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1.
Acta Neuropathol Commun ; 11(1): 123, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37491342

RESUMEN

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) and characterized by perivascular accumulations of hyperphosphorylated tau protein (p-tau) at the depths of the cortical sulci. Studies of living athletes exposed to RHI, including concussive and nonconcussive impacts, have shown increased blood-brain barrier permeability, reduced cerebral blood flow, and alterations in vasoreactivity. Blood-brain barrier abnormalities have also been reported in individuals neuropathologically diagnosed with CTE. To further investigate the three-dimensional microvascular changes in individuals diagnosed with CTE and controls, we used SHIELD tissue processing and passive delipidation to optically clear and label blocks of postmortem human dorsolateral frontal cortex. We used fluorescent confocal microscopy to quantitate vascular branch density and fraction volume. We compared the findings in 41 male brain donors, age at death 31-89 years, mean age 64 years, including 12 donors with low CTE (McKee stage I-II), 13 with high CTE (McKee stage III-IV) to 16 age- and sex-matched non-CTE controls (7 with RHI exposure and 9 with no RHI exposure). The density of vessel branches in the gray matter sulcus was significantly greater in CTE cases than in controls. The ratios of sulcus versus gyrus vessel branch density and fraction volume were also greater in CTE than in controls and significantly above one for the CTE group. Hyperphosphorylated tau pathology density correlated with gray matter sulcus fraction volume. These findings point towards increased vascular coverage and branching in the dorsolateral frontal cortex (DLF) sulci in CTE, that correlates with p-tau pathology.


Asunto(s)
Encefalopatía Traumática Crónica , Enfermedades Neurodegenerativas , Humanos , Masculino , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más Años , Encefalopatía Traumática Crónica/patología , Enfermedades Neurodegenerativas/patología , Encéfalo/patología , Proteínas tau/metabolismo , Lóbulo Frontal/metabolismo , Atletas
2.
J Trauma Dissociation ; 19(2): 232-246, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28509661

RESUMEN

Non-suicidal self-injury (NSSI) has been reported to serve a range of functions for individuals who engage in it. Despite considerable variation in NSSI functions between individuals, limited attention has been paid to exploring relationships between NSSI functions and other characteristics of self-injuring individuals, such as trauma history. This is despite allusion to trauma history in the suggested etiology of some NSSI functions (e.g., anti-dissociation, self-punishment). The present study used a 21-day online daily diary to explore possible relationships between common NSSI functions and past interpersonal trauma in community young adults (n = 38). The interpersonal boundaries and anti-dissociation functions significantly related to interpersonal trauma severity in multiple regression analyses; the interpersonal boundaries function continued to significantly relate to interpersonal trauma severity when controlling for the number of NSSI functions endorsed.


Asunto(s)
Adultos Sobrevivientes del Maltrato a los Niños/psicología , Relaciones Interpersonales , Conducta Autodestructiva/psicología , Adolescente , Adulto , Factores de Edad , Evaluación Ecológica Momentánea , Femenino , Humanos , Masculino , Ontario , Factores de Riesgo , Índices de Gravedad del Trauma
3.
Eur Eat Disord Rev ; 20(3): e116-22, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22311824

RESUMEN

UNLABELLED: Individuals with eating disorders are said to be highly ambivalent towards change and thus have difficulty maintaining a commitment to, and motivation for, treatment. Self-Determination Theory postulates that autonomous motivation for therapy exists when individuals view their participation as freely chosen. OBJECTIVE: The present study was designed to ascertain whether or not autonomous motivation was associated with treatment response in individuals with bulimia-spectrum eating disorders (BSED). METHOD: One hundred and fifty-five women with DSM-IV-TR BSED participated in multimodal group therapy and completed measures to assess motivation, eating and comorbid symptoms. RESULTS: Hierarchical multiple regression analyses demonstrated that higher levels of autonomous motivation at pretreatment predicted lower post-treatment scores on measures of eating preoccupations (shape, weight and eating concerns), binge eating, anxiety/depression, relationship to self and others and impulsivity. DISCUSSION: These results indicate that autonomous motivation may be an important predictor of outcome following treatment for BSED.


Asunto(s)
Imagen Corporal , Bulimia Nerviosa/psicología , Bulimia/psicología , Motivación , Adulto , Bulimia/terapia , Bulimia Nerviosa/terapia , Femenino , Humanos , Autoeficacia , Autoinforme , Encuestas y Cuestionarios , Resultado del Tratamiento
4.
Leuk Lymphoma ; 52(2): 214-22, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21142785

RESUMEN

We analyzed 67 patients with lymphoma who received alemtuzumab-based conditioning regimens for allogeneic stem cell transplant and no post-transplant DLI. The median age was 54 (24-70), 43% had unrelated donors, 34% had chemotherapy refractory disease, and 25% had an elevated LDH. With a median follow-up for survivors of 35 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 30% and 47%, respectively. Chemosensitivity by CT and pre-transplant LDH were independent prognostic factors for both overall survival and progression-free survival. Patient age, performance status, donor type, lymphoma subtype, disease sensitivity by PET, and conditioning regimen did not correlate with PFS and OS. Patients who relapsed greater than 6 months after allogeneic transplant were frequently able to re-enter a subsequent durable remission. Our experience confirms the curative potential of alemtuzumab-containing RIC regimens for allogeneic HCT in patients with relapsed lymphoma without prophylactic DLI. An elevated pre-transplant LDH and chemorefractory disease prior to transplant confer a worse prognosis, while PET scan findings do not have this same implication. Patients who relapse greater than 6 months after their transplant are likely to achieve a subsequent remission with any of a variety of interventions, suggesting that GVL effects can be operative even after recurrence. Our outcomes challenge the utility of the common practice of prophylactic DLI after T-depleted transplant for lymphoma.


Asunto(s)
Efecto Injerto vs Tumor/inmunología , Trasplante de Células Madre Hematopoyéticas , Transfusión de Leucocitos , Depleción Linfocítica , Linfoma/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , L-Lactato Deshidrogenasa/metabolismo , Linfoma/inmunología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tasa de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto Joven
5.
Leuk Lymphoma ; 51(12): 2240-9, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20919852

RESUMEN

Disease recurrence after allogeneic hematopoietic cell transplant (alloHCT) remains common, making improvements in conditioning regimens desirable. A dose-response relationship between busulfan exposure and outcome is known. Using individual real-time monitoring of the busulfan area under the curve (AUC), we aimed to determine the maximum-tolerated busulfan AUC in a conditioning regimen with fludarabine/alemtuzumab. Thirty-six patients with advanced hematologic malignancies were treated. Busulfan levels after a test dose and conditioning dose 1 allowed targeting of subsequent AUCs and dose-escalation above the starting AUC of 4800 µmol-min/L. Clearance of busulfan test doses was not always sufficiently predictive of treatment dose AUC and, on average, test dose clearance was faster than treatment dose clearance. When the study was modified to use conditioning dose 1 pharmacokinetics instead, accurately targeted treatment AUCs were achieved, and dose-escalation was possible. Severe, late-occurring sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) was the dose-limiting toxicity seen in 5/8 patients at an AUC level of 6800 µmol-min/L. The risk for SOS/VOD correlated with the highest observed AUC (AUC(max)) rather than with the average cumulative AUC (AUC(avg)). Busulfan dose-escalation to a maximum-tolerated AUC of 5800 µmol-min/L-higher than that achieved by current standard busulfan regimens-was accurate and achievable using real-time pharmacokinetics monitoring of the first conditioning dose. This AUC is now being studied in phase II for patients receiving busulfan/fludarabine/alemtuzumab as alloHCT conditioning.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antineoplásicos , Busulfano , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/inducido químicamente , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Alemtuzumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Anticuerpos Antineoplásicos/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Busulfano/farmacocinética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Combinación de Medicamentos , Femenino , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Veno-Oclusiva Hepática/epidemiología , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Incidencia , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Trasplante Homólogo , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/farmacocinética
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