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1.
Am Fam Physician ; 95(11): 717-724, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28671445

RESUMEN

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.


Asunto(s)
Urticaria/diagnóstico , Ciclosporina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Diagnóstico Diferencial , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Omalizumab/uso terapéutico , Urticaria/tratamiento farmacológico
2.
Appl Psychophysiol Biofeedback ; 41(3): 301-5, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26969177

RESUMEN

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.


Asunto(s)
Adaptación Psicológica , Estrés Psicológico/terapia , Estudiantes de Medicina/psicología , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Calidad de Vida , Autoeficacia , Adulto Joven
3.
Blood ; 121(10): 1814-8, 2013 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-23319569

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/fisiología , Integrina alfa4/química , Neoplasia Residual/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Médula Ósea/patología , Adhesión Celular , Niño , Citometría de Flujo , Humanos , Integrasas/metabolismo , Integrina alfa4/genética , Integrina alfa4/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Natalizumab , Neoplasia Residual/metabolismo , Neoplasia Residual/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/patología
4.
J Chem Ecol ; 41(8): 732-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26271674

RESUMEN

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.


Asunto(s)
Antenas de Artrópodos/fisiología , Insectos/metabolismo , Atractivos Sexuales/metabolismo , Animales , Femenino , Cromatografía de Gases y Espectrometría de Masas , Masculino
5.
Med Clin North Am ; 108(4): 687-702, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38816111

RESUMEN

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.


Asunto(s)
Angioedema , Urticaria , Humanos , Angioedema/diagnóstico , Angioedema/etiología , Urticaria/diagnóstico , Urticaria/etiología , Urticaria/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Diagnóstico Diferencial
6.
Blood ; 118(8): 2191-9, 2011 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-21715311

RESUMEN

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.


Asunto(s)
Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Proteínas Inhibidoras de la Apoptosis/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animales , Terapia Combinada , Resistencia a Antineoplásicos/genética , Expresión Génica , Marcación de Gen , Humanos , Proteínas Inhibidoras de la Apoptosis/deficiencia , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Neoplasia Residual , Oligonucleótidos/genética , Oligonucleótidos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , ARN Interferente Pequeño/genética , Proteínas Represoras/deficiencia , Proteínas Represoras/genética , Survivin , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Prim Care ; 50(2): 237-252, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37105604

RESUMEN

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.


Asunto(s)
Angioedema , Urticaria , Humanos , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Urticaria/etiología , Angioedema/diagnóstico , Angioedema/tratamiento farmacológico , Histamina/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Enfermedad Crónica
8.
J Chem Ecol ; 38(3): 253-61, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22392084

RESUMEN

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.


Asunto(s)
Interacciones Huésped-Parásitos , Mariposas Nocturnas/parasitología , Feromonas/metabolismo , Avispas/fisiología , Animales , Femenino , Masculino , Pupa/parasitología
9.
J Chem Ecol ; 38(10): 1306-17, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23007309

RESUMEN

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.


Asunto(s)
Atractivos Sexuales/química , Conducta Sexual Animal/efectos de los fármacos , Avispas/fisiología , Animales , Antenas de Artrópodos/efectos de los fármacos , Femenino , Cromatografía de Gases y Espectrometría de Masas , Hidrocarburos/síntesis química , Hidrocarburos/química , Hidrocarburos/metabolismo , Masculino , Pennsylvania , Atractivos Sexuales/síntesis química , Atractivos Sexuales/metabolismo , Estereoisomerismo , Avispas/química , Avispas/efectos de los fármacos
10.
Am Fam Physician ; 86(11): 1055-61, 2012 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-23198673

RESUMEN

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.


Asunto(s)
Antibacterianos/administración & dosificación , Hidrocortisona/administración & dosificación , Neomicina/administración & dosificación , Otitis Externa/tratamiento farmacológico , Otitis Externa/microbiología , Polimixina B/administración & dosificación , Pseudomonas aeruginosa/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificación , Ácido Acético/administración & dosificación , Enfermedad Aguda , Bacterias/aislamiento & purificación , Bencetonio/administración & dosificación , Combinación de Medicamentos , Humanos , Otitis Externa/diagnóstico , Otitis Externa/prevención & control , Guías de Práctica Clínica como Asunto , Glicoles de Propileno/administración & dosificación , Factores de Riesgo , Resultado del Tratamiento
11.
Curr Sports Med Rep ; 11(6): 316-22, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23147020

RESUMEN

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.


Asunto(s)
Traumatismos en Atletas , Enfermedades Musculoesqueléticas , Música , Enfermedades Profesionales , Traumatismos en Atletas/diagnóstico , Traumatismos en Atletas/fisiopatología , Traumatismos en Atletas/terapia , Trastornos de Traumas Acumulados/diagnóstico , Trastornos de Traumas Acumulados/fisiopatología , Trastornos de Traumas Acumulados/terapia , Humanos , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/terapia , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/fisiopatología , Enfermedades Profesionales/terapia , Traumatismos de los Nervios Periféricos/diagnóstico , Traumatismos de los Nervios Periféricos/fisiopatología , Traumatismos de los Nervios Periféricos/terapia , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/terapia
12.
Support Care Cancer ; 19(10): 1601-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20820817

RESUMEN

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.


Asunto(s)
Antineoplásicos/efectos adversos , Erupciones por Medicamentos/prevención & control , Receptores ErbB/antagonistas & inhibidores , Tetraciclina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Método Doble Ciego , Erupciones por Medicamentos/etiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad
13.
Am Fam Physician ; 83(9): 1078-84, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21534521

RESUMEN

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.


Asunto(s)
Urticaria/diagnóstico , Enfermedad Crónica , Diagnóstico Diferencial , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Antagonistas de Leucotrieno/uso terapéutico , Pronóstico , Piel/patología , Urticaria/tratamiento farmacológico , Urticaria/etiología , Urticaria/patología
14.
J Support Oncol ; 8(3): 128-32, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20552926

RESUMEN

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)


Asunto(s)
Aminas/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Sofocos/tratamiento farmacológico , Neoplasias de la Próstata/terapia , Sobrevivientes , Ácido gamma-Aminobutírico/uso terapéutico , Anciano , Aminas/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Método Doble Ciego , Gabapentina , Sofocos/psicología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/mortalidad , Calidad de Vida , Ácido gamma-Aminobutírico/efectos adversos
15.
Breast Cancer Res Treat ; 117(3): 603-9, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19214743

RESUMEN

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.


Asunto(s)
Antineoplásicos/uso terapéutico , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Osteoporosis Posmenopáusica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Densidad Ósea/efectos de los fármacos , Difosfonatos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Imidazoles/efectos adversos , Letrozol , Persona de Mediana Edad , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Osteoporosis Posmenopáusica/inducido químicamente , Tamoxifeno/uso terapéutico , Triazoles/administración & dosificación , Triazoles/efectos adversos , Ácido Zoledrónico
16.
Support Care Cancer ; 17(4): 451-60, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19142669

RESUMEN

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.


Asunto(s)
Anestésicos Locales/uso terapéutico , Lidocaína/uso terapéutico , Neuralgia/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Administración Cutánea , Anciano , Anestésicos Locales/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias/cirugía , Neuralgia/etiología , Dimensión del Dolor , Dolor Postoperatorio/etiología , Resultado del Tratamiento
17.
PRiMER ; 3: 24, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32537595

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-18319412

RESUMEN

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.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Fluorouracilo/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Desoxicitidina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirugía , Análisis de Supervivencia , Gemcitabina
19.
JAMA ; 299(21): 2515-23, 2008 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-18523220

RESUMEN

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.


Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/mortalidad , Recurrencia Local de Neoplasia/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Reparación de la Incompatibilidad de ADN , Femenino , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estudios Prospectivos , Recurrencia , Análisis de Supervivencia
20.
J Pain Symptom Manage ; 34(6): 628-38, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17703910

RESUMEN

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

Asunto(s)
Neoplasias Encefálicas/psicología , Costo de Enfermedad , Glioma/psicología , Psicometría/normas , Calidad de Vida , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
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