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1.
Ann Surg Oncol ; 29(2): 1327-1333, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34625880

RESUMEN

BACKGROUND: For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS: ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS: Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION: Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Quimioradioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/terapia , Esofagectomía , Fluorodesoxiglucosa F18 , Humanos , Terapia Neoadyuvante , Tomografía de Emisión de Positrones , Radiofármacos/uso terapéutico , Estudios Retrospectivos
3.
Ann Surg Oncol ; 24(11): 3237-3244, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28770482

RESUMEN

BACKGROUND: Open inguinal lymphadenectomy (OIL) has a high incidence of complications. The authors adapted and reported a minimally invasive technique [videoscopic inguinal lymphadenectomy (VIL)] for use with melanoma, subsequently pursuing a randomized, prospective trial comparing open and minimally invasive approaches in an attempt to confirm retrospective findings illustrating reduced complications with the minimally invasive approach. METHODS: A randomized, prospective trial (NCT01526486) was designed to compare outcomes for patients undergoing VIL versus OIL. Patients with a diagnosis of malignancies requiring inguinal lymphadenectomy at Emory University were enrolled in the study, and informed consent was obtained. Failure to accrue sufficient patients resulted in suspension of the randomization process. Clinicopathologic, procedural, and outcomes data on VILs were prospectively collected. The primary outcome was wound complications, and the secondary outcome was recurrence-free survival. RESULTS: The results are limited to VILs. In this study, 102 patients underwent 137 procedures. Most of the complications were Clavien-Dindo 1 or 2, accounting for 89.7% of all postoperative issues. The wound infection rate was 47.4%. Skin necrosis or wound dehiscence occurred after 13 of the procedures (9.5%). For the patients with melanoma, the median overall survival was 68.8 months, and the recurrence-free survival was 18.5 months. The median inguinal recurrence-free survival was not reached. The median stage-specific recurrence-free survival was not reached for stage IIIA, was 22.8 months for stage IIIB, and was 8.8 months for stage IIIC disease (p < 0.001). CONCLUSIONS: The long-term findings presented in this report expand on and confirm previously published results demonstrating decreased morbidity and oncologic noninferiority of VIL, further validating the technique for patients requiring lymphadenectomy.


Asunto(s)
Conducto Inguinal/cirugía , Escisión del Ganglio Linfático/métodos , Melanoma/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/mortalidad , Neoplasias Urogenitales/cirugía , Cirugía Asistida por Video/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Conducto Inguinal/patología , Masculino , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Tasa de Supervivencia , Neoplasias Urogenitales/patología , Adulto Joven
4.
Ann Surg ; 262(6): 999-1005, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25607760

RESUMEN

OBJECTIVES: To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma. STUDY DESIGN: Multi-institutional retrospective analysis. BACKGROUND: Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established. METHODS: Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively. RESULTS: Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival. CONCLUSIONS: Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.


Asunto(s)
Adenocarcinoma/patología , Gastrectomía , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Gástricas/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
5.
Br J Cancer ; 111(12): 2262-7, 2014 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-25393368

RESUMEN

BACKGROUND: AT7519 is a small-molecular inhibitor of multiple cyclin-dependent kinases (CDKs). It shows encouraging anti-cancer activity against multiple cell lines and in tumour xenografts. This phase I study was conducted to evaluate the safety and tolerability of AT7519 given as 1-h intravenous infusion on days 1, 4, 8 and 11 every 3 weeks. METHODS: Patients with advanced refractory solid tumours or non-Hodgkin's lymphoma were enroled. Dose escalation occurred in a 3+3 manner based on toxicity assessment. Pharmacokinetic samples were collected after first AT7519 infusion, whereas pharmacodynamics (PD) samples were obtained in selected patients. RESULTS: Thirty-four patients were enroled, and 32 received study treatments over 4 dose levels. Dose-limiting toxicities included mucositis, febrile neutropenia, rash, fatigue and hypokalemia. The recommended phase II dose (RP2D) was 27.0 mg m(-2). Ten of 19 patients evaluable for efficacy had stable disease as the best response (median duration: 3.3 months; range: 2.5 to 11.1 months). There was no clinically significant QTc prolongation. There was an apparent dose proportional increase in AT7519 exposure. The PD studies showed reduction in markers of CDK activity in selected patients' skin biopsies post treatment. CONCLUSIONS: AT7519, when administered as an intravenous infusion on days 1, 4, 8 and 11, was well tolerated. The RP2D is 27.0 mg m(-2). At this dose level, plasma AT7519 concentrations were above the biologically active concentrations, and preliminary anti-cancer activity was observed in patients. This dosing schedule is being further evaluated in multiple phase II studies.


Asunto(s)
Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Piperidinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirazoles/administración & dosificación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/enzimología , Neoplasias/metabolismo , Piperidinas/efectos adversos , Piperidinas/farmacocinética , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Pirazoles/efectos adversos , Pirazoles/farmacocinética
6.
Ann Oncol ; 23(5): 1307-1313, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22015452

RESUMEN

BACKGROUND: AT9283 is an inhibitor of aurora kinases A and B with antitumor activity in preclinical models. This a First in Human phase I study assessed the safety, tolerability, pharmacokinetic and pharmacodynamic properties and preliminary efficacy of AT9283. PATIENTS AND METHODS: Patients with advanced tumors received AT9283 as a continuous central venous infusion over 3 days in cohorts of three to six patients starting at 1.5 mg/m(2)/day (equivalent to 4.5 mg/m(2)/72 h). The oral bioavailability of AT9283 was assessed in a cohort of seven patients. Pharmacodynamic analysis of biomarkers included phosphorylation of histone H3 on serine 10, proliferating cell nuclear antigen, Ki67, M30 and M65 in skin and plasma. RESULTS: Forty patients were included in all analyses. AT9283 was generally well tolerated with main toxic effects of reversible dose-related myelosuppression, gastrointestinal disturbance, fatigue and alopecia. The dose-limiting toxicity of AT9283 was grade 3 febrile neutropenia in two patients at 36 mg/m(2)/72 h and the maximum tolerated dose (MTD) was established at 27 mg/m(2)/72 h. Systemic exposure was dose proportional. The mean oral bioavailability of a 0.9 mg/m(2) dose was 29.4% (range 11.2%-36.7%). Pharmacodynamic analyses indicated antiproliferative and apoptotic activity of AT9283. Four patients with esophageal, non-small-cell lung cancer (n = 2) and colorectal cancer demonstrated RECIST stable disease ≥ 6 months. CONCLUSION: AT9283 was well tolerated up to the MTD of 27 mg/m(2)/72 h. AT9283 is currently assessed in phase II trials.


Asunto(s)
Bencimidazoles/administración & dosificación , Neoplasias/tratamiento farmacológico , Urea/análogos & derivados , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Aurora Quinasas , Bencimidazoles/efectos adversos , Bencimidazoles/sangre , Bencimidazoles/farmacocinética , Estudios de Cohortes , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/sangre , Inhibidores Enzimáticos/farmacocinética , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Urea/administración & dosificación , Urea/efectos adversos , Urea/sangre , Urea/farmacocinética
7.
Ann Oncol ; 22(9): 2137-2143, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21325451

RESUMEN

BACKGROUND: AT7519 is an inhibitor of multiple cyclin-dependent kinases (CDKs). Based on potent antitumor activity in preclinical models, a first-in-human clinical trial in refractory solid tumors investigated its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD). PATIENTS AND METHODS: AT7519 was administered in a '3 + 3' dose- escalation scheme on 5 consecutive days every 3 weeks to patients with advanced, refractory solid tumors. Samples to monitor AT7519 PK and PD were obtained. RESULTS: Twenty-eight patients were treated at seven dose levels (1.8-40 mg/m(2)/day). At 40 mg/m(2)/day, one patient developed hypotension and ST segment elevation. At 34 mg/m(2)/day, dose-limiting toxic effects (DLTs) were QTc prolongation with one death (grade 5), fatigue (grade 4) and mucositis (grade 3). Electrocardiogram review suggested a dose-dependent increase in QTc and recruitment was discontinued without establishing a maximum tolerated dose. Four patients exhibited stable disease for >6 months and one had a prolonged partial response. PK profile revealed modest interpatient variation with linear exposure at increasing doses. Inhibition of markers of CDK activity was observed across the dose range and manifested in antiproliferative activity at a dose of 28 mg/m(2). CONCLUSION: AT7519 elicited clinical and PD activity resulting from CDK inhibition at doses below the appearance of DLT of QTc prolongation.


Asunto(s)
Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Piperidinas/administración & dosificación , Piperidinas/farmacocinética , Pirazoles/administración & dosificación , Pirazoles/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/enzimología , Piperidinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Pirazoles/efectos adversos
8.
Leuk Res ; 109: 106628, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34134067

RESUMEN

A prospective pilot study was carried out on 34 CLL patients treated with ibrutinib, evaluating the effects on symptoms and physical function with changes in plasma exosomes (EXs), ß2-microglobulin (ß2M) and 26 plasma cytokines. The revised Edmonton Symptom Assessment Scale (ESAS-R) demonstrated moderate fatigue, shortness of breath and a sense of unwellness before treatment, which significantly improved within 2 weeks of starting ibrutinib. These changes were associated with a rapid improvement in sit-to-stand and 4 m walking speeds. The plasma levels of CCL11, IL-7, -8 and -10 dropped initially while the levels of TNF-α/-ß, CCL3, CCL4, CCL17, and IL-16 continued to decline for 12 months. Despite the initial lymphocytosis, plasma ß2M levels fell but no consistent change in plasma EXs occurred. Thus, ibrutinib can produce a rapid and sustained improvement in symptoms and physical function in CLL, associated with a decline in multiple plasma cytokines.


Asunto(s)
Actividades Cotidianas , Adenina/análogos & derivados , Citocinas/sangre , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Piperidinas/uso terapéutico , Evaluación de Síntomas/métodos , Adenina/uso terapéutico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Proyectos Piloto , Pronóstico , Estudios Prospectivos
9.
J Gastrointest Surg ; 25(12): 3040-3048, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34729696

RESUMEN

BACKGROUND: Sarcopenia, loss of muscle mass and strength, has been associated with more frequent complications after esophagectomy. This study compared hand-grip strength, muscle mass, and intramuscular adipose tissue as predictors of postoperative outcomes and mortality after esophagectomy. METHODS: Minimally invasive esophagectomy was performed on 175 patients with esophageal cancer. Skeletal muscle index and skeletal muscle density were derived from preoperative CTs. Hand-grip strength was measured using dynamometer. Univariate and multivariable analyses were performed. RESULTS: Preoperative hand-grip strength was normal in 91 (52%), intermediate in 43 (25%), and weak in 41 (23%) patients. Hand-grip strength was significantly correlated with both skeletal muscle index and skeletal muscle density. Postoperative pneumonia occurred in 8/41 (20%) patients with weak strength compared to 4/91 (4%) with normal strength (p = 0.006; Cochran-Armitage Test). Prolonged postoperative ventilation occurred in 11/41 (27%) patients with weak strength compared to 11/91 (12%) with normal strength (p = 0.036). Median length of stay was 9 days in patients with weak strength compared to 7 days for those with normal strength (p = 0.005; Kruskal-Wallis Test). Discharge to non-home location occurred in 15/41 (37%) with weak strength compared to 8/91 (9%) with normal strength (p < 0.001). Postoperative mortality at 90 days was 4/41 (10%) with weak strength compared with no mortalities (0/91) in the normal strength group (p = 0.004). Mortality at 1 year was 18/39 (46%) in patients with weak strength compared to 6/81 (7%) with normal strength, among 158 patients with 1-year follow-up (p < 0.001). CONCLUSIONS: Preoperative hand-grip strength was found to be a powerful predictor of postoperative pneumonia, length of stay, discharge to non-home location, and mortality after esophagectomy.


Asunto(s)
Neoplasias Esofágicas , Fuerza de la Mano , Sarcopenia , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Humanos , Músculo Esquelético , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Sarcopenia/etiología
10.
Neurogastroenterol Motil ; 28(12): 1915-1920, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27353222

RESUMEN

BACKGROUND: About half of adult irritable bowel syndrome (IBS) patients report symptoms with eating and disordered eating habits. However, little is known about eating in adolescent IBS patients, a common age at which eating disorders develop. The aim of the study was to investigate if adolescents with IBS are more likely than healthy controls (HCs) to experience eating-associated symptoms (EAS), report disordered eating patterns, and show differences in diet composition. METHODS: A total of 99 adolescents between 15 and 21 years-of-age participated (n = 48 IBS; n = 51 HCs). All subjects completed three 24-h dietary recalls and questionnaires on EAS and disordered eating. KEY RESULTS: IBS patients were more likely to report EASs than HC (91.7% vs 28%, p < 0.001). Eating-associated symptoms were controlled by avoiding the offending food (97.7%), not eating any food even when hungry (43.2%), or vomiting after eating (13.6%). Compared to HC, IBS patients reported reduced daily intake of overall calories (1828 vs 2139; p < 0.05), fat (65.4 g vs 81.4 g, p < 0.05), and lactose (8.2 g vs 12.8 g, p < 0.01). No differences were found between IBS and HC in screening for disordered eating patterns or BMI, though IBS patients endorsed using potentially unhealthy eating behaviors in an attempt to control symptoms. CONCLUSIONS & INFERENCES: Eating-associated symptoms are very common in adolescents with IBS and associated with changes in eating behaviors and dietary composition. They do not appear to change BMI and risk for eating disorders. More research is needed to guide adolescents with IBS in making appropriate dietary changes to control EASs.


Asunto(s)
Conducta del Adolescente/psicología , Conducta Alimentaria/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/psicología , Adolescente , Conducta del Adolescente/fisiología , Registros de Dieta , Ingestión de Energía/fisiología , Conducta Alimentaria/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Femenino , Humanos , Síndrome del Colon Irritable/fisiopatología , Masculino , Proyectos Piloto , Adulto Joven
11.
J Immunol Methods ; 30(1): 47-53, 1979.
Artículo en Inglés | MEDLINE | ID: mdl-92506

RESUMEN

Enzacryl polythiolactone is a cross-linked acrylamide polymer with an active thiolactone group, capable of coupling to lysine, serine and tyrosine residues. Gamma globulins from antisera specific to human chorionic gonadotropin, carcinoembryonic antigen, alpha-foetoprotein or casein were isolated using Protein A Sepharose and were subsequently coupled to enzacryl. The resulting coupled antibodies were found to provide greater sensitivity and convenience in radioimmunoassay studies than conventional double antibody precipitation methods using the same antisera.


Asunto(s)
Resinas Acrílicas , gammaglobulinas/aislamiento & purificación , Animales , Antígeno Carcinoembrionario/inmunología , Caseínas/inmunología , Humanos , Concentración de Iones de Hidrógeno , Sueros Inmunes/farmacología , Inmunoglobulina G/inmunología , Conejos , Radioinmunoensayo , Ovinos , Compuestos de Sulfhidrilo , alfa-Fetoproteínas/inmunología
12.
Vision Res ; 37(12): 1557-64, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9231222

RESUMEN

The aim of this study was to determine whether an integrator of neural activity influences the amount of myopia and axial elongation resulting from deprivation of form vision. The effects on ocular parameters of a continuous period of 30 min per day of normal vision was compared to two exposures of 15 min duration each, or three exposures of 10 min each. For the remaining time, chicks had monocular translucent occlusion in a 12 hr light/12 hr dark diurnal cycle, for either 2 or 3 weeks. Fellow eyes and the eyes of bilaterally unoccluded chicks were used as controls. We found that several short periods of normal visual stimulation per day were more effective in preventing the development of form deprivation myopia and axial elongation than was one single period of the same total duration, after both 2 and 3 weeks of treatment. This study suggests that the level of neural activity in the retina may have a cumulative effect in influencing ocular growth.


Asunto(s)
Percepción de Forma/fisiología , Miopía/etiología , Privación Sensorial/fisiología , Animales , Segmento Anterior del Ojo/patología , Biometría , Pollos , Ojo/patología , Miopía/patología , Tamaño de los Órganos , Factores de Tiempo , Cuerpo Vítreo/patología
13.
Vision Res ; 35(9): 1337-44, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7610595

RESUMEN

The aim of this study was to determine the minimum daily period of exposure to normal visual stimulation required to prevent occlusion induced myopia in chicks. Chicks were treated with monocular translucent occlusion in a 12 hr light/12 hr dark cycle. Occluders were removed for 0 (constant occlusion), 15, 20, 30, 40, 60, 75, 90, 120, 150, 240 or 720 (no occlusion) minutes each day for either 2 or 3 weeks. Fellow eyes and the eyes of normal chicks (bilaterally unoccluded) were used as controls. Occlusion-induced myopia and axial elongation were found to decrease significantly (P < 0.01) with increasing daily exposure to normal visual stimulation. Application of a time series equation to the data estimates that 30 and 130 min of normal visual exposure per day reduces myopia by 50 and 95% respectively. This study demonstrated that the regulation of ocular growth is affected strongly by short periods of normal visual stimulation in the presence of long periods of abnormal stimulation.


Asunto(s)
Miopía/etiología , Privación Sensorial/fisiología , Visión Ocular/fisiología , Animales , Cámara Anterior/patología , Biometría , Pollos , Ojo/patología , Miopía/patología , Retina/patología , Factores de Tiempo
14.
Toxicol Lett ; 112-113: 499-505, 2000 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-10720772

RESUMEN

Many dietary constituents are chemopreventive in animal models, and experiments with cultured cells are revealing various potential mechanisms of action. Compounds classified as blocking agents can prevent, or greatly reduce, initiation of carcinogenesis, while suppressing agents affect later stages of the process by reducing cell proliferation. Many compounds have both types of activity. Blocking mechanisms include alteration of drug metabolising activities and scavenging of reactive oxygen species. Mechanisms which suppress tumorigenesis often involve modulation of signal transduction pathways, leading to altered gene expression, cell cycle arrest or apoptosis. As our knowledge of how these dietary components affect cell biochemistry improves, so the likelihood of success in chemoprevention trials and in provision of dietary advice to the general population to optimise the chances of preventing disease is increased.


Asunto(s)
Dieta , Neoplasias/prevención & control , Anticarcinógenos/uso terapéutico , Apoptosis/efectos de los fármacos , Ácido Araquidónico/metabolismo , Ciclo Celular/efectos de los fármacos , Curcumina/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Humanos , Indoles/uso terapéutico , Transducción de Señal/efectos de los fármacos
15.
Avian Dis ; 37(2): 274-83, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8363493

RESUMEN

Two groups of 100 white leghorn hens were fed rations either supplemented or deficient in vitamin A for 32 weeks. At the conclusion of the study, vitamin A-supplemented hens laying normally were also compared with a group of vitamin A-supplemented hens in a state of low egg production. Mean egg retinol equivalents (microgram retinol/g egg yolk), egg production, and hatchability in the vitamin A-deficient group were decreased significantly by 4, 20, and 28 weeks, respectively, after beginning treatment. The ovaries of vitamin A-deficient chickens had increased numbers of atretic follicles compared with the ovaries of vitamin A-supplemented hens (20, 24, 28, and 32 weeks), and these atretic follicles contained moderate to severe hemorrhage. Hemorrhage was located either uniformly throughout the follicle or more commonly between the detached granulosa cell layer and the theca interna. Hemorrhagic follicles were uncommon in both vitamin A-supplemented hens and low-production vitamin A-supplemented hens.


Asunto(s)
Pollos , Huevos/análisis , Riñón/patología , Ovario/patología , Enfermedades de las Aves de Corral/patología , Deficiencia de Vitamina A/veterinaria , Vitamina A/análisis , Animales , Femenino , Hemorragia/etiología , Folículo Ovárico/patología , Oviposición , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina A/patología
16.
Man Ther ; 6(1): 40-7, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11243908

RESUMEN

Although several mechanical devices have been developed to objectively assess posteroanterior (PA) stiffness of the lumbar spine, no standardized testing protocol has been adopted. Two factors that may vary across protocols, and that effect measured stiffness and the comfort of the test subject, are the size of the indenter head used to apply the PA pressure, and indenting frequency. Three variables; PA stiffness, defined as the slope of the stiffness curve (K), the displacement of the indenter at 30N (D30), and rating of perceived comfort, were measured in 36 subjects asymptomatic for low back pain. For each subject nine tests were conducted, using three different indenter head sizes (300mm(2), 720mm(2)and 1564mm(2)) at each of three different testing frequencies (0.25 Hz, 0.5 Hz and 2 Hz). Machine testing with a large indenter head produced a lower K value, an increased D30 value and higher perceived comfort, while a fast testing frequency produced a higher K value and a lower D30 value. An indenter size by frequency interaction showed small indenter heads to be least comfortable at slow speed. The differences found suggest that the indenter head size and the testing frequency should be standardized during mechanical spinal stiffness testing.


Asunto(s)
Dolor de la Región Lumbar/diagnóstico , Vértebras Lumbares , Dolor/etiología , Examen Físico/efectos adversos , Examen Físico/instrumentación , Enfermedad Aguda , Adulto , Análisis de Varianza , Fenómenos Biomecánicos , Elasticidad , Diseño de Equipo , Análisis Factorial , Humanos , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/fisiopatología , Dolor/diagnóstico , Dimensión del Dolor , Examen Físico/normas , Modalidades de Fisioterapia/instrumentación , Modalidades de Fisioterapia/normas
17.
Poult Sci ; 71(12): 2075-82, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1470591

RESUMEN

Hens of a type used for egg production were fed a corn and soybean meal diet supplemented with no vitamin B12 or with vitamin B12 levels to provide one, two, or four times the National Research Council (1984) breeding hen requirement of 4 micrograms/kg diet for 27 wk. All hens were placed on a recovery diet containing one and one-half times the requirement level of vitamin B12 from Weeks 27 through 30. Egg yolk vitamin B12 concentrations were determined frequently by radioisotope dilution analysis. Egg production records were kept continuously, and eggshell thickness, egg weight, hatchability of eggs, and hen body weights were measured at selected times. Although egg yolk vitamin B12 concentrations were high at the outset, they decreased markedly in 2 wk from hens fed the two lowest dietary levels. After 12 wk on the diets, egg concentrations of vitamin B12 stabilized and were proportional to the amount of vitamin added to the diet. Egg concentrations of vitamin B12 between 1.3 and 2.6 micrograms/100 g yolk appeared to be needed to support maximum hatchability and egg weight. Egg production was reduced after 12 wk on the diets in the hens fed the two lowest vitamin B12 levels. As vitamin B12 level increased, shell thickness decreased and egg weight, hen weight, and hatchability increased. Maximum egg production, egg weight, hen weight, and hatchability were obtained when the diet contained 8.0 micrograms/kg of vitamin B12. Egg yolk vitamin B12 concentrations respond rapidly to dietary changes in the level of this vitamin and are indicative of the vitamin B12 status of the hen.


Asunto(s)
Pollos/fisiología , Estado Nutricional , Oviposición/fisiología , Óvulo/metabolismo , Vitamina B 12/administración & dosificación , Animales , Radioisótopos de Cobalto , Dieta , Cáscara de Huevo/anatomía & histología , Yema de Huevo/metabolismo , Femenino , Técnicas de Dilución del Indicador , Vitamina B 12/metabolismo
18.
Poult Sci ; 72(1): 154-64, 1993 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8426843

RESUMEN

Laying hens were fed deficient diets, unsupplemented or supplemented with one, two, or four times the National Research Council requirement level of vitamin A for 27 wk. Vitamin A levels of egg yolk from hens fed the unsupplemented diet slowly declined but levels of vitamin A stabilized at 12 wk in the supplemented groups and were related to dietary level. Egg production of hens fed the unsupplemented diet declined significantly after 12 wk and egg yolk levels continued to decline to Week 27. Hatchability of eggs laid by the unsupplemented hens was significantly lower at Weeks 25 and 26 than hatchability for those hens receiving dietary vitamin A. Hen weight, egg weight, and shell thickness were not consistently changed by treatment. In a second experiment, hens were fed a diet with and without 9,000 IU vitamin A/kg of diet. With birds receiving the supplemented diet, egg yolk vitamin A levels were stable after 13 wk, whereas egg yolk levels from unsupplemented hens declined slowly. Egg production with the unsupplemented diet was significantly reduced after 16 wk but the magnitude of the reduction was less than that in the first experiment, although egg vitamin A levels were as low as those in the first experiment. Hatchability of eggs during Weeks 25 to 28 was greatly reduced. Egg weight, albumen score, and chick weight were not consistently altered by vitamin A status. Because declines in egg yolk vitamin A do not precede declines in egg production they are not useful to predict future vitamin A deficiency in laying hens.


Asunto(s)
Pollos , Yema de Huevo/química , Estado Nutricional , Vitamina A/análisis , Animales , Pollos/metabolismo , Femenino , Vitamina A/farmacocinética
19.
Poult Sci ; 72(3): 483-94, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8464790

RESUMEN

Two experiments determined the effect of dietary riboflavin supplementation on egg yolk and albumen riboflavin concentrations, egg production, egg weight, shell thickness, hen weight, hatchability, incidence of clubbed down, and incidence of hemorrhagic embryos. In the first experiment, hens were fed rations containing 1.55, 2.20, 4.40, and 8.80 mg of riboflavin/kg of diet for 27 wk. Significant (P < .05) depressions in both yolk and albumen riboflavin concentrations were noted at the two lower riboflavin levels after 1 wk. Egg production, egg weight, hatchability, and hen weight were all significantly depressed by the two lower riboflavin levels later in the experiment when compared with the two higher levels. Results indicate that egg riboflavin concentrations are related to important production parameters that may be used to predict future dietary riboflavin inadequacies. In the second experiment, hens were fed either an unsupplemented diet or a riboflavin-adequate diet. Measurements of egg albumen riboflavin content, egg production, hatchability, and embryo abnormalities were made twice each week. Results showed depressed albumen riboflavin concentrations and hatchability and increased incidence of hemorrhagic embryos and clubbed down without changes in egg production during the 4- to 7-day period following feeding of the unsupplemented diet. These results show that low albumen riboflavin content immediately affect hatchability and embryonic development. The estimated minimum critical albumen riboflavin concentrations needed to support maximum reproductive function are between 1.9 and 2.9 micrograms of riboflavin/g of egg albumen. These critical values might be used to evaluate riboflavin status of laying and breeding flocks.


Asunto(s)
Pollos/fisiología , Huevos/análisis , Estado Nutricional , Riboflavina/análisis , Vitaminas/análisis , Alimentación Animal , Animales , Peso Corporal/efectos de los fármacos , Embrión de Pollo , Cáscara de Huevo/efectos de los fármacos , Femenino , Alimentos Fortificados , Oviposición/efectos de los fármacos , Riboflavina/farmacología
20.
Poult Sci ; 71(3): 522-9, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1313976

RESUMEN

Two experiments were conducted to determine the effects of heat, water, acid, and alkali treatment of tomato pomace on gain, feed to gain ratio, nitrogen utilization, and ME of diets for broiler chicks. In Experiment 1, both treated and untreated tomato pomace was included in broiler diets at a 10 or 20% level. Results indicated that the level or antinutritional factors present in untreated tomato cannery waste did not appreciably depress any measured production parameter. Hence, it appeared that untreated tomato cannery wastes might be used as a feed ingredient in low-energy poultry diets (broiler breeder and laying hen recycling rations), ruminant diets, and as a protein source in regions of the world where such feed ingredients are scarce. The second experiment was designed to test the effect of alkali concentration and treatment time of tomato pomace on the performance of broiler chicks. Alkali treatment of tomato cannery wastes increased gain and decreased feed to gain ratios of broiler chicks over those of untreated tomato waste controls. Results indicated that the increased gain and decreased feed to gain ratios of the chicks were due in part to the acid neutralization phase of the alkali treatment. Alkali treatment apparently affects the tomato cannery wastes almost instantaneously, as differences among actual treatment times and concentrations were small. However, only the highest alkali treatment increased the pH of the tomato cannery waste above 7, suggesting that a true alkali treatment might cause additional improvements in gain and feed to gain ratio when fed to broiler chicks.


Asunto(s)
Alimentación Animal , Pollos/crecimiento & desarrollo , Metabolismo Energético , Manipulación de Alimentos , Nitrógeno/metabolismo , Animales , Pollos/metabolismo , Fibras de la Dieta/administración & dosificación , Ingestión de Alimentos , Ingestión de Energía , Femenino , Frutas , Calor , Concentración de Iones de Hidrógeno , Masculino , Semillas , Hidróxido de Sodio/farmacología , Sodio en la Dieta/administración & dosificación , Agua , Aumento de Peso
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