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1.
Urol Pract ; 8(4): 466-471, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37145468

RESUMEN

INTRODUCTION: Disposable single-use cystoscopes have become increasingly available, demonstrating comparable quality to reusable cystoscopes while eliminating the need for reprocessing and repairs. However, high costs remain a concern. To clarify the role for these scopes, we performed a cost analysis comparison between the single-use Ambu® aScope™ 4 cystoscope and reusable Olympus® CYF-VHR and V2 cystoscopes in 2 clinical settings: a high-volume multi-provider practice and low-volume single-provider practice. METHODS: The number of cystoscopies at each center was recorded between January and December 2019. Elements in the micro-costing analysis included the original purchasing price of the cystoscopes plus accessory equipment, sterilization supplies, repair costs, and personnel. Costs were amortized over 5 or 10 years and calculated on a per-case basis. An annual total cost analysis was performed to evaluate the cost-effectiveness of each device for each facility. RESULTS: In 2019, 1,984 and 245 cystoscopic procedures were performed at the high and low-volume clinics, respectively. At the high-volume multi-provider practice, per-case cost for reusable cystoscopy amounted to $65.98 compared to $227.18 for single-use cystoscopy, with reusable equipment more cost-effective after 294 cystoscopies. At the low-volume single-provider practice, the per-case cost for reusable cystoscopy was $232.62 compared to $461.18 for single-use cystoscopy, with reusable equipment more cost-effective after 19 cases. CONCLUSIONS: Based on this micro-costing analysis, per-case costs favor reusable cystoscopes. While single-use cystoscope pricing may be prohibitive for large and small facilities at this present time, these instruments are powerful adjuncts to urologists' armamentaria when portability and efficiency are prioritized.

2.
Mil Med ; 184(5-6): e248-e254, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30690457

RESUMEN

INTRODUCTION: Many epidemiologic studies have been performed in military recruit populations, but little is known about the health of those who conduct the training. This study aims to characterize the physical and mental health of a military trainer cohort. MATERIALS AND METHODS: All US Air Force military training instructors (MTIs) who served between 1 October 2011 and 30 September 2016 were included in this retrospective descriptive study. All International Classification of Diseases, Ninth or Tenth Revision codes received by MTIs as inpatients or outpatients in the TRICARE system were obtained and mapped to Clinical Classifications Software levels. After excluding routine and administrative codes, the relative burden of disease by diagnostic category and subcategory was calculated, with further classification of musculoskeletal conditions by anatomic site. For all conditions accounting for at least 1.0% of the burden of care, incidence density rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated to compare males and females. RESULTS: A total of 1,269 MTIs received 32,601 non-administrative, non-routine diagnoses while accumulating 50,376 person-months of exposure during the surveillance period. Musculoskeletal conditions were the greatest contributor to overall disease burden, accounting for 39.1% of all diagnoses, followed by mental health (10.4%), respiratory (10.1%), and neurologic and sensory (9.8%). The burden attributed to mental health conditions decreased by 54% over the 5-year period. Twenty-three conditions accounted for at least 1.0% of the healthcare burden. The highest incidence conditions were connective tissue disease (27.18 per 1,000 person-months), non-traumatic joint disorders (25.74), upper respiratory infections (25.14), and back pain (23.70). As compared to males, females had a higher incidence of several conditions, including adjustment disorders (IRR: 2.57; 95% CI: 1.61, 4.11) and anxiety disorders (IRR: 2.24; 95% CI: 1.33, 3.77). CONCLUSIONS: Musculoskeletal conditions are the leading contributor to burden of care among US Air Force MTIs, followed by mental health, respiratory, and neurologic and sensory conditions. The burden of healthcare among US Air Force MTIs more closely resembles active component service members than recruit trainees.


Asunto(s)
Docentes/psicología , Estado de Salud , Personal Militar/psicología , Adulto , Docentes/estadística & datos numéricos , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Salud Mental/normas , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Enfermedades Musculoesqueléticas/epidemiología , Estudios Retrospectivos , Enseñanza/psicología , Enseñanza/normas , Estados Unidos/epidemiología
3.
Ann Surg Oncol ; 24(7): 1853-1860, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27864694

RESUMEN

BACKGROUND: NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not receive bev. METHODS: A total of 1206 women with HER2-negative operable breast cancer were randomly assigned to receive one of three different docetaxel-plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks) for the first 6 of 8 cycles and for 10 doses postoperatively. Surgical complications were assessed from date of surgery through 24 months following study entry. RESULTS: Early surgical complications were significantly more frequent in the bev group (25.4 vs. 18.9%; trend test p = 0.008), but most were grade 1-2. Early noninfectious wound dehiscences were infrequent and not significantly different (5.4 vs. 3.1%; trend test p = 0.15). Long-term noninfectious wound complications were significantly higher for patients receiving bev (11.8 vs. 5.1%; trend test p = 0.0007), but the incidence of grade ≥3 wound dehiscence was low in both groups (<1%). Among 193 patients undergoing expander or implant reconstructions, 19 (19.6%) of 97 in the bev-receiving group versus 10 (10.4%) of 96 in the non-bev group had grade ≥3 complications (Pearson, p = 0.11). CONCLUSIONS: Overall, adding bev increased surgical complications, but most serious complications were not significantly increased. In particular, the need for surgical intervention in patients undergoing breast reconstruction with prosthetic implants was higher with bev but was not statistically significantly different. With precautions, bev can be used safely perioperatively in patients undergoing surgery for breast cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Infección de la Herida Quirúrgica/etiología , Antraciclinas/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Terapia Combinada , Docetaxel , Femenino , Estudios de Seguimiento , Humanos , Mamoplastia/efectos adversos , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Taxoides/administración & dosificación
5.
Lancet Oncol ; 16(9): 1037-1048, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26272770

RESUMEN

BACKGROUND: NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. METHODS: In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and overall survival. This study is registered with ClinicalTrials.gov, number NCT00408408. FINDINGS: Between Jan 5, 2007, and June 30, 2010, 1206 patients were enrolled in the study. Follow-up data were collected from Oct 31, 2007 to March 27, 2014, and were available for overall survival in 1186 patients, disease-free survival in 1184, and distant recurrence-free interval in 1181. Neither capecitabine nor gemcitabine increased disease-free survival or overall survival. Median follow-up was 4·7 years (IQR 4·0-5·2). The addition of bevacizumab significantly increased overall survival (hazard ratio 0·65 [95% CI 0·49-0·88]; p=0·004) but did not significantly increase disease-free survival (0·80 [0·63-1·01]; p=0·06). Four deaths occurred on treatment due to vascular disorder (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), sudden death (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), infective endocarditis (docetaxel plus bevacizumab followed by doxorubicin plus cyclophosphamide and bevacizumab group), and visceral arterial ischaemia (docetaxel followed by doxorubicin plus cyclophosphamide group). The most common grade 3-4 adverse events in the bevacizumab group were neutropenia (grade 3, 99 [17%]; grade 4, 37 [6%]), hand-foot syndrome (grade 3, 63 [11%]), and hypertension (grade 3, 60 [10%]; grade 4, two [<1%]) and in the non-bevacizumab group were neutropenia (grade 3, 98 [16%]; grade 4, 36 [6%]), fatigue (grade 3, 53 [9%]), and hand-foot syndrome (grade 3, 43 [7%]). INTERPRETATION: The addition of gemcitabine or capecitabine to neoadjuvant docetaxel plus doxorubicin plus cyclophosphamide does not seem to provide any benefit to patients with operable breast cancer, and should not change clinical practice in the short term. The improved overall survival with bevacizumab contradicts the findings of other studies of bevacizumab in breast cancer and may indicate the need for additional investigation of this agent. FUNDING: National Institutes of Health, Genentech, Roche Laboratories, Lilly Research Laboratories, and Precision Therapeutics.


Asunto(s)
Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Neoplasias de la Mama/patología , Capecitabina/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Taxoides/administración & dosificación , Estados Unidos , Gemcitabina
7.
N Engl J Med ; 366(4): 310-20, 2012 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-22276821

RESUMEN

BACKGROUND: Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response. METHODS: We randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy. RESULTS: The addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P=0.69). Both capecitabine and gemcitabine were associated with increased toxic effects--specifically, the hand-foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P=0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand-foot syndrome, and mucositis. CONCLUSIONS: The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.).


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2 , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Capecitabina , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Modelos Logísticos , Mastectomía Segmentaria , Persona de Mediana Edad , Terapia Neoadyuvante , Taxoides/administración & dosificación , Resultado del Tratamiento , Gemcitabina
8.
Pharmacol Ther ; 134(1): 1-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21893094

RESUMEN

Traumatic brain injury (TBI) is a devastating neurological injury with broad manifestations. Unfortunately, its diagnosis and efficacious treatments remain elusive. Different post injury symptoms are exhibited at different time frames, indicative of a time-related progression of the pathology. Therefore, particular treatments must be tailored to the post injury time frame. This overview is focused on the secondary chronic phase following TBI and the value of sympathomimetic therapy during this phase. The various direct- and indirect-acting drugs are reviewed, and the treatment protocol employed by the author is described.


Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Simpatomiméticos/uso terapéutico , Humanos
9.
Am J Ther ; 18(1): 70-80, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21192249

RESUMEN

Stroke represents a major cause of death and disability. In just the last two decades, science has begun to appreciate the central nervous system's attempts to repair itself through a process termed neuroplasticity. The remodeling is a dynamic process subject to endogenous and exogenous forces. Rehabilitation has started to implement approaches based on objective measures such as diffusion tensor imaging and functional magnetic resonance. Newer modalities such as constraint-induced movement therapy and robotic interventions are being used for both short- and long-term functional gains. This review describes the various studies on neuroplasticity and the variety of interventions now available.


Asunto(s)
Plasticidad Neuronal/fisiología , Rehabilitación de Accidente Cerebrovascular , Encéfalo/patología , Imagen de Difusión Tensora , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Modalidades de Fisioterapia , Recuperación de la Función , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/terapia , Estimulación Magnética Transcraneal
10.
Physiol Genomics ; 39(2): 120-9, 2009 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-19671659

RESUMEN

Mice homozygous for the smallie (slie) mutation lack a collagen receptor, discoidin domain receptor 2 (DDR2), and are dwarfed and infertile due to peripheral dysregulation of the endocrine system of unknown etiology. We used a systems biology approach to identify biological networks affected by Ddr2(slie/slie) mutation in ovaries using microarray analysis and validate findings using molecular, cellular, and functional biological assays. Transcriptome analysis indicated several altered gene categories in Ddr2(slie/slie) mutants, including gonadal development, ovulation, antiapoptosis, and steroid hormones. Subsequent biological experiments confirmed the transcriptome analysis predictions. For instance, a significant increase of TUNEL-positive follicles was found in Ddr2(slie/slie) mutants vs. wild type, which confirm the transcriptome prediction for decreased chromatin maintenance and antiapoptosis. Decreases in gene expression were confirmed by RT-PCR and/or qPCR; luteinizing hormone receptor and prostaglandin type E and F receptors in Ddr2(slie/slie) mutants, compared with wild type, confirm hormonal signaling pathways involved in ovulation. Furthermore, deficiencies in immunohistochemistry for DDR2 and luteinizing hormone receptor in the somatic cells, but not the oocytes, of Ddr2(slie/slie) mutant ovaries suggest against an intrinsic defect in germ cells. Indeed, Ddr2(slie/slie) mutants ovulated significantly fewer oocytes; their oocytes were competent to complete meiosis and fertilization in vitro. Taken together, our convergent data signify DDR2 as a novel critical player in ovarian function, which acts upon classical endocrine pathways in somatic, rather than germline, cells.


Asunto(s)
Colágeno/metabolismo , Perfilación de la Expresión Génica , Ovario/enzimología , Ovario/fisiología , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Mitogénicos/genética , Receptores Mitogénicos/metabolismo , Animales , Apoptosis/genética , Receptores con Dominio Discoidina , Desarrollo Embrionario/genética , Femenino , Regulación de la Expresión Génica , Gonadotropinas/metabolismo , Ratones , Mutación/genética , Oocitos/citología , Oocitos/enzimología , Folículo Ovárico/citología , Folículo Ovárico/enzimología , Ovario/citología , Ovulación/genética , Ovulación/fisiología , Periodicidad , Reproducibilidad de los Resultados , Transducción de Señal/genética
11.
Head Neck ; 31(9): 1144-51, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19340861

RESUMEN

BACKGROUND: This article reviews our community cancer center's experience treating head and neck cancer primarily with accelerated fractionation intensity-modulated radiation therapy (IMRT), with or without concurrent chemotherapy, focusing on acute toxicity and efficacy. METHODS: Fifty-two patients treated with IMRT at the Penrose Cancer Center between 2002 and 2007 constitute the cohort. The majority (75%) received an accelerated, altered fractionation regimen, typically concomitant boost to 7200 cGy. Concurrent chemotherapy was delivered to 32 (62%). The median follow-up was 24 months. RESULTS: The 2-year actuarial rates of local control, regional control, and distant metastasis-free survival were 100%, 91%, and 94%, respectively. Relapse-free survival and overall survival at 2 years were 89% and 91%, respectively. Overall, 32 of 52 patients (62%) experienced at least 1 type of grade 3 or 4 acute toxicity. CONCLUSION: Accelerated fractionation IMRT, with or without chemotherapy, can be given safely and effectively in a community cancer center setting.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Fraccionamiento de la Dosis de Radiación , Neoplasias de Oído, Nariz y Garganta/radioterapia , Radioterapia de Intensidad Modulada , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/secundario , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Oído, Nariz y Garganta/tratamiento farmacológico , Neoplasias de Oído, Nariz y Garganta/patología , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Estomatitis/etiología , Análisis de Supervivencia
12.
Top Stroke Rehabil ; 16(6): 389-410, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20139041

RESUMEN

Cerebrovascular accidents remain the third leading cause of death in the United States, with many left with life-long disabilities. The causes and contributing factors of stroke are beginning to be well defined, but what is not appreciated are the various techniques for assisting recovery. Understanding what parts of the neurological and musculoskeletal exams predict short-term and long-term disabilities helps guide patients and families. Newer and effective rehabilitative approaches are available as are home, outpatient, and hospital-based sites for recovery. Improvements after stroke are now recognized to continue for months to years after the event. Available therapeutic techniques and evaluative studies are presented in this review.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/complicaciones , Humanos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patología
13.
Int J Environ Res Public Health ; 5(4): 258-77, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19190356

RESUMEN

The paper offers a review and commentary, with particular reference to the production of fish from wild capture fisheries and aquaculture, on neglected aspects of health impact assessments which are viewed by a range of international and national health bodies and development agencies as valuable and necessary project tools. Assessments sometimes include environmental health impact assessments but rarely include specific occupational health and safety impact assessments especially integrated into a wider public health assessment. This is in contrast to the extensive application of environmental impact assessments to fishing and the comparatively large body of research now generated on the public health effects of eating fish. The value of expanding and applying the broader assessments would be considerable because in 2004 the United Nations Food and Agriculture Organization reports there were 41,408,000 people in the total 'fishing' sector including 11,289,000 in aquaculture. The paper explores some of the complex interactions that occur with regard to fishing activities and proposes the wider adoption of health impact assessment tools in these neglected sectors through an integrated public health impact assessment tool.


Asunto(s)
Acuicultura , Monitoreo del Ambiente , Peces , Salud Laboral , Salud Pública , Animales , Humanos
14.
Phys Med Rehabil Clin N Am ; 18(1): 145-63, vii-viii, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17292817

RESUMEN

For the patient who has sustained traumatic brain injury (TBI), understanding the problem and listening to and believing the patient are prerequisites to treating pain. Because the information provided may be limited, communication skills problematic, and consistency variable, the challenge of treating individuals with TBI and pain can be daunting. Most painful conditions after TBI involve the musculoskeletal system; however, in conditions that are neurologically based, a careful and well-organized neurologic examination can be helpful to direct one's attention toward ordering the appropriate tests and treatments. The primary focus for helping patients with pain involves not only understanding the problem and assisting with symptom relief but also providing the opportunity to improve their functioning, physically and cognitively.


Asunto(s)
Lesiones Encefálicas/complicaciones , Cefalea/etiología , Dolor/etiología , Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/rehabilitación , Ejercicio Físico , Cefalea/terapia , Humanos , Pruebas Neuropsicológicas , Dolor/clasificación , Manejo del Dolor , Dimensión del Dolor , Examen Físico
15.
Cancer Chemother Pharmacol ; 60(1): 61-7, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17009032

RESUMEN

INTRODUCTION: This phase II trial was conducted to assess the efficacy and safety of 10-Ethyl-10-Deaza-Aminopterin (10-EDAM), a folate antagonist, in metastatic breast cancer patients who had received no more than one prior chemotherapy regimen. METHODS: Fifty-five patients were treated on an initial weekly dose 80 mg/m(2) of 10-EDAM. Patients who had received a prior chemotherapy regimen in the adjuvant setting (group 1) were considered separately from patients who had received a prior chemotherapy regimen in the metastatic setting (group 2). RESULTS: The response rate for both groups combined was 18%, and median time to progression was 3 months. Median overall survival was 12 months. Treatment was associated with common chemotherapy-related toxicities, such as 25% grade three or four neutropenia and 20% grade three or four stomatitis. CONCLUSION: In patients with metastatic breast cancer who had received one prior chemotherapy regimen, 10-EDAM was well tolerated. In general, while definite antitumor activity was documented, time to progression was brief.


Asunto(s)
Aminopterina/análogos & derivados , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Agranulocitosis/inducido químicamente , Alopecia/inducido químicamente , Aminopterina/efectos adversos , Aminopterina/uso terapéutico , Anemia/inducido químicamente , Antineoplásicos/efectos adversos , Neoplasias de la Mama/secundario , Progresión de la Enfermedad , Femenino , Humanos , Leucopenia/inducido químicamente , Persona de Mediana Edad , Náusea/inducido químicamente , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
16.
Gynecol Oncol ; 94(2): 533-9, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15297200

RESUMEN

OBJECTIVE: Incorporating topotecan into standard platinum/taxane chemotherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclitaxel and carboplatin, in newly diagnosed advanced ovarian cancer patients. METHODS: Forty-five patients (median age, 56 years; range, 38-77 years) with stage III/IV disease and GOG performance status <2 were enrolled and received four cycles of topotecan (1.0 mg/m(2)/day on days 1 to 3) and carboplatin (AUC 4 on day 1), followed by four cycles of paclitaxel (175 mg/m(2) via 3-h IV infusion on day 1) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete response (CR) underwent second-look laparotomy for determination of pathologic CR (PCR). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia, and for grade 3/4 nonhematologic toxicity. RESULTS: Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, respectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progression was 14 months and actuarial survival was 23 months. Neutropenia was the primary toxicity and cause of dose adjustments and delays, including two deaths. CONCLUSION: The antitumor activity observed is comparable with other series, although neutropenic complications were increased. Progression-free and actuarial survivals were slightly inferior. A Phase III trial (GOG 182) of sequential doublets in the reverse sequence is ongoing.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno Ca-125/sangre , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cistadenocarcinoma Papilar/sangre , Cistadenocarcinoma Papilar/tratamiento farmacológico , Cistadenocarcinoma Papilar/patología , Cistadenocarcinoma Seroso/sangre , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Topotecan/administración & dosificación , Topotecan/efectos adversos
17.
Hum Mol Genet ; 12(17): 2179-89, 2003 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-12915475

RESUMEN

Mutations within the CRB1 gene have been shown to cause human retinal diseases including retinitis pigmentosa and Leber congenital amaurosis. We have recently identified a mouse model, retinal degeneration 8 (rd8) with a single base deletion in the Crb1 gene. This mutation is predicted to cause a frame shift and premature stop codon which truncates the transmembrane and cytoplasmic domain of CRB1. Like in Drosophila crumbs (crb) mutants, staining for adherens junction proteins known to localize to the external limiting membrane, the equivalent of the zonula adherens in the mammalian retina, is discontinuous and fragmented. Shortened photoreceptor inner and outer segments are observed as early as 2 weeks after birth, suggesting a developmental defect in these structures rather than a degenerative process. Photoreceptor degeneration is observed only within regions of retinal spotting, which is seen predominantly in the inferior nasal quadrant of the eye, and is caused by retinal folds and pseudorosettes. Photoreceptor dysplasia and degeneration in Crb1 mutants strongly vary with genetic background, suggesting that the variability in phenotypes of human patients that carry mutations in CRB1 may be due to interactions with background modifiers in addition to allelic variations. The Crb1rd8 mouse model will facilitate the analysis of Crb1 function in the neural retina and the identification of interacting factors as candidate retinal disease genes.


Asunto(s)
Membrana Basal/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas del Tejido Nervioso/fisiología , Células Fotorreceptoras de Vertebrados/citología , Retina/embriología , Empalme Alternativo , Animales , Proteínas de Ciclo Celular/inmunología , Proteínas de Ciclo Celular/metabolismo , Mapeo Cromosómico , Mutación del Sistema de Lectura , Ratones , Ratones Endogámicos C57BL , Morfogénesis , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/inmunología , Proteínas Nucleares/inmunología , Proteínas Nucleares/metabolismo , Fragmentos de Péptidos/inmunología , Células Fotorreceptoras de Vertebrados/metabolismo , Isoformas de Proteínas , Retina/crecimiento & desarrollo , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Proteínas de Schizosaccharomyces pombe/inmunología , Proteínas de Schizosaccharomyces pombe/metabolismo
18.
Ann Thorac Surg ; 75(5): 1392-9, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12735552

RESUMEN

BACKGROUND: The association between perioperative hyperglycemia and outcomes in patients with and without diabetes mellitus undergoing coronary artery bypass grafting is not well defined. We measured the association between perioperative hyperglycemia and outcomes among patients undergoing coronary artery bypass grafting. METHODS: We report a historic cohort study of 1574 patients who had undergone coronary artery bypass grafting between 1998 and 1999, 545 (34.6%) with diabetes. Perioperative blood glucose level was defined as the average of all blood glucose tests obtained on the day of and the day after surgery. Outcomes were 30-day mortality, infection rates (sternum, harvest site, sepsis, pneumonia, urinary tract), and resource utilization. RESULTS: After adjusting for diabetes status and calculated preoperative mortality or mediastinitis risk scores, each 50 mg/dL (2.78 mmol/L) blood glucose increase was not statistically associated with higher mortality (odds ratio 1.37; 95% confidence interval, 0.98 to 1.92; p = 0.07), or higher infection rate (odds ratio 1.23, 95% confidence interval 0.94 to 1.60; p = 0.14). Each 50 mg/dL blood glucose increase was associated with longer postoperative days by 0.76 days (95% confidence interval 0.36 to 1.17 days; p < 0.001), increased hospitalization charges by 2824 dollars (95% confidence interval 1599 dollars to 4049 dollars; p < 0.001), and increased hospitalization cost by 1769 dollars (95% confidence interval 928 dollars to 2610 dollars; p < 0.001). In the unadjusted analysis, infections occurred more frequently in patients with diabetes (6.6% vs 4.1%, p = 0.03). CONCLUSIONS: Perioperative hyperglycemia is associated with increased resource utilization in patients undergoing coronary artery bypass grafting with and without diabetes.


Asunto(s)
Puente de Arteria Coronaria , Diabetes Mellitus/sangre , Hiperglucemia , Glucemia/análisis , Estudios de Cohortes , Puente de Arteria Coronaria/economía , Puente de Arteria Coronaria/mortalidad , Infección Hospitalaria , Diabetes Mellitus/economía , Femenino , Precios de Hospital , Costos de Hospital , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Medición de Riesgo , Factores de Riesgo , Infección de la Herida Quirúrgica , Resultado del Tratamiento
19.
J Laparoendosc Adv Surg Tech A ; 12(3): 155-9, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12184899

RESUMEN

Laparoscopic splenectomy has become the standard of care for the surgical treatment of idiopathic thrombocytopenic purpura (ITP). The minimally invasive approach to splenic disorders such as ITP clearly results in the same benefits to the patients as have been demonstrated with the laparoscopic cholecystectomy techniques. New technologies in minimally invasive surgery have resulted in the development of robotic devises that assist the surgeon during the procedures. Robotic surgery is in its infancy at this point in time. Herein, we report a splenectomy performed with the assistance of the da Vinci surgical robot. With advancement of technology, robotic systems will play an integral role in future minimally invasive surgery.


Asunto(s)
Laparoscopía/métodos , Púrpura Trombocitopénica Idiopática/cirugía , Robótica , Esplenectomía/métodos , Cirugía Asistida por Computador , Anciano , Femenino , Humanos
20.
Surg Laparosc Endosc Percutan Tech ; 12(1): 33-40, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12008760

RESUMEN

In the past decade, robot-assisted surgery has become increasingly used to assist in minimally invasive surgical procedures. In this article we review the evolution of robotic devices, from the first use of an industrial robot for stereotactic biopsies to pioneering work with robots used for hip and prostate surgery, to the development of robotic guidance systems that enabled solo endoscopic surgery, to telemanipulative surgery with master-servant computer-enhanced robotic devices. In addition, we review our early experience with da Vinci Robotic Surgical Systems (Intuitive Surgical, Inc., Mountain View, CA, U.S.A.), which we used to perform robot-assisted laparoscopic cholecystectomies.


Asunto(s)
Colecistectomía Laparoscópica/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Robótica/instrumentación , Cirugía Asistida por Computador/instrumentación , Adulto , Anciano , Humanos , Persona de Mediana Edad , Robótica/métodos , Cirugía Asistida por Computador/métodos , Factores de Tiempo
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