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1.
J Invest Dermatol ; 138(7): 1539-1545, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29452121

RESUMO

Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Adulto , Alopecia em Áreas/diagnóstico por imagem , Alopecia em Áreas/imunologia , Alopecia em Áreas/patologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biópsia , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/patologia , Humanos , Inibidores de Janus Quinases/farmacologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/imunologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Fotografação , Projetos Piloto , Piperidinas/farmacologia , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas/farmacologia , Pirróis/farmacologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
2.
Phytopathology ; 88(7): 621-36, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18944934

RESUMO

ABSTRACT Citrus tristeza virus (CTV) was monitored for 4 years by monoclonal antibody probes via enzyme-linked immunosorbent assay in four citrus orchards in northern Costa Rica and four orchards in the Dominican Republic following the introduction of the brown citrus aphid, Toxoptera citricida. The Gompertz nonlinear model was selected as the most appropriate in most cases to describe temporal increase of CTV. Ordinary runs analysis for association of CTV-positive trees failed to show a spatial relationship of virus status among immediately adjacent trees within or across rows. The beta-binomial index of dispersion for various quadrat sizes suggested aggregations of CTV-positive trees for all plots within the quadrat sizes tested. Spatial autocorrelation analysis of proximity patterns suggested that aggregation often existed among quadrats of various sizes up to four lag distances; however, significant lag positions discontinuous from the main proximity pattern were rare. Some asymmetry was also detected for some spatial autocorrelation proximity patterns. These results were interpreted to mean that, although CTV-positive trees did not often influence immediately adjacent trees, virus transmission was common within a local area of influence that extended two to eight trees in all directions. Where asymmetry was indicated, this area of influence was somewhat elliptical. The spatial and temporal analyses gave some insight into possible underlying processes of CTV spread in the presence of T. citricida and suggested CTV spread was predominantly to trees within a local area. Patterns of longer-distance spread were not detected within the confines of the plot sizes tested. Longer-distance spread probably exists, but may well be of a complexity beyond the detection ability of the spatial analysis methods employed, or perhaps is on a scale larger than the dimensions of the plots studied.

3.
J Nematol ; 22(4S): 707-11, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19287784

RESUMO

Field experiments were conducted to evaluate the efficacy of five nematicides for the management of Rotylenchulus reniformis and for their effects on growth, development, and yield of cotton. Treatments included 1,3-dichloropropene (1,3-D), fenamiphos, phorate, terbufos, aldicarb, and 1,3-D + aldicarb. Average R. reniformis population densities across all treatments increased from 5,284 at 10 days after planting to a final density at harvest of 15,622 nematodes/500 cm(3) soil. The 1,3-D + aldicarb combination was the only treatment with an average R. reniformis population density significantly (P

4.
Am J Prev Med ; 2(1): 26-9, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3453157

RESUMO

In Arizona, undocumented pregnant Hispanic women without private care have no recourse but to enter an emergency room after labor begins. A survey we conducted showed over 150 such "emergency" births annually in Tucson. As a result, a prenatal care program, "Dar a Luz," specifically targeted at this population, was developed. It includes prenatal obstetrical care and anticipatory birthing education that is sensitive to Mexican-American traditions, community consciousness-raising, and a cooperative obstetrical agreement with Tucson hospitals. Bilingual community volunteers act as patient advocates, following these patients through pregnancy and accompanying them to emergency rooms for hospital deliveries. Based in an Hispanic neighborhood community center, professional and lay volunteers provide health care coordinated by medical students in the paracurricular Commitment to Underserved People Program at the University of Arizona College of Medicine.


Assuntos
Hispânico ou Latino , Cuidado do Lactente/organização & administração , Cuidado Pré-Natal/organização & administração , Fatores Etários , Arizona , Feminino , Idade Gestacional , Humanos , Recém-Nascido , México/etnologia , Gravidez , Fatores Socioeconômicos
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