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1.
Ann R Coll Surg Engl ; 104(4): 257-260, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34939845

RESUMO

INTRODUCTION: The aim of this study was to assess faecal immunochemical test (FIT) negativity in terms of its effect on cancer risk in the local symptomatic two-week wait (2WW) population. FIT was introduced to the colorectal 2WW pathway at the start of the pandemic. This study analyses the FIT-negative (<10µg Hb/g) cohort and calculates the relative risk and odds ratio associated with a negative FIT test. METHODS: FIT tests were sent to symptomatic 2WW patients without rectal bleeding, iron-deficient anaemia or palpable mass. Where FIT was <10µg Hb/g investigations were moved to a radiology protocol. RESULTS: The test return rate was 91% with a FIT-negative (<10µg Hb/g) rate of 82%. The FIT-negative group in the symptomatic referral pathway in Cornwall have a low (1.4%) risk of colon cancer but a significant risk (6.6%) when all cancer types are considered. The impact of a negative quantitative FIT changes the odds ratio of a patient having a luminal cancer by 0.26. The odds ratio for 'all cancer' risk was affected by 0.83. CONCLUSION: A negative FIT test within the local NG12 symptomatic patient group signifies a low risk of colon cancer and identifies patients who can be initially investigated with cross-sectional imaging. However, when all cancer types are considered, cancer prevalence in this group remains above 6%. In relative risk terms a negative FIT represents a small change in overall risk and this patient group still qualify for investigation through 2WW pathways.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Fezes , Humanos , Sangue Oculto , Reto , Encaminhamento e Consulta
2.
Nat Commun ; 8(1): 592, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28928380

RESUMO

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

3.
Food Funct ; 8(5): 1955-1965, 2017 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-28470309

RESUMO

An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 µg mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Fusobacterium nucleatum/efeitos dos fármacos , Boca/microbiologia , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Vaccinium macrocarpon/química , Sucos de Frutas e Vegetais/análise , Fusobacterium nucleatum/fisiologia , Humanos , Extratos Vegetais/química , Porphyromonas gingivalis/fisiologia , Streptococcus/fisiologia
4.
Dis Esophagus ; 30(3): 1-5, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28184470

RESUMO

Barrett's esophagus is a well-recognized risk factor for esophageal adenocarcinoma. The natural history of Barrett's esophagus classified as 'indefinite for dysplasia' (IND) is poorly characterized. The aim of this study is to characterize the natural history of IND by determining the rate of neoplastic progression and identifying risk factors for progression. Patients from the University of Pennsylvania Health System pathology database and Barrett's esophagus registry with a diagnosis of IND between 2000 and 2014 were identified. Exclusion criteria included: (1) prior diagnosis of low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma (EAC); (2) presence of LGD, HGD, or EAC at the time of diagnosis of IND; and (3) lack of follow-up endoscopy after diagnosis. Patients with neoplastic progression were classified as having either prevalent disease (LGD, HGD, or EAC on surveillance biopsy within 12 months of IND diagnosis) or incident disease (LGD, HGD, or EAC on surveillance biopsy >12 months after IND diagnosis). One hundred six patients were eligible for analysis. Of 87 patients with follow-up endoscopy and biopsies within 1 year of IND diagnosis, 7 (8%) had prevalent disease (2 LGD, 4 HGD, 1 EAC). The prevalence of LGD was 2.3%, HGD was 4.6%, and EAC was 1.1%. Importantly, four of the seven prevalent (2 LGD, 2 HGD) cases were found to have dysplasia within 6 months of IND diagnosis. No demographic or endoscopic characteristics studied were associated with prevalent disease. Of the 106 IND patients, there were 66 patients without prevalent dysplasia with >1-year follow-up. Three (4.5%) progressed (1 to LGD after 12 months, 2 to HGD after 16.5 and 28 months), yielding an incidence rate for any dysplasia of 1.4 cases/100 person-years and HGD/EAC of 0.9/100 person-years. Risk factors for incident disease were smoking (p = 0.02) and Barrett's esophagus segment length (p = 0.03). IND is associated with considerable risk of prevalent dysplasia, especially within the first 6 months after diagnosis. However, the incidence of HGD/EAC is low and similar to previous studies of IND. These data suggest that IND patients should have repeat endoscopy within 6 months with careful surveillance protocols. Longer BE length and smoking history may help predict which patients are more likely to develop dysplasia, and therefore identify patients who may warrant even closer monitoring.


Assuntos
Adenocarcinoma/parasitologia , Esôfago de Barrett/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Esofágicas/patologia , Sistema de Registros , Centros Médicos Acadêmicos , Adenocarcinoma/fisiopatologia , Adenocarcinoma/cirurgia , Idoso , Esôfago de Barrett/fisiopatologia , Esôfago de Barrett/cirurgia , Biópsia por Agulha , Progressão da Doença , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/parasitologia , Neoplasias Esofágicas/fisiopatologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagectomia/mortalidade , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida
5.
Nanotechnology ; 24(2): 025606, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23238021

RESUMO

A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm.


Assuntos
Cristalização/métodos , Ouro/química , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Absorção , Adsorção , Raios Infravermelhos , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
6.
J Appl Microbiol ; 113(2): 438-47, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22563853

RESUMO

AIMS: Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model. METHODS AND RESULTS: Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1ß, TNF-α, IL-6 and IL-8 in a macrophage model. CONCLUSIONS: A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease.


Assuntos
Chalconas/farmacologia , Macrófagos/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Proantocianidinas/farmacologia , Vaccinium macrocarpon/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/microbiologia , Humanos , Inflamação/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos , Macrófagos/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Colagenase Microbiana/metabolismo , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/crescimento & desenvolvimento , Porphyromonas gingivalis/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo , Virulência
7.
Genome ; 53(6): 430-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20555432

RESUMO

Two classes of 5S DNA units, namely the short (containing units of 410 bp) and the long (containing units of 500 bp), are recognized in species of the wheat (the genera Aegilops and Triticum) group. While every diploid species of this group contains 2 unit classes, the short and the long, every allopolyploid species contains a smaller number of unit classes than the sum of the unit classes of its parental species. The aim of this study was to determine whether the reduction in these unit classes is due to the process of allopolyploidization, that is, interspecific or intergeneric hybridization followed by chromosome doubling, and whether it occurs during or soon after the formation of the allopolyploids. To study this, the number and types of unit classes were determined in several newly formed allotetraploids, allohexaploids, and an allooctoploid of Aegilops and Triticum. It was found that elimination of unit classes of 5S DNA occurred soon (in the first 3 generations) after the formation of the allopolyploids. This elimination was reproducible, that is, the same unit classes were eliminated in natural and synthetic allopolyploids having the same genomic combinations. No further elimination occurred in the unit classes of the 5S DNA during the life of the allopolyploid. The genetic and evolutionary significance of this elimination as well as the difference in response to allopolyploidization of 5S DNA and rDNA are discussed.


Assuntos
DNA Ribossômico/genética , Poaceae/genética , Poliploidia , RNA Ribossômico 5S/genética , Cromossomos de Plantas/genética , DNA de Plantas/química , DNA de Plantas/genética , DNA Ribossômico/classificação , Genoma de Planta/genética , Hibridização Genética/genética , Análise de Sequência de DNA , Especificidade da Espécie , Triticum/genética
8.
Genome ; 52(3): 275-85, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19234556

RESUMO

Nuclear DNA amount (1C) was determined by flow cytometry in the autotetraploid cytotype of Hordeum bulbosum, in the cytologically diploidized autotetraploid cytotypes of Elymus elongatus, Hordeum murinum subsp. murinum and Hordeum murinum subsp. leporinum, in Hordeum marinum subsp. gussoneanum, in their progenitor diploid cytotypes, and in a newly synthesized autotetraploid line of E. elongatus. Several lines collected from different regions of the distribution area of every taxon, each represented by a number of plants, were analyzed in each taxon. The intracytotype variation in nuclear DNA amount of every diploid and autotetraploid cytotype was very small, indicating that no significant changes have occurred in DNA amount either after speciation or after autopolyploid formation. The autotetraploid cytotypes of H. bulbosum and the cytologically diploidized H. marinum subsp. gussoneanum had the expected additive amount of their diploid cytotypes. On the other hand, the cytologically diploidized autotetraploid cytotypes of E. elongatus and H. murinum subsp. murinum and H. murinum subsp. leporinum had considerably less nuclear DNA (10%-23%) than the expected additive value. Also, the newly synthesized autotetraploid line of E. elongatus showed similar reduction in DNA as its natural counterpart, indicating that the reduction in genome size occurred in the natural cytotype during autopolyploidization. It is suggested that the diploid-like meiotic behavior of these cytologically dipolidized autotetraploids is caused by the instantaneous elimination of a large number of DNA sequences, different sequences from different homologous pairs, leading to differentiation of the constituent genomes. The eliminated sequences are likely to include those that participate in homologous recognition and initiation of meiotic pairing. A gene system determining exclusive bivalent pairing by utilizing the differentiation between the two groups of homologues has been presumably superimposed on the DNA reduction process.


Assuntos
Núcleo Celular/genética , DNA de Plantas/genética , Genoma de Planta , Poliploidia , Triticum/genética , Cromossomos de Plantas , Triticum/classificação
9.
Genome ; 51(8): 616-27, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18650951

RESUMO

Recent molecular studies in the genera Aegilops and Triticum showed that allopolyploidization (interspecific or intergeneric hybridization followed by chromosome doubling) generated rapid elimination of low-copy or high-copy, non-coding and coding DNA sequences. The aims of this work were to determine the amount of nuclear DNA in allopolyploid species of the group and to see to what extent elimination of DNA sequences affected genome size. Nuclear DNA amount was determined by the flow cytometry method in 27 natural allopolyploid species (most of which were represented by several lines and each line by several plants) as well as 14 newly synthesized allopolyploids (each represented by several plants) and their parental plants. Very small intraspecific variation in DNA amount was found between lines of allopolyploid species collected from different habitats or between wild and domesticated forms of allopolyploid wheat. In contrast to the constancy in nuclear DNA amount at the intraspecific level, there are significant differences in genome size between the various allopolyploid species, at both the tetraploid and hexaploid levels. In most allopolyploids nuclear DNA amount was significantly less than the sum of DNA amounts of the parental species. Newly synthesized allopolyploids exhibited a similar decrease in nuclear DNA amount in the first generation, indicating that genome downsizing occurs during and (or) immediately after the formation of the allopolyploids and that there are no further changes in genome size during the life of the allopolyploids. Phylogenetic considerations of the origin of the B genome of allopolyploid wheat, based on nuclear DNA amount, are discussed.


Assuntos
DNA de Plantas/análise , Genoma de Planta , Poliploidia , Triticum/genética , Especificidade da Espécie
10.
Am J Hematol ; 80(2): 95-100, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16184593

RESUMO

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.


Assuntos
Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/métodos , Transfusão de Sangue , Estudos de Coortes , Humanos , Laparoscopia , Tempo de Internação , Contagem de Plaquetas , Complicações Pós-Operatórias , Púrpura Trombocitopênica Idiopática/sangue , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Resultado do Tratamento
11.
Cytogenet Genome Res ; 109(1-3): 250-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15753584

RESUMO

Recent studies have shown that allopolyploidy accelerates genome evolution in wheat in two ways: (1) allopolyploidization triggers rapid genome changes (revolutionary changes) through the instantaneous generation of a variety of cardinal genetic and epigenetic alterations, and (2) the allopolyploid condition facilitates sporadic genomic changes during the life of the species (evolutionary changes) that are not attainable at the diploid level. The revolutionary changes comprise (1) non-random elimination of coding and non-coding DNA sequences, (2) epigenetic changes such as DNA methylation of coding and non-coding DNA leading, among others, to gene silencing, (3) activation of genes and retroelements which in turn alters the expression of adjacent genes. These highly reproducible changes occur in the F1 hybrids or in the first generation(s) of the nascent allopolyploids and were similar to those that occurred twice in nature: first in the formation of allotetraploid wheat (approximately 0.5 million years ago) and second in the formation of hexaploid wheat (approximately 10,000 years ago). Elimination of non-coding sequences from one of the two homoeologous pairs in tetraploids and from two homoeologous pairs in hexaploids, augments the differentiation of homoeologous chromosomes at the polyploid level, thus providing the physical basis for the diploid-like meiotic behavior of allopolyploid wheat. Regulation of gene expression may lead to improved inter-genomic interactions. Gene inactivation brings about rapid diploidization while activation of genes through demethylation or through transcriptional activation of retroelements altering the expression of adjacent genes, leads to novel expression patterns. The evolutionary changes comprise (1) horizontal inter-genomic transfer of chromosome segments between the constituent genomes, (2) production of recombinant genomes through hybridization and introgression between different allopolyploid species or, more seldom, between allopolyploids and diploids, and (3) mutations. These phenomena, emphasizing the plasticity of the genome with regards to both structure and function, might improve the adaptability of the newly formed allopolyploids and facilitate their rapid and successful establishment in nature.


Assuntos
Evolução Molecular , Genoma de Planta , Poliploidia , Triticum/genética , Cromossomos de Plantas/genética , Modelos Genéticos , Recombinação Genética
12.
Genome ; 47(5): 860-7, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15499400

RESUMO

The genomic content of the subtelomeric repeated sequences Spelt1 and Spelt52 was studied by dot, Southern, and in situ hybridization in 11 newly synthesized amphiploids of Aegilops and Triticum, and data were compared with the parental plants. Spelt1 had reduced copy numbers in the first generation of three synthetic amphiploids, but two others did not change; Spelt52 was amplified in nine amphiploids and did not change in two. In the second allopolyploid generation, Spelt1 copy number did not change, whereas there was amplification of Spelt52 in some allopolyploids and decreases in others. Neither allopolyploidy level nor the direction of the cross affected the patterns of change in the newly synthesized amphiploids. Changes did not result from intergenomic recombination because similar alterations were noticed in allopolyploids with and without Ph1, a gene that suppresses homoeologous pairing. No differences in Spelt1 and Spelt52 tandem organization were found by Southern hybridization. The significance of these data are discussed in relation to the establishment of newly formed allopolyploids.


Assuntos
Grão Comestível/genética , Evolução Molecular , Genoma de Planta , Poliploidia , Sequências de Repetição em Tandem/genética , Dosagem de Genes , Regulação da Expressão Gênica de Plantas/genética , Hibridização in Situ Fluorescente , Recombinação Genética
14.
Rev Laryngol Otol Rhinol (Bord) ; 124(4): 211-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15038562

RESUMO

OBJECTIVE: A number of well validated quality of life (QoL) instruments are available. Head and neck cancer patients often find these exhaustive questionnaires too long or bothersome. The purpose of our study was to evaluate a patient self-reported very simple assessment of quality of life and to compare it with the well-validated European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaire. METHODS: A departmental simple questionnaire was designed consisting of 2 components: 1. A visual analogue scale; 2. A space for patients to enter up to 3 specific problems which prevent quality of life being better. These may be physical, emotional, social or practical problems. 112 patients attending the head and neck oncology clinic completed both questionnaires (half completed the simple questionnaire first and the other half the EORTC questionnaire first). RESULTS: There was a good correlation between the global health scores of the EORTC and the visual analogue scale of the simple questionnaire. There was poor correlation between specific domains in the EORTC questionnaire and the 3 comments mentioned by patients in the simple questionnaire. CONCLUSION: A simple patient assessment of quality of life can be used as a simple outcome tool in head and neck cancer data bases when specific details are not required.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Qualidade de Vida , Inquéritos e Questionários , Determinação de Ponto Final , Neoplasias de Cabeça e Pescoço/psicologia , Neoplasias de Cabeça e Pescoço/terapia , Nível de Saúde , Humanos , Medição da Dor , Psicometria , Resultado do Tratamento
15.
Eur J Surg Oncol ; 28(6): 615-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12359196

RESUMO

AIM: Understanding the likely net benefit of chemotherapy for the individual patient helps physicians to give objective information. A prognostic table has been constructed detailing the percentage absolute survival advantage offered by polychemotherapy for patients with early breast cancer, according to their age and the Nottingham Prognostic Index of their tumour. This study aims to assess its first year of use in the Leicestershire Breast Unit. METHOD: Demographic, pathological and treatment data were collected prospectively onto the Leicestershire breast cancer database. Patients with a potential survival advantage of 2% or greater in the year 01/05/99 to 30/04/00 (after the prognostic table was used routinely to determine oncology referrals) were identified. Chemotherapy usage was compared with the previous year's patient group. RESULTS: Two hundred and eighty-eight had early breast cancer, requiring surgery, eligible for consideration of adjuvant therapy. Of these, 98% of women with a potential survival advantage of 6% or more received chemotherapy. Ninety-one percent of those with a survival advantage of 4% or more was seen by an oncologist. Of those with a 2% survival advantage, 48% were referred to discuss the issues with an oncologist. Use of the table resulted in increased chemotherapy rates for women with a 4% potential survival advantage. CONCLUSIONS: We have found the prognostic table to be a useful and workable tool and advocate its use.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Tomada de Decisões , Adulto , Fatores Etários , Idoso , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/psicologia , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Cooperação do Paciente/psicologia , Prognóstico , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Saúde da Mulher
16.
Cancer Res ; 61(21): 7747-53, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11691788

RESUMO

This study compares two potential magnetic resonance imaging (MRI) indices for noninvasive early detection of tumor response to chemotherapy: the spin-lattice relaxation in the rotating frame (T1rho) and the transverse relaxation time (T2). Measurements of these relaxation parameters were performed on a s.c. murine radiation-induced fibrosarcoma (RIF-1) model before and after cyclophosphamide treatment. The number of pixels exhibiting T1rho values longer than controls in viable regions of the tumor increased significantly as early as 18 h after drug administration and remained elevated up to 36 h after treatment (P < 0.005). Although a trend of increasing T2s relative to controls was noted in viable regions of the tumor 36 h after treatment, the changes were not statistically significant. Histological examination indicated a decrease in mitotic index that paralleled the changes in T1rho. We conclude that T1rho measurements may be useful for noninvasive monitoring of early response of tumors to chemotherapy.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Ciclofosfamida/farmacologia , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Induzidas por Radiação/tratamento farmacológico , Neoplasias Induzidas por Radiação/patologia , Animais , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fibrossarcoma/etiologia , Camundongos , Camundongos Endogâmicos C3H
18.
Ophthalmology ; 108(10): 1721-6, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11581040

RESUMO

OBJECTIVE: To compare adverse medical events by different anesthesia strategies for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Patients 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada between June 1995 and June 1997. INTERVENTION: Local anesthesia applied topically or by injection, with or without oral and intravenous sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). MAIN OUTCOME MEASURES: Intraoperative and postoperative adverse medical events. RESULTS: Twenty-six percent of surgeries were performed with topical anesthesia and the remainder with injection anesthesia. There was no increase in deaths and hospitalizations associated with any specific anesthesia strategy. No statistically significant difference was observed in the prevalence of intraoperative events between topical and injection anesthesia without intravenous sedatives (0.13% and 0.78%, respectively). The use of intravenous sedatives was associated with a significant increase in adverse events for topical (1.20%) and injection anesthesia (1.18%), relative to topical anesthesia without intravenous sedation. The use of short-acting hypnotic agents with injection anesthesia was also associated with a significant increase in adverse events when used alone (1.40%) or in combination with opiates (1.75%), sedatives (2.65%), and with the combination of opiates and sedatives (4.04%). These differences remained after adjusting for age, gender, duration of surgery, and American Society of Anesthesiologists risk class. CONCLUSIONS: Adjuvant intravenous anesthetic agents used to decrease pain and alleviate anxiety are associated with increases in medical events. However, cataract surgery is a safe procedure with a low absolute risk of medical complications with either topical or injection anesthesia. Clinicians should weigh the risks and benefits of their use for individual patients.


Assuntos
Adjuvantes Anestésicos/efeitos adversos , Anestesia Local/efeitos adversos , Extração de Catarata , Complicações Intraoperatórias , Administração Tópica , Idoso , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Injeções , Masculino , Pessoa de Meia-Idade , Razão de Chances , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias , Estudos Prospectivos , Fatores de Risco
19.
Plant Cell ; 13(8): 1749-59, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11487690

RESUMO

Interspecific or intergeneric hybridization, followed by chromosome doubling, can lead to the formation of new allopolyploid species. Recent studies indicate that allopolyploid formation is associated with genetic and epigenetic changes, although little is known about the type of changes that occur, how rapidly they occur, and the type of sequences involved. To address these matters, we have surveyed F1 hybrids between diploid species from the wheat (Aegilops and Triticum) group and their derived allotetraploids by screening a large number of loci using amplified fragment length polymorphism and DNA gel blot analysis and by assaying the extent of cytosine methylation. We found that sequence elimination is one of the major and immediate responses of the wheat genome to wide hybridization or allopolyploidy, that it affects a large fraction of the genome, and that it is reproducible. In one cross between AE: sharonensis x AE: umbellulata, 14% of the loci from AE: sharonensis were eliminated compared with only 0.5% from AE: umbellulata, with most changes occurring in the F1 hybrid. In contrast, crosses between AE: longissima x T. urartu showed that sequence elimination was more frequent after chromosome doubling. Alterations in cytosine methylation occurred in approximately 13% of the loci, either in the F1 hybrid or in the allopolyploid. For eight of nine bands that were isolated, the sequences that underwent elimination corresponded to low-copy DNA, whereas alterations in methylation patterns affected both repetitive DNA sequences, such as retrotransposons, and low-copy DNA in approximately equal proportions.


Assuntos
Citosina/metabolismo , Metilação de DNA , Genoma de Planta , Hibridização Genética , Poliploidia , Triticum/genética , Sequência de Bases , Impressões Digitais de DNA , Primers do DNA , Heterozigoto , Polimorfismo Genético , Reprodutibilidade dos Testes
20.
Plant Cell ; 13(8): 1735-47, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11487689

RESUMO

To better understand genetic events that accompany allopolyploid formation, we studied the rate and time of elimination of eight DNA sequences in F1 hybrids and newly formed allopolyploids of Aegilops and TRITICUM: In total, 35 interspecific and intergeneric F1 hybrids and 22 derived allopolyploids were analyzed and compared with their direct parental plants. The studied sequences exist in all the diploid species of the Triticeae but occur in only one genome, either in one homologous pair (chromosome-specific sequences [CSSs]) or in several pairs of the same genome (genome-specific sequences [GSSs]), in the polyploid wheats. It was found that rapid elimination of CSSs and GSSs is a general phenomenon in newly synthesized allopolyploids. Elimination of GSSs was already initiated in F1 plants and was completed in the second or third allopolyploid generation, whereas elimination of CSSs started in the first allopolyploid generation and was completed in the second or third generation. Sequence elimination started earlier in allopolyploids whose genome constitution was analogous to natural polyploids compared with allopolyploids that do not occur in nature. Elimination is a nonrandom and reproducible event whose direction was determined by the genomic combination of the hybrid or the allopolyploid. It was not affected by the genotype of the parental plants, by their cytoplasm, or by the ploidy level, and it did not result from intergenomic recombination. Allopolyploidy-induced sequence elimination occurred in a sizable fraction of the genome and in sequences that were apparently noncoding. This finding suggests a role in augmenting the differentiation of homoeologous chromosomes at the polyploid level, thereby providing the physical basis for the diploid-like meiotic behavior of newly formed allopolyploids. In our view, this rapid genome adjustment may have contributed to the successful establishment of newly formed allopolyploids as new species.


Assuntos
Evolução Molecular , Genoma de Planta , Poliploidia , Triticum/genética , Southern Blotting , Sondas de DNA , DNA de Plantas , Meiose/genética , Triticum/citologia
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