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1.
J Clin Ethics ; 34(1): 92-97, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36940360

RESUMEN

AbstractPrior to the COVID-19 pandemic, the United States housed 2.3 million inmates in 7,147 incarceration structures that, because of age, overcrowding, and poor ventilation, exacerbated the spread of airborne infections. The flow of individuals into and out of correctional facilities compounded the challenges in keeping them COVID-free. This article focuses on the work of the health and administrative leadership, in partnership with judicial and police personnel, to prevent COVID-19 inside the Albemarle-Charlottesville Regional Jail and to mitigate its spread when the jail population and/or its staff became infected. From the onset, implementing science-based policies and upholding the human right to health and healthcare for all were priorities.


Asunto(s)
COVID-19 , Prisioneros , Humanos , Estados Unidos/epidemiología , Pandemias/prevención & control , Cárceles Locales , Atención a la Salud
2.
Am J Physiol Lung Cell Mol Physiol ; 320(4): L600-L614, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33295836

RESUMEN

The growing interest in regulating flavored E-liquids must incorporate understanding of the "flavoring profile" of each E-liquid-which flavorings (flavoring chemicals) are present and at what concentrations not just focusing on the flavor on the label. We investigated the flavoring profile of 10 different flavored E-liquids. We assessed bronchial epithelial cell viability and apoptosis, phagocytosis of bacteria and apoptotic cells by macrophages after exposure to E-cigarette vapor extract (EVE). We validated our data in normal human bronchial epithelial cells (NHBE) and alveolar macrophages (AM) from healthy donors. We also assessed cytokine release and validated in the saliva from E-cigarette users. Increased necrosis/apoptosis (16.1-64.5% apoptosis) in 16HBE cells was flavor dependent, and NHBEs showed an increased susceptibility to flavors. In THP-1 differentiated macrophages phagocytosis was also flavor dependent, with AM also showing increased susceptibility to flavors. Further, Banana and Chocolate were shown to reduce surface expression of phagocytic target recognition receptors on alveolar macrophages. Banana and Chocolate increased IL-8 secretion by NHBE, whereas all 4 flavors reduced AM IL-1ß secretion, which was also reduced in the saliva of E-cigarette users compared with healthy controls. Flavorant profiles of E-liquids varied from simple 2 compound mixtures to complex mixtures containing over a dozen flavorants. E-liquids with high benzene content, complex flavoring profiles, high chemical concentration had the greatest impacts. The Flavorant profile of E-liquids is key to disruption of the airway status quo by increasing bronchial epithelial cell apoptosis, causing alveolar macrophage phagocytic dysfunction, and altering airway cytokines.


Asunto(s)
Apoptosis , Bronquios/patología , Citocinas/metabolismo , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Aromatizantes/efectos adversos , Macrófagos/patología , Fagocitosis , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Humanos , Macrófagos/efectos de los fármacos , Factores de Riesgo
3.
Appl Environ Microbiol ; 87(8)2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33579683

RESUMEN

The gut microbiota has a significant impact on host health. Dietary interventions using probiotics, prebiotics and postbiotics have the potential to alter microbiota composition and function. Other therapeutic interventions such as antibiotics and faecal microbiota transplantation have also been shown to significantly alter the microbiota and its metabolites. Supplementation of a faecal fermentation model of the human gut with a postbiotic product Lactobacillus LB led to changes in microbiome composition (i.e. increase in beneficial bifidobacteria) and associated metabolic changes (i.e. increased acid production). Lactobacillus LB is a heat-treated preparation of cellular biomass and a fermentate generated by Limosilactobacillus fermentum CNCM MA65/4E-1b (formerly known as Lactobacillus fermentum CNCM MA65/4E-1b) and Lactobacillus delbrueckii ssp. delbrueckii CNCM MA65/4E-2z, medically relevant strains used to produce antidiarrheal preparations. In pure culture, Lactobacillus LB also stimulates the growth of a range of bifidobacterial species and strains. Lactobacillus LB-like preparations generated using other Lactobacillaceae, including commercially available probiotic bacteria, did not have the same impact on a model strain (Bifidobacterium longum subsp. infantis ATCC 15697). This bifidogenic activity is heat- and enzyme-stable and cannot be attributed to lactose, which is a major constituent of Lactobacillus LB. L fermentum CNCM MA65/4E-1b is largely responsible for the observed activity and there is a clear role for compounds smaller than 1 kDa.Importance In general, disruptions to the gut microbiota are associated with multiple disorders in humans. The presence of high levels of Bifidobacterium spp. in the human gut is commonly considered to be beneficial. Bifidobacteria can be supplemented in the diet (as probiotics) or those bifidobacteria already present in the gut can be stimulated by the consumption of prebiotics such as inulin. We demonstrate that Lactobacillus LB (a product consisting of two heat-killed lactic acid bacteria and their metabolites) can stimulate the growth of bifidobacteria in human fermented faecal communities and in pure culture. Given the heat-treatment applied during the production process, there is no risk of the lactic acid bacteria colonising (or causing bacteraemia) in vulnerable consumers (infants, immunocompromised, etc). Lactobacillus LB has the potential to affect human health by selectively promoting the growth of beneficial bacteria.

4.
Cancer Causes Control ; 31(12): 1115-1128, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32981009

RESUMEN

PURPOSE: There is provocative, yet inconsistent, evidence that sleep deficiency may influence the development of breast cancer. The purpose of this study was to evaluate the risk of breast cancer associated with sleep deficiency among postmenopausal women in the California Teachers Study (CTS). METHODS: We conducted a case-control study of 2,856 invasive breast cancer cases and 38,649 cancer-free controls, nested within the CTS. Self-administered questionnaires were used to ascertain several components of sleep deficiency, including quality, latency, duration, disturbance and use of sleep medications. Additionally, a Global Sleep Index (GSI) was created by summing the individual sleep components and categorizing into quartiles. Multivariable logistic regression analyses were used to estimate odds ratios and 95% confidence intervals (OR, 95% CI). RESULTS: Increased breast cancer risks were associated with sleep deficiency. With the exception of duration, linear increases in risk were associated with all the other individual components of sleep deficiency (p-trend ≤ 0.002). The OR for the highest GSI quartile vs. lowest was 1.24, 95% CI 1.12-1.38; p-trend < 0.001). CONCLUSIONS: Sleep deficiency may be a risk factor for breast cancer. Additional prospective studies and those aimed at elucidating underlying mechanism are warranted.


Asunto(s)
Neoplasias de la Mama/epidemiología , Posmenopausia , Sueño , Adulto , Anciano , Anciano de 80 o más Años , California/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven
6.
J Gen Intern Med ; 34(1): 137-143, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29907914

RESUMEN

In 2016, over 65 million individuals were displaced from their homes due to human rights abuses, and 262,000 people applied for asylum in the USA. Individuals who have experienced persecution are present in many primary and specialty clinics. A medical forensic evaluation can increase the likelihood of a successful asylum case. This paper reviews the legal framework for asylum and the contribution forensic evaluations can make to this vulnerable population. Physicians without asylum expertise can help these patients by recognizing their legal right to residential protection and referring them to lawyers and physicians with expert skills. Performing forensic examinations of asylum seekers offers physicians the opportunity to collaborate with attorneys, immigration officials, and human rights experts. Clinicians who do this work find it personally and professionally rewarding, especially when they impart their expert knowledge and skills to future clinicians by involving trainees in these evaluations. Physicians who encounter refugees or asylum seekers in their roles as providers or as preceptors should have familiarity with the field of asylum medicine to enhance the comprehensive care they deliver.


Asunto(s)
Rol del Médico , Médicos/legislación & jurisprudencia , Refugiados/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricos , Derechos Humanos/legislación & jurisprudencia , Humanos , Estados Unidos
7.
Ann Intern Med ; 176(11): 1552-1553, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37903366
8.
Clin Exp Immunol ; 192(2): 242-250, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29352737

RESUMEN

Immunosuppressive therapy fails to suppress the production of proinflammatory cytokines, particularly by CD8+ T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant. Pgp/GCR expression and interferon (IFN)-γ/tumour necrosis factor (TNF)-α proinflammatory cytokine production was measured in blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (± prednisolone ± Pgp inhibitor, cyclosporin A ± GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp- lymphocyte subsets from all subjects produced IFN-γ/TNF-α proinflammatory cytokines. Pgp expression was increased in CD8+ Pgp+ T cells and correlated with IFN-γ/TNF-α expression and BOS grade. Reduced GCR was observed in CD8+ Pgp- T, natural killer (NK) T-like and NK cells from stable patients compared with controls, and reduced further in CD8+ Pgp- T cells in BOS. The addition of 2·5 ng/ml cyclosporin A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+ Pgp+ T cells from BOS patients. The addition of 10 µM Compound A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+ Pgp- T cells from BOS patients. BOS is associated with increased Pgp expression and loss of GCR from steroid-resistant proinflammatory CD8+ T cells. Treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells may improve graft survival.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Bronquiolitis Obliterante/inmunología , Linfocitos T CD8-positivos/metabolismo , Trasplante de Pulmón , Receptores de Glucocorticoides/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Bronquiolitis Obliterante/genética , Linfocitos T CD8-positivos/efectos de los fármacos , Resistencia a Medicamentos , Citometría de Flujo , Humanos , Interferón gamma/sangre , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Persona de Mediana Edad , Receptores de Glucocorticoides/genética , Esteroides/administración & dosificación , Factor de Necrosis Tumoral alfa/sangre , Miembro 4 de la Subfamilia B de Casete de Unión a ATP
9.
Clin Exp Allergy ; 48(6): 650-662, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29676834

RESUMEN

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.


Asunto(s)
Absentismo , Asma/epidemiología , Eficiencia , Calidad de Vida , Lugar de Trabajo , Actividades Cotidianas , Adulto , Anciano , Asma/diagnóstico , Asma/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
10.
J Gen Intern Med ; 33(3): 370-375, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29256088

RESUMEN

Spurred on by recent health care reforms and the Triple Aim's goals of improving population health outcomes, reducing health care costs, and improving the patient experience of care, emphasis on population health is increasing throughout medicine. Population health has the potential to improve patient care and health outcomes for individual patients. However, specific population health activities may not be in every patient's best interest in every circumstance, which can create ethical tensions for individual physicians and other health care professionals. Because individual medical professionals remain committed primarily to the best interests of individual patients, physicians have a unique role to play in ensuring population health supports this ethical obligation. Using widely recognized principles of medical ethics-nonmaleficence/beneficence, respect for persons, and justice-this article describes the ethical issues that may arise in contemporary population health programs and how to manage them. Attending to these principles will improve the design and implementation of population health programs and help maintain trust in the medical profession.


Asunto(s)
Ética Médica , Rol del Médico , Salud Poblacional , Desarrollo de Programa , Humanos , Desarrollo de Programa/métodos
11.
Int Arch Occup Environ Health ; 91(8): 1041-1050, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30099583

RESUMEN

OBJECTIVES: We assessed the efficacy of trainings with Vietnamese nail salon owners and workers on knowledge and behaviors that could reduce exposures to toxic chemicals in nail products. METHODS: We trained Vietnamese salon owners in California (n = 77) who then trained their workers (n = 200) on best practices. In a cluster randomized controlled trial, we assessed the efficacy of the training on change in knowledge and self-reported behaviors. Data were collected from 2013 to 2016 and analyzed from 2016 to 2017. RESULTS: Compared to the control group, the intervention group had significantly greater increases in knowledge about: safer nail polishes [odds ratio (OR) 3.7 (95% confidence interval (CI) 1.9, 7.2)]; proper ventilation methods (OR 4.2; 95% CI 2.2, 8.1); recommended glove types (OR 3.4; 95% CI 1.9, 6.3); and recommended product handling and storage (OR 4.1; 95% CI 1.7, 9.9). The intervention also increased best practices: using safer nail polishes (OR 3.6; 95% CI 1.9, 6.8); reading product labels (OR 2.6; 95% CI 1.3, 5.0); and wearing long sleeves (OR 2.4; 95% CI 1.3, 4.2). CONCLUSIONS: The owner-to-worker intervention with culturally and linguistically appropriate training for salon owners who then trained workers was effective in promoting knowledge and self-reported behaviors that can reduce workplace chemical exposures.


Asunto(s)
Industria de la Belleza , Educación en Salud/métodos , Conocimientos, Actitudes y Práctica en Salud/etnología , Exposición Profesional/prevención & control , Lugar de Trabajo/psicología , Adulto , Contaminantes Ocupacionales del Aire , Asiático/psicología , California , Femenino , Guantes Protectores , Humanos , Masculino , Persona de Mediana Edad , Uñas , Evaluación de Programas y Proyectos de Salud , Vietnam/etnología , Compuestos Orgánicos Volátiles/toxicidad
12.
Eur J Dent Educ ; 22(4): 243-257, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29573165

RESUMEN

INTRODUCTION: Games involving technology have the potential to enhance hand-eye coordination and decision-making skills. As a result, game characteristics have been applied to education and training, where they are known as serious games. There is an increase in the volume of literature on serious games in healthcare education; however, evidence on their impact is still ambiguous. AIMS: The aims of this study were (i) to identify high-quality evidence (systematic reviews or meta-analyses) regarding impacts of serious games on healthcare education; and (ii) to explore evidence regarding impacts of serious games in dental education. METHODS: A rapid review of the literature was undertaken to synthesise available evidence and examine serious games in healthcare education (Stage 1) and dental education (Stage 2). RESULTS: Nine systematic reviews were included in Stage 1, four of which were of high, three of moderate and two of low quality. For Stage 2, two randomised control trials with moderate quality were included. The findings demonstrated that serious games are potentially effective learning tools in terms of knowledge and skills improvement, although outcomes of serious games over traditional learning approaches were not consistent. In addition, serious games appeared to be more engaging and satisfying for students, which could be considered as the most important positive impact. CONCLUSION: Serious games provide an option for healthcare and dental education but remain underutilised and researched. At best, they offer a similar experience to other methods in relation to educational outcome; however, they can provide a supplementary strategy to engage students and improve learner satisfaction.


Asunto(s)
Toma de Decisiones/fisiología , Educación en Odontología/métodos , Educación Médica/métodos , Desempeño Psicomotor/fisiología , Estudiantes de Odontología/psicología , Juegos de Video , Humanos , Aprendizaje , Satisfacción Personal , Revisiones Sistemáticas como Asunto
13.
BMC Oral Health ; 17(1): 122, 2017 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-28882136

RESUMEN

BACKGROUND: Recruitment and retention are documented as two of the most difficult elements of conducting clinical trials. These issues are even more challenging in paediatric trials, particularly when the families being recruited and retained are deemed 'hard to reach'. METHODS: Through the authors' own reflection on the conduct of the trial this paper examines recruitment and retention with hard to reach families from the perspective of a recently completed clinical trial on preparatory information for children undergoing general anaesthesia for tooth extractions in which approximately 83% of those approached and eligible agreed to participate. RESULTS: The lessons learned for recruitment include: the importance of children's assent; maximising limited resources when screening and approaching potential participants; valuing families' time; and developing effective professional relationships. The retention rate was 83-85.5% at follow up time points up to 3.5 weeks following recruitment, insights into how this was accomplished include: ensuring continuity of care; determination to connect via telephone; valuing families' time; and close monitoring of appointment date changes. CONCLUSIONS: Implications for future paediatric trials with hard to reach families are discussed. TRIAL REGISTRATION: ISRCTN18265148 ; NIHR Portfolio 10,006. Date of Registration: 29 November 2013. The trial was registered after commencement but before completion of data collection.


Asunto(s)
Anestesia Dental , Anestesia General , Ensayos Clínicos Fase III como Asunto , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Niño , Comunicación , Continuidad de la Atención al Paciente , Familia/psicología , Humanos , Relaciones Interprofesionales , Investigadores/psicología , Factores de Tiempo , Extracción Dental
14.
Clin Exp Allergy ; 46(1): 60-70, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26767492

RESUMEN

BACKGROUND: Non-eosinophilic asthma (NEA) is a distinct, often corticosteroid-resistant inflammatory asthma phenotype. NK and NKT-like cells are effector lymphocytes that we have shown, like CD28null T cells, to be relatively resistant to steroids and major sources of pro-inflammatory/cytotoxic mediators. We hypothesized that these cells and mediators would be increased in peripheral blood in NEA. METHODS: Adults with severe asthma and variable airflow obstruction, poorly controlled despite maintenance therapy with inhaled glucocorticosteroids and long-acting bronchodilators, were recruited. Blood was assessed in those with eosinophilic asthma (n = 12), NEA (n = 25) and healthy non-smoking controls (n = 30). We applied flow cytometry to measure T, CD28null, NK and NKT-like cells and their expression of granzyme B, perforin, and killer inhibitory/activating receptors CD94(Kp43), CD158b and CD107A. Intracellular pro-inflammatory cytokine production (IFN-γ and TNF-α) was assessed in 18 controls and 10 patients with asthma/group. RESULTS: In NEA, there was increased expression of granzyme B by CD8+ T cells vs. CONTROLS: There was increased expression of granzyme B and CD158 and decreased CD94 on NK cells, vs. healthy controls and those with eosinophilic asthma. IFN-γ production by NK cells and TNF-α production by NKT-like cells in NEA were significantly increased vs. CONTROLS: In both eosinophilic and NEA phenotypes, there were significant increases in CD4+28null T cells (72% and 81% increases, respectively, vs. controls) and their expression of pro-inflammatory cytokines. Significant correlations were noted between blood CD4+28null T cells and neutrophil numbers in induced sputum, and between corticosteroid dose and blood NKT-like cells, and their production of granzyme B and TNF-α and NK IFN-γ. CONCLUSION AND CLINICAL RELEVANCE: In poorly controlled asthma, altered expression of cytotoxic/pro-inflammatory mediators can be seen on a variety of lymphocyte subsets in the peripheral blood; these changes are most apparent in NEA. Whether this pattern of expression is a marker of treatment responsiveness and future risk of exacerbations remains to be determined.


Asunto(s)
Asma/sangre , Asma/inmunología , Citocinas/sangre , Mediadores de Inflamación/sangre , Anciano , Asma/diagnóstico , Biomarcadores , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Femenino , Granzimas/sangre , Humanos , Inmunofenotipificación , Mediadores de Inflamación/metabolismo , Espacio Intracelular/metabolismo , Recuento de Leucocitos , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Masculino , Persona de Mediana Edad , Perforina/sangre , Pruebas de Función Respiratoria , Factores de Riesgo , Esputo/citología , Esputo/inmunología
15.
J Gen Intern Med ; 30(7): 1013-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25707941

RESUMEN

As American medicine continues to undergo significant transformation, the patient-centered medical home (PCMH) is emerging as an interprofessional primary care model designed to deliver the right care for patients, by the right professional, at the right time, in the right setting, for the right cost. A review of local, state, regional and national initiatives to train professionals in delivering care within the PCMH model reveals some successes, but substantial challenges. Workforce policy recommendations designed to improve PCMH effectiveness and efficiency include 1) adoption of an expanded definition of primary care, 2) fundamental redesign of health professions education, 3) payment reform, 4) responsiveness to local needs assessments, and 5) systems improvement to emphasize quality, population health, and health disparities.


Asunto(s)
Personal de Salud/educación , Atención Dirigida al Paciente/organización & administración , Atención Primaria de Salud/organización & administración , Atención a la Salud/organización & administración , Educación de Postgrado en Medicina/organización & administración , Reforma de la Atención de Salud/organización & administración , Política de Salud , Humanos , Modelos Organizacionales , Estados Unidos
16.
FASEB J ; 28(10): 4563-70, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25063845

RESUMEN

Lymphocyte responses from 208 individuals: 20 with melanoma, 34 with colon cancer, and 4 with lung cancer (58), 18 with suspected melanoma, 28 with polyposis, and 10 with COPD (56), and 94 healthy volunteers were examined. The natural logarithm of the Olive tail moment (OTM) was plotted for exposure to UVA through 5 different agar depths (100 cell measurements/depth) and analyzed using a repeated measures regression model. Responses of patients with cancer plateaued after treatment with different UVA intensities, but returned toward control values for healthy volunteers. For precancerous conditions and suspected cancers, intermediate responses occurred. ROC analysis of mean log OTMs, for cancers plus precancerous/suspect conditions vs. controls, cancer vs. precancerous/suspect conditions plus controls, and cancer vs. controls, gave areas under the curve of 0.87, 0.89, and 0.93, respectively (P<0.001). Optimization allowed test sensitivity or specificity to approach 100% with acceptable complementary measures. This modified comet assay could represent a stand-alone test or an adjunct to other investigative procedures for detecting cancer.


Asunto(s)
Detección Precoz del Cáncer/métodos , Genoma Humano , Linfocitos/efectos de la radiación , Neoplasias/diagnóstico , Tolerancia a Radiación , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Rayos Ultravioleta
17.
Clin Exp Immunol ; 178(1): 79-85, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24894428

RESUMEN

There is a limited understanding how of lung cancer cells evade cytotoxic attack. Previously, we have shown reduced production of the cytotoxic mediator granzyme B by CD8(+) T cells in lung cancer tissue. We hypothesized that lung cancer would be further associated with decreased production of granzyme B, perforin and proinflammatory cytokines by other cytotoxic lymphocytes, natural killer (NK) T-like and NK cells, and that this would result from soluble mediators released by the cancer cells. Lung cancer and non-cancer tissue from five patients was identified by experienced pathologists. Tumour necrosis factor (TNF)-α, interferon (IFN)-γ, granzyme B and perforin were measured in CD4 and CD8(+) T, NK T-like cells and NK cells by flow cytometry. Correlation between cancer stage and granzyme B was analysed retrospectively for 21 patients. The effects of soluble factors released by lung cancer cells on production of cytotoxic mediators and cytokines was assessed, and the role of prostaglandin E2 (PGE)2 /COX investigated using indomethacin inhibition. There were significantly decreased percentages of T, NK T-like and NK cells expressing perforin, TNF-α and IFN-γ in cancer versus non-cancer tissue, and of CD8(+) T cells and CD8(+) NK T-like cells expressing granzyme B (e.g. NK T-like cells: non-cancer 30% ± 7 versus cancer 6% ± 2·5). Cancer cells released soluble factors that inhibited granzyme B, perforin and IFN-γ production that was partially associated with the PGE2 /COX2 pathway. Thus, lung cancer is associated with decreased expression of granzyme B, perforin and IFN-γ by infiltrating T cells, NK T-like and NK cells, possibly as a result of soluble factors produced by the cancer cells including PGE2 . This may be an important immune evasion mechanism.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Granzimas/biosíntesis , Interferón gamma/metabolismo , Células Asesinas Naturales/metabolismo , Neoplasias Pulmonares/metabolismo , Perforina/biosíntesis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Dinoprostona/metabolismo , Femenino , Granzimas/inmunología , Granzimas/metabolismo , Humanos , Interferón gamma/inmunología , Células Asesinas Naturales/inmunología , Pulmón/metabolismo , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Perforina/inmunología , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
18.
Clin Exp Allergy ; 44(9): 1137-45, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24849076

RESUMEN

BACKGROUND: In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice. OBJECTIVE: To investigate whether white blood cell counts and/or their derived ratios can predict sputum eosinophils or neutrophils in uncontrolled asthma. METHODS: This cross-sectional study evaluated 164 treated but uncontrolled asthmatic patients with sputum induction and blood collection. Receiver-operating characteristic (ROC) curves were used to assess the relationship between blood and sputum parameters. RESULTS: There was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophil count. A weak but significant correlation was found between sputum neutrophil percentage and blood neutrophil percentage (r = 0.219, P = 0.005). ROC curve analysis identified that blood eosinophil percentage count was the best predictor for eosinophilic asthma, with an area under the curve (AUC) of 0.907 (P < 0.001). The optimum cut-point for blood eosinophil percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity of 75.8%. The absolute blood eosinophil count was also highly predictive with an AUC of 0.898 (P < 0.0001) at a blood eosinophil cut-off of 0.26 × 10(9) /L. The blood eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) were increased in eosinophilic asthma, and the neutrophil/lymphocyte ratio (NLR) was increased in neutrophilic asthma. Neutrophilic asthma could also be detected by blood neutrophil percentages and NLR, but with less accuracy. CONCLUSIONS AND CLINICAL RELEVANCE: Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.


Asunto(s)
Asma/sangre , Asma/diagnóstico , Recuento de Leucocitos , Fenotipo , Adolescente , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Anciano , Asma/tratamiento farmacológico , Estudios Transversales , Eosinófilos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos , Curva ROC , Pruebas de Función Respiratoria , Factores de Riesgo , Esputo/citología , Adulto Joven
19.
Environ Res ; 133: 388-95, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24948546

RESUMEN

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.


Asunto(s)
Polvo/análisis , Hidrocarburos Policíclicos Aromáticos/envenenamiento , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , California/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Vivienda , Humanos , Lactante , Masculino , Hidrocarburos Policíclicos Aromáticos/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología
20.
Int Psychogeriatr ; 26(4): 693-702, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24429062

RESUMEN

BACKGROUND: Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings. METHODS: A multi-site database, including motor symptom assessments conducted in 487 patients from palliative care, adult and old age consultation-liaison psychiatry services was used to document motor activity disturbances as per the Delirium Motor Checklist (DMC). Latent class analysis (LCA) was used to identify the class structure underpinning DMC data and also items for a brief subtyping scale. The concordance of the abbreviated scale was then compared with the original Delirium Motor Subtype Scale (DMSS) in 375 patients having delirium as per the American Psychiatric Association's Diagnostic and Statistical Manual (4th edition) criteria. RESULTS: Latent class analysis identified four classes that corresponded closely with the four recognized motor subtypes of delirium. Further, LCA of items (n = 15) that loaded >60% to the model identified four features that reliably identified the classes/subtypes, and these were combined as a brief motor subtyping scale (DMSS-4). There was good concordance for subtype attribution between the original DMSS and the DMSS-4 (κ = 0.63). CONCLUSIONS: The DMSS-4 allows for rapid assessment of clinical subtypes in delirium and has high concordance with the longer and well-validated DMSS. More consistent clinical subtyping in delirium can facilitate better delirium management and more focused research effort.


Asunto(s)
Delirio/clasificación , Actividad Motora , Trastornos Psicomotores/diagnóstico , Anciano , Delirio/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Trastornos Psicomotores/psicología , Curva ROC , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
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