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1.
J Oncol Pharm Pract ; : 10781552241258151, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819392

RESUMEN

BACKGROUND: The purpose of this study was to describe taking, timing, and dosing adherence to home caregiver-administered intravenous (IV) immunosuppressants in a sample of pediatric hematopoietic stem cell transplant (HCT) recipients. PROCEDURES: Sixteen children who had undergone HCT, ages 3 months to 15 years, and their caregivers participated. All caregivers were biological mothers. Caregivers completed a demographic questionnaire as part of a larger study and brought in portable infusion pumps to download the pump data at the time of their child's post-HCT clinic visit. Pump data were then examined for dose taking, timing, and amount for 30 days following discharge. RESULTS: Despite the importance of the precise timing of IV immunosuppressants, adherence taking, dosing, and timing varied widely in this sample. The mean percentage of doses administered was 98.72%, and 81.3% of children received all doses of immunosuppressant. However, only 62% of doses were given on time and the mean difference between the prescribed and actual administration time was 67.03 minutes. CONCLUSIONS: Although taking adherence was high, the timing and dosing adherence to IV immunosuppressants in the home was poor. Additional support to promote adherence should be provided including assisting caregivers to identify and use adherence strategies specific to their child's IV immunosuppressant regimen in the home.

2.
Pediatr Blood Cancer ; 70(6): e30291, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36951413

RESUMEN

BACKGROUND: Caregivers and adolescents and young adult (AYA) cancer survivors may be at greater psychosocial risk from the COVID-19 pandemic than healthy peers due to complex and traumatic medical histories. This study describes COVID-19-related event exposures, impact, and distress among a large sample of caregivers and AYA cancer survivors and the relationship of these variables to demographic and cancer characteristics. PROCEDURE: From May 2020 to December 2021, 422 caregivers and 531 AYA survivors completed the COVID-19 Exposures and Family Impact Survey (CEFIS) and CEFIS-AYA, respectively. Total COVID-19-related exposures, average COVID-19-related impact, and COVID-19-related distress were calculated. Conventional content analysis was used to analyze free-text responses about the negative and positive effects of COVID-19. RESULTS: Caregivers and AYA reported an average of 7.4-7.8 COVID-19 exposures to pandemic-related events and a slightly negative impact of COVID-19 across psychosocial domains, with some positive impacts reported. COVID-19-related distress was moderate and clinically meaningful (4.9-5.2/10) for AYA and caregivers. Racial and ethnically minoritized AYA and caregivers reported higher COVID-19-related distress than non-Hispanic white caregivers. For AYA, distress was also higher among female, college-age (18-22 years), and long-term survivors compared with males, younger AYA, White and those recently off treatment. CEFIS outcomes remained relatively stable over time. CONCLUSIONS: COVID-19 had a significant and consistent negative impact on caregivers and AYA survivors. Racial and ethnically minoritized families and female, college-age, and long-term AYA survivors may require additional psychosocial support. Assessing for COVID-19 impact and distress is important in pediatric oncology to evaluate adjustment and plan targeted interventions.


Asunto(s)
COVID-19 , Supervivientes de Cáncer , Neoplasias , Masculino , Humanos , Adolescente , Femenino , Adulto Joven , Niño , Adulto , Neoplasias/psicología , Supervivientes de Cáncer/psicología , Cuidadores/psicología , Pandemias , Calidad de Vida/psicología , Sobrevivientes/psicología
3.
Pediatr Blood Cancer ; 69(10): e29846, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35730649

RESUMEN

OBJECTIVE: Pediatric hematopoietic stem cell transplant (HCT) is an intensive medical procedure associated with significant late effects, of which pain is a prominent example. While pain is associated with increased depressive symptoms and health-related quality-of-life (HRQoL) impairments in other pediatric chronic illness populations, associations between these variables are not well understood in pediatric HCT. Clarifying these associations may inform clinical interventions to improve health outcomes following pediatric HCT. This study aimed to investigate the relations between pain intensity, depressive symptoms, and HRQoL in survivors of pediatric HCT. METHOD: Fifty-one survivors of pediatric HCT (Mage  = 14.3 years, standard deviation [SD] = 4.3; 58.8% male; 80.4% White) completed self-report measures of pain intensity, depressive symptoms, and HRQoL. Demographic and disease information was collected via demographic forms and medical record review. Path analysis was used to examine hypothesized associations between pain intensity, depressive symptoms, and HRQoL. RESULTS: Analyses revealed direct effects of pain intensity on depressive symptoms (estimate [Est.] = .23, p < .001) and HRQoL (Est. = -.2, p = .04), and direct effects of depressive symptoms on HRQoL (Est. = -.68, p < .001). Depressive symptoms also mediated the relationship between pain intensity and HRQoL (Est. = -.16, p = .006). CONCLUSIONS: Greater pain intensity was associated directly with increased depressive symptoms and indirectly with HRQoL through depressive symptoms. Results of this study suggest that multitargeted cognitive behavioral interventions that address pain and depressive symptoms may improve HRQoL ratings in survivors of pediatric HCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Calidad de Vida , Adolescente , Niño , Depresión/etiología , Depresión/psicología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Dolor/etiología , Calidad de Vida/psicología , Sobrevivientes/psicología
4.
J Pediatr Psychol ; 45(4): 463-473, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32196095

RESUMEN

OBJECTIVE: Little is known about relations between domains of psychosocial risk among pediatric cancer populations. The Psychosocial Assessment Tool 2.0 (PAT2.0) is one internationally validated screening measure that can examine these relations. This study aimed to examine risk profiles and predictors of these patterns exhibited by American and Dutch families. METHODS: Caregivers of children newly diagnosed with cancer (N = 262; nUSA=145, nNL=117) completed the PAT2.0 as part of larger studies conducted in the United States and the Netherlands. Latent profile analysis and multinomial logistic regression examined differences in demographic and medical variables across risk profiles. Domains assessed included Family Structure/Resources, Child Problems, Sibling Problems, Family Problems, Caregiver Stress Reactions, and Family Beliefs. RESULTS: Four groups were identified: "Low-Risk" (n = 162) defined by generally low risk across domains; "Moderate-Caregiver" (n = 55) defined by elevated Caregiver Stress Reactions domain; "Moderate-Children" (n = 25) defined by elevated Child Problems and/or Sibling Problems, and "Elevated-Risk" (n = 20) marked by generally high overall risk. Dutch families had higher odds of being in the Elevated-Risk group, compared to the Low-Risk group. Caregiver age, gender, and educational attainment predicted group membership. Families classified as Targeted or Clinical had higher odds of being in the Moderate or Elevated risk groups. CONCLUSION: The PAT2.0 appears to identify largely similar patterns of risk, suggesting that families experience common psychosocial difficulties in both American and Dutch societies. The two Moderate groups demonstrated specific risk sources, suggesting that evaluation of domain patterns, rather than reliance on PAT2.0 risk level, could be of clinical benefit.


Asunto(s)
Etnicidad , Neoplasias , Padres , Estrés Psicológico , Cuidadores , Niño , Femenino , Humanos , Países Bajos/epidemiología , Padres/psicología , Medición de Riesgo , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Estados Unidos
5.
Biol Blood Marrow Transplant ; 24(2): 381-385, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29102720

RESUMEN

We prospectively examined rates of outpatient oral medication adherence in children after hematopoietic stem cell transplant (post-HSCT). For 6 months after first discharge post-HSCT, 50 patients (aged 0 to 16 years) and their primary caregivers agreed to store 1 oral medication in an electronic pill bottle that date and time stamps each bottle opening. Demographics, disease, donor type, and prescribed post-HSCT medication regimen were collected via chart review. For each patient percent adherence was calculated by dividing the number of doses taken as indicated by the electronic pill bottle by the number of doses prescribed for the same time period. Average percent adherence ranged from 63% at 1 month after discharge to 57% at 6 months after discharge. For patients who received an allogeneic transplant, lower adherence was associated (P < .005) with higher infection rates, after controlling for age and time since transplant. No such relationship was observed for patients who received an autologous transplant. This study demonstrates that poor oral medication adherence is prevalent, persistent, and, for patients receiving an allogeneic transplant, associated with increased incidence of infections during the outpatient treatment period. This study highlights the need for further research examining factors that hinder medication adherence as well as monitoring, promoting, and intervening to maximize medication adherence throughout the HSCT course.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones/etiología , Cumplimiento de la Medicación/estadística & datos numéricos , Adolescente , Aloinjertos , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pacientes Ambulatorios , Periodo Posoperatorio
6.
Apoptosis ; 21(12): 1447-1452, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27738771

RESUMEN

Portimine is a recently discovered member of a class of marine micro-algal toxins called cyclic imines. In dramatic contrast to related compounds in this toxin class, portimine has very low acute toxicity to mice but is highly cytotoxic to cultured cells. In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC50 values of 6 and 2.5 nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death. Jurkat cells overexpressing the anti-apoptotic protein Bcl-2 or Bax/Bak knockout MEFs were completely protected from portimine. This protection was apparent even at high concentrations of portimine, with no evidence of necrotic cell death, indicating that portimine is a selective chemical inducer of apoptosis. Treatment of the Bcl-2-overexpressing cells with both portimine and the Bcl-2 inhibitor ABT-737 proved a powerful combination, causing >90 % death. We conclude that portimine is one of the most potent naturally derived inducers of apoptosis to be discovered, and it displays strong selectivity for the induction of apoptotic pathways.


Asunto(s)
Apoptosis/efectos de los fármacos , Citotoxinas/toxicidad , Iminas/toxicidad , Toxinas Marinas/toxicidad , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Citotoxinas/química , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Iminas/química , Células Jurkat , Toxinas Marinas/química , Ratones , Estructura Molecular
7.
Pediatr Blood Cancer ; 63(10): 1834-9, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27332623

RESUMEN

BACKGROUND: Advances in hematopoietic stem cell transplantation (HSCT) have contributed to increased survival for pediatric patients. However, there are inconsistent findings regarding the impact of HSCT on health-related quality of life (HRQOL) outcomes for children. This study aimed to establish trajectories of HRQOL following HSCT and identify predictors of the HRQOL course. PROCEDURE: Ninety caregivers of a child who received HSCT (mean age = 6.42 years) for various oncologic, immunologic, and metabolic conditions completed questionnaires regarding family psychosocial functioning and child HRQOL at the time of discharge from HSCT and follow-up HRQOL at four additional time points. RESULTS: There was a significant change in overall HRQOL in 3 months postdischarge, with the greatest improvement in physical functioning. Caregiver stress and social support, and child psychosocial problems predicted changes in HRQOL over time. CONCLUSIONS: These results point to potentially modifiable factors that are related to the course of HRQOL following HSCT, and interventions aimed at these factors should be implemented.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/psicología , Calidad de Vida , Cuidadores , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino
8.
J Pediatr Psychol ; 41(4): 406-18, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26384715

RESUMEN

OBJECTIVE: To provide a comprehensive summary (systematic review) of medication adherence rates by assessment method and medication type for pediatric patients with sickle cell disease (SCD), as well as identify important correlates for future research. METHODS: Articles assessing medication adherence and published between 1982 and February 2015 (n = 49) were identified using electronic databases. A meta-analysis of 14 studies examining demographic, medical, and psychosocial factors and medication adherence was conducted. RESULTS: Adherence rates ranged from 12% to 100% across all medications. Approximately 30% of studies reported associations between adherence and key demographic, medical, and psychosocial correlates. Mean effect sizes were small to moderate (r = .02-.53). CONCLUSIONS: The wide range of adherence rates reported in the literature may be because of, in part, the use of variable assessment strategies. Future studies examining pediatric SCD adherence should incorporate key correlates with the goal of replication.


Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Anemia de Células Falciformes/psicología , Niño , Humanos , Cumplimiento de la Medicación/psicología
10.
JTCVS Open ; 18: 91-103, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38690428

RESUMEN

Objective: Donor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data. Methods: We analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance. Results: DCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth. Conclusions: DCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives.

11.
Catheter Cardiovasc Interv ; 82(7): E952-8, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-22926967

RESUMEN

Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri- and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patient's selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector-computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI.


Asunto(s)
Estenosis de la Válvula Aórtica/terapia , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Calcinosis/terapia , Cateterismo Cardíaco , Implantación de Prótesis de Válvulas Cardíacas/métodos , Tomografía Computarizada Multidetector , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Humanos , Selección de Paciente , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
12.
J Pediatr Hematol Oncol Nurs ; 39(5): 277-289, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36129887

RESUMEN

Purpose: The purpose of this study was to describe symptoms experienced by survivors of pediatric hematopoietic stem cell transplant (HSCT), and demographic and treatment-factors associated with ongoing symptomology. Methods: Fifty pediatric survivors completed a cross-sectional pilot study. Questionnaires were administered online via REDCap to assess symptoms experienced in the last week. Survivors also consented to a medical record chart review. Results: Survivors were on average 5.4 years post-HSCT (range 1.1 to 9 years), male (58%), and Caucasian (80%) who received an allogeneic HSCT (92%). The most commonly reported symptoms were difficulty concentrating (42.5%), pain (38%), worry (38%), nervousness (37.5%), and lack of energy/fatigue (34%). Survivors reported up to 14 symptoms, with 90% of the sample experiencing at least one symptom in the previous week. Average number of symptoms varied by age group between 2.1 (8-9 years) and 6.8 (18 and older). Age and female gender were associated with higher levels of fatigue. Conclusions: The majority of survivors experienced at least one symptom in the previous week. Neuropsychological symptoms and pain endure well into survivorship that can influence outcomes such as function and health-related quality of life (HRQOL). Research is needed on biological mechanisms of ongoing symptomology, effective interventions to prevent or mitigate symptoms, and the impact of symptoms on patient outcomes including daily functioning and HRQOL. Implications Survivors of pediatric HSCT continued to experience symptoms for up to nine years. Survivors should be frequently screened for symptoms, as symptoms may affect function, learning/employment outcomes, and HRQOL.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Calidad de Vida , Niño , Preescolar , Estudios Transversales , Fatiga/epidemiología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Dolor , Proyectos Piloto , Calidad de Vida/psicología , Sobrevivientes/psicología
13.
ERJ Open Res ; 8(3)2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36105153

RESUMEN

Background: The normal range of fractional exhaled nitric oxide (F ENO) is influenced by demographic factors. However, single, fixed cut-off values are used for clinical interpretation in children despite rapid growth. We aimed to define the normal range of F ENO during childhood and evaluate its utility in a diagnostic setting. Method: F ENO percentile charts were developed using data from nonasthmatic children in a population-based birth cohort (Manchester Asthma and Allergy Study). Children were skin prick tested, F ENO measured at the ages of 8, 11, 13-16 and 18 years and clinical information collected. This chart was externally validated in the Study of Eczema and Asthma to Observe the Influence of Nutrition (SEATON) cohort before being prospectively tested in symptomatic, treatment-naïve patients with suspected asthma in a diagnostic setting (Rapid Access Diagnostics for Asthma study). Results: Height, weight, body mass index and age were predictive of F ENO in univariate analysis using 1220 F ENO measurements. Only height remained significant after adjustment in the overall, nonatopic and atopic populations, and was included in the predictive equations for 50th, 75th 90th and 98th percentiles. The proposed percentile lines corresponded to the 57th (95% CI 53rd-61st), 80th (76th-83rd), 90th (87th-92nd) and 98th (96th-99th) percentiles in the SEATON cohort (660 measurements). When tested in 73 symptomatic treatment-naïve children and young adults (median (interquartile range) age: 11 (8-14) years), an F ENO >90th percentile gave a 96% specificity and positive predictive value of 97%, identifying 59% of children who were subsequently diagnosed with asthma after extensive testing. Conclusion: We developed a height-based F ENO percentile chart which quantifies the probability of asthma in symptomatic children and merits further validation towards clinical implementation.

14.
PLoS One ; 16(7): e0255209, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34311467

RESUMEN

Collective memory studies show that Americans remember their presidents in a predictable pattern, which can be described as a serial position curve with an additional spike for Abraham Lincoln. However, all prior studies have tested Americans' collective memory for the presidents by their names. How well do Americans know the faces of the presidents? In two experiments, we investigated presidential facial recognition and compared facial recognition to name recognition. In Experiment 1, an online sample judged whether each of the official portraits of the US presidents and similar portraits of nonpresidents depicted a US president. The facial recognition rate (around 60%) was lower than the name recognition rate in past research (88%), but the overall pattern still fit a serial position curve. Some nonpresidents, such as Alexander Hamilton, were still falsely identified as presidents at high rates. In Experiment 2, a college sample completed a recognition task composed of both faces and names to directly compare the recognition rates. As predicted, subjects recognized the names of the presidents more frequently than the faces. Some presidents were frequently identified by their names but not by their faces (e.g. John Quincy Adams), while others were the opposite (e.g. Calvin Coolidge). Together, our studies show that Americans' memory for the faces of the presidents is somewhat worse than their memory for the names of the presidents but still follows the same pattern, indicating that collective memories contain more than just verbal information.


Asunto(s)
Reconocimiento Facial , Memoria , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nombres , Estimulación Luminosa , Estados Unidos , Adulto Joven
15.
J Allergy Clin Immunol Pract ; 9(12): 4243-4251.e7, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34303020

RESUMEN

BACKGROUND: Asthma diagnostic guidelines require procedures with aerosol-generating potential (aerosol-generating procedures [AGPs]) to guide decision making. Restricted access to AGPs poses significant challenges in primary care and resource-poor countries, further amplified during the coronavirus disease 2019 pandemic. OBJECTIVE: To establish an approach to asthma diagnosis that does not require AGPs. METHOD: Symptomatic yet untreated (beyond as-required bronchodilator use) adults with clinician-suspected asthma and maximum 10 pack year smoking history were recruited. Clinical history, physical examination, spirometry with bronchodilator reversibility, home peak flow monitoring, and bronchial challenges were performed, and fractional exhaled nitric oxide and serum eosinophils measured. Tests were then repeated following treatment with inhaled corticosteroids before an asthma diagnosis was confirmed or refuted by an expert panel. RESULTS: A total of 65 adults (mean age, 34.8 ± 12.2 years) were recruited. Five were excluded as "unclassifiable," because of borderline results or missing data. Of the remainder, 36 were diagnosed with asthma and 24 were not. Using data from non-AGPs only (wheeze on auscultation and blood eosinophilia) and home peak flow variability, a "rule-in" diagnostic model provided comparable discriminative ability to the application of established guidelines. Clinical suspicion of asthma together with at least 1 positive non-AGP test result provided a sensitivity of 55%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 60%. Application of this model reduced the need for spirometry-based tests by one-third. CONCLUSIONS: The proposed diagnostic algorithm may be clinically useful in "ruling-in" asthma in adults when access to AGPs is limited. This algorithm is not suitable for those with low clinical probability, with a significant smoking history, or where alternative diagnoses are more likely. This pragmatic approach to asthma diagnosis merits prospective validation.


Asunto(s)
Asma , COVID-19 , Adulto , Aerosoles , Asma/diagnóstico , Pruebas Respiratorias , Prueba de Óxido Nítrico Exhalado Fraccionado , Humanos , Persona de Mediana Edad , Óxido Nítrico , SARS-CoV-2 , Espirometría , Adulto Joven
16.
Blood ; 112(13): 5193-201, 2008 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-18824600

RESUMEN

We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated during CIA. Reciprocal bone marrow chimeras using G-CSF(-/-), G-CSFR(-/-), and wild-type (WT) mice identified nonhematopoietic cells as the major producers of G-CSF and hematopoietic cells as the major responders to G-CSF during CIA. Protection against CIA was associated with relative neutropenia. Depletion of neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically attenuated the progression of established CIA in WT mice. Intravital microscopy of the microcirculation showed that both local and systemic administration of G-CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF-induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint during CIA revealed significantly fewer adherent Gr-1(+) neutrophils in G-CSF(-/-) mice compared with WT mice. These data confirm a central proinflammatory role for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF-induced neutrophil production.


Asunto(s)
Artritis Experimental/patología , Factor Estimulante de Colonias de Granulocitos/farmacología , Neutrófilos/efectos de los fármacos , Animales , Artritis Reumatoide/patología , Antígeno CD11b , Quimiotaxis de Leucocito/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos/genética , Articulación de la Rodilla/patología , Leucopoyesis/efectos de los fármacos , Antígeno de Macrófago-1 , Ratones , Ratones Noqueados , Líquido Sinovial
17.
J Clin Invest ; 116(6): 1571-81, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16710471

RESUMEN

RA is an autoimmune disease characterized by sustained imbalance between pro- and antiinflammatory immune mechanisms. The SOCS proteins are negative regulators of cytokine signaling, but to date there has been little information on their function in disease. The generation of Socs3(-/Delta vav) mice, which lack SOCS-3 in the hematopoietic and endothelial cell compartment, allowed us to explore the role of endogenous SOCS-3 during acute inflammatory arthritis. Joint inflammation in Socs3(-/Delta vav) mice was particularly severe and was characterized by increased numbers of neutrophils in the inflamed synovium, bone marrow, peripheral blood, and spleen. These features were most likely due to increased production of and enhanced responsiveness to G-CSF and IL-6 during arthritis in these mice. Local osteoclast generation and bone destruction were also dramatically increased in the absence of SOCS-3, as was macrophage activation. Finally, SOCS-3 was found to negatively regulate CD4+ T lymphocyte activation, including production of the pleiotropic cytokine IL-17. The absence of SOCS-3 therefore had dramatic effects in this disease model, with a broader impact on cellular responses than SOCS-1 deficiency. These findings provide direct in vivo evidence that endogenous SOCS-3 is a critical negative regulator of multiple cell types orchestrating inflammatory joint disease.


Asunto(s)
Artritis Reumatoide/inmunología , Inmunidad/fisiología , Interleucina-1/inmunología , Transducción de Señal/fisiología , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Animales , Artritis Reumatoide/patología , Bovinos , Células Cultivadas , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Inmunidad/inmunología , Interleucina-6/sangre , Articulaciones/citología , Articulaciones/inmunología , Articulaciones/patología , Macrófagos/citología , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/citología , Neutrófilos/inmunología , Osteoclastos/citología , Osteoclastos/metabolismo , Albúmina Sérica Bovina/inmunología , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Linfocitos T/citología , Linfocitos T/inmunología
18.
Hepatology ; 47(5): 1737-44, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18393371

RESUMEN

UNLABELLED: HFE-related hereditary hemochromatosis results in hepatic iron overload. Hepatocytes acquire transferrin-bound iron via transferrin receptor (Tfr) 1 and Tfr1-independent pathways (possibly Tfr2-mediated). In this study, the role of Hfe in the regulation of hepatic transferrin-bound iron uptake by these pathways was investigated using Hfe knockout mice. Iron and transferrin uptake by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice were measured after incubation with 50 nM (125)I-Tf-(59)Fe (Tfr1 pathway) and 5 microM (125)I-Tf-(59)Fe (Tfr1-independent or putative Tfr2 pathway). Tfr1 and Tfr2 messenger RNA (mRNA) and protein expression were measured by real-time polymerase chain reaction and western blotting, respectively. Tfr1-mediated iron and transferrin uptake by Hfe knockout hepatocytes were increased by 40% to 70% compared with iron-loaded wild-type hepatocytes with similar iron levels and Tfr1 expression. Iron and transferrin uptake by the Tfr1-independent pathway was approximately 100-fold greater than by the Tfr1 pathway and was not affected by the absence of Hfe. Diferric transferrin increased hepatocyte Tfr2 protein expression, resulting in a small increase in transferrin but not iron uptake by the Tfr1-independent pathway. CONCLUSION: Tfr1-mediated iron uptake is regulated by Hfe in hepatocytes. The Tfr1-independent pathway exhibited a much greater capacity for iron uptake than the Tfr1 pathway but it was not regulated by Hfe. Diferric transferrin up-regulated hepatocyte Tfr2 protein expression but not iron uptake, suggesting that Tfr2 may have a limited role in the Tfr1-independent pathway.


Asunto(s)
Hepatocitos/fisiología , Antígenos de Histocompatibilidad Clase I/fisiología , Hierro/metabolismo , Proteínas de la Membrana/fisiología , Transferrina/metabolismo , Animales , Transporte Biológico , Técnicas de Cultivo de Célula , Cartilla de ADN , Proteína de la Hemocromatosis , Hepatocitos/citología , Hepatocitos/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Cinética , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Unión Proteica , ARN/genética , ARN/aislamiento & purificación , ARN Mensajero/genética
19.
Pulm Ther ; 5(2): 103-115, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32026404

RESUMEN

Asthma, the most common chronic respiratory disease, is frequently misdiagnosed, and accounts for a significant proportion of healthcare expenditure. This has driven the National Institute for Health and Care Excellence (NICE) in the United Kingdom (UK) to produce recent guidance; in places, this contrasts to that of the British Thoracic Society/Scottish Intercollegiate Guideline Network (BTS/SIGN), which have been producing their own guidance since 2003. Here we review the history of asthma diagnostic guidelines, and compare and review the evidence behind them, in adults and in children. We discuss the definitions of asthma and how these drive the concepts behind diagnostic strategies. We anticipate future directions in asthma diagnosis which will take into account the concepts of personalised medicine and disease endotypes. We also consider the utility of tests in use now and in the future, in particular novel tests relating to small airway inflammation and obstruction.

20.
Am J Infect Control ; 47(9): 1157-1159, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30904371

RESUMEN

Therapeutic ultrasound (US) is commonly used in the rehabilitation of soft tissue injuries including wounds. US heads and coupling gel come into direct contact with patient skin, increasing the risk for health care-associated infections owing to cross contamination. In this study, nearly 80% of Staphylococcus aureus placed on US heads in gel survived for 1 hour, with survival of 3 days possible in other types of organic matter.


Asunto(s)
Equipos y Suministros/microbiología , Fómites/microbiología , Geles , Viabilidad Microbiana , Staphylococcus aureus/fisiología , Ultrasonografía/instrumentación , Humanos
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