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1.
J Agric Food Chem ; 68(37): 10167-10173, 2020 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-32786844

RESUMEN

For pesticide registration a post application assessment is made on the safety of any residue remaining in the edible portion of the treated crop. This assessment does not typically consider the bioaccessibility of pesticide residues. The effects of this on potential exposure to incurred difenoconazole residues passing through the human gastrointestinal tract were studied, including the impact of commodity processing. It has previously been demonstrated that solvent extraction methods have the potential to overestimate the bioaccessible fraction, so in vitro simulated gut systems may offer a better approach to determine residue bioaccessibility to refine the risk assessment process. The bioaccessibility of difenoconazole residues associated with processed rice samples was assessed using in vitro intestinal extraction and colonic fermentation methods. The mean bioaccessibility following intestinal digestion was 33.3% with a range from 13% to 70.6%. Quantification of the colonic bioaccessible fraction was not possible due to compound metabolism. Mechanical processing methods generally increased the residue bioaccessibility, while chemical methods resulted in a decrease. Both mechanical and chemical processing methods reduced the total difenoconazole residue level by ca. 50%.


Asunto(s)
Dioxolanos/química , Manipulación de Alimentos/métodos , Oryza/química , Residuos de Plaguicidas/química , Triazoles/química , Disponibilidad Biológica , Digestión , Dioxolanos/metabolismo , Tracto Gastrointestinal/metabolismo , Humanos , Oryza/metabolismo , Residuos de Plaguicidas/metabolismo , Medición de Riesgo , Semillas/química , Semillas/metabolismo , Triazoles/metabolismo
2.
Acta Oncol ; 57(7): 965-972, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29419331

RESUMEN

BACKGROUND: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. METHODS: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. FINDINGS: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. INTERPRETATION: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.


Asunto(s)
Fraccionamiento de la Dosis de Radiación , Neoplasias/radioterapia , Calidad de Vida , Compresión de la Médula Espinal/radioterapia , Anciano , Anciano de 80 o más Años , Estudios de Equivalencia como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/patología , Compresión de la Médula Espinal/etiología , Resultado del Tratamiento
3.
Clin Oncol (R Coll Radiol) ; 30(1): 30-38, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29097074

RESUMEN

AIMS: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial. The protocol allocated patients between three radiation schedule dose levels (60, 66 or 72 Gy, in 20, 22 and 24 fractions, respectively, 3 Gy daily, five fractions per week) according to combined lung V25Gy (V25Gy ≤ 30%) with built-in early stopping toxicity rules. The primary end point was toxicity with evaluation of dose-limiting toxicity. The secondary objectives included radiological tumour response rate at 3 months after the completion of radiation therapy and the thoracic progression-free survival time. RESULTS: Sixty patients were recruited from August 1999 to June 2009. Forty-nine patients were included in the primary per-protocol analysis. Eleven patients were not evaluable. In the first 30 evaluable patient cohort, severe oesophageal toxicity was reported in two patients (2/49; 4% experiencing grade 5 oesophageal late toxicity, related to the 97% oesophageal length). The trial was temporarily closed and was then reopened to validate an oesophageal dose volume constraint (DVC) of limiting the length of oesophagus fully encompassed by the 97% isodose to less than 1 cm (applied to 21 patients). The trial prospectively showed the safety of the oesophageal DVC, with no oesophageal toxicity above grade 3 thereafter. Thirty-nine per cent of patients had disease progression at 3-4 months after radiotherapy, 22% had stable disease, 20% had a complete response and 14% had a partial response. The median overall survival was 13.6 months (95% confidence interval 10.5-16.7) and overall survival at 1 and 3 years was 57% and 29%, respectively. CONCLUSION: A strategy using accelerated hypofractionated 3DCRT is feasible and reasonably safe for patients with inoperable NSCLC. It is safe to deliver for centrally located tumours if DVCs are applied to the oesophagus, which is the primary dose-limiting toxicity. Further studies are required to assess the efficacy of hypofractionated regimens for centrally located tumours using an oesophageal DVC and monitoring for oesophageal toxicity.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosis de Radiación , Hipofraccionamiento de la Dosis de Radiación , Análisis de Supervivencia
4.
Clin Radiol ; 71(4): 375-80, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26880299

RESUMEN

AIM: To correlate the results of transrectal ultrasound (TRUS)-guided targeted prostate biopsies (performed in the setting of at least one previous negative biopsy) with the Prostate Imaging Reporting and Data System (PI-RADS). MATERIAL AND METHODS: Fifty-two patients (mean age 64 years, range 52-76 years), with previous negative prostate biopsy underwent magnetic resonance imaging (MRI)-directed TRUS-guided targeted and sectoral biopsy. A retrospective review of MRI examinations was carried out, blinded to biopsy results. PI-RADS scores (T2, diffusion-weighted imaging [DWI] and overall) were assigned on a per lesion basis, and localised to sextants. The scores were correlated with biopsy results, and the positive predictive values (PPV) of PIRADS scores for positive biopsies were calculated. RESULTS: Overall, biopsies were positive in 23/52 (44.2%) patients. Eighty-one areas were targeted in 52 patients. On a per lesion basis, there was significant correlation between positive targeted biopsy and both T2 and overall PI-RADS score (p<0.001). The correlation between biopsy and DWI score was significant for peripheral zone tumours only, not for transitional zone tumours. The PPV of overall PI-RADS scores of 3, 4, and 5 were 10.6%, 44%, and 100%, respectively. The PPV of T2 PI-RADS scores of 3, 4, and 5 were 19.6%, 60%, and 100%, respectively. The PPV of DWI PI-RADS scores of 3, 4, and 5 were 50%, 27.3%, and 33%, respectively. When transitional tumours were excluded, the PPV of DWI PI-RADS 3, 4, and 5 were 40%, 43%, and 78%. CONCLUSION: The PIRADS score provides an effective framework for determining the likelihood of prostate cancer on MRI. The DWI PI-RADS score correlates well with the presence of peripheral zone tumour on targeted biopsy, but not with transitional zone tumours.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias de la Próstata/patología , Sistemas de Información Radiológica , Ultrasonografía Intervencional , Anciano , Biopsia , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Retrospectivos
5.
Eur J Radiol ; 84(6): 1019-22, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25795196

RESUMEN

OBJECTIVES: Prostate cancer staging MR examinations commonly include abdominal sequences to assess for non-regional (common iliac or para-aortic) nodal metastasis. In our experience the diagnostic yield of this is limited, but incidental findings are frequent, often necessitating further investigations. The aim of this study is to assess the diagnostic utility of abdominal sequences in routine prostate cancer MR staging studies. METHODS: Findings on abdominal sequences of consecutive MRI prostate studies performed for staging newly diagnosed prostate cancer between September 2011 and September 2013 were reviewed with respect to adenopathy and additional incidental findings. Results were correlated with Gleason grade and serum prostate-specific antigen (PSA) level in each case. RESULTS: 355 MRI prostate examinations were reviewed. 4 (1.1%) showed enlarged non-regional lymph nodes. Incidental findings were found in 82(23.1%) cases, neccessitating further investigation in 45 (12.7%) cases. Enlarged non-regional nodes were associated with higher PSA level and Gleason grade (p=0.007, p=0.005 respectively). With a combined threshold of PSA > 20 ng/mL and/or Gleason grade ≥ 8 the sensitivity, specificity, PPV and NPV were 100, 60, 3 and 100% respectively for predicting the presence of non-regional adenopathy. CONCLUSIONS: Routine abdominal sequences are of very low yield in routine prostate cancer MR staging, frequently resulting in incidental findings requiring further work-up and should be reserved for high-risk cases. Our experience supports the use of an abdominal staging sequence in high-risk cases only.


Asunto(s)
Abdomen/patología , Detección Precoz del Cáncer , Hallazgos Incidentales , Imagen por Resonancia Magnética , Neoplasias de la Próstata/patología , Anciano , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Estadificación de Neoplasias , Examen Físico , Guías de Práctica Clínica como Asunto , Antígeno Prostático Específico/sangre , Sensibilidad y Especificidad
6.
Environ Pollut ; 181: 128-32, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23850629

RESUMEN

Bioaccessibility tests can be used to improve contaminated land risk assessments. For organic pollutants a 'sink' is required within these tests to better mimic their desorption under the physiological conditions prevailing in the intestinal tract, where a steep diffusion gradient for the removal of organic pollutants from the soil matrix would exist. This is currently ignored in most PBET systems. By combining the CEPBET bioaccessibility test with an infinite sink, the removal of PAH from spiked solutions was monitored. Less than 10% of spiked PAH remained in the stomach media after 1 h, 10% by 4 h in the small intestine compartment and c.15% after 16 h in the colon. The addition of the infinite sink increased bioaccessibility estimates for field soils by a factor of 1.2-2.8, confirming its importance for robust PBET tests. TOC or BC were not the only factors controlling desorption of the PAH from the soils.


Asunto(s)
Monitoreo del Ambiente/métodos , Compuestos Orgánicos/análisis , Contaminantes del Suelo/análisis , Suelo/química , Cinética , Medición de Riesgo
7.
Neurogenetics ; 14(2): 143-52, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23625158

RESUMEN

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin.


Asunto(s)
Trastorno Autístico/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad/genética , Transcriptoma/genética , Adolescente , Niño , Preescolar , Análisis por Conglomerados , Regulación hacia Abajo , Femenino , Pruebas Genéticas/métodos , Humanos , Masculino , Fenotipo , Hermanos , Regulación hacia Arriba
8.
Ir J Med Sci ; 181(4): 499-509, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22426901

RESUMEN

PURPOSE: To compare the relative diagnostic performance of MDCT, PET/CT and Primovist-enhanced MRI (P-MRI) in the pre-resection work-up of colorectal cancer (CRC) liver metastases. METHOD AND MATERIALS: This was a retrospective study of consecutive referrals for CRC liver metastases. All patients had MDCT, PET/CT and P-MRI examinations within 3 months of each other. They were divided into 2 groups: resected and unresected. Patients in the resected group underwent liver resection within 3 months of the imaging studies. In the unresected group, patients were unresectable by imaging criteria or are awaiting surgery. Standard of reference (SOR) was intra-operative ultrasound findings and pathology for the resected group. Intermodality comparison was the SOR for the unresected group. Number of lesions identified by each imaging modality for each patient was recorded. Sensitivity (95% CI) and PPV were calculated for each imaging modality in the resected group. RESULTS: There were 19 patients in the resected group and 11 patients in the unresected group. The sensitivity (96%) and PPV (0.91) of P-MRI were both superior to that of MDCT (P = 0.0009) and PET/CT (P = 0.0003). Intermodality comparison showed that P-MRI detected more lesions than MDCT and PET/CT. CONCLUSION: The sensitivity and PPV of P-MRI was superior to that of MDCT and PET/CT. P-MRI probably has the most added value if used after MDCT and PET/CT in patients still considered eligible for liver resection.


Asunto(s)
Neoplasias Colorrectales/patología , Gadolinio DTPA , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada Multidetector , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Medios de Contraste , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad
9.
Environ Sci Technol ; 45(12): 5301-8, 2011 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-21568264

RESUMEN

Assessment of the risk to human health posed by contaminated land may be seriously overestimated if reliant on total pollutant concentration. In vitro extraction tests, such as the physiologically based extraction test (PBET), imitate the physicochemical conditions of the human gastro-intestinal tract and offer a more practicable alternative for routine testing purposes. However, even though passage through the colon accounts for approximately 80% of the transit time through the human digestive tract and the typical contents of the colon in vivo are a carbohydrate-rich aqueous medium with the potential to promote desorption of organic pollutants, PBET comprises stomach and small intestine compartments only. Through addition of an eight-hour colon compartment to PBET and use of a carbohydrate-rich fed-state medium we demonstrated that colon-extended PBET (CE-PBET) increased assessments of soil-bound PAH bioaccessibility by up to 50% in laboratory soils and a factor of 4 in field soils. We attribute this increased bioaccessibility to a combination of the additional extraction time and the presence of carbohydrates in the colon compartment, both of which favor PAH desorption from soil. We propose that future assessments of the bioaccessibility of organic pollutants in soils using physiologically based extraction tests should have a colon compartment as in CE-PBET.


Asunto(s)
Colon/metabolismo , Monitoreo del Ambiente/métodos , Hidrocarburos Policíclicos Aromáticos/análisis , Suelo/química , Benzo(a)pireno/análisis , Disponibilidad Biológica , Mucosa Gástrica/metabolismo , Humanos , Intestino Delgado/metabolismo , Factores de Tiempo
11.
Environ Sci Technol ; 43(16): 6190-5, 2009 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19746712

RESUMEN

An understanding of the primary pathways of plant uptake of organic pollutants is important to enable the risks from crops grown on contaminated soils to be assessed. A series of experiments were undertaken to quantify the importance of the pathways of contamination and the subsequent transport within the plant using white clover plants grown in solution culture. Root uptake was primarily an absorption process, but a component of the contamination was a result of the transpiration flux to the shoot for higher solubility compounds. The root contamination can be easily predicted using a simple relationship with K(OW), although if a composition model was used based on lipid content, a significant under prediction of the contamination was observed. Shoot uptake was driven by the transpiration stream flux which was related to the solubility of the individual PAH rather than the K(OW). However, the experiment was over a short duration, 6 days, and models based on K(OW) may be better for crops grown in the field where the vegetation will approach equilibrium and transpiration cannot easily be measured. A significant fraction of the shoot contamination resulted from aerial deposition derived from volatilized PAH. This pathway was more significant for compounds approaching log K(OA) > 9 and log K(AW) < -3. The shoot uptake pathways need further investigation to enable them to be modeled separately. There was no evidence of significant systemic transport of the PAH, so transfer outside the transpiration stream is likely to be limited.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos/metabolismo , Trifolium/metabolismo , Biodegradación Ambiental , Transporte Biológico , Cinética , Lípidos/química , Modelos Biológicos , Raíces de Plantas/metabolismo , Brotes de la Planta/metabolismo , Soluciones , Factores de Tiempo
13.
J Med Imaging Radiat Oncol ; 53(1): 139-41, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19453540

RESUMEN

We report the case of a 41-year-old mentally retarded male with recurrent pilomatrix carcinoma of the occipital region which invaded the occipital bone, left cerebellum and left temporal lobe. At his initial presentation the patient had a craniotomy and subtotal excision of the lesion with positive margins. He received no adjuvant therapy. After an early intracranial recurrence he had subtotal debulking and was referred for external beam radiotherapy. At 27 months follow-up after adjuvant external beam radiotherapy the intracranial component has not progressed and the patient remains clinically well.


Asunto(s)
Neoplasias Encefálicas/terapia , Invasividad Neoplásica/diagnóstico por imagen , Recurrencia Local de Neoplasia/prevención & control , Hueso Occipital/diagnóstico por imagen , Pilomatrixoma/terapia , Neoplasias Craneales/diagnóstico , Neoplasias Craneales/terapia , Neoplasias Encefálicas/diagnóstico , Craneotomía , Humanos , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Pilomatrixoma/diagnóstico , Radiografía , Radioterapia Adyuvante , Resultado del Tratamiento
14.
Glob Public Health ; 4(2): 183-204, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19333808

RESUMEN

This paper assesses whether a nation-state's participation in conflict influences its ability to confront global pandemic or disease. Two alternative hypotheses are proposed. First, increased levels of conflict participation lead to increased abilities of states to confront pandemics. A second and alternative hypothesis is that increased conflict participation decreases the ability of states to confront pandemics. The hypotheses are tested through the ultimate case of war and pandemic: the 1918 Influenza pandemic (Spanish Flu or 'La Grippe') that killed 20-100 million people worldwide. Using simple correlation and case illustrations, we test these hypotheses with special focus upon the ability of the participant countries to confront the pandemic. The findings suggest, in a limited and varied fashion, that while neutral countries enjoyed the lowest levels of pandemic deaths, of the participant countries greater levels of conflict participation correlate with lower levels of pandemic deaths. The paper concludes with some propositions regarding the relationship between the current 'war on terror' and prospective pandemics such as avian flu.


Asunto(s)
Planificación en Desastres , Brotes de Enfermedades , Gripe Humana/epidemiología , Guerra , Historia del Siglo XX , Humanos , Gripe Humana/historia , Personal Militar , Primera Guerra Mundial
15.
Ir J Med Sci ; 178(1): 83-4, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19214646

RESUMEN

INTRODUCTION: Insertion of a percutaneous nephrostomy (PCN) catheter decompresses the upper urinary tract, thereby removing the hydroureteronephrosis upon which magnetic resonance (MR) urography is dependent for diagnosing the precise level and cause of ureteric obstruction. METHOD: We present the case of a young woman who required PCN insertion during pregnancy. RESULT: Only when unenhanced T2-weighted MR urography was repeated after the creation of an artificial hydronephrosis by an injection of sterile saline via the PCN catheter was the diagnosis of stone in the mid-ureter later made possible. CONCLUSION: This case highlights an easy solution to a limitation with the use of MR urography during pregnancy, when a physiological hydroureteronephrosis has been relieved by the insertion of a PCN catheter.


Asunto(s)
Hidronefrosis/diagnóstico , Imagen por Resonancia Magnética , Nefrostomía Percutánea/métodos , Adulto , Femenino , Humanos , Hidronefrosis/fisiopatología , Nefrostomía Percutánea/instrumentación , Embarazo
16.
Environ Pollut ; 156(3): 1284-9, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18433956

RESUMEN

Nonylphenol polyethoxylates (NPEOs) are surfactants found ubiquitously in the environment due to widespread industrial and domestic use. Biodegradation of NPEOs produces nonylphenol (NP), an endocrine disruptor. Sewage sludge application introduces NPEOs and NP into soils, potentially leading to accumulation in soils and crops. We examined degradation of NP and nonylphenol-12-ethoxylate (NP12EO) in four soils. NP12EO degraded rapidly (initial half time 0.3-5 days). Concentrations became undetectable within 70-90 days, with a small increase in NP concentrations after 30 days. NP initially degraded quickly (mean half time 11.5 days), but in three soils a recalcitrant fraction of 26-35% remained: the non-degrading fraction may consist of branched isomers, resistant to biodegradation. Uptake of NP by bean plants was also examined. Mean bioconcentration factors for shoots and seeds were 0.71 and 0.58, respectively. Removal of NP from the soil by plant uptake was negligible (0.01-0.02% of initial NP). Root concentrations were substantially higher than shoot and seed concentrations.


Asunto(s)
Agricultura , Disruptores Endocrinos/metabolismo , Glicoles de Etileno/metabolismo , Fabaceae/metabolismo , Fenoles/metabolismo , Contaminantes del Suelo/metabolismo , Biodegradación Ambiental , Ecología/métodos , Disruptores Endocrinos/análisis , Glicoles de Etileno/análisis , Fabaceae/química , Fenoles/análisis , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Brotes de la Planta/química , Brotes de la Planta/metabolismo , Semillas/química , Suelo/análisis , Microbiología del Suelo , Contaminantes del Suelo/análisis , Factores de Tiempo
17.
Ir Med J ; 100(4): 422-4, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17566474

RESUMEN

In patients with malignant melanoma, Breslow depth increases with age. However, studies suggest that the frequency of sentinel lymph node metastases in malignant melanoma decreases with age. We investigated whether this applied to the cohort of patients undergoing sentinel lymph node biopsy (SLNB) in our institution. In a prospectively accrued database we identified 149 patients undergoing SLNB from 1997 to 2005. Tumour thickness as measured by Breslow depth was assessed in stratified age groups. We assessed the relationship between SLNB positivity and age using the Chi-square for trend. We directly examined the relationship between SLNB positivity in patients aged less than 65 and aged 65 years of age and over. Disease-free and overall survival in patients aged less than 65 and aged 65 years of age and over were also assessed. Comparing the age groups, there was no significant difference identified in Breslow depth (<65 years, median Breslow > or = 1.2 mm (range 0.2-9.7); > or =65 years, median Breslow > or = 1.4 mm (range 0.12-8.5); p > or = 0.06, Mann-Whitney U). Chi-square for trend identified no significant relationship between SLNB positivity and age. We found n=120 patients <65 had SLNB, of which 26 (21.7%) were positive. In patients =65, n=29 had SLNB of which 3 (10.3%) were positive. These differences were not statistically significant (Fisher's exact test, p > or = 0.2). There was no difference in disease-free or overall survival between patients aged <65 or > or =65 who had SLNB (median follow-up 37.5 months (range 5-70); disease-free survival, p > 0.08; overall survival, p > or = 0.3, Logrank test). We did not find that elderly patients with malignant melanoma had a demonstrable difference in tumour thickness when compared to younger patients. In those patients who underwent SLNB there was no significant difference in node positivity between the age groups. Disease-free and overall survival were not significantly different between the age groups. Further study and longer follow-up will help establish the relationship between age and SLNB positivity.


Asunto(s)
Ganglios Linfáticos/patología , Metástasis Linfática/patología , Melanoma/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Bases de Datos como Asunto , Femenino , Humanos , Irlanda , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Análisis de Supervivencia
18.
Cancer Chemother Pharmacol ; 59(1): 79-87, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16642371

RESUMEN

PURPOSE: Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines. METHODS: We conducted a dose-escalating, single arm, prospective, open label, non-randomised phase I trial of epirubicin (75 mg/m(2)) in combination with escalating oral doses of sulindac (0-800 mg) in patients with advanced cancer to identify an appropriate dose of sulindac to use in future resistance studies. Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3. RESULTS: Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1 ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy) were enrolled. Eight patients received a full six cycles of treatment; 14 patients received three or more cycles. Dose-limiting toxicity was observed in two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a patient with advanced lung cancer), and sulindac 600 mg was deemed to be the maximum tolerated dose. Sulindac had no effect on epirubicin pharmacokinetics. Among 15 patients with evaluable tumour, two partial responses were seen (malignant melanoma and breast cancer). Four others had prolonged stable disease. CONCLUSION: Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Epirrubicina/uso terapéutico , Neoplasias/tratamiento farmacológico , Sulindac/farmacocinética , Sulindac/uso terapéutico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Epirrubicina/efectos adversos , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Recuento de Plaquetas , Estudios Prospectivos , Sulindac/efectos adversos , Troponina/metabolismo
19.
Vascul Pharmacol ; 45(5): 258-67, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17030152

RESUMEN

The long asymptomatic period before the onset of chronic diseases offers good opportunities for disease prevention. Indeed, many chronic diseases may be preventable by avoiding those factors that trigger the disease process (primary prevention) or by use of therapy that modulates the disease process before the onset of clinical symptoms (secondary prevention). Accurate prediction is vital for disease prevention so that therapy can be given to those individuals who are most likely to develop the disease. The utility of predictive markers is dependent on three parameters, which must be carefully assessed: sensitivity, specificity and positive predictive value. Specificity is important if a biomarker is to be used to identify individuals either for counseling or for preventive therapy. However, a reciprocal relationship exists between sensitivity and specificity. Thus, successful biomarkers will be highly specific without sacrificing sensitivity. Unfortunately, biomarkers with ideal specificity and sensitivity are difficult to find for many diseases. One potential solution is to use the combinatorial power of a large number of biomarkers, each of which alone may not offer satisfactory specificity and sensitivity. Recent technological advances in genetics, genomics, proteomics, and bioinformatics offer a great opportunity for biomarker discovery. The newly identified biomarkers have the potential to bring increased accuracy in disease diagnosis and classification, as well as therapeutic monitoring. In this review, we will use type 1 diabetes (T1D) as an example, when appropriate, to discuss pertinent issues related to high throughput biomarker discovery.


Asunto(s)
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Genómica , Proteómica , Enfermedad Crónica , Interpretación Estadística de Datos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/prevención & control , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Genómica/métodos , Humanos , Modelos Estadísticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Valor Predictivo de las Pruebas , Análisis por Matrices de Proteínas , Proteínas/metabolismo , Proteómica/métodos , Sensibilidad y Especificidad
20.
Gynecol Oncol ; 101(3): 441-4, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16337996

RESUMEN

BACKGROUND AND PURPOSE: Many patients with Stage IIIB cervix cancer (Ca) and hydronephrosis will require ureteral stenting. The timing is important as delays or prolonged overall treatment times adversely affect outcome. Our aim was to measure the effect of pelvic radiotherapy (R/T) on renal function and identify a subset of patients at high risk of acute urinary obstruction during R/T. PATIENTS AND METHODS: From 1/1/2000 to 1/1/2002, all patients with Stage IIIB cervix Ca and hydronephrosis were analysed retrospectively. To quantify the impact of pelvic R/T, all eligible patients from 1/7/2002-1/7/2004 had prospectively recorded baseline biochemistry, creatinine clearance and renal ultrasounds; these were repeated weekly to detect any change in renal function or degree of hydronephrosis. RESULTS: 13 eligible patients were analysed retrospectively, 5 with unilateral hydronephrosis with 40% requiring urinary diversion (UD). 8 had bilateral hydronephrosis, with 75% requiring UD; 50% before R/T and 35% during R/T. Average creatinine clearance (CrCl) was 74 mL/min (1.24 mL/s) in unilateral hydronephrosis , bilateral = 52 mL/min (0.87 mL/s), in those stented during R/T it was < 40 mL/min (0.67 mL/s). The resulting break in R/T was 6 and 19 days. In the prospective study, 5 patients were eligible and 4 consented. 75% had unilateral hydronephrosis and did not require UD with an average CrCl = 71 mL/min (1.19 mL/s). 1 patient with bilateral hydronephrosis had a CrCl of < 20 mL/min (0.33 mL/s) with bilateral stents placed before R/T. CONCLUSIONS: Patients with bilateral hydronephrosis and a low CrCl < 50 mL/min (0.84 mL/s) should be considered for elective UD prior to R/T. Pelvic R/T did not induce any deterioration in renal function or degree of hydronephrosis.


Asunto(s)
Lesión Renal Aguda/etiología , Hidronefrosis/cirugía , Traumatismos por Radiación/etiología , Derivación Urinaria/métodos , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma/inducido químicamente , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/orina , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/orina , Creatinina/orina , Femenino , Humanos , Hidronefrosis/etiología , Hidronefrosis/orina , Estadificación de Neoplasias , Estudios Prospectivos , Traumatismos por Radiación/prevención & control , Estudios Retrospectivos , Stents , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/orina
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