Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 340
Filtrar
Más filtros

Intervalo de año de publicación
1.
Eur J Nucl Med Mol Imaging ; 49(9): 3162-3172, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35165788

RESUMEN

PURPOSE: Chronic traumatic encephalopathy refers to a neurodegenerative disease resulting from repetitive head injury of participants in contact sports. Similar to other neurodegenerative diseases, neuroinflammation is thought to play a role in the onset and progression of the disease. Limited knowledge is available regarding the neuroinflammatory consequences of repetitive head injury in currently active contact sports athletes. PET imaging of the 18-kDa translocator protein (TSPO) allows quantification of microglial activation in vivo, a marker of neuroinflammation. METHODS: Eleven rank A kickboxers and 11 age-matched controls underwent TSPO PET using [11C]-PK11195, anatomical MRI, diffusion tensor imaging, and neuropsychological testing. Relevant imaging parameters were derived and correlated with the outcomes of the neuropsychological testing. RESULTS: On a group level, no statistically significant differences were detected in non-displaceable binding potential (BPND) using PET. Individually, 3 kickboxers showed increased BPNDs in widespread regions of the brain without a correlation with other modalities. Increased FA was observed in the superior corona radiata bilaterally. DTI parameters in other regions did not differ between groups. CONCLUSION: Despite negative results on a group level, individual results suggest that neuroinflammation may be present as a consequence of repetitive head injury in active kickboxers. Future studies using a longitudinal design may determine whether the observed TSPO upregulation is related to the future development of neuropsychiatric symptoms.


Asunto(s)
Traumatismos en Atletas , Traumatismos Craneocerebrales , Enfermedades Neurodegenerativas , Enfermedades Neuroinflamatorias , Traumatismos en Atletas/diagnóstico por imagen , Encéfalo/metabolismo , Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/metabolismo , Imagen de Difusión Tensora , Humanos , Artes Marciales/lesiones , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Receptores de GABA/metabolismo
3.
Br J Cancer ; 111(8): 1646-56, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25137020

RESUMEN

BACKGROUND: Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. METHODS: Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were labelled with [1-(3)H]-Etn hydrochloride. PKC was activated with phorbol ester (TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD (phospholipase D). [(3)H]-labelled Etn metabolites were resolved by ion-exchange chromatography. Sodium oleate and mastoparan were tested as activators of PLD2. Phospholipase D activity was measured by a transphosphatidylation reaction. Cells were treated with ionomycin to raise intracellular Ca(2+) levels. RESULTS: Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to the medium. Phorbol ester treatment over 3h increased Etn metabolite release from the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a transphosphatidylation reaction. Only metastatic PC3 cells specifically upregulated Etn release in response to TPA treatment. Oleate and mastoparan increased GPEtn release from all cell lines at the expense of Etn. Ionomycin stimulated GPEtn release from benign PNT2C2 cells but not from cancer-derived cell lines P4E6 or PC3. Ethanolamine did not stimulate the proliferation of LNCaP or PC3 cell lines but decreased the uptake of choline (Cho). CONCLUSIONS: Only the metastatic basal PC3 cell line specifically increased the release of Etn on TPA treatment most probably by PKC activation of PLD1 and increased turnover of EtnPGs. The phosphatidic acid formed will maintain a cancer phenotype through the regulation of mTOR. Ethanolamine released from cells may reduce Cho uptake, regulating the membrane PtdEtn:PtdCho ratio and influencing the action of PtdEtn-binding proteins such as RKIP and the anti-apoptotic hPEBP4. The work highlights a difference between LNCaP cells used as a model of androgen-dependent early stage PCa and androgen-independent PC3 cells used to model later refractory stage disease.


Asunto(s)
Etanolamina/metabolismo , Metástasis de la Neoplasia , Próstata/efectos de los fármacos , Neoplasias de la Próstata/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Línea Celular , Línea Celular Tumoral , Activación Enzimática , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular , Masculino , Péptidos/farmacología , Fosfolipasa D/metabolismo , Próstata/citología , Próstata/metabolismo , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/patología , Venenos de Avispas/farmacología
4.
Br J Cancer ; 110(8): 1977-84, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24556618

RESUMEN

BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP) inhibitors (PARPi) exploit tumour-specific defects in homologous recombination DNA repair and continuous dosing is most efficacious. Early clinical trial data with rucaparib suggested that it caused sustained PARP inhibition. Here we investigate the mechanism of this durable inhibition and potential exploitation. METHODS: Uptake and retention of rucaparib and persistence of PARP inhibition were determined by radiochemical and immunological assays in human cancer cell lines. The pharmacokinetics and pharmacodynamics of rucaparib were determined in tumour-bearing mice and the efficacy of different schedules of rucaparib was determined in mice bearing homologous recombination DNA repair-defective tumours. RESULTS: Rucaparib accumulation is carrier mediated (Km=8.4±1.2 µM, Vmax=469±22 pmol per 10(6) cells per 10 min), reaching steady-state levels >10 times higher than the extracellular concentration within 30 min. Rucaparib is retained in cells and inhibits PARP ≥50% for ≥72 h days after a 30-min pulse of 400 nM. In Capan-1 tumour-bearing mice rucaparib accumulated and was retained in the tumours, and PARP was inhibited for 7 days following a single dose of 10 mg kg(-1) i.p or 150 mg kg(-1) p.o. by 70% and 90%, respectively. Weekly dosing of 150 mg kg(-1) p.o once a week was as effective as 10 mg kg(-1) i.p daily for five days every week for 6 weeks in delaying Capan-1 tumour growth. CONCLUSIONS: Rucaparib accumulates and is retained in tumour cells and inhibits PARP for long periods such that weekly schedules have equivalent anticancer activity to daily dosing in a pre-clinical model, suggesting that clinical evaluation of alternative schedules of rucaparib should be considered.


Asunto(s)
Inhibidores Enzimáticos/administración & dosificación , Indoles/administración & dosificación , Poli(ADP-Ribosa) Polimerasas/genética , Animales , Línea Celular Tumoral , Reparación del ADN/efectos de los fármacos , Esquema de Medicación , Inhibidores Enzimáticos/sangre , Inhibidores Enzimáticos/farmacocinética , Recombinación Homóloga/efectos de los fármacos , Humanos , Indoles/sangre , Indoles/farmacocinética , Ratones , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Br J Cancer ; 111(4): 716-25, 2014 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-24921920

RESUMEN

BACKGROUND: A frequent mechanism of acquired multidrug resistance in human cancers is overexpression of ATP-binding cassette transporters such as the Multi-Drug Resistance Protein 1 (MDR-1). Nutlin-3, an MDM2-p53 antagonist, has previously been reported to be a competitive MDR-1 inhibitor. METHODS: This study assessed whether the structurally diverse MDM2-p53 antagonists, MI-63, NDD0005, and RG7388 are also able to modulate MDR-1 function, particularly in p53 mutant neuroblastoma cells, using XTT-based cell viability assays, western blotting, and liquid chromatography-mass spectrometry analysis. RESULTS: Verapamil and the MDM2-p53 antagonists potentiated vincristine-mediated growth inhibition in a concentration-dependent manner when used in combination with high MDR-1-expressing p53 mutant neuroblastoma cell lines at concentrations that did not affect the viability of cells when given alone. Liquid chromatography-mass spectrometry analyses showed that verapamil, Nutlin-3, MI-63 and NDD0005, but not RG7388, led to increased intracellular levels of vincristine in high MDR-1-expressing cell lines. CONCLUSIONS: These results show that in addition to Nutlin-3, other structurally unrelated MDM2-p53 antagonists can also act as MDR-1 inhibitors and reverse MDR-1-mediated multidrug resistance in neuroblastoma cell lines in a p53-independent manner. These findings are important for future clinical trial design with MDM2-p53 antagonists when used in combination with agents that are MDR-1 substrates.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neuroblastoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Subfamilia B de Transportador de Casetes de Unión a ATP , Antineoplásicos/metabolismo , Línea Celular Tumoral , Cisplatino/farmacología , Doxorrubicina/farmacología , Sinergismo Farmacológico , Humanos , Imidazoles/farmacología , Indoles/farmacología , Concentración 50 Inhibidora , Neuroblastoma/metabolismo , Piperazinas/farmacología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Pirrolidinas/farmacología , Compuestos de Espiro/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Verapamilo/farmacología , Vincristina/metabolismo , Vincristina/farmacología , para-Aminobenzoatos/farmacología
6.
J Theor Biol ; 363: 1-12, 2014 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-25109589

RESUMEN

The lodging of cereal crops due to high wind and rain is of considerable significance in many parts of the world, leading to major economic losses and yield reductions. In earlier papers the authors have developed a model of the lodging of winter wheat that identified the major parameters of the problem and enabled the relationship between root and stem lodging to be examined. It has formed the basis of a methodology used in the UK for guidance to farmers and agronomists on ways of reducing lodging risk. However the authors would be the first to acknowledge that there are limitations to the model that make it difficult to apply for a wide range of crops--particularly in the specification of the wind field and the root/soil interaction, and in allowing for stem lodging elsewhere than at the base of the stem. This paper thus describes the development of a generalised model that overcomes these shortcomings. After a discussion of the lodging phenomenon in general and a description of the earlier work, the basis of the new model is set out, based upon a mechanical model of the wind/plant/soil interactions that capture most of the important physical processes. The manner in which this model can be applied to clarify the nature of the lodging process and calculate lodging risk through a simple graphical formulation is discussed. In particular simple formulae are defined for lodging risk that are functions of a small number of dimensionless variables with identified physical meanings. The model is then applied to the lodging of wheat, oat and oilseed rape crops and considers the sensitivity of the risk calculations to uncertainties in the model parameters. In general it is suggested that the risk of lodging can be determined from very simple functions of dimensionless stem and root lodging velocities.


Asunto(s)
Productos Agrícolas/crecimiento & desarrollo , Modelos Biológicos , Tallos de la Planta/fisiología , Suelo/química , Fenómenos Biomecánicos , Simulación por Computador , Tallos de la Planta/anatomía & histología , Lluvia , Viento
7.
BMC Geriatr ; 13: 62, 2013 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-23782932

RESUMEN

BACKGROUND: Ongoing growth in health care expenditures and changing patterns in the demand for health care challenge societies worldwide. The Chronic Care Model (CCM), combined with classification for care needs based on Kaiser Permanente (KP) Triangle, may offer a suitable framework for change. The aim of the present study is to investigate the effectiveness of Embrace, a population-based model for integrated elderly care, regarding patient outcomes, service use, costs, and quality of care. METHODS/DESIGN: The CCM and the KP Triangle were translated to the Dutch setting and adapted to the full elderly population living in the community. A randomized controlled trial with balanced allocation was designed to test the effectiveness of Embrace. Eligible elderly persons are 75 years and older and enrolled with one of the participating general practitioner practices. Based on scores on the INTERMED-Elderly Self-Assessment and Groningen Frailty Indicator, participants will be stratified into one of three strata: (A) robust; (B) frail; and (C) complex care needs. Next, participants will be randomized per stratum to Embrace or care as usual. Embrace encompasses an Elderly Care Team per general practitioner practice, an Electronic Elderly Record System, decision support instruments, and a self-management support and prevention program - combined with care and support intensity levels increasing from stratum A to stratum C. Primary outcome variables are patient outcomes, service use, costs, and quality of care. Data will be collected at baseline, twelve months after starting date, and during the intervention period. DISCUSSION: This study could provide evidence for the effectiveness of Embrace. TRIAL REGISTRATION: The Netherlands National Trial Register NTR3039.


Asunto(s)
Costos de la Atención en Salud/normas , Atención al Paciente/economía , Atención al Paciente/normas , Calidad de la Atención de Salud/economía , Calidad de la Atención de Salud/normas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Países Bajos/epidemiología , Atención al Paciente/estadística & datos numéricos , Calidad de la Atención de Salud/estadística & datos numéricos , Resultado del Tratamiento
8.
Acute Med ; 12(4): 232-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24364057

RESUMEN

The rates of liver disease in the UK are rising and hence more patients than ever are presenting to acute medical units with potentially life threatening sequelae. Early recognition and treatment of sepsis, kidney injury, bleeding and alcoholic hepatitis can significantly improve outcomes, but requires a comprehensive approach to assessment. This patient cohort often suffers from a perceived uniform poor prognosis, especially in alcohol related disease, but evidence for this is changing and reassessment of prognosis after 48 hours of organ support may be more accurate than that made 'at the front door'. This article summarises the most important complications of decompensated cirrhosis, their early management, and presents a targeted system of care: 'RING Liver'--Renal failure, Infection, Nutrition, Gastrointestinal bleeding and transit, Liver dysfunction/transplantation. Factors favouring transfer to tertiary units are also explored.


Asunto(s)
Manejo de la Enfermedad , Hepatitis Alcohólica/complicaciones , Cirrosis Hepática , Adulto , Progresión de la Enfermedad , Femenino , Hemorragia Gastrointestinal/etiología , Hospitalización , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/terapia , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Evaluación de Resultado en la Atención de Salud , Pronóstico , Insuficiencia Renal/etiología , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria
9.
Stroke ; 43(4): 1134-6, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22198984

RESUMEN

BACKGROUND AND PURPOSE: There is uncertainty whether bilateral near infrared spectroscopy (NIRS) can be used for monitoring of patients with acute stroke. METHODS: The NIRS responsiveness to systemic and stroke-related changes was studied overnight by assessing the effects of brief peripheral arterial oxygenation and mean arterial pressure alterations in the affected versus nonaffected hemisphere in 9 patients with acute stroke. RESULTS: Significantly more NIRS drops were registered in the affected compared with the nonaffected hemisphere (477 drops versus 184, P<0.001). In the affected hemispheres, nearly all peripheral arterial oxygenation drops (n=128; 96%) were detected by NIRS; in the nonaffected hemispheres only 23% (n=30; P=0.17). Only a few mean arterial pressure drops were followed by a significant NIRS drop. This was however significantly different between both hemispheres (32% versus 13%, P=0.01). CONCLUSIONS: This pilot study found good responsiveness of NIRS signal to systemic and stroke-related changes at the bedside but requires confirmation in a larger sample.


Asunto(s)
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Arterias Cerebrales/metabolismo , Oxígeno/metabolismo , Accidente Cerebrovascular/metabolismo , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Encéfalo/fisiopatología , Isquemia Encefálica/fisiopatología , Arterias Cerebrales/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrofotometría Infrarroja/métodos , Accidente Cerebrovascular/fisiopatología
10.
Psychopathology ; 45(3): 193-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22441213

RESUMEN

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by mutations in the SACS gene (13q12) encoding the protein sacsin. It is characterized by early-onset cerebellar ataxia, lower limb spasticity, sensorimotor axonal polyneuropathy, and atrophy of the superior cerebellar vermis. Cerebellar disorders in general may be accompanied by the cerebellar cognitive affective syndrome (CCAS) which presents with disturbances of executive functioning, spatial cognition, linguistic capacities, and affect. SAMPLING AND METHODS: Two middle-aged brothers with ARSACS, one of whom was referred for behavioral disinhibition, are described. A detailed neuropsychiatric and neuropsychological assessment was performed. RESULTS: Apart from motor symptoms, motivational deficits along with cognitive and behavioral dysfunctions were present; these were much more pronounced in the older sib. CONCLUSIONS: These observations add to the literature which suggests that the cerebellum, apart from its significance for motor behavior, plays a functional role in human cognition and affect. The nonmotor symptoms of ARSACS are discussed in terms of the CCAS.


Asunto(s)
Encéfalo/patología , Enfermedades Cerebelosas/diagnóstico , Trastornos del Conocimiento/diagnóstico , Trastornos del Humor/diagnóstico , Espasticidad Muscular/diagnóstico , Ataxias Espinocerebelosas/congénito , Atrofia , Enfermedades Cerebelosas/genética , Enfermedades Cerebelosas/patología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Humor/genética , Trastornos del Humor/patología , Espasticidad Muscular/genética , Espasticidad Muscular/patología , Pruebas Neuropsicológicas , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología
11.
J Stroke Cerebrovasc Dis ; 21(6): 459-66, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21185742

RESUMEN

BACKGROUND: Blood pressure (BP) is one of the major vital parameters monitored in the stroke unit. The accuracy of indirect BP measurement is strongly influenced by the position of both patient and arm during the measurement. Acute stroke patients are often nursed in lateral decubitus positions. The effect of these alternating body positions in relation to affected body side on the outcome and reliability of BP readings in acute stroke patients is unknown. METHODS: An automatic oscillometric BP device was used. BP was measured in both arms in the (back) supine and both lateral decubitus positions. RESULTS: In total, 54 consecutive acute stroke patients were included. Thirty-five patients had right-sided deficits and 19 patients had left-sided deficits. Supine BP readings were similar in the right and left arms regardless of side of deficit. Measurements of BP in the lateral decubitus positions resulted in significantly lower BP readings in the uppermost arm (around 12 mm Hg in both arms) and significantly higher readings in the right lowermost arm (around 6 mm Hg) compared to the supine position. This effect seemed less pronounced when the left lowermost arm was measured. There was no relation between change of BP readings in various lateral positions and side of stroke. CONCLUSIONS: Alternating lateral decubitus positions according to nursing standards in acute stroke patients lead to a mean 18 mm Hg BP fluctuation. This may largely be explained by hydrostatic pressure effects, partly by anatomic factors in the left lowermost arm, but not by the side of stroke.


Asunto(s)
Determinación de la Presión Sanguínea , Presión Sanguínea , Unidades Hospitalarias , Posicionamiento del Paciente , Accidente Cerebrovascular/fisiopatología , Posición Supina , Extremidad Superior/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Determinación de la Presión Sanguínea/métodos , Femenino , Humanos , Presión Hidrostática , Masculino , Persona de Mediana Edad , Países Bajos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Factores de Tiempo
13.
Psychiatry Res Neuroimaging ; 311: 111284, 2021 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-33774451

RESUMEN

Pornographic addiction refers to an addiction model associated with compulsive and repeated use of pornographic material. Whether the use of pornography may indeed become addictive remains a matter of debate. The current study investigated whether compulsive pornography use (CPU) is accompanied by reduced D2/3 receptor availability in the striatum and frontal hypofunctionality. Male subjects between 18 and 50 years of age with and without CPU were recruited using online and newspaper advertisements. Questionnaires were used to the assess the severity of compulsive pornography use (CIUS) and symptoms of depression, impulsivity and sensation seeking. Dopaminergic imaging was performed using [11C]-raclopride PET. Striatal binding potentials (BPND) and regional frontal cerebral influx values (R1) of [11C]-raclopride were calculated. Arterial Spin Labeling (ASL) MRI was performed to assess regional cerebral blood flow. No group differences between striatal BPND's of [11C]-raclopride in subjects with (n = 15) and without (n = 10) CPU were detected. In CPU subjects, no correlation was found between the CIUS score and striatal BPND's. Cerebral R1 values in frontal brain regions and cerebral blood flow measurements did not differ between groups. The current study fails to provide imaging support for sharing similar neurobiological alterations as previously has been reported in other addictive modalities.


Asunto(s)
Literatura Erótica , Tomografía de Emisión de Positrones , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Humanos , Masculino , Racloprida , Receptores de Dopamina D2/metabolismo
14.
Stroke ; 41(11): 2697-704, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20930158

RESUMEN

BACKGROUND AND PURPOSE: Cerebral autoregulation may become impaired after stroke. To provide a review of the nature and extent of any autoregulation impairment after stroke and its course over time, a technique allowing repeated bedside measurements with good temporal resolution is required. Transcranial Doppler (TCD) in combination with continuous blood pressure measurements allows noninvasive continuous bedside investigation with high temporal resolution of the dynamic and the steady-state components of cerebral autoregulation. Therefore, this review focuses on all TCD studies on cerebral autoregulation in the setting of documented ischemic stroke. METHODS: PubMed and EMBASE were searched for studies of stroke, autoregulation, and TCD. Studies were either acute phase (<96 hours after index stroke) or chronic phase (>96 hours after index stroke) autoregulation studies. Quality of studies was studied in a standardized fashion. RESULTS: Twenty-three studies met the inclusion criteria. General agreement existed on cerebral autoregulation being impaired, even after minor stroke. Bilateral impairment of autoregulation was documented, particularly after lacunar stroke. Studies showed progressive deterioration of cerebral autoregulation in the first 5 days after stroke and recovery over the next 3 months. Impaired cerebral autoregulation as assessed by TCD was related to neurological deterioration, the necessity for decompressive surgery, and poor outcome. Synthesis of the data of various studies was, however, limited by studies not meeting key methodological criteria for observational studies. CONCLUSIONS: TCD in combination with continuous blood pressure measurement offers a method with a high temporal resolution feasible for bedside evaluation of cerebral autoregulation in the stroke unit. TCD studies have shown impairment of cerebral autoregulation in various subtypes of ischemic stroke. To improve the synthesis of data from various research groups, there is urgent need for standardization of methodology of TCD studies in cerebral autoregulation.


Asunto(s)
Encéfalo/fisiopatología , Homeostasis/fisiología , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Humanos , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal
15.
Ann Neurol ; 66(2): 245-9, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19743453

RESUMEN

Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid beta proteins toward the cerebrospinal fluid.


Asunto(s)
Péptidos beta-Amiloides/líquido cefalorraquídeo , Angiopatía Amiloide Cerebral/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Área Bajo la Curva , Biomarcadores/líquido cefalorraquídeo , Angiopatía Amiloide Cerebral/diagnóstico , Angiopatía Amiloide Cerebral/genética , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fosforilación , Curva ROC , Proteínas tau/líquido cefalorraquídeo
16.
Opt Express ; 18(14): 15062-72, 2010 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-20639992

RESUMEN

We demonstrate high-power Cr(2+):ZnSe master oscillator power amplifier (MOPA) pure continuous wave (CW) laser systems with output power of 14 W and amplifier gain greater than 2X. In addition, we develop a theoretical model for this type of amplification and show single-knob tunability at high powers over 400 nm.

17.
Cerebellum ; 9(2): 232-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20157791

RESUMEN

To investigate the frequency, details, and consequences of falls in patients with autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease-related risk factors that are associated with an increased fall frequency. Two hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the EuroSCA natural history study, completed a fall questionnaire that assessed the frequency, consequences, and several details of falls in the previous 12 months. Relevant disease characteristics were retrieved from the EuroSCA registry. The database of the natural history study provided the ataxia severity scores as well as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at least one fall in the preceding 12 months. There was a high rate of fall-related injuries (74%). Factors that were associated with a higher fall frequency included: disease duration, severity of ataxia, the presence of pyramidal symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors associated with a lower fall frequency were: the presence of extrapyramidal symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2. The total number of non-ataxia symptoms and longer disease duration were independently associated with a higher fall frequency in a logistic regression analysis, while the presence of extrapyramidal symptoms was independently associated with a lower fall frequency. Our findings indicate that, in addition to more obvious factors that are associated with frequent falls, such as disease duration and ataxia severity, non-ataxia manifestations in SCA play a major role in the fall etiology of these patients.


Asunto(s)
Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/prevención & control , Adulto , Anciano , Europa (Continente)/epidemiología , Femenino , Genotipo , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/fisiopatología , Encuestas y Cuestionarios
18.
Liver Int ; 30(5): 733-40, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20456041

RESUMEN

BACKGROUND & AIM: Immunoparesis contributes to prognosis in acute liver failure (ALF) and decompensated cirrhosis, a phenomenon thought to be mediated by the anti-inflammatory cytokine interleukin (IL)-10. We investigated the prognostic value of admission IL-10 levels and their evolution during the early phase of treatment in intensive care, in comparison to the pro-inflammatory cytokines IL-6 and tumour necrosis factor (TNF)-alpha. METHODS: We measured these cytokines within 48 h of admission in 51 ALF and 39 decompensated cirrhosis patients admitted to intensive care, and obtained follow-up measurement a median of 2 days later in 35 patients. RESULTS: Levels of all cytokines were higher in those with a poor outcome. IL-10 performed as well as TNF-alpha and IL-6 in the whole cohort (area under receiver operator curve 0.73 vs 0.66 and 0.72). However IL-10 outperfomed pro-inflammatory cytokines in the subgroups with ALF (0.80 vs 0.63 and 0.70) and acetaminophen-induced ALF (0.92 vs 0.67 and 0.81). Levels of all cytokines rose significantly in non-surviving patients (n=15); IL-10 by a factor of 2, TNF-alpha by 2.6 and IL-6 by 1.13. No significant changes were seen in the surviving patients. In ALF, IL-10 was an independent predictor of outcome in multivariate analysis. CONCLUSION: The magnitude of the compensatory anti-inflammatory response at admission, and its development during the early phase of treatment, predicts outcome as well as the pro-inflammatory response in acute hepatic syndromes and supports a vital role for this immunological phenomenon in the outcome of these patients.


Asunto(s)
Interleucina-10/sangre , Cirrosis Hepática/inmunología , Fallo Hepático Agudo/inmunología , Estudios de Cohortes , Antígenos HLA-DR/análisis , Humanos , Interleucina-6/sangre , Admisión del Paciente , Factor de Necrosis Tumoral alfa/sangre
19.
J Int Med Res ; 38(2): 449-57, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20515559

RESUMEN

This was a randomized, controlled, four-way crossover study in 45 subjects with a tendency to suffer from moderate heartburn following some meals. The study was designed to assess the time to onset of the perceived soothing and cooling effects of the alginate raft-forming products, Gaviscon Liquid (peppermint), Gaviscon Double Action Liquid (peppermint) and Gaviscon Powder Formulation (fresh tropical), compared with a non-active sublingual control. All three Gaviscon products provided significantly faster soothing and cooling effects compared with the control. Based on the upper 95% confidence limits for the median, time to onset of soothing was perceived within 3.15 min, 3.08 min and 4.05 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. Similarly, time to onset of cooling was perceived within 1.95 min, 1.23 min and 11.22 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. The results show that Gaviscon Liquid and Gaviscon Double Action soothe within 3.15 min and cool within 1.95 min.


Asunto(s)
Alginatos/uso terapéutico , Hidróxido de Aluminio/uso terapéutico , Antiácidos/uso terapéutico , Pirosis/tratamiento farmacológico , Ácido Silícico/uso terapéutico , Bicarbonato de Sodio/uso terapéutico , Administración Oral , Adolescente , Adulto , Anciano , Estudios Cruzados , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medicamentos sin Prescripción , Percepción , Suspensiones , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
20.
Neuroimage Clin ; 25: 102161, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31981888

RESUMEN

AIM: L -3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA PET may be used to distinguish subjects with Parkinsonism from those with symptoms not originating from impaired dopaminergic transmission. However, it is not routinely utilized to discriminate Idiopathic Parkinson's disease (IPD) from Atypical Parkinsonian Disorders (APD). We investigated the potential of FDOPA PET to discriminate between IPD and APD, with a focus on the anterior-to-posterior decline in het striatum, considered to be more specific for IPD. MATERIALS AND METHODS: 18F-DOPA PET data from a total of 58 subjects were retrospectively analyzed. 28 subjects had idiopathic Parkinson's disease (14 male, 14 female; age at scan 61 +- 11,5), 13 atypical Parkinsonian disease (7 male, 6 females; age at scan: 69,6 +- 6,4) and 17 were controls (6 male, 11 female; age at scan 65,3 +-8,6). Regional striatal-to-occipital ratio's (RSOR's) were calculated, as well as multiple in-line VOI's from the caudate nucleus to the posterior part of the putamen. The linearity of anteroposterior decline was determined by a linear regression fit and associated R squared values. ROC curves were calculated to assess the diagnostic performance of these measurements. Data contralateral to the clinically most affected side were used for analysis. RESULTS: ROC curve analysis for differentiation between controls and Parkinsonism patients showed the highest AUC for the caudate nucleus-to-posterior putamen ratio (AUC = 0.930; p < 0.00) and for the R squared value for the linear regression fit (AUC = 0.948; p = 0.006). For discrimating IPD from APD, the highest AUC was found for the caudate nucleus-to-anterior putamen ratio (0.824; p < 0.001) CONCLUSIONS: Subregional analysis of the striatum in F-DOPA PET scans may provide additional diagnostic information in patients screened for a  presynaptic dopaminergic deficit. A more linear decrease from the head of the caudate nucleus to the posterior putamen was  present in patients with IPD, although this feature did not have additional diagnostic value over the RSOR analysis.


Asunto(s)
Cuerpo Estriado/diagnóstico por imagen , Dihidroxifenilalanina/análogos & derivados , Neuroimagen/métodos , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Anciano , Núcleo Caudado/diagnóstico por imagen , Diagnóstico Diferencial , Dihidroxifenilalanina/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Putamen/diagnóstico por imagen , Estudios Retrospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA