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1.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35217624

RESUMEN

An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARS-CoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as "covid toes" during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.


Asunto(s)
COVID-19/complicaciones , Eritema Pernio/inmunología , Adulto , COVID-19/epidemiología , Eritema Pernio/epidemiología , Eritema Pernio/virología , Connecticut/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/inmunología , Adulto Joven
2.
Anticancer Drugs ; 21(4): 339-50, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20016367

RESUMEN

Aurora kinases are serine and threonine kinases that function as key regulators of the mitosis process. There are three distinct human aurora kinases known as Aurora A, Aurora B, and Aurora C. Aurora A and Aurora B are overexpressed in a number of human cancers including non-small cell lung cancer, glioblastomas, and upper gastrointestinal adenocarcinomas. Given their association with tumorigenesis, both Aurora A and Aurora B have been targeted for cancer therapy. Currently, a number of selective and nonselective aurora kinase inhibitors are being tested in preclinical and clinical settings as anti-tumor agents. We review the biology of human aurora kinases, followed by an overview of inhibitors undergoing current clinical investigations.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Antineoplásicos/farmacología , Aurora Quinasa B , Aurora Quinasa C , Aurora Quinasas , Benzamidas/farmacología , Benzamidas/uso terapéutico , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Ácidos Ciclohexanocarboxílicos/farmacología , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática , Humanos , Neoplasias/enzimología , Organofosfatos/farmacología , Organofosfatos/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Pirazoles/farmacología , Pirazoles/uso terapéutico , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico , Urea/análogos & derivados , Urea/farmacología , Urea/uso terapéutico
3.
J Am Acad Dermatol ; 57(6): 937-43, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17923170

RESUMEN

BACKGROUND: The current diagnostic criteria for dermatomyositis (DM) exclude patients without muscle involvement. As a result there is a paucity of research related to the complete spectrum of the disease. OBJECTIVE: The goal of this study was to evaluate differences in the clinical manifestations of DM seen by dermatology relative to rheumatology. We hypothesized that patients with minimal (hypomyopathic) or no (amyopathic) muscle disease would more likely be seen in dermatology, whereas those with more severe (classic) muscle disease would be seen in rheumatology. METHODS: We performed a retrospective chart review of patients with DM seen by our dermatology and rheumatology departments to classify spectrum, presentation, and complications. Patients seen between July 1, 2003, and June 30, 2006, were identified by Current Procedural Terminology billing code 710.3. Patients with mixed connective tissue diseases or miscoded DM were excluded. RESULTS: In all, 131 (65%) patients seen in dermatology, 58 (29%) in rheumatology, and 13 (6%) in both departments were identified. In all, 83 (69%) patients seen in dermatology, 27 (23%) in rheumatology, and 10 (8%) in both departments met criteria for inclusion in the study. The number of patients seen in rheumatology given the classification of classic DM (CDM) (24 of 27 [89%]), hypomyopathic DM (2 of 27 [7%]), and amyopathic DM (ADM) (1 of 27 [4%]) differed significantly from dermatology, where CDM comprised 27 of 83 (33%), hypomyopathic DM comprised 23 of 83 (28%), and ADM comprised 33 of 83 (40%) of the population, respectively (P < .001). Sex, ethnicity, and rates of interstitial lung disease differed between departments. There was no difference in the rates of interstitial lung disease between CDM and ADM (P = .30). The degree of muscle involvement did not correlate with the rates of DM-associated malignancy (P = .57). Few patients with ADM had muscle biopsy (n = 1) or electromyography (n = 7) testing. Positive anti-Jo-1 was seen in 2 of 96 patients (2%; one CDM and one ADM, both with interstitial lung disease), reflecting an overall low prevalence of this autoantibody, or a potential problem with the laboratory assay. LIMITATIONS: Patients reflect the population in only one institution and, thus, the results may not be generalizable to other settings or referral centers. Because this is a retrospective chart review, results are limited by missing data and nonstandardized physical examinations and laboratory data across patients and physicians. CONCLUSIONS: There is a clear difference in DM presentation to dermatology and rheumatology by degree of myositis-complicated disease.


Asunto(s)
Dermatomiositis/epidemiología , Adulto , Dermatología , Dermatomiositis/clasificación , Dermatomiositis/diagnóstico , Femenino , Departamentos de Hospitales , Humanos , Masculino , Persona de Mediana Edad , Philadelphia/epidemiología , Estudios Retrospectivos , Reumatología
4.
Am J Clin Oncol ; 36(5): 481-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22706179

RESUMEN

OBJECTIVE: To determine whether clinical response to total skin electron beam (TSEB) and relapse after TSEB differs by ethnicity and sex. METHODS: Retrospective chart review of 77 patients with mycosis fungoides (MF), treated with TSEB in 2002 to 2008 at Yale University School of Medicine, Departments of Dermatology and Therapeutic Radiology. RESULTS: Women had better odds of response to TSEB than men (OR=6.4; 95% CI, 1.45-28.5; P=0.01). No significant difference was observed in response to TSEB between white and black patients (OR=0.69; 95% CI, 0.16-2.91; P=0.62). When stratified by race and sex, in comparison with black females, all other groups had lower odds of complete response (CR) to TSEB: black males (OR=0.39; 95% CI, 0.002-0.70; P=0.03), white females (OR=0.24; 95% CI, 0.02-2.53; P=0.24), and white males (OR=0.06; 95% CI, 0.006-0.60; P=0.02). Clinical CR was significantly predicted by the duration of symptoms (OR=0.98; 95% CI, 0.97-0.99; P=0.01); and nearly significant by clinical stage; stage III to stage I (OR=0.17; 95% CI, 0.02-1.02; P=0.07). Adjuvant treatment, previous treatment, and time from diagnosis to treatment have no significant effect on CR to TSEB. There was no statistically significant association between relapse after treatment and race, sex, clinical stage, or symptom duration. CONCLUSIONS: The odds of achieving a CR to TSEB decrease when diagnosis of MF is delayed and when patients present with advanced-stage disease. Women with MF were more likely to have a CR to treatment, and this response was even more significant in black women.


Asunto(s)
Electrones , Micosis Fungoide/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias Cutáneas/radioterapia , Irradiación Corporal Total , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/etnología , Micosis Fungoide/mortalidad , Recurrencia Local de Neoplasia/etnología , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/mortalidad , Tasa de Supervivencia
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