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1.
BMJ Mil Health ; 166(E): e21-e24, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31123090

RESUMEN

BACKGROUND: Open-book pelvic fractures are associated with significant mortality. Emergency management may require a commercial pelvic circumferential compression device to reduce the fracture and compress haemorrhaging pelvic vasculature. Standard, commercial, twin-sized bedsheets are acceptable should commercial devices be unavailable. However, obese victims or personnel with insufficient body strength may impede successful reduction. OBJECTIVE: To demonstrate the value of an improvisational windlass (intravenous pole) in improving the ability to reduce an open-book pelvic fracture. METHODS: The Institutional Review Board-approved study involved 28 diverse healthcare students and emergency medicine residents. Each participant's demographic information and physical characteristics were recorded. A METIman was prepared with knee and ankle binding and a sphygmomanometer set at 40 mm Hg placed over the symphysis pubis. Two-person teams were randomly selected to place a bedsheet at greater trochanter level and atop the sphygmomanometer. The bedsheet was secured with maximum effort by the pairs and the pressure recorded. Following this, the pairs inserted an intravenous pole in the knot and torqued the pole to maximum effort and a repeat pressure recorded. RESULTS: The mean increase in pressure using only the bedsheet was 106.43 mm Hg per team. With bedsheet and intravenous pole, the mean pressure increase was 351.79 mm Hg per team. The difference was statistically significant (independent samples t-test: t = 17.177, p < 0.001, 95% CI (216.65 to 274.07 mm Hg). There was no correlation between pressure increases and the individual physical characteristics of the subjects (r = - 0.183, p = 0.352). CONCLUSIONS: Regardless of personnel's physical attributes, the addition of an improvisational windlass to a pelvic circumferential compression bedsheet can improve the ability to reduce an open-book fracture, especially in obese victims.


Asunto(s)
Fracturas Óseas/cirugía , Procedimientos Ortopédicos/métodos , Huesos Pélvicos/lesiones , Entrenamiento Simulado/normas , Fenómenos Biomecánicos , Vendajes de Compresión/efectos adversos , Vendajes de Compresión/normas , Humanos , Maniquíes , Procedimientos Ortopédicos/normas , Procedimientos Ortopédicos/estadística & datos numéricos , Huesos Pélvicos/cirugía , Entrenamiento Simulado/métodos , Entrenamiento Simulado/estadística & datos numéricos , Esfigmomanometros/efectos adversos , Esfigmomanometros/normas
2.
Eur J Cancer ; 80: 63-72, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28551430

RESUMEN

AIMS: We examined the efficacy of exercise training for improving physical functioning and cardiopulmonary fitness in survivors of paediatric brain tumours (BTs) treated with cranial irradiation. METHODS: We conducted a controlled clinical trial with crossover of exercise training versus no training in the community in either a group or combined group/home setting. A volunteer sample of 28 children treated with cranial irradiation for brain tumours completed training (mean age = 11.53 years; mean time since diagnosis = 5.25 years). end-points were physical functioning assessed by four subtests from the Bruininks-Oseretsky Test of motor performance (BOT-2) and pro-rated work rate from a cycle ergometer. Linear mixed modelling was used to evaluate time, training, training setting, and carryover effects. RESULTS: Adherence to training was 84%. Performance on the BOT-2 was below average for all assessments. However, training resulted in improvement in bilateral coordination (F (1, 30) = 6.59, p = 0.02), irrespective of training setting and improved performance was maintained even approximately 12°weeks after training had ended (F (1, 24) = 9.60, p = 0.005). Training resulted in increased pro-rated work rate for participants in the group training setting only (F (1, 25) = 4.57, p = 0.04) and these participants maintained their improved work rate approximately 12°weeks after training had ended (F (1, 20) = 8.38, p = 0.01). CONCLUSION: Exercise training improves physical functioning and fitness in paediatric BT survivors. Exercise interventions that ameliorate adverse physical effects and promote health in long-term survivors are highly recommended in this vulnerable population. (ClinicalTrials.gov, NCT01944761).


Asunto(s)
Neoplasias Encefálicas , Irradiación Craneana/efectos adversos , Terapia por Ejercicio , Destreza Motora/fisiología , Acondicionamiento Físico Humano , Aptitud Física/fisiología , Sobrevivientes , Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/radioterapia , Capacidad Cardiovascular/fisiología , Niño , Preescolar , Femenino , Humanos , Modelos Lineales , Masculino , Calidad de Vida
5.
Gene Ther ; 23(3): 237-46, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26588709

RESUMEN

Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.


Asunto(s)
Células Endoteliales/trasplante , Proteínas de la Matriz Extracelular/uso terapéutico , Enfermedades Vasculares Periféricas/terapia , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Injerto Vascular/métodos , Animales , Células Endoteliales/fisiología , Proteínas de la Matriz Extracelular/genética , Humanos , Modelos Animales , Ratas , Ovinos , Factor A de Crecimiento Endotelial Vascular/genética , Grado de Desobstrucción Vascular
6.
Transpl Infect Dis ; 17(6): 868-71, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26288159

RESUMEN

Aspergillus thyroiditis (AT) has historically been considered a postmortem diagnosis in immunocompromised patients; most have disseminated disease. This report summarizes the clinical challenge of diagnosing AT. It also highlights the value of the early use of thyroid fine-needle aspiration culture and the need for a high index of suspicion to reach the final diagnosis before disease dissemination.


Asunto(s)
Aspergilosis/diagnóstico , Aspergillus/aislamiento & purificación , Trasplante de Células Madre/efectos adversos , Tiroiditis/microbiología , Adolescente , Aspergilosis/etiología , Humanos , Huésped Inmunocomprometido , Masculino , Tiroiditis/diagnóstico
7.
Pediatr Obes ; 10(4): 296-304, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25170967

RESUMEN

BACKGROUND: Childhood maltreatment is associated with adult obesity, but there is conflicting evidence regarding the relationship between childhood maltreatment and obesity during adolescence. OBJECTIVES: To compare the body mass index (BMI) trajectory of adolescents with a specific type of maltreatment (sexual abuse, physical abuse, emotional abuse or neglect) to adolescents with another type of maltreatment (maltreated sample n = 303) and to a comparison group (n = 151). METHODS: Individual growth models were used to estimate average growth trajectories of BMI percentile separately by sex (ages 9 to 22 years). Unconditional and conditional linear and quadratic growth models were estimated and maltreatment types were added before including covariates (ethnicity, anxiety, depression and pubertal stage). RESULTS: BMI growth trajectories of sexually abused girls and neglected girls were significantly different from comparison girls. Comparison girls had a growth trajectory that reached its apex at 15 years and then began to decline, whereas sexually abused girls and neglected girls had lower BMI than comparison girls until age 16-17 years when their BMI was higher than comparison girls. CONCLUSIONS: Late adolescence appears to be the developmental period during which differences in BMI percentiles become pronounced between girls with sexual abuse or with neglect vs. comparison girls.


Asunto(s)
Maltrato a los Niños/psicología , Obesidad/psicología , Adolescente , Ansiedad/epidemiología , Índice de Masa Corporal , Niño , Maltrato a los Niños/estadística & datos numéricos , Depresión/epidemiología , Emociones , Femenino , Humanos , Estudios Longitudinales , Masculino , Obesidad/epidemiología , Obesidad/etiología , Prevalencia , Estudios Prospectivos , Pubertad , Estados Unidos , Adulto Joven
8.
J Appl Physiol (1985) ; 116(1): 76-82, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24235101

RESUMEN

Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre-early pubertal girls had higher max FOR [6.9 ± 1.4 mg·kg fat free mass (FFM)(-1)·min(-1)] than NW mid-late pubertal girls (2.2 ± 0.9 mg·kg FFM(-1)·min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 ± 2.1 mg·kg FFM(-1)·min(-1)), and OW mid-late pubertal girls (3.3 ± 0.9 mg·kg FFM(-1)·min(-1)) (P < 0.05). Bivariable analyses showed positive associations between FOR with homeostatic model assessment of IR (P = 0.001), leptin (P < 0.001), and leptin-to-adiponectin ratio (P = 0.001), independent of percent body fat. Max FOR decreased in NW girls during mid-late puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls.


Asunto(s)
Tejido Adiposo/metabolismo , Peso Corporal/fisiología , Ejercicio Físico/fisiología , Sobrepeso/fisiopatología , Pubertad/fisiología , Adiponectina/metabolismo , Adolescente , Composición Corporal/fisiología , Niño , Femenino , Humanos , Resistencia a la Insulina/fisiología , Leptina/metabolismo , Obesidad/metabolismo , Obesidad/fisiopatología , Sobrepeso/metabolismo , Oxidación-Reducción , Pubertad/metabolismo , Maduración Sexual/fisiología
9.
Brain Imaging Behav ; 6(2): 137-92, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22438191

RESUMEN

Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.


Asunto(s)
Encefalopatías/diagnóstico , Encefalopatías/etiología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/diagnóstico , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Humanos
10.
Psychol Med ; 41(5): 959-69, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20663254

RESUMEN

BACKGROUND: Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. METHOD: Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. RESULTS: While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus. CONCLUSIONS: These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.


Asunto(s)
Imagen de Difusión Tensora , Electroencefalografía , Retroalimentación Sensorial , Alucinaciones/fisiopatología , Vías Nerviosas , Esquizofrenia/fisiopatología , Adulto , Anciano , Corteza Auditiva/fisiopatología , Estudios de Casos y Controles , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Inhibición Neural , Percepción del Habla
11.
Eur J Clin Nutr ; 64(12): 1494-500, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20877392

RESUMEN

BACKGROUND/OBJECTIVES: The purpose of this study was to develop an activity energy expenditure (AEE) prediction equation for the Actiheart activity monitor for use in children with chronic disease. SUBJECTS/METHODS: In total, 63 children, aged 8-18 years with different types of chronic disease (juvenile arthritis, hemophilia, dermatomyositis, neuromuscular disease, cystic fibrosis or congenital heart disease) participated in an activity testing session, which consisted of a resting protocol, working on the computer, sweeping, hallway walking, steps and treadmill walking at three different speeds. During all activities, actual AEE was measured with indirect calorimetry and the participants wore an Actiheart on the chest. Resting EE and resting heart rate were measured during the resting protocol and heart rate above sleep (HRaS) was calculated. RESULTS: Mixed linear modeling produced the following prediction equation: This equation results in a nonsignificant mean difference of 2.1 J/kg/min (limits of agreement: -144.2 to 148.4 J/kg/min) for the prediction of AEE from the Actiheart compared with actual AEE. CONCLUSIONS: The Actiheart is valid for the use of AEE determination when using the new prediction equation for groups of children with chronic disease. However, the prediction error limits the use of the equation in individual subjects.


Asunto(s)
Enfermedad Crónica , Metabolismo Energético/fisiología , Ejercicio Físico , Actividad Motora , Caminata , Adolescente , Calorimetría Indirecta , Niño , Prueba de Esfuerzo , Frecuencia Cardíaca , Humanos , Modelos Lineales , Modelos Biológicos , Sueño
12.
Clin Nephrol ; 71(1): 43-9, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19203549

RESUMEN

BACKGROUND: Hemodialysis arteriovenous graft (AVG) patency is dependent on favorable flow characteristics. We examined hemodynamic, humoral risk factors, and the effects of stringent flow surveillance coupled with prompt corrective intervention on long-term graft patency. METHODS: Over a 29-month period 92 chronic hemodialysis patients with AVG were evaluated monthly by flow surveillance. Clinical diagnosis of failing graft, which promoted angiography and corrective intervention was based on flow reduction, and patient's unique medical history and hemodynamic parameters. RESULTS: Graft arteriography revealed stenotic lesions in 94.5% of the cases, necessitating endovascular or surgical angioplasty. Low ejection fraction, early postoperative intervention, and low baseline flow were associated with a statistically significant reduction in intervention-free interval (p < 0.05). Mean AVG flow threshold prior to intervention was 463 +/- 154 ml/min, corresponding to a mean flow reduction of 45 +/- 12%. Total graft thrombosis rate was 0.21 thrombotic episodes/patient year. Primary graft patency at 6, 12, and 24 months was 76, 44 and 35%, and secondary patency 99, 97, 88%, respectively. CONCLUSIONS: Stringent flow surveillance policy coupled with prompt intervention has been proven effective in maintaining AVG long-term patency. Patients with decreased ejection fraction, early post-operative intervention, and low baseline AVG flow are prone to graft thrombosis.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Oclusión de Injerto Vascular/diagnóstico , Oclusión de Injerto Vascular/terapia , Fallo Renal Crónico/terapia , Flujo Sanguíneo Regional/fisiología , Diálisis Renal , Anciano , Catéteres de Permanencia , Estudios de Cohortes , Femenino , Oclusión de Injerto Vascular/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trombosis/diagnóstico , Trombosis/etiología , Trombosis/terapia , Grado de Desobstrucción Vascular/fisiología
13.
Bone Marrow Transplant ; 44(3): 145-56, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19182832

RESUMEN

We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients < or =4 years of age (group 1) and 33 patients >4 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 microM min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 microM min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 microM min. A higher AUC was attained (4825 microM min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 microM min is recommended.


Asunto(s)
Busulfano/farmacocinética , Trasplante de Células Madre Hematopoyéticas , Agonistas Mieloablativos/farmacocinética , Neoplasias/metabolismo , Neoplasias/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Factores de Edad , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Humanos , Lactante , Masculino , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Tasa de Supervivencia , Quimera por Trasplante , Resultado del Tratamiento
14.
Haemophilia ; 13(3): 244-8, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17498072

RESUMEN

Haemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult. We previously reported the safety of using a combination of rFVIIa and APCC given in sequential fashion. In this report, we update our experience with sequential therapy. A retrospective review of medical records was conducted including all reports of sequential therapy defined as receiving both rFVIIa and APCC within 6 h. Data extracted included demographic data, treatment prior to and following hospital admission, clinical data including type and location of bleed, response to therapy, physical examination and laboratory data. In addition, for some patients, thromboelastography was performed to document the effect of sequential therapy on clot formation characteristics. Four patients comprising 35 admissions, 209 hospital days and 115 days of sequential therapy were included in the updated dataset. No patient developed thrombosis or overt disseminated intravascular coagulation (DIC) although elevations in the D-dimer above 5 microg mL(-1) were noted in 42% of the courses that lasted >3 days. Efficacy is suggested by the fact that patients had resolution of their bleeds after a median of 3 days of sequential therapy after failing to respond to a median of 3 days of monotherapy. Thromboelastography demonstrated an additive effect. Sequential therapy is a safe, potentially efficacious approach in the management of refractory bleeding episodes in patients with haemophilia and inhibitors.


Asunto(s)
Factor IX/antagonistas & inhibidores , Factor VII/uso terapéutico , Factor V/uso terapéutico , Factor Xa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Quimioterapia Combinada , Factor VIIa , Humanos
15.
Biochem Biophys Res Commun ; 348(3): 1024-33, 2006 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-16904068

RESUMEN

BACKGROUND: Fibulin-5 is a novel extracellular protein that is thought to act as a bridging peptide between elastin fibers and cell surface integrins in blood vessel wall. Fibulin-5 binding to endothelial cell (EC) surface integrins may effect cell proliferation and cell attachment to extracellular matrix (ECM) or to artificial surfaces. In this paper, we describe the effects of fibulin-5 on attachment, adhesion, and proliferation of primary human EC. After demonstrating that fibulin-5 over-expression inhibited EC proliferation, we tested the hypothesis that co-expression of fibulin-5 and VEGF165 will lead to unique EC phenotype that will exhibit increased adherence properties and retain its proliferation capacity. METHODS AND RESULTS: Fibulin-5 and VEGF165 gene transfer to primary human saphenous vein endothelial cells was accomplished using retroviral vectors encoding the two genes. Transgene expression was verified using immunohistochemistry, Western blotting, and ELISA. Fibulin 5 over-expression tended to improve immediate EC attachment (30 min after seeding) and improved significantly adhesion (>40%) under shear stress tested 24h after EC seeding. The effects of fibulin-5 and VEGF165 on EC proliferation in the presence or absence of basic FGF were also tested. EC expressing fibulin-5 had reduced proliferation while VEGF165 co-expression ameliorated this effect. CONCLUSION: Fibulin-5 improved EC attachment to artificial surfaces. Dual transfer of fibulin-5 and VEGF165 resulted in EC phenotype with increased adhesion and improved proliferation. This unique EC phenotype can be useful for tissue engineering on endovascular prostheses.


Asunto(s)
Proliferación Celular , Células Endoteliales/citología , Células Endoteliales/fisiología , Proteínas de la Matriz Extracelular/fisiología , Inhibidores de Crecimiento/fisiología , Adhesión Celular/fisiología , Separación Celular , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Proteínas de la Matriz Extracelular/genética , Técnicas de Transferencia de Gen , Inhibidores de Crecimiento/genética , Humanos
16.
EuroIntervention ; 2(1): 77-83, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-19755240

RESUMEN

AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR) Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND RESULTS: Prospective, multi-centre study in patients with stable or unstable angina that were scheduled for percutaneous coronary diagnostic or therapeutic catheterization. We assessed the feasibility of an intravascular MR catheter, capable of analysing the arterial wall without external magnets or coils, by differentiating lipid rich, intermediate and fibrotic areas of the atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine patients were included at 4 centres. The intracoronary MR-spectroscopy procedure was well tolerated; no MACE and no device related serious adverse event was observed. The MR catheter was successfully advanced into the lesion in 28 patients. Introduction of the MR catheter was not possible in one patient with a tortuous proximal right coronary artery. MR data were obtained in 22 patients. According to the predominant MR pattern, lesions were classified as fibrous plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich plaque in 8 patients. Six patients were excluded from analysis because artifacts impeded the quality of the MR signal. Plaque type did not show a correlation with angina status (p=0.552; all groups) or angiographic parameters, such as minimal lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre study demonstrates for the first time that coronary artery assessment of potentially vulnerable, non-flow limiting lesions using a dedicated intravascular MR catheter, free of external magnets or coils, is feasible in clinical practice. Assessment of the coronary wall may provide important data regarding the composition of the atherosclerotic lesion, which then could contribute to predicting the likelihood of eventual rupture and clinical instability.

17.
Haemophilia ; 10(4): 347-51, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15230948

RESUMEN

Patients with haemophilia and inhibitors have bleeding episodes that can be refractory to home therapy with either activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (rFVIIa). Sequential therapy with these products has not been widely used because of concern regarding the possibility of thrombosis. This report describes the results of a retrospective chart review of five hospitalized children with severe haemophilia and inhibitors who have been treated with sequential doses of APCC and rFVIIa for refractory bleeding. These patients all had failed home therapy with APCC and rFVIIa alone. A total of 20 admissions were documented covering 170 hospital days, including 91 days of combination therapy. While being closely monitored in the hospital, they received alternating doses of APCC and rFVIIa every 6 h. Anywhere from one to three doses of rFVIIa were given every 2 h between APCC doses. Doses of APCC ranged from 35 to 80 U kg(-1) dose(-1), and doses of rFVIIa ranged from 80 to 225 mcg kg(-1) dose(-1). There was no clinical or laboratory evidence of thrombosis, thrombocytopenia, or disseminated intravascular coagulation (DIC). We found the combination of these factors to be safe and effective for patients with refractory bleeds. However, we recommend this aggressive therapy only in the inpatient setting with careful monitoring of the physical examination and frequent laboratory screening to assess for thrombosis and DIC, and without the concurrent use of antifibrinolytic medications.


Asunto(s)
Factor VII/uso terapéutico , Factor V/uso terapéutico , Factor Xa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Factor IX/antagonistas & inhibidores , Factor VIII/antagonistas & inhibidores , Factor VIIa , Humanos , Lactante , Tiempo de Internación , Masculino
19.
Int J Cardiol ; 75 Suppl 1: S167-70; discussion S171-3, 2000 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-10980358

RESUMEN

Almost a century after Buerger's original description of thromboangiitis obliterans, there is still no consensus about diagnostic criteria. The lack of a universally accepted method of diagnosis causes confusion, and mars research efforts. Some authors quote 'hematological disease' as one of the exclusion criteria. But in most recent reports, suspected Buerger patients did not undergo hematological tests to diagnose or rule out any primary or secondary hypercoagulable states. However, immunogenetic studies of Buerger's disease have led to a revived interest in the role of blood coagulation in the pathogenesis of thromboangiitis obliterans. Some association has been suggested between Buerger's disease and the antiphospholipid syndrome, as well as hyperhomocysteinemia. Other thrombophilic conditions have been described anecdotally in patients with Buerger's disease. In view of this developing line of investigation, there is a clear need to redefine the diagnostic algorithm and the criteria for diagnosing Buerger's disease.


Asunto(s)
Tromboangitis Obliterante/diagnóstico , Síndrome Antifosfolípido/complicaciones , Humanos , Hiperhomocisteinemia/complicaciones , Tromboangitis Obliterante/complicaciones , Tromboangitis Obliterante/inmunología
20.
J Endovasc Ther ; 7(4): 263-72, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10958289

RESUMEN

PURPOSE: To report intermediate results of a pilot study in which the glycoprotein IIb/IIIa receptor antagonist abciximab was given to patients during percutaneous carotid stenting for recurrent internal carotid artery (ICA) stenosis. The objective was to prevent procedure-related cerebral embolic events and decrease the incidence of recurrent stenosis. METHODS: Sixteen patients (9 women; mean age 66.5 years, range 39-78) with severe ICA recurrent stenosis (>80%) underwent balloon angioplasty and stenting. Before the procedure, abciximab was administered intravenously as a bolus (0.25 mg/kg) followed by a 12-hour continuous infusion (10 microg/min). RESULTS: Fifteen patients received stents (14 Wallstent and 1 Strecker); 1 vessel was dilated with only 50% improvement in luminal diameter. Two stented arteries had residual stenosis (<30%) but satisfactory luminal diameter was achieved in the remaining 13 (81%) arteries. There were no neurological ischemic events during or following the procedure, nor were there any bleeding or peripheral vascular complications. Duplex surveillance studies up to 12 months revealed no significant recurrent stenosis in the treated vessels. CONCLUSIONS: The administration of abciximab in conjunction with percutaneous revascularization procedures for postsurgical carotid artery stenosis may reduce cerebral ischemic episodes. It may also attenuate restenosis in the treated artery.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Arteria Carótida Interna , Estenosis Carotídea/terapia , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Stents , Abciximab , Adulto , Anciano , Angioplastia de Balón , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Endarterectomía Carotidea , Femenino , Humanos , Embolia Intracraneal/etiología , Embolia Intracraneal/prevención & control , Masculino , Persona de Mediana Edad , Proyectos Piloto , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Radiografía , Recurrencia
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