-induced fluorescence colonoscopy. PATIENTS AND METHODS: This prospective phase II clinical pilot study from two hospital study centers included 25 patients with known or highly suspected colorectal neoplasia. They underwent sensitization with locally applied 500 ml HAL enemas at a concentration of 1.6 mmol/L. At 60 minutes after enteral HAL administration, fluorescence imaging was done using a special light source capable of delivering either white light or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. RESULTS: Using histology as the gold standard, 55 / 93 of neoplastic lesions were detected with white light endoscopy, 53 / 93 with both white and blue light, 38 / 93 with blue light and second-pass white light, and 27/93 with blue light only. Of all neoplastic lesions, 91 / 93 revealed red fluorescence under fluorescence imaging ( P < 0.0001). Fluorescence mode showed 38.7 % (36 / 93) more neoplasms than did white light endoscopy. An isolated slight elevation of bilirubin, by a factor of 1.5, was noted after the administration of HAL. CONCLUSIONS: Administration of HAL as enema induces selective lesion fluorescence and increases lesion detection rate in patients with colorectal neoplasia, especially of flat, nonvisible adenomas.


Asunto(s)
Ácido Aminolevulínico/análogos & derivados , Neoplasias del Colon/patología , Colonoscopía/métodos , Fármacos Fotosensibilizantes , Anciano , Femenino , Fluorescencia , Humanos , Masculino
18.
Br J Anaesth ; 104(2): 239-44, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20034967

RESUMEN

BACKGROUND: This randomized, double-blinded volunteer study was designed to evaluate the ED(99) volume of local anaesthetic for sciatic nerve blocks using a step-up/step-down methodology. METHODS: A maximum of 20 volunteers were included to receive an ultrasound-guided sciatic nerve block with mepivacaine 1.5% and a starting volume of 0.2 ml mm(-2) cross-sectional nerve area. In cases of a complete sensory block, the volume was reduced by 0.02 ml mm(-2) cross-sectional nerve area until the first block failed. Thereafter, the volume of local anaesthetic was increased by 0.02 ml mm(-2) cross-sectional nerve area. After three cycles of successful/failed blocks, the ED(99) volume of local anaesthetic could be calculated by a probability function. The influence of the volumes of local anaesthetics on sensory onset times and duration of sensory block was evaluated by linear regression. RESULTS: The ED(99) volume of local anaesthetic for sciatic nerve block was calculated with 0.10 ml mm(-2) cross-sectional nerve area. The correlation between the volume of local anaesthetic and the sensory onset time was weak (r=0.14), whereas the correlation between the volume of local anaesthetic and the duration of sensory block was moderate (r=0.65). CONCLUSIONS: This is the first study where an ED(99) volume of local anaesthetic for sciatic nerve block has been evaluated. The resulting local anaesthetic volume of 0.10 ml mm(-2) cross-sectional nerve area seems to have no impact on sensory onset time, whereas the duration of sensory block is shorter.


Asunto(s)
Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Masculino , Mepivacaína/administración & dosificación , Persona de Mediana Edad , Nervio Ciático/anatomía & histología , Nervio Ciático/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adulto Joven
19.
Vasa ; 38(1): 53-9, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19229804

RESUMEN

BACKGROUND: Bleeding complications in the groin are one of the major disadvantages of femoral catheter procedures. The immobilisation of the patient and the compression bandages can jeopardize the patients' comfort. Aim of the study was a randomized comparison of safety and patient comfort of mechanical pressure followed by pressure bandage overnight using two different haemostatic pads after femoral artery sheath removal. PATIENTS AND METHODS: Nine hundred and eight consecutive patients undergoing diagnostic or therapeutic procedures via a 5 or 6 F femoral sheath were randomly selected either for mechanical compression therapy followed by a compression bandage (302 patients, group 1), or manual compression with application of a calcium ion releasing device (compression bandage only after application of > 5000 IU of heparin; 303 patients; group 2), or manual compression with a thrombin covered PAD without compression bandage (303 patients, group 3). RESULTS: No major hemorrhage or death occurred. A false aneurysm was found in 10 (3.3%), 13 (4.3%), and 10 patients (3.3%) of group 1, 2, and 3, respectively (p = 0.38). Three patients (0.3%) needed surgical treatment. 69 (22.7%) patients in thrombin covered PAD-group required a compression bandage overnight due to seeping hemorrhage after 15 minutes. In the calcium ion releasing PAD-group 124 (40.9%) patients had continued bandaging, 46 (15.2%) due to seeping hemorrhage after 15 min, and 78 (25.7%) due to application of heparin > 5000 IU. CONCLUSIONS: The use of mechanical compression combined with a pressure bandage, and the use of haemostatic wound dressing assisted sheath removal technique offer a comparable level of safety. Patient comfort is improved with the usage of PAD devices, however the technical failure rate of the PAD should be taken into account.


Asunto(s)
Vendajes , Cateterismo Cardíaco/efectos adversos , Cateterismo Periférico/efectos adversos , Arteria Femoral , Hemorragia/prevención & control , Técnicas Hemostáticas , Hemostáticos/uso terapéutico , Anciano , Alginatos/uso terapéutico , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Anticoagulantes/efectos adversos , Femenino , Ácido Glucurónico/uso terapéutico , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hemorragia/etiología , Técnicas Hemostáticas/efectos adversos , Heparina/efectos adversos , Ácidos Hexurónicos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Presión , Estudios Prospectivos , Punciones/efectos adversos , Trombina/uso terapéutico , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex
20.
Vasa ; 38(1): 73-5, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19229807

RESUMEN

The purpose of this report is to present a rare case of lumbar artery aneurysm. We report the case of a 54-years-old male patient who was misdiagnosed over years having a chronic infrarenal aortic aneurysm. A 64-slice CT at our institution revealed a large lumbar artery aneurysm. The conclusion of this case report is that a lumbar or accessory renal artery aneurysm has to be taken into consideration if there is a localized enlargement of the lower abdominal aorta and a high resolution CT-scan is strongly recommended to make the exact diagnosis.


Asunto(s)
Aneurisma/diagnóstico por imagen , Aneurisma de la Aorta/diagnóstico , Errores Diagnósticos , Vértebras Lumbares/irrigación sanguínea , Tomografía Computarizada por Rayos X , Aneurisma/cirugía , Arterias/patología , Implantación de Prótesis Vascular , Enfermedad Crónica , Humanos , Aneurisma Ilíaco/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Renal/cirugía , Reimplantación
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