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1.
Am Fam Physician ; 95(11): 717-724, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28671445

RESUMO

Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%. Although often self-limited and benign, it can cause significant discomfort, continue for months to years, and uncommonly represent a serious systemic disease or life-threatening allergic reaction. Urticaria is caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically; anaphylaxis must be ruled out. Chronic urticaria is idiopathic in 80% to 90% of cases. Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers, if identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses. First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, high-potency antihistamines, and brief corticosteroid bursts may be used as adjunctive treatment. In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year.


Assuntos
Urticária/diagnóstico , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Diagnóstico Diferencial , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Omalizumab/uso terapêutico , Urticária/tratamento farmacológico
2.
Appl Psychophysiol Biofeedback ; 41(3): 301-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26969177

RESUMO

Approximately 10 % of first year medical students have clinically relevant anxiety or depression which may affect academic success and quality of life. This study tested the effects of a stress management intervention on indicators of anxiety, depression and self-efficacy in self-selected first year medical students. Forty two medical students volunteered to participate and provided informed consent. An eight session intervention was offered and focused on building relaxation skills, adaptive coping, and basic nutrition. Anxiety, depression, and self-efficacy were assessed pre and post intervention. This group of students had significantly higher baseline values of depression and anxiety but lower self-efficacy compared to a previous study of medical students at the same institution (p < 0.03). After the intervention, statistically significant improvements were observed in anxiety (p < 0.05), and self-efficacy (p < 0.05), but not in depression. The entering levels of anxiety and depression in this group suggested that these students were at risk for later clinical syndromes. Intervention directed to decreasing the effects of stress was associated with improvement in indicators of distress and may modify the longer term risk.


Assuntos
Adaptação Psicológica , Estresse Psicológico/terapia , Estudantes de Medicina/psicologia , Ansiedade/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Qualidade de Vida , Autoeficácia , Adulto Jovem
3.
Blood ; 121(10): 1814-8, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-23319569

RESUMO

Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to gene expression analyses from 207 children with minimal residual disease, is highly associated with poorest outcome. We tested whether interference with alpha4-mediated stromal adhesion might be a new ALL treatment. Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210(+)] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL). Conditional deletion of alpha4 sensitized leukemia cell to nilotinib. Adhesion of primary pre-B ALL cells was alpha4-dependent; alpha4 blockade sensitized primary ALL cells toward chemotherapy. Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/fisiologia , Integrina alfa4/química , Neoplasia Residual/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Medula Óssea/patologia , Adesão Celular , Criança , Citometria de Fluxo , Humanos , Integrases/metabolismo , Integrina alfa4/genética , Integrina alfa4/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Natalizumab , Neoplasia Residual/metabolismo , Neoplasia Residual/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
4.
J Chem Ecol ; 41(8): 732-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26271674

RESUMO

Xenos peckii is a strepsipteran parasitoid of the common North American paper wasp, Polistes fuscatus. Mate-seeking X. peckii males respond to a long-range sex pheromone emitted by the female, which remains permanently embedded within the abdomen of a mobile host wasp. During peak pheromone signalling, we excised the female from her host, severed the cephalothorax containing the pheromone gland, extracted it in hexane, and analyzed aliquots of combined extracts by coupled gas chromatographic-electroantennographic detection (GC-EAD). These analyses revealed a candidate pheromone component (CPC) that consistently elicited strong responses from male antennae. We identified the CPC as (7E,11E)-3,5,9,11-tetramethyltridecadienal based on its retention indices (RI) on three GC-columns, RI inter-column differentials, mass and NMR spectra, and synthesis of an authentic standard that matched the GC-retention and spectrometric characteristics of the CPC. For a field experiment, we prepared (7E,11E)-3,5,9R,11-tetramethyltridecadienal and (7E,11E)-3,5,9S,11-tetramethyltridecadienal. Xenos peckii males were caught in traps baited with either compound singly or a 1:1 mixture of the two but not in unbaited control traps. The sex pheromone of X. peckii resembles that reported for the strepsipterans Stylops mellittae and S. muelleri, (R,R,R)-3,5,9-trimethyldodecanal, suggesting a common biosynthetic pathway across taxonomic genera.


Assuntos
Antenas de Artrópodes/fisiologia , Insetos/metabolismo , Atrativos Sexuais/metabolismo , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino
5.
Med Clin North Am ; 108(4): 687-702, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38816111

RESUMO

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.


Assuntos
Angioedema , Urticária , Humanos , Angioedema/diagnóstico , Angioedema/etiologia , Urticária/diagnóstico , Urticária/etiologia , Urticária/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Diagnóstico Diferencial
6.
Blood ; 118(8): 2191-9, 2011 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-21715311

RESUMO

Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patient-derived ALL can eradicate leukemia. Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy eliminated drug-resistant ALL cells. These findings show the importance of survivin expression in drug resistance and demonstrate that survivin inhibition may represent a powerful approach to overcoming drug resistance and preventing relapse in patients with ALL.


Assuntos
Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animais , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Marcação de Genes , Humanos , Proteínas Inibidoras de Apoptose/deficiência , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Neoplasia Residual , Oligonucleotídeos/genética , Oligonucleotídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Survivina , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Prim Care ; 50(2): 237-252, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37105604

RESUMO

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.


Assuntos
Angioedema , Urticária , Humanos , Urticária/diagnóstico , Urticária/tratamento farmacológico , Urticária/etiologia , Angioedema/diagnóstico , Angioedema/tratamento farmacológico , Histamina/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Doença Crônica
8.
J Chem Ecol ; 38(3): 253-61, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22392084

RESUMO

Males of the parasitoid wasp Pimpla disparis Viereck (Hymenoptera: Ichneumonidae) aggregate on parasitized gypsy moth, Lymantria dispar, host pupae when the emergence of a prospective mate is imminent or under way. We tested the hypotheses that the developing parasitoid ("DePa") inside the host pupal case produces a pheromone that attracts and arrests mate-seeking males, and that the pheromone is most effective during the emergence of the parasitoid from the host. Results obtained in two-choice laboratory experiments, with 4-7-d-old virgin males, indicate that (1) DePa-derived semiochemicals arrest males, (2) the opening of a host pupal case strongly arrests males, and (3) the arrestment cue emanates from oral fluid secreted by both female and male parasitoids while they chew their way out of a host pupal case. This phenomenon implies that emerging females, which are haplodiploid and can reproduce without mating, do not engage in active pheromone signaling to attract males, and that mate-seeking males co-opt chemicals involved in eclosion as a mate-finding cue, taking a 50% chance that the prospective mate is a female.


Assuntos
Interações Hospedeiro-Parasita , Mariposas/parasitologia , Feromônios/metabolismo , Vespas/fisiologia , Animais , Feminino , Masculino , Pupa/parasitologia
9.
J Chem Ecol ; 38(10): 1306-17, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23007309

RESUMO

Close-range sexual communication of the egg parasitoid wasp Ooencyrtus kuvanae (Hymenoptera: Encyrtidae) takes place on host gypsy moth, Lymantria dispar (Lepidoptera: Lymantriidae), egg masses. We tested the hypothesis that mate recognition in O. kuvanae is mediated, in part, by low-volatility cuticular hydrocarbon (CHC) pheromone components. Gas chromatographic and GC-mass spectrometric analyses of body surface extracts of male and female wasps revealed no sex-specific components, but 5-methylheptacosane (5-me-27Hy) and 5,17-dimethylheptacosane (5,17-dime-27Hy) were consistently more abundant in extracts of males. The ratio of 5-me-27Hy and 5,17-dime-27Hy was similar in extracts of males and females, and quantitative differences alone seemed insufficient to impart sex-specific CHC profiles. Therefore, we further hypothesized that the absolute configuration of 5-me-27Hy and 5,17-dime-27Hy contributes to mate recognition or attraction. As the stereoisomers of 5-me-27Hy and 5,17-dime-27Hy cannot currently be separated chromatographically, we could not determine the stereochemistry of the insect-produced components. Instead, we synthesized all stereoisomers and bioassayed synthetic blends in laboratory experiments. Of eight 2-component blends, each blend containing one of the two enantiomers of 5-me-27Hy and one of the four stereoisomers of 5,17-dime-27Hy, the blend of (5S)-methylheptacosane and (5R,17S)-dimethylheptacosane attracted males, whereas the blend of (5R)-methylheptacosane and (5R,17R)-dimethylheptacosane repelled males. Apparent recognition of both pheromone components and pheromone antagonists by males supports the hypothesis that the stereochemistry of 5-me-27Hy and 5,17-dime-27Hy, and possibly other methylated CHCs, may differ between male and female O. kuvanae, and that these differences may serve in mate attraction and recognition.


Assuntos
Atrativos Sexuais/química , Comportamento Sexual Animal/efeitos dos fármacos , Vespas/fisiologia , Animais , Antenas de Artrópodes/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos/síntese química , Hidrocarbonetos/química , Hidrocarbonetos/metabolismo , Masculino , Pennsylvania , Atrativos Sexuais/síntese química , Atrativos Sexuais/metabolismo , Estereoisomerismo , Vespas/química , Vespas/efeitos dos fármacos
10.
Am Fam Physician ; 86(11): 1055-61, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23198673

RESUMO

Acute otitis externa is a common condition involving inflammation of the ear canal. The acute form is caused primarily by bacterial infection, with Pseudomonas aeruginosa and Staphylococcus aureus the most common pathogens. Acute otitis externa presents with the rapid onset of ear canal inflammation, resulting in otalgia, itching, canal edema, canal erythema, and otorrhea, and often occurs following swimming or minor trauma from inappropriate cleaning. Tenderness with movement of the tragus or pinna is a classic finding. Topical antimicrobials or antibiotics such as acetic acid, aminoglycosides, polymyxin B, and quinolones are the treatment of choice in uncomplicated cases. These agents come in preparations with or without topical corticosteroids; the addition of corticosteroids may help resolve symptoms more quickly. However, there is no good evidence that any one antimicrobial or antibiotic preparation is clinically superior to another. The choice of treatment is based on a number of factors, including tympanic membrane status, adverse effect profiles, adherence issues, and cost. Neomycin/polymyxin B/hydrocortisone preparations are a reasonable first-line therapy when the tympanic membrane is intact. Oral antibiotics are reserved for cases in which the infection has spread beyond the ear canal or in patients at risk of a rapidly progressing infection. Chronic otitis externa is often caused by allergies or underlying inflammatory dermatologic conditions, and is treated by addressing the underlying causes.


Assuntos
Antibacterianos/administração & dosagem , Hidrocortisona/administração & dosagem , Neomicina/administração & dosagem , Otite Externa/tratamento farmacológico , Otite Externa/microbiologia , Polimixina B/administração & dosagem , Pseudomonas aeruginosa/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Ácido Acético/administração & dosagem , Doença Aguda , Bactérias/isolamento & purificação , Benzetônio/administração & dosagem , Combinação de Medicamentos , Humanos , Otite Externa/diagnóstico , Otite Externa/prevenção & controle , Guias de Prática Clínica como Assunto , Propilenoglicóis/administração & dosagem , Fatores de Risco , Resultado do Tratamento
11.
Curr Sports Med Rep ; 11(6): 316-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23147020

RESUMO

The fields of sports medicine and performing arts medicine have begun recent initiatives to collaborate more closely and to share information pertinent to the treatment of athletes and performing artists. This article provides a review of the common musculoskeletal and neurological problems encountered among performing artists who play instruments. Approaches to history, examination, diagnosis, and treatment are offered, based on literature reviews, expert opinion, and the authors' own experiences in a musician's clinic. Treatments focus on conservative management within a multidisciplinary framework, and indications are given for appropriate surgical referral. Providers are encouraged to build an understanding of the unique issues affecting instrumental athletes.


Assuntos
Traumatismos em Atletas , Doenças Musculoesqueléticas , Música , Doenças Profissionais , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/terapia , Transtornos Traumáticos Cumulativos/diagnóstico , Transtornos Traumáticos Cumulativos/fisiopatologia , Transtornos Traumáticos Cumulativos/terapia , Humanos , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/fisiopatologia , Doenças Musculoesqueléticas/terapia , Doenças Profissionais/diagnóstico , Doenças Profissionais/fisiopatologia , Doenças Profissionais/terapia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/terapia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/terapia
12.
Support Care Cancer ; 19(10): 1601-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20820817

RESUMO

PURPOSE: Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings. METHODS: Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided). RESULTS: Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated. CONCLUSION: Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors.


Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/prevenção & controle , Receptores ErbB/antagonistas & inibidores , Tetraciclina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Método Duplo-Cego , Toxidermias/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença
13.
Am Fam Physician ; 83(9): 1078-84, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21534521

RESUMO

Urticaria involves intensely pruritic, raised wheals, with or without edema of the deeper cutis. It is usually a self-limited, benign reaction, but can be chronic. Rarely, it may represent serious systemic disease or a life-threatening allergic reaction. Urticaria has a lifetime prevalence of approximately 20 percent in the general population. It is caused by immunoglobulin E- and nonimmunoglobulin E-mediated mast cell and basophil release of histamine and other inflammatory mediators. Diagnosis is made clinically. Chronic urticaria is usually idiopathic and requires only a simple laboratory workup unless elements of the history or physical examination suggest specific underlying conditions. Treatment includes avoidance of triggers, although these can be identified in only 10 to 20 percent of patients with chronic urticaria. First-line pharmacotherapy for acute and chronic urticaria is nonsedating second-generation antihistamines (histamine H1 blockers), which can be titrated to larger than standard doses. First-generation antihistamines, histamine H2 blockers, leukotriene receptor antagonists, and brief corticosteroid bursts may be used as adjunctive treatment. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within one year.


Assuntos
Urticária/diagnóstico , Doença Crônica , Diagnóstico Diferencial , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Prognóstico , Pele/patologia , Urticária/tratamento farmacológico , Urticária/etiologia , Urticária/patologia
14.
J Support Oncol ; 8(3): 128-32, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20552926

RESUMO

Hot flashes are a complication of androgen deprivation therapy for prostate cancer. A phase III study showed that use of low-dose gabapentin was well tolerated and moderately decreased the frequency of hot flashes due to androgen deprivation therapy when taken for 4 weeks. The current study, an open-label continuation of the randomized study, examined the efficacy and toxicity of gabapentin when taken for (an additional) 8 weeks. Patients were allowed to start, or continue, gabapentin and to titrate the dose to maximum efficacy, up to 900 mg/d. They were asked to complete a hot flash diary daily and keep weekly logs of toxicity, satisfaction with hot flash control, and quality of life. The moderate reduction in hot flash frequency and severity in the randomized phase of the study appeared to be maintained during this continuation phase. Men originally receiving the placebo or lowest dose of gabapentin (300 mg/d) had improved hot flash control relative to that at the end of the randomized phase. Minimal adverse effects were reported. These findings suggest that low-dose gabapentin is moderately efficacious for at least 12 weeks of hot flash treatment in men undergoing androgen deprivation therapy for prostate cancer and seems to be well tolerated. (NCT00028572)


Assuntos
Aminas/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Fogachos/tratamento farmacológico , Neoplasias da Próstata/terapia , Sobreviventes , Ácido gama-Aminobutírico/uso terapêutico , Idoso , Aminas/efeitos adversos , Ácidos Cicloexanocarboxílicos/efeitos adversos , Método Duplo-Cego , Gabapentina , Fogachos/psicologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Neoplasias da Próstata/mortalidade , Qualidade de Vida , Ácido gama-Aminobutírico/efeitos adversos
15.
Breast Cancer Res Treat ; 117(3): 603-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19214743

RESUMO

Postmenopausal women with breast cancer (BC) are at increased risk for bone loss. Bisphosphonates improve bone mineral density (BMD) in normal postmenopausal women. The purpose of this study was to determine if immediate treatment with zoledronic acid preserves BMD in postmenopausal women with BC starting letrozole after tamoxifen. Postmenopausal women with BC completing tamoxifen were treated with daily letrozole 2.5 mg/vitamin D 400 I.U., calcium 500 mg twice daily and were randomized to upfront or delayed zoledronic acid 4 mg every 6 months. Patients in the delayed arm were only given zoledronic acid if they developed a post-baseline BMD T score <-2.0 or had a fracture. The primary endpoint was the mean percent change in lumbar spine (LS) BMD at 1 year. About 558 women enrolled; 395 provided 1 year BMD data. The upfront arm experienced a mean change of +3.66% in LS BMD versus -1.66% for the delayed group (P < 0.001). Changes at the femoral neck/total hip were also greater for the upfront versus delayed arms (P < 0.001; P < 0.001) with differences persisting at 2 years. Patients in the delayed arm were more likely to experience a clinically meaningful 5% loss of BMD at all sites versus the upfront zoledronate group. Patients in the upfront arm were slightly more likely to report limb edema, fatigue, fever, nausea and jaw osteonecrosis(1%). Upfront zoledronic acid prevents bone loss in postmenopausal women with BC starting letrozole after tamoxifen.


Assuntos
Antineoplásicos/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Osteoporose Pós-Menopausa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Imidazóis/efeitos adversos , Letrozol , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Osteoporose Pós-Menopausa/induzido quimicamente , Tamoxifeno/uso terapêutico , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Ácido Zoledrônico
16.
Support Care Cancer ; 17(4): 451-60, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19142669

RESUMO

OBJECTIVE: Current therapies often have limited efficacy and untenable side effects when used to treat persistent incisional pain following cancer-related surgery. Lidocaine patches reduce neuropathic pain from herpes zoster but their benefits for persistent cancer-related postsurgical incisional pain remain unclear. STUDY DESIGN: Multicenter, double-blind, randomized, two-period crossover trial. MATERIALS AND METHODS: Twenty-eight cancer patients with postsurgical incisional pain were randomly assigned to receive either lidocaine patches followed by placebo patches or the reverse. Each study period lasted 4 weeks. Patches were applied daily upon waking and left in place for a maximum of 18 h. The primary outcome measure, an 11-point pain intensity rating scale, was administered weekly. Secondary outcomes were administered weekly (Brief Pain Inventory-Short Form(BPI-SF), Subject Global Impression of Change) and at the end of each study period (Short Form-Magill Pain Questionnaire, Linear Analogue Self Assessment Scale, Neuropathy Pain Scale, Pain Catastrophizing Scale, Profile of Mood States Short Form). RESULTS: Twenty-one patients completed the first period and 18 completed their crossover second phase. No significant intergroup differences were detected in pain intensity ratings. Few secondary end points were significantly different when subjects used the lidocaine versus placebo patches. BPI-SF interference scores were lower in patients using the lidocaine patch during the first study period, including several scores that achieved statistical significance, general activity (p = 0.02), work (p = 0.04), and relations with others (p = 0.02). CONCLUSION: Lidocaine patch use did not significantly reduce pain intensity ratings or the majority of related secondary end points in cancer patients with persistent incisional pain.


Assuntos
Anestésicos Locais/uso terapêutico , Lidocaína/uso terapêutico , Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Administração Cutânea , Idoso , Anestésicos Locais/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias/cirurgia , Neuralgia/etiologia , Medição da Dor , Dor Pós-Operatória/etiologia , Resultado do Tratamento
17.
PRiMER ; 3: 24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32537595

RESUMO

INTRODUCTION: The goal of this research project was to retrospectively evaluate the effect of a voluntary hands-on musculoskeletal knee exam workshop, presented to medical students in the family medicine rotation at the University of Toledo, on the outcomes of a required objective structured clinical examination (OSCE). METHODS: We analyzed student OSCE scores for both knee and back exams before (July 2011 to June 2012) and after (August 2013 to June 2015) the workshop was offered. The analysis was based on those who attended the voluntary knee exam workshop and those who did not. We compared scores between the two groups of students using two-tailed t testing and χ 2 testing, and assessed the correlation of attending the workshop to passing the knee OSCE. RESULTS: One hundred eighty-seven students attended the workshop and 279 did not. During the period when the workshop was offered, the overall mean score on the knee OSCE was 59.5% for the 187 who attended the workshop and 35.9% for the 116 who did not, which was significantly different (P<.001). A χ2 test with α=0.05 showed that attending the workshop correlated with completing at least 70% of maneuvers acceptably during the knee OSCE (P<.001). CONCLUSIONS: Our study yielded positive outcomes on OSCE scores, comparable to other studies that investigated the effect of similar teaching techniques. Comparison of the scores of those who attended the knee workshop on the simpler back exam OSCE, in which no workshop was offered, demonstrated the efficacy of the workshop.

18.
JAMA ; 299(9): 1019-26, 2008 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-18319412

RESUMO

CONTEXT: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. OBJECTIVE: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. INTERVENTION: Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). MAIN OUTCOME MEASURES: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. RESULTS: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P < .001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). CONCLUSIONS: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003216.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Análise de Sobrevida , Gencitabina
19.
JAMA ; 299(21): 2515-23, 2008 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-18523220

RESUMO

CONTEXT: A family history of colorectal cancer in a first-degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain. OBJECTIVE: To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study of 1087 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients provided data on family history at baseline and were followed up until March 2007 for disease recurrence and death (median follow-up, 5.6 years). In a subset of patients, we assessed microsatellite instability (MSI) and expression of the mismatch repair (MMR) proteins MLH1 and MSH2 in tumor specimens. MAIN OUTCOME MEASURES: Disease-free survival, recurrence-free survival, and overall survival according to the presence or absence of a family history of colorectal cancer. RESULTS: Among 1087 eligible patients, 195 (17.9%) reported a family history of colorectal cancer in a first-degree relative. Cancer recurrence or death occurred in 57 of 195 patients (29%; 95% confidence interval [CI], 23%-36%) with a family history of colorectal cancer and 343 of 892 patients (38%; 95% CI, 35%-42%) without a family history. Compared with patients without a family history, the adjusted hazard ratios (HRs) among those with 1 or more affected first-degree relatives were 0.72 (95% CI, 0.54-0.96) for disease-free survival, 0.74 (95% CI, 0.55-0.99) for recurrence-free survival, and 0.75 (95% CI, 0.54-1.05) for overall survival. This reduction in risk of cancer recurrence or death associated with a family history became stronger with an increasing number of affected first-degree relatives. Compared with participants without a family history of colorectal cancer, those with 1 affected relative had a multivariate HR of 0.77 (95% CI, 0.57-1.04) for disease-free survival. For participants with 2 or more affected relatives, we observed a greater reduction in risk (multivariate HR for disease-free survival, 0.49; 95% CI, 0.23-1.04; P for trend with increasing number of affected relatives = .01). The improved disease-free survival associated with a family history was independent of tumoral MSI or MMR status. CONCLUSION: Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Recidiva Local de Neoplasia/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Recidiva Local de Neoplasia/mortalidade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estudos Prospectivos , Recidiva , Análise de Sobrevida
20.
J Pain Symptom Manage ; 34(6): 628-38, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17703910

RESUMO

Assessment of patient quality of life (QOL) requires balancing the details provided by multi-item assessments with the reduced burden of single-item assessments. In this project, we investigated the psychometric properties of single-item Linear Analog Scale Assessments (LASAs) for patients with newly diagnosed high-grade gliomas. Measures included QOL LASAs (overall, physical, emotional, spiritual, intellectual), Symptom Distress Scale (SDS), Profile of Mood States (POMS; overall, confusion, fatigue), and Functional Assessment of Cancer Therapy-Brain (FACT-Br; overall, brain, physical, emotional). Associations of LASA measures with SDS, POMS, and FACT-Br domains and with Eastern Cooperative Oncology Group performance score (PS) and Mini-Mental State Examination (MMSE) were assessed. Repeated measures ANOVA models compared the change over time of LASAs and SDS, POMS, and FACT-Br. Two hundred five patients completed the assessments across three time points. To allow comparison across measures, all scores were converted to a scale of 0-100, with higher scores indicating better QOL. LASA mean scores ranged from 60 to 78; SDS, POMS, and FACT-Br ranged from 62 to 81. FACT-Br physical (P<0.001) and POMS fatigue subscale (P=0.005) decreased over time, as did LASA physical (P=0.08). LASA scales were strongly associated with corresponding scales on SDS, POMS, and FACT-Br (0.44

Assuntos
Neoplasias Encefálicas/psicologia , Efeitos Psicossociais da Doença , Glioma/psicologia , Psicometria/normas , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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