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1.
J Am Pharm Assoc (2003) ; 63(4S): S43-S47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36424294

RESUMO

BACKGROUND: Adolescents should receive timely doses of recommended vaccinations. The coronavirus disease 2019 (COVID-19) vaccination approval for adolescents presented an opportunity for community pharmacists to address gaps in adolescent immunization schedules. OBJECTIVES: The objectives of this research were to (1) identify adolescent immunization gaps, (2) identify number of patients receiving recommended vaccination(s) at the community pharmacy, and (3) determine how many vaccinations were administered after the intervention. METHODS: Three pharmacies conducted the prospective intervention. Adolescents aged 11-17 years initiating the Pfizer-BioNTech COVID-19 vaccination series were eligible to receive a personalized vaccination recommendation (PVR), which included up to 3 other vaccinations. State immunization information systems were assessed after dose 1 of the COVID-19 vaccine to create the recommendation(s) and reassessed 6 months after providing the PVR for accepted recommendations. Patient demographics and number of vaccinations administered were assessed using descriptive statistics. RESULTS: Of the 225 adolescents who received COVID-19 vaccine dose 1, 74.7%, 75.1%, and 83.1% were indicated to receive tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate (MenACWY), or human papillomavirus (HPV) vaccine, respectively. Thirty-three (14.7%) adolescents were up to date on all 3 vaccinations assessed. Of the 225 adolescents, 180 returned to the same location for COVID-19 vaccine dose 2 and received a PVR. Forty-two caregivers reported that their adolescent previously received 1 or more of the recommended vaccinations, indicating that state immunization information systems were inaccurate. Six months after the PVRs were given, 24 vaccinations had been administered. CONCLUSIONS: Most adolescents presenting for a COVID-19 vaccine were indicated, according to state immunization information systems, to receive at least 1 additional vaccination. After pharmacist-provided PVR and education, vaccine uptake occurred. Considering caregiver-reported inaccuracies, pharmacists should be cognizant of potential discrepancies when providing PVRs. In addition, this study highlights the value of a state immunization information system.

2.
J Vasc Surg ; 76(4): 951-959.e2, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688351

RESUMO

OBJECTIVE: To report the 1-year clinical outcomes from the GORE EXCLUDER Conformable AAA Endoprosthesis system in the US regulatory trial. METHODS: The study is a prospective, multicenter, investigational device exemption clinical trial at 31 US sites with core laboratory assessment of imaging and independent event adjudication. The primary safety (incidence of major adverse events at 30 days) and effectiveness end points (successful aneurysm treatment at 1 year) were assessed in a cohort of patients with abdominal aortic aneurysms (AAAs). RESULTS: We enrolled 80 patients between December 19, 2017, and February, 27, 2019. The mean maximum aortic diameter was 57.7 ± 7.95 mm (range, 42.5-82.7 mm) with an average patient age of 73.5 ± 8.14 years (range, 56-96 years). Overall technical success was 100% (80/80). The mean hospital length stay was 1.2 ± 0.6 days (range, 1-4 days). No primary safety end point events were observed, including no death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, procedural blood loss of more than 1000 mL, or thromboembolic events including limb occlusion or distal emboli. There were no type I or III endoleaks detected on the 1-, 6-, or 12-month follow-up computed tomography scans. There were no stent fractures, device migrations (≥10 mm), AAA ruptures, or conversions to open surgical repair observed. Two patients had AAA sac growth of more than 5 mm at 1 year owing to type II endoleaks. There were no aneurysm-related deaths within the 12-month follow-up, and freedom from aneurysm-related mortality was 100% through 1 year. CONCLUSIONS: The safety and effectiveness of the GORE EXCLUDER Conformable AAA Endoprosthesis system has been demonstrated with 98.5% freedom from primary effectiveness end point events at 1 year and 100% freedom from primary safety end point events assessed through 30 days.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular/efeitos adversos , Endoleak/etiologia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Desenho de Prótese , Stents/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
3.
J Sport Rehabil ; 31(2): 230-234, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438363

RESUMO

Clinical Scenario: Due to the Female Athlete Triad (Triad) being a 3-pronged syndrome, treatments can vary depending on the symptoms that clinicians focus on. With reproductive and bone health compromised, assessment and recovery methods include monitoring menstrual regularity and dual-energy X-ray absorptiometry scans. Low levels of estrogen have demonstrated negative effects on bone mineral density (BMD). Clinical Question: Does supplemental estrogen improve BMD in athletes with Female Athlete Triad symptoms? Summary of Key Findings: Supplemental estrogen does improve BMD with estrogen patches demonstrating increased improvement compared with oral contraceptive pills. Clinical Bottom Line: Restoration of regular menstruation, improvement of BMD, and ensuring optimal energy levels is the best approach for treating Triad symptoms. Transdermal patches are a new treatment option that address both menstrual function and BMD but still require further research. Strength of Recommendation: Available studies demonstrated a level 2 evidence for supplemental estrogen (oral contraceptive pills and estrogen patches) providing improvements for bone health related to the Triad.


Assuntos
Síndrome da Tríade da Mulher Atleta , Absorciometria de Fóton , Amenorreia , Atletas , Densidade Óssea , Estrogênios/uso terapêutico , Feminino , Síndrome da Tríade da Mulher Atleta/tratamento farmacológico , Humanos
4.
J Vasc Surg Cases Innov Tech ; 5(3): 319-322, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31334409

RESUMO

Endovascular repair has become the standard of care for treatment of abdominal aortic aneurysms. The endografts and delivery systems for endovascular aneurysm repair have undergone multiple generations of technologic advancements. However, a significant remaining challenge for a satisfactory long-term outcome is to improve the performance of these devices in nonideal proximal sealing zones. In particular, short (<15 mm) and highly angulated (>60 degrees) necks can threaten long-term exclusion of the aneurysm even with the current generation of endografts. One of the main reasons for proximal infrarenal neck failure is the inability to accurately position the endograft precisely below both renal arteries. This is a report of the first-in-human implantations of the GORE EXCLUDER Conformable AAA Endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz), an investigational device, in anatomies with standard neck lengths and angulation. This device has been designed to provide repositionability, conformability, and, for the first time, optional angulation control. This device is commercially available in Europe.

5.
AIDS Behav ; 23(1): 76-90, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30121728

RESUMO

The updated National HIV/AIDS Strategy recommends widespread HIV education and testing and calls the faith community to assist in these efforts. Yet, limited information exist on church-based HIV testing interventions. This study examined feasibility and assessed HIV testing outcomes of Taking It to the Pews (TIPS), a multilevel HIV education and testing intervention. Four African American churches were matched and randomized to TIPS or a standard-information control arm. Intervention churches delivered the religiously-tailored TIPS Tool Kit, which included educational materials to individuals and ministry groups; pastoral activities (e.g., sermons preached, receipt of HIV testing role-modeled), responsive readings, and church bulletin inserts in church services; and HIV testing during church services and church outreach events. All churches delivered 2-3 tools/month and coordinated 3 HIV testing events. At 12 months, significant increases in receipt of HIV testing (59% vs. 42%, p = 0.008), and particularly church-based testing (54% vs. 15%, p < 0.001), relative to controls were found. TIPS has great potential to increase reach, feasibility, and impact of HIV testing in African American churches.


Assuntos
Negro ou Afro-Americano , Relações Comunidade-Instituição , Infecções por HIV/diagnóstico , Promoção da Saúde , Programas de Rastreamento/métodos , Religião , Adolescente , Adulto , Atitude Frente a Saúde , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Religiosos , Testes Sorológicos , Estigma Social , Adulto Jovem
6.
PLoS One ; 12(5): e0177140, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28481943

RESUMO

It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1*01:01 and DRB1*04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.


Assuntos
Citrulina/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Peptídeos/metabolismo , Alelos , Epitopos/metabolismo , Humanos , Ligação Proteica
7.
JMIR Res Protoc ; 6(4): e71, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28455274

RESUMO

BACKGROUND: Pediatric chronic illness care models are traditionally organized around acute episodes of care and may not meet the needs of patients and their families. Interventions that extend the patient-clinician interaction beyond the health care visit, allow for asynchronous and bidirectional feedback loops that span visits and daily life, and facilitate seamless sharing of information are needed to support a care delivery system that is more collaborative, continuous, and data-driven. Orchestra is a mobile health technology platform and intervention designed to transform the management of chronic diseases by optimizing patient-clinician coproduction of care. OBJECTIVE: The aim of this study is to assess the feasibility, acceptability, and preliminary impact of the Orchestra technology and intervention in the context of pediatric chronic illness care. METHODS: This study will be conducted in the cystic fibrosis and inflammatory bowel disease clinics at Cincinnati Children's Hospital Medical Center. We will enroll interested patients and their caregivers to work with clinicians to use the Orchestra technology platform and care model over a 6-month period. In parallel, we will use quality improvement methods to improve processes for integrating Orchestra into clinic workflows and patient/family lifestyles. We will use surveys, interviews, technology use data, and measures of clinical outcomes to assess the feasibility, acceptability, and preliminary impact of Orchestra. Outcome measures will include assessments of: (1) enrollment and dropout rates; (2) duration of engagement/sustained use; (3) symptom and patient-reported outcome tracker completion rates; (4) perceived impact on treatment plan, communication with the clinical team, visit preparation, and overall care; (5) changes in disease self-efficacy and engagement in care; and (6) clinical outcomes and health care utilization. RESULTS: Participant recruitment began in mid-2015, with results expected in 2017. CONCLUSIONS: Chronic disease management needs a dramatic transformation to support more collaborative, effective, and patient-centered care. This study is unique in that it is testing not only the impact of technology, but also the necessary processes that facilitate patient and clinician collaboration. This pilot study is designed to examine how technology-enabled coproduction can be implemented in real-life clinical contexts. Once the Orchestra technology and intervention are optimized to ensure feasibility and acceptability, future studies can test the effectiveness of this approach to improve patient outcomes and health care value.

8.
J Relig Health ; 55(5): 1786-99, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27272330

RESUMO

This study sought to identify characteristics, including religiosity, related to having received health screenings among persons who attend African-American churches or receive church-based community outreach services. A sample of 602 was recruited during two phases as part of a larger project. Blood pressure, cholesterol, and blood glucose screenings were the most frequently reported screenings ever and in the last 12 months. Although religiosity was significantly related to several of the health screenings in bivariate analysis, it is not a predictor of health screenings in multivariate analyses. Innovative strategies are needed to promote screenings such as church-based health fairs.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Promoção da Saúde/métodos , Programas de Rastreamento/estatística & dados numéricos , Religião e Medicina , Características de Residência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Promoção da Saúde/estatística & dados numéricos , Humanos , Kansas , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
9.
J Int AIDS Soc ; 16(3 Suppl 2): 18644, 2013 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-24242259

RESUMO

INTRODUCTION: The African American church is a highly influential institution with the potential to greatly increase the reach of HIV prevention interventions and address HIV-related stigma in US African American communities. However, there are few studies on HIV-related stigma and African American church populations. This study explored HIV-related stigma among church and community members participating in an HIV education and testing intervention pilot study in African American churches, named Taking It to the Pews. METHODS: Four African American churches located in Kansas City, MO and KS, were randomized to either intervention or comparison groups. Churches assigned to the intervention group received religiously tailored HIV education, testing and compassion messages/activities (e.g. sermons, brochures/church bulletins, testimonials) via the Taking It to the Pews HIV Tool Kit. Comparison churches received non-religiously tailored HIV information. HIV-related stigma was assessed with 543 church members and with community members served through church outreach services (e.g. food/clothing pantries, social services) in the four churches. Participants completed surveys at baseline, 6 months and 12 months to assess their HIV-related stigma beliefs, exposure to intervention components and satisfaction with the study. RESULTS: At baseline, HIV-related stigma beliefs were similar across experimental groups and were quite low. Mean HIV-related stigma scores were not significantly different between experimental groups at 6 months (p=0.92) or at 12 months (p=0.70). However, mean HIV-related stigma scores within both groups showed decreasing trends at six months, which approached significance. Analysis of previously studied HIV-related stigma factors (e.g. age, gender, income, HIV knowledge, religiosity) did not yield changes in the null findings. Intervention group participants were highly exposed to several intervention components (sermons, HIV resource tables, posters, brochures/church bulletins). Overall, participants were highly satisfied with the intervention pilot study. CONCLUSIONS: African American churches may be well positioned to increase the reach of HIV prevention interventions to church and community members and could serve an important role in addressing HIV-related stigma in their church communities. Future research is needed on measuring HIV-related stigma beliefs and on testing intensive, scalable, religiously tailored HIV interventions to impact HIV-related stigma in African American churches.


Assuntos
Discriminação Psicológica/fisiologia , Infecções por HIV/psicologia , Educação em Saúde/métodos , Estigma Social , Adolescente , Adulto , Negro ou Afro-Americano , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Religião , Estados Unidos , Adulto Jovem
10.
J Urban Health ; 90(3): 482-99, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22815053

RESUMO

Increasingly, African American churches have been called upon to assist in efforts to address HIV/AIDS in underserved communities. African Americans churches may be well-positioned to provide HIV education, screening, and support services, particularly if they are equipped with church-appropriate, easy-to-deliver HIV tools that can be implemented through the naturalistic church environment. To inform the development of a church-based HIV tool kit, we examined church capacity with African American church leaders (N = 124 participants; n = 58 churches represented by senior pastors). Nearly all participants (96%) wanted to learn more about HIV and how to discuss it with their parishioners. Regarding church capacity, most of their representative churches held three regular services each week, facilitated various inreach and community outreach ministries, and had paid staff and computers. Also, many of their churches facilitated HIV/AIDS education/prevention and adolescent sex education activities. Guided by church capacity findings, an ecological framework, and a CBPR approach, we describe the resulting church-based HIV Tool Kit that "fits" naturalistically within a multilevel church infrastructure, builds upon churches' HIV-related experience, and equips faith leaders to efficiently promote HIV services with the communities they serve.


Assuntos
Negro ou Afro-Americano , Relações Comunidade-Instituição , Infecções por HIV/prevenção & controle , Promoção da Saúde/métodos , Protestantismo , Adolescente , Adulto , Idoso , Clero , Feminino , Educação em Saúde , Humanos , Disseminação de Informação/métodos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
11.
Cancer Chemother Pharmacol ; 68(5): 1331-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21461889

RESUMO

PURPOSE: Paclitaxel is an effective therapy for patients with solid tumors. While the albumin-bound formulation eliminates the hypersensitivity reaction caused by the Cremaphor solvent, significant peripheral neuropathy persists when given over the standard 30-min infusion time. We sought to determine if the incidence and severity of peripheral neuropathy could be reduced when the infusion time is lengthened to 2-h. METHODS: This was an open-label, single-arm, phase 2 study of albumin-bound paclitaxel given over 2 h. Twenty-five patients with advanced non-small-cell lung cancer were enrolled to determine whether the longer infusion reduced the severity of neuropathy compared to data from an earlier cohort of 40 similar patients treated over 30 min Patients received 125 mg/m(2) of albumin-bound paclitaxel IV over 2 h without premedication on days 1, 8, and 15 of a 28-day cycle. Radiologic assessment was performed every 8 weeks. RESULTS: There was a significant 0.45 grade decrease in average peripheral neuropathy experienced by patients in the 2-h group versus the 30-min group (90% CI, 0.03-0.87). There was, in addition, a significant decrease in grade ≥2 peripheral neuropathy in patients treated over 2 h versus 30 min (28% vs. 55%, 2-sided P = 0.04). A decrease in grade ≥2 neutropenia (20% vs. 48%, 2-sided P = 0.07) was also observed. The median survival, 11 months, was the same for both groups. CONCLUSION: Increasing the infusion time of albumin-bound paclitaxel from 30 min to 2 h resulted in a significant reduction in both average and grade ≥2 peripheral neuropathy without affecting survival.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Paclitaxel Ligado a Albumina , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Análise de Sobrevida
12.
Chem Biol ; 17(11): 1177-82, 2010 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-21095567

RESUMO

To identify new protein and pharmacological regulators of Wnt/ß-catenin signaling, we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the ß-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance ß-catenin signaling. The unexpected regulation of ß-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug.


Assuntos
Antineoplásicos/uso terapêutico , Melanoma Experimental/metabolismo , Riluzol/uso terapêutico , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Proliferação de Células , Regulação da Expressão Gênica , Genes Reporter , Melanoma Experimental/tratamento farmacológico , Camundongos , Interferência de RNA , RNA Interferente Pequeno , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais , Pigmentação da Pele , Proteína Wnt3 , Proteína Wnt3A
13.
AIDS Educ Prev ; 22(3): 218-37, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20528130

RESUMO

Utilizing a community-based participatory research (CBPR) approach is a potentially effective strategy for exploring the development, implementation, and evaluation of HIV interventions in African American churches. This CBPR-guided study describes a church-based HIV awareness and screening intervention (Taking It to the Pews [TIPS]) that fully involved African American church leaders in all phases of the research project. Findings from the implementation and evaluation phases indicated that church leaders delivered TIPS Tool Kit activities on an ongoing basis (about twice a month) over a 9-month period. TIPS church members were highly exposed to TIPS activities (e.g., 91% reported receiving HIV educational brochures, 84% heard a sermon about HIV). Most (87%) believed that the church should talk about HIV, and 77% believed that the church should offer HIV screening. These findings suggest that implementing an HIV intervention in Black church settings is achievable, particularly when a CBPR approach is used.


Assuntos
Negro ou Afro-Americano , Pesquisa Participativa Baseada na Comunidade , Infecções por HIV/diagnóstico , Infecções por HIV/etnologia , Programas de Rastreamento/métodos , Religião , Adulto , Feminino , Grupos Focais , Humanos , Kansas , Masculino , Missouri , Educação de Pacientes como Assunto
14.
Vascular ; 17(6): 355-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19909684

RESUMO

Iatrogenic venous pseudoaneurysm following venipuncture is an extremely rare complication of a very common medical procedure. A review of the vascular surgical literature revealed that only two cases of venous pseudoaneurysm secondary to venipuncture have been reported in the past half-century. We report the case of a 64-year-old anticoagulated male with a 7-month history of right arm swelling after venipuncture. The patient, on warfarin therapy for chronic atrial fibrillation, described progressive swelling at a previous venipuncture site. He eventually underwent limited two-dimensional ultrasonography, performed for a suspected hematoma, revealing a 4.3 x 3.3 x 2.0 cm pseudoaneurysm of the right basilic vein. These findings were later confirmed by a formal venous duplex sonogram. Similar to other forms of aneurysm and focal vascular dilation, the risks of venous psuedoaneurysm include embolism, thrombosis, and the compression of adjacent structures. Although both thrombin injection and coil embolization have been described as nonsurgical treatment options for arterial pseudoaneurysms, surgical resection may be the most appropriate approach for those with a venous equivalent. The segment of basilic vein containing the pseudoaneurysm was resected. This case demonstrates the need for physicians to consider venous pseudoaneurysm as a possible complication of venipuncture in individuals undergoing anticoagulation therapy.


Assuntos
Falso Aneurisma/etiologia , Anticoagulantes/efeitos adversos , Doença Iatrogênica , Flebotomia/efeitos adversos , Extremidade Superior/irrigação sanguínea , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Procedimentos Cirúrgicos Vasculares
15.
Proc Natl Acad Sci U S A ; 106(4): 1193-8, 2009 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-19144919

RESUMO

This study demonstrates that in malignant melanoma, elevated levels of nuclear beta-catenin in both primary tumors and metastases correlate with reduced expression of a marker of proliferation and with improved survival, in contrast to colorectal cancer. The reduction in proliferation observed in vivo is recapitulated in B16 murine melanoma cells and in human melanoma cell lines cultured in vitro with either WNT3A or small-molecule activators of beta-catenin signaling. Consistent with these results, B16 melanoma cells expressing WNT3A also exhibit decreased tumor size and decreased metastasis when implanted into mice. Genome-wide transcriptional profiling reveals that WNT3A up-regulates genes implicated in melanocyte differentiation, several of which are down-regulated with melanoma progression. These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/beta-catenin signaling in normal melanocyte development, thereby altering melanoma cell fate to one that may be less proliferative and potentially less aggressive. Our results may explain the observed loss of nuclear beta-catenin with melanoma progression in human tumors, which could reflect a dysregulation of cellular differentiation through a loss of homeostatic Wnt/beta-catenin signaling.


Assuntos
Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Linhagem da Célula , Núcleo Celular/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Humanos , Melanócitos/metabolismo , Melanócitos/patologia , Camundongos , Análise de Sobrevida , Regulação para Cima , Proteína Wnt3 , Proteína Wnt3A
17.
Clin Cancer Res ; 13(17): 5150-5, 2007 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-17785570

RESUMO

PURPOSE: Ten percent of U.S. patients with non-small cell lung cancer experience partial radiographic responses to erlotinib or gefitinib. Despite initial regressions, these patients develop acquired resistance to erlotinib or gefitinib. In these patients, we sought to assess changes in tumor metabolism and size after stopping and restarting erlotinib or gefitinib and to determine the effect of adding everolimus. EXPERIMENTAL DESIGN: Patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib were eligible. Patients had 18-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography and computed tomography scans at baseline, 3 weeks after stopping erlotinib or gefitinib, and 3 weeks after restarting erlotinib or gefitinib. Three weeks after restarting erlotinib or gefitinib, everolimus was added to treatment. RESULTS: Ten patients completed all four planned studies. Three weeks after stopping erlotinib or gefitinib, there was a median 18% increase in SUV(max) and 9% increase in tumor diameter. Three weeks after restarting erlotinib or gefitinib, there was a median 4% decrease in SUV(max) and 1% decrease in tumor diameter. No partial responses (0 of 10; 95% confidence interval, 0-31%) were seen with the addition of everolimus to erlotinib or gefitinib. CONCLUSIONS: In patients who develop acquired resistance, stopping erlotinib or gefitinib results in symptomatic progression, increase in SUV(max), and increase in tumor size. Symptoms improve and SUV(max) decreases after restarting erlotinib or gefitinib, suggesting that some tumor cells remain sensitive to epidermal growth factor receptor blockade. No responses were observed with combined everolimus and erlotinib or gefitinib. We recommend a randomized trial to assess the value of continuing erlotinib or gefitinib after development of acquired resistance.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Sirolimo/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Resistencia a Medicamentos Antineoplásicos , Cloridrato de Erlotinib , Everolimo , Feminino , Fluordesoxiglucose F18 , Gefitinibe , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Sirolimo/administração & dosagem , Tomografia Computadorizada por Raios X
18.
J Thorac Oncol ; 2(7): 638-44, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17607120

RESUMO

INTRODUCTION: We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer. METHODS: The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data. The first cohort was treated with docetaxel 35 mg/m2 intravenously (IV) on days 1, 8, and 15, and cisplatin 80 mg/m2 IV on day 15, every 4 weeks for four planned cycles. A second cohort was treated with docetaxel 75 mg/m2 IV plus cisplatin 80 mg/m2 IV on day 1 every 3 weeks for four planned cycles. RESULTS: Sixteen patients were treated with weekly docetaxel and cisplatin every 4 weeks, with five of 16 (31%) unable to complete three cycles. Subsequently, 11 patients were treated with docetaxel and cisplatin every 3 weeks, with six of 11 (55%) unable to complete three cycles. Among the 11 patients who failed to complete three cycles, the reasons for stopping included one or more of the following: fatigue (n = 8), nausea (n = 4), febrile neutropenia (n = 1), hypotension (n = 1), and nephrotoxicity (n = 1). CONCLUSIONS: The combination of cisplatin at 80 mg/m2 with docetaxel 35 mg/m2 weekly or 75 mg/m2 every 3 weeks is no better tolerated than older chemotherapy regimens. The most common reason to stop chemotherapy was intolerable fatigue. These results suggest that the most common dose-limiting toxicities are attributable to the cisplatin, given similar problems were encountered whether the docetaxel was delivered as a single dose every 3 weeks or as a lower weekly dose.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , New York/epidemiologia , Radiossensibilizantes , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
19.
Mil Med ; 172(6): 628-33, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17615846

RESUMO

OBJECTIVE: The purpose of this study was to determine the effects of dichloroacetate (DCA) in acute limb ischemia. METHODS: Anterior tibialis muscle samples of DCA-treated and control animals (Sprague Dawley rats) were collected and assayed for pyruvate dehydrogenase activity, lactate, adenosine triphosphate, and creatine phosphate using spectrophotometry. A physiograph was used to measure fatigability. In an ischemia/reperfusion model using New Zealand rabbits, serum lactate and end-tidal CO2 were compared. Skeletal muscle was evaluated microscopically for muscle necrosis. RESULTS: DCA administration resulted in a 50% increase in pyruvate dehydrogenase activity (p = 0.025), reversal of the increase in lactate levels seen during acute limb ischemia (p = 0.41), a significant increase in the time to skeletal muscle fatigue (p = 0.05), a trend toward increased adenosine triphosphate (p = 0.07), and a significant increase in creatine phosphate (p < 0.02). DCA treatment resulted in a decrease in serum lactate (p < 0.01) and end-tidal CO2 (p < 0.001). CONCLUSION: In acute limb ischemia and reperfusion, DCA administration provides metabolic protection to skeletal muscle.


Assuntos
Síndrome do Compartimento Anterior/tratamento farmacológico , Ácido Dicloroacético/uso terapêutico , Isquemia/tratamento farmacológico , Doença Aguda , Trifosfato de Adenosina , Animais , Síndrome do Compartimento Anterior/complicações , Isquemia/complicações , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Necrose , Resistência Física , Ratos , Ratos Sprague-Dawley , Reperfusão
20.
Dermatol Online J ; 13(3): 9, 2007 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-18328203

RESUMO

Keloid formation occurs as a result of abnormal wound healing. Despite the high prevalence of keloids in the general population, they remain one of the more challenging dermatologic conditions to manage. More than a cosmetic nuisance, they are often symptomatic and can have a significant psychosocial burden for the patient. Although multiple treatment modalities exist, no single treatment has proven widely effective. In fact, recurrence following treatment is generally the norm. Combination therapy is likely the optimal strategy. In this review, we highlight the clinical features, pathophysiology and management of keloids.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Crioterapia/métodos , Glucocorticoides/administração & dosagem , Queloide , Terapia com Luz de Baixa Intensidade/métodos , Géis de Silicone/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Administração Tópica , Animais , Apoptose , Bandagens , Colágeno/biossíntese , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Injeções Intralesionais , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Queloide/etiologia , Queloide/patologia , Queloide/terapia , Radioterapia Adjuvante/métodos , Fatores de Risco , Resultado do Tratamento , Ferimentos e Lesões/complicações
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