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2.
J Hum Nutr Diet ; 25(2): 117-20, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21910765

RESUMEN

BACKGROUND: Obesity is increasing in the UK and this is having an impact on the health of pregnant women and their infants. It is recommended that all pregnant women have their height and weight measured and their body mass index (BMI, kg m(-) ²) calculated and recorded in the midwifery notes. The aim of the present audit was to determine the extent of compliance with this recommendation. METHODS: An audit was undertaken in a large district general hospital in the South West of England. A convenience sample of the midwifery notes was accessed retrospectively on the post-natal wards. Data collected from the notes included weight, height, BMI and gestational age when first recorded. RESULTS: A total of 486 maternal notes were audited; of these, 9% did not have the BMI recorded. In total, 53.8% of the sample had either height or weight not recorded; however, 90.9% of the sample had a BMI recorded. In addition, 39.7% (n = 126) of heights and 16.0% (n = 63) of weights were recorded in imperial format. There was a high prevalence overweight (26.2%) and obesity (21.3%) amongst the sample. CONCLUSIONS: Recommendations for measurement of height, weight and calculation of BMI were not always followed. Where BMI was recorded, many notes had either height or weight missing or had measurements recorded in imperial units. This raises the question of how BMI was calculated and its accuracy. Inaccuracies in BMI could lead to individuals being overlooked as high risk and may not be referred for appropriate care including dietetic care. Accurate anthropometric measurements are important for dietary management and monitoring of weight gain.


Asunto(s)
Antropometría/métodos , Estatura , Índice de Masa Corporal , Peso Corporal , Partería/normas , Inglaterra , Femenino , Edad Gestacional , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Pautas de la Práctica en Enfermería/normas , Pautas de la Práctica en Enfermería/estadística & datos numéricos , Embarazo , Complicaciones del Embarazo/prevención & control , Reproducibilidad de los Resultados , Aumento de Peso
3.
J Neuroendocrinol ; 18(9): 672-84, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16879166

RESUMEN

Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.


Asunto(s)
Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Testículo/fisiología , Hormona Adrenocorticotrópica/sangre , Análisis de Varianza , Animales , Arginina Vasopresina/genética , Arginina Vasopresina/metabolismo , Castración , Corticosterona/sangre , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hormona Luteinizante/sangre , Masculino , Sistema Hipófiso-Suprarrenal/metabolismo , Embarazo , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Factores Sexuales , Estrés Psicológico/fisiopatología , Testosterona/sangre
4.
J Biol Chem ; 278(46): 45135-44, 2003 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-12960169

RESUMEN

A genome-wide search using major histocompatibility complex (MHC) class I binding and proteosome cleavage site algorithms identified 101 influenza A PR8 virus-derived peptides as potential epitopes for CD8+ T cell recognition in the H-2b mouse. Cytokine-based flow cytometry, ELISPOT, and cytotoxic T lymphocyte assays reveal that 16 are recognized by CD8+ T cells recovered directly ex vivo from infected animals, accounting for greater than 70% of CD8+ T cells recruited to lung after primary infection. Only six of the 22 highest affinity MHC class I binding peptides comprise cytotoxic T lymphocyte epitopes. The remaining non-immunogenic peptides have equivalent MHC affinity and MHC-peptide complex half-lives, eliciting T cell responses when given in adjuvant and with T cell receptor-ligand avidity comparable with their immunogenic counterparts. As revealed by a novel high sensitivity nanospray tandem mass spectrometry methodology, failure to process those predicted epitopes may contribute significantly to the absent response. These results have important implications for rationale design of CD8+ T cell vaccines.


Asunto(s)
Genoma , Complejo Mayor de Histocompatibilidad , Linfocitos T Citotóxicos/química , Linfocitos T Citotóxicos/inmunología , Algoritmos , Animales , Linfocitos T CD8-positivos/metabolismo , Cromo/metabolismo , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Epítopos/química , Femenino , Interferón gamma/metabolismo , Pulmón/inmunología , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Orthomyxoviridae/genética , Péptidos/química , Pruebas de Precipitina , Unión Proteica
5.
Int J Radiat Oncol Biol Phys ; 51(1): 176-83, 2001 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-11516868

RESUMEN

PURPOSE: To analyze the overall pattern of treatment failure and sites of pelvic disease recurrence relative to the radiation fields used in treating patients with clinically staged T4 rectal cancer with preoperative chemoradiation followed by multivisceral resection. METHODS AND MATERIALS: Between 1990 and 1998, 45 patients with T4 rectal cancer were treated with preoperative chemoradiation. Clinical staging was according to the system of the American Joint Cancer Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and physical examination. A diagnosis of T4 disease required evidence of invasion of a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6), vaginal mucosal involvement on pelvic examination (n = 6), or a combination of these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3-field belly-board technique. The median total dose was 45 Gy in all patients (range 45-63). Nine patients received a boost with external beam radiotherapy (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk). Resection was not performed in 13 (29%) of the 45 patients because of metastases detected before resection or patient refusal. Multivisceral resection and pelvic exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively. We compared the location of pelvic disease recurrence with the RT simulation films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic and distant recurrent rates and the overall survival rate. RESULTS: The median length of follow-up was 31.0 months for all patients and 40.0 months for patients alive at last follow-up. When only the resected cases were considered, the local recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall survival rate was 69%. When all patients were considered, the local recurrence rate was similar (24%), but the rate of distant recurrence (51%) was higher and the overall survival rate lower (50%). Pelvic disease was controlled in all 8 patients whose disease responded well to chemoradiation (either a histologically complete response or microscopic residual disease). Three of 4 patients with close or positive margins had pelvic recurrences despite intraoperative RT and brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field. Elective external iliac nodal irradiation was not used, and nodal metastases were not seen in that region. In 1 case, marginal recurrence occurred in a common iliac node at the superior edge of the treatment field. CONCLUSIONS: Despite aggressive multimodality therapy including multivisceral resection, a high rate of pelvic and distant disease recurrence occurred in patients with clinically staged T4 disease. Regional disease recurred almost exclusively in the radiation field. The intraoperative RT and interstitial brachytherapy doses used did not prevent pelvic disease recurrence in patients with close or positive margins. Novel strategies such as higher preoperative doses of RT with or without altered fractionation or more effective radiosensitizers are needed to improve locoregional control in patients with T4 disease. Future strategies must also include more effective systemic therapy.


Asunto(s)
Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Radiodermatitis/patología , Dosificación Radioterapéutica , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Análisis de Supervivencia , Insuficiencia del Tratamiento
6.
Am J Clin Oncol ; 24(2): 107-12, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11319280

RESUMEN

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.


Asunto(s)
Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Dosificación Radioterapéutica , Neoplasias del Recto/patología , Análisis de Supervivencia
7.
Br J Cancer ; 84(6): 844-50, 2001 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-11259102

RESUMEN

Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 microM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day(-1)mouse(-1)starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF.


Asunto(s)
Catequina/análogos & derivados , Catequina/farmacología , Neoplasias del Colon/metabolismo , Factores de Crecimiento Endotelial/biosíntesis , Linfocinas/biosíntesis , Té/química , Animales , Apoptosis , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Activación Enzimática , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
8.
Int J Exp Pathol ; 82(6): 309-16, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11846837

RESUMEN

Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent.


Asunto(s)
Anticarcinógenos/uso terapéutico , Catequina/uso terapéutico , Invasividad Neoplásica/prevención & control , Neovascularización Patológica/prevención & control , Té/química , Inhibidores de la Angiogénesis/uso terapéutico , Catequina/análogos & derivados , Humanos , Neoplasias/irrigación sanguínea , Fitoterapia , Extractos Vegetales/uso terapéutico
9.
Br J Nurs ; 10(22): 1469-76, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11842462

RESUMEN

The convergence of a number of factors has led to the emergence of what has come to be known as the 'professional doctorate'. This new doctoral education diverges from the model of research doctorates that have historically predominated for more than a century. The background to these changes and the impetus for the development of this relatively new approach to doctoral preparation is outlined in this article. The infancy of the professional doctorate means little empirical data exist about their operation or their success. In this light, the development of an evaluative framework is described in relation to the implementation of a new professional doctorate for nurses and midwives that has been introduced at the University of Sheffield.


Asunto(s)
Educación de Postgrado en Enfermería , Partería/educación , Curriculum , Inglaterra , Humanos , Investigación en Educación de Enfermería , Especialización
10.
Alcohol Clin Exp Res ; 24(10): 1566-74, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11045866

RESUMEN

BACKGROUND: Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed "postnatal handling," has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors. METHODS: Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone-21-phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min). RESULTS: For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts. CONCLUSIONS: These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex-specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.


Asunto(s)
Glándulas Suprarrenales/fisiopatología , Etanol/toxicidad , Manejo Psicológico , Hipotálamo/fisiopatología , Hipófisis/fisiopatología , Efectos Tardíos de la Exposición Prenatal , Hormona Adrenocorticotrópica/sangre , Animales , Corticosterona/sangre , Dexametasona/farmacología , Etanol/administración & dosificación , Retroalimentación , Femenino , Glucocorticoides/farmacología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Restricción Física , Estrés Fisiológico/fisiopatología
11.
Ann Surg ; 232(3): 381-91, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10973388

RESUMEN

OBJECTIVE: To determine the treatment efficacy, safety, local tumor control, and complications related to radiofrequency ablation (RFA) in patients with cirrhosis and unresectable hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Most patients with HCC are not candidates for resection because of tumor size, location, or hepatic dysfunction related to cirrhosis. RFA is a technique that permits in situ destruction of tumors by means of local tissue heating. METHODS: One hundred ten patients with cirrhosis and HCC (Child class A, 50; B, 31; C, 29) were treated during a prospective study using RFA. Patients were treated with RFA using an open laparotomy, laparoscopic, or percutaneous approach with ultrasound guidance to place the RF needle electrode into the hepatic tumors. All patients were followed up at regular intervals to detect treatment-related complications or recurrence of disease. RESULTS: All 110 patients were followed up for at least 12 months after RFA (median follow-up 19 months). Percutaneous or intraoperative RFA was performed in 76 (69%) and 34 patients (31%), respectively. A total of 149 discrete HCC tumor nodules were treated with RFA. The median diameter of tumors treated percutaneously (2.8 cm) was smaller than that of lesions treated during laparotomy (4.6 cm). Local tumor recurrence at the RFA site developed in four patients (3.6%); recurrent HCC subsequently developed in other areas of the liver in all four. New liver tumors or extrahepatic metastases developed in 50 patients (45. 5%), but 56 patients (50.9%) had no evidence of recurrence. There were no treatment-related deaths, but complications developed in 14 patients (12.7%) after RFA. CONCLUSIONS: In patients with cirrhosis and HCC, RFA produces effective local control of disease in a significant proportion of patients and can be performed safely with minimal complications.


Asunto(s)
Carcinoma Hepatocelular/terapia , Hipertermia Inducida , Cirrosis Hepática/terapia , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Humanos , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía
12.
Percept Mot Skills ; 90(3 Pt 2): 1231-4, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10939074

RESUMEN

15 women with formal training in speech and hearing sciences and 15 women with no formal training provided magnitude estimation scaling responses for the intelligibility and annoyance of audiotaped speech samples. Analysis indicated that both groups scaled intelligibility and annoyance the same. As samples became more unintelligible, they also became more annoying.


Asunto(s)
Juicio , Ruido/efectos adversos , Psicoacústica , Inteligibilidad del Habla , Percepción del Habla , Patología del Habla y Lenguaje/educación , Estimulación Acústica , Adulto , Escolaridad , Femenino , Humanos , Grabación en Cinta
13.
Nurs Manage ; 31(3): 47-8, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10827722

RESUMEN

Nurses are inevitable givers who ignore their own needs. Nurse leaders are in a key position to encourage staff members to care for themselves.


Asunto(s)
Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Personal de Enfermería/psicología , Terapia por Relajación , Autocuidado/métodos , Autocuidado/psicología , Humanos , Supervisión de Enfermería/organización & administración
14.
Cancer ; 75(8): 2083-8, 1995 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-7697597

RESUMEN

BACKGROUND: Gastrointestinal leiomyosarcoma metastatic to the liver is considered most resistant to any combination of systemic chemotherapy containing doxorubicin and/or ifosphamide. METHODS: Fourteen patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated with hepatic chemoembolization infusion consisting of polyvinyl alcohol sponge particles mixed with cisplatin powder (150 mg) followed by an intrahepatic arterial infusion of vinblastine (10 mg/m2). RESULTS: Ten major (> 50% regression) tumor responses were observed (70%) in patients lasting from 8 to 31+ months (median, 12 months) after an average of two hepatic chemoembolization procedures, usually 4 weeks apart. Transient side effects included right upper quadrant pain requiring narcotics, significant hepatic enzyme elevation, particularly of lactic dehydrogenase with a minimal increase in bilirubin, paralytic ileus requiring nasogastric suction up to 72 hours, urinary electrolyte losses (potassium+, magnesium++, sodium+) requiring supplements, and occasionally mild but transient leukopenia and thrombocytopenia. CONCLUSIONS: Hepatic chemoembolization infusion appears to induce a high rate of durable tumor response in patients with notoriously chemoresistant gastrointestinal leiomyosarcoma metastatic to the liver.


Asunto(s)
Quimioembolización Terapéutica , Neoplasias Gastrointestinales/patología , Leiomiosarcoma/secundario , Leiomiosarcoma/terapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Adulto , Anciano , Cisplatino/administración & dosificación , Femenino , Estudios de Seguimiento , Arteria Hepática , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Vinblastina/administración & dosificación
15.
J Biol Chem ; 270(14): 8122-30, 1995 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-7713916

RESUMEN

The deduced primary sequence of the cytoplasmic protein-tyrosine kinase domain of the insulin receptor contains a conserved kinase homology region (receptor residues 1002-1257) flanked by a juxtamembrane region and a C-terminal tail. A soluble 48-kDa derivative (residues 959-1355) containing these regions but lacking the first six residues of the juxtamembrane region had earlier been synthesized in Sf9 cells using a baculovirus expression system. The catalytic core of the kinase domain was studied first by proteolytic analysis of the 48-kDa kinase and then by expressing a series of truncated kinase domains in transiently transfected COS cells. Based on these studies, two core kinases of 34 (residues 985-1283) and 35 (residues 978-1283) kDa, respectively, were overexpressed in Sf9 cells. Biochemical characterization of the 35-kDa kinase revealed that the core kinase conserved the major functional properties of the native receptor kinase domain. Activity of the 35-kDa kinase toward a synthetic peptide increased more than 200-fold upon autophosphorylation, which occurred exclusively at Tyr-1158, Tyr-1162, and Tyr-1163; the largest increase was observed between bis- and trisphosphorylation of the kinase. The activated 35- and 48-kDa kinases were similar with respect to specific activity and ATP and Mg2+ requirements for peptide phosphorylation. Moreover, autophosphorylation appeared to initiate predominantly at Tyr-1162, immediately followed by phosphorylation at Tyr-1158 and then at Tyr-1163. The rate of autophosphorylation was dependent on enzyme concentration, consistent with a trans-phosphorylation mechanism. Finally, the 35-kDa kinase was crystallized, making possible elucidation of its three-dimensional structure by x-ray crystallography.


Asunto(s)
Receptor de Insulina/química , Receptor de Insulina/genética , Secuencia de Aminoácidos , Animales , Baculoviridae/genética , Secuencia de Bases , Catálisis , Línea Celular , Clonación Molecular , Cristalización , ADN Complementario , Humanos , Datos de Secuencia Molecular , Fosforilación , Receptor de Insulina/metabolismo , Spodoptera , Tirosina/metabolismo
16.
Curr Opin Oncol ; 4(4): 741-51, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1380839

RESUMEN

Although hepatic resection for hepatocellular carcinoma is the only known modality that offers an opportunity for cure, the practicing oncologist must be aware of alternative modes of therapy. A multidisciplinary approach between surgeon, medical oncologist, and invasive radiologist is necessary in exploring all potential therapeutic options. The oncologist must not only consider the stage of the tumor, but must also take into account the functional reserve of the nontumor-bearing liver in selecting appropriate therapy. More recently, hepatic transplantation has been recognized as a potential curative modality for specific tumor types and stages. Percutaneous ethanol injection and chemoembolization are excellent palliative measures. However, it remains clear that new and innovative techniques are necessary in the therapeutic, adjuvant, and palliative settings in the comprehensive care of the patient with hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Aneuploidia , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/mortalidad , Embolización Terapéutica , Etanol/uso terapéutico , Hepatectomía/métodos , Humanos , Inyecciones , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado , Cuidados Paliativos , Pronóstico , Radioisótopos/uso terapéutico
17.
Gastroenterology ; 101(1): 207-13, 1991 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2044909

RESUMEN

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid; and (c) the effect of coadministration of a liquid meal. Sixty-nine children 91.6 +/- 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids; and (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.


Asunto(s)
Ácido 4-Aminobenzoico/sangre , Dieta , Insuficiencia Pancreática Exocrina/diagnóstico , para-Aminobenzoatos , Ácido 4-Aminobenzoico/administración & dosificación , Análisis de Varianza , Insuficiencia Pancreática Exocrina/sangre , Femenino , Humanos , Lactante , Masculino
18.
Pediatr Res ; 27(1): 32-5, 1990 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2296468

RESUMEN

Longitudinal changes in selenium (Se) and protein concentrations and glutathione peroxidase (GSH-Px) activity of milk collected from healthy mothers of term (n = 12), preterm (n = 10), and very preterm (n = 12) infants were assessed. All infants were size appropriate for gestational age. Milk samples representative of colostrum (d 3), transitional (d 7), and mature milk (d 21 and 42) were assayed. The content of Se in the colostrum secreted by mothers of preterm infants was significantly greater than the Se content of milk secreted by the same mothers at d 21 and 42 of lactation. Mothers of term and very preterm infants, however, produced colostrum with significantly higher levels of Se than milk produced at d 7 (p less than 0.05), d 21 (p less than 0.01), or d 42 (p less than 0.001). Significant differences between the protein concentrations measured in early lactation and in late lactation were evident in all maternal groups. Protein content did not differ significantly among groups at anytime during lactation. An age-related difference was detected in milk GSH-Px activities of mature milk (d 21). Mature milk produced by mothers of very preterm infants on d 21 of lactation contained significantly greater enzyme activity (p less than 0.05) than milk produced by mothers of term infants at the same stage of lactation. Activity of GSH-Px in milk from mothers of very preterm and preterm infants paralleled previously noted changes in long-chain polyunsaturated fatty acid content in human milk with the progression of lactation.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Edad Gestacional , Glutatión Peroxidasa/análisis , Proteínas de la Leche/análisis , Leche Humana/análisis , Selenio/análisis , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Leche Humana/enzimología
19.
Artículo en Inglés | MEDLINE | ID: mdl-6131767

RESUMEN

1. Maximum testicular development and plasma testosterone levels occurred at spring emergence from aestivation-hibernation (A-H), followed by a regression to basal state in June. 2. A slight testicular recrudescense occurred just prior to immergence into A-H, but this development was not accompanied by a definitive increase in plasma testosterone levels or seminal vesicle weights. 3. Four lines of evidence were consistent with the hypothesis that FSH stimulates testicular MAO activity. 4. Changes in pituitary and hypothalamic MAO activity suggested a functional role for this enzyme in controlling releasing factor and gonadotropin production by these organs.


Asunto(s)
Reproducción , Sciuridae/fisiología , Testículo/fisiología , Testosterona/sangre , Animales , Estivación , Hibernación , Hipotálamo/enzimología , Masculino , Monoaminooxidasa/metabolismo , Tamaño de los Órganos , Hipófisis/enzimología , Vesículas Seminales/anatomía & histología , Testículo/anatomía & histología , Testículo/enzimología
20.
J Neurocytol ; 11(1): 3-17, 1982 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6174702

RESUMEN

The retrograde transport of horseradish peroxidase (HRP) has been employed to identify thalamic projection neurons (TPN) in the feline nucleus cuneatus by means of light microscopy and high voltage electron microscopy. Forty-eight hours after injection of HRP in the contralateral ventrobasal complex of the thalamus, labelled neurons at levels caudal to the obex are concentrated in the cell clusters of the dorsal two-thirds of the nucleus. In plastic sections, labelled TPN are identified by the presence of HRP-positive granules in the perinuclear cytoplasm. TPN are typically about 25 micrometers in diameter, have a round nucleus with a smooth contour and abundant cytoplasm. In contrast, neurons unlabelled after thalamic injection are located at the periphery of clusters of TPN. Unlabelled neurons are characterized by their fusiform shape (hence, round when encountered in cross-section), small diameter (10-15 micrometers), a nucleus with an irregular or highly indented contour, and sparse cytoplasm. At the ultrastructural level, TPN are identified by the presence of HRP-positive, membrane-bound, dense bodies in the perinuclear cytoplasm. Furthermore, the presence of such dense bodies in cross-sections of dendrites allows their identification as processes of TPN. The perikarya of adjacent neurons in a cluster are often closely apposed and separated by an extracellular space of 20 to 25 nm. Adjacent to such sites of apposition, small boutons are often presynaptic to one or both of the neurons. The possible functional implications of such an arrangement are discussed.


Asunto(s)
Vías Aferentes/anatomía & histología , Bulbo Raquídeo/anatomía & histología , Neuronas/fisiología , Tálamo/anatomía & histología , Animales , Transporte Axonal , Encéfalo/ultraestructura , Gatos , Peroxidasa de Rábano Silvestre , Microscopía Electrónica , Neuronas/ultraestructura
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