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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 73 records · Page 4Linked to original sources
PubMed2001

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer.

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Selective binding of cis-1,3,5-cyclohexane tricarboxylic acid vs its epimeric trans isomer by a tripodal amidopyridine receptor; crystal structures of the 1:1 complexes.

[figure: see text] A tripodal tris-amidopyridine receptor forms a 1:1 complex with trans-1,3,5-cyclohexane tricarboxylic acid that is 1 order of magnitude less stable than the one formed with the corresponding cis-triacid epimer. The X-ray crystal structures of the complexes have been determined, confirming the binding geometry derived from NMR data in solution and force-field calculations, and its geometrical features are used to explain the observed selectivity.

Crystallography, X-Ray↗
PubMed2001

Set size and repetition in the picture--word interference paradigm: implications for models of naming.

Caramazza and Costa (Cognition 75 (2000) B51) reported results which demonstrate that a semantically related word distractor interferes in picture naming even when it is not in the response set and there is no possibility for mediated interference. They interpreted the results to be problematic for the model of lexical access proposed by Levelt, Roelofs, and Meyer (Behavioral and Brain Sciences 22 (1999) 1). Roelofs (Cognition 80 (2001, this issue 283--90)) argues that those results are not inconsistent with Levelt et al.'s model when certain new assumptions about the mechanism of lexical selection are considered. Here we show that even with these assumptions the model still makes the wrong predictions. We report new results which demonstrate that the semantic interference and facilitation effects that are obtained respectively in the basic-level and category-level naming variants of the picture-word interference paradigm are not the result of response set size and response repetitions.

Humans↗
PubMed2001

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Aged↗
PubMed2001

Alpha-interferon improves liver fibrosis in chronic hepatitis C: clinical significance of the serum N-terminal propeptide of procollagen type III.

Our objective was to estimate the effect of interferon (IFN) on the evolution of fibrosis in chronic hepatitis C and the significance of the N-terminal propeptide of procollagen type III (PIIIP) as a marker of fibrogenesis. One hundred seventeen patients, 72 male (61%) and 45 female (39%), with a mean age of 40.7+/-11.9 years were treated with a2b-IFN, 3 to 5 MU, for 12 months: sustained responders (SR = 44), relapsers (RR = 35), and nonresponders (NR = 38). Liver biopsies were performed before treatment and 1 year after cessation of IFN for evaluation of the histological activity index (HAI). Serum PIIIP was obtained at the time of liver biopsy, at the beginning, during, and end of therapy and during the follow-up. The normal value in 29 healthy individuals was 0.37+/-0.18 U/L. Staging was reduced in 58% of SR, 12.5% of RR, and 11.5% of NR. There was a correlation between PIIIP and the HAI before (n = 71, r(s) = 0.41, P < 0.0004) and after IFN (n = 71, r(s) = 0.58, P < 0.0001). The SR had a better improvement in grading (90.3%; P < 0.05) and staging (58%; P < 0.001). The correlation of the HAI parameters with the variation of PIIIP showed significance only for fibrosis (r(s) = 0.36, P < 0.002) and portal inflammation (r(s) = 0.35, P < 0.01). PIIIP normalized only in patients whose fibrosis improved (P < 0.01). At the end of therapy, PIIIP had a predictive value in the distinction of SR from RR (PPV, 64; PNV, 55.6). During the follow-up, PIIIP remained lower in SR compared with RR and NR (P < 0.002). The response to a-IFN improved liver inflammation and fibrosis. Serum PIIIP is a useful noninvasive method to evaluate serially fibrogenesis in chronic hepatitis C treated with IFN.

Adult↗
PubMed2001

Attitudes towards intramural continuing medical education: a european perspective.

Continuing medical education (CME) is now one of the key areas of development in medical education. This paper describes the development of an intramural continuing medical education programme de novo in a newly opened cancer institute in Italy, which provided a unique opportunity to study attitudes towards the concepts and goals of continuing medical education as most of the individuals involved in this programme were exposed to continuing medical education for the first time. The continuing medical education programme was overseen by a CME committee for 1 year. Three 1-hour sessions were delivered each week and one credit point was awarded for each session. The sessions included grand rounds, clinical-based teaching and a 3-weekly rotating schedule of pathology, radiology and research. Participants were all the medical doctors attending the European Institute of Oncology. Attendance at greater than 50% of the total sessions available yearly qualified the individual for certification by the CME committee of the Institute. A questionnaire was circulated to all medical doctors at the Institute at the end of the academic year to assess attitudes to CME in general. Forty-six out of 84 questionnaires were returned. The majority of those involved in this CME intramural programme undertook self-directed CME activities and at least 50% had not previously attended either grand rounds or research seminars. Most felt that CME should not be mandatory but that its activities should be monitored. The greatest difficulty with CME was in its timing.

Attitude↗
PubMed2001

An autoregulatory feedback loop directs the localized expression of the Drosophila CPEB protein Orb in the developing oocyte.

The RRM-type RNA binding protein Orb plays a central role in the establishment of polarity in the Drosophila egg and embryo. In addition to its role in the formation and initial differentiation of the egg chamber, orb is required later in oogenesis for the determination of the dorsoventral (DV) and anteroposterior (AP) axes. In DV axis formation, Orb protein is required to localize and translate gurken mRNA at the dorsoanterior part of the oocyte. In AP axis formation, Orb is required for the translation of oskar mRNA. In each case, Orb protein is already localized at the appropriate sites within the oocyte before the arrival of the mRNAs encoding axis determinants. We present evidence that an autoregulatory mechanism is responsible for directing the on site accumulation of Orb protein in the Drosophila oocyte. This orb autoregulatory activity ensures the accumulation of high levels of Orb protein at sites in the oocyte that contain localized orb message.

3' Untranslated Regions↗
PubMed2001

[Prognosis and risk evaluation of postoperative coronary patients (PERISCOP). Methodology and study population characteristics].

The aim of the PERISCOP study was to evaluate the predictive value of cardiological investigations performed after recent coronary bypass surgery with regards to cardiac event and mortality at one year. The treatment of lipid abnormalities was also analysed. This first article describes the methodology and patient characteristics at inclusion. This prospective national multicenter trial included 2065 patients (86% men) with an average age of 63.1 +/- 9.9 years. The number of diseased vessels was 2.6 +/- 0.6. Preoperative left ventricular function was normal (ejection fraction 60 +/- 13%). Revascularisation was complete in 73% of cases (22% of arterial grafts). The cardiological investigations were performed at Day 20 +/- 10 after surgery. The duration of exercise on stress testing was 429 +/- 170 seconds. It was positive or doubtful in 9% of cases. Ventricular arrhythmias were observed in 6.5% of cases. The blood pressure response was abnormal in 6% of cases. Holter monitoring showed a median number of ventricular extrasystoles over 24 hours of 44. Three per cent of patients had one episode of ventricular tachycardia and 7% had ischaemic episodes. The echocardiographic index of segmental contractility was on average 1.75 (ejection fraction: 52.6%). The lipid analysis performed at one month, under lipid therapy in 34% of cases, showed a total cholesterol level at 1.91 +/- 0.10 g/l, an LDL-cholesterol of 1.27 +/- 0.08 g/l. The therapeutic target (LDL-cholesterol < 1 g/l) was attained in 46% of cases with treatment and in 18% of cases without treatment.

Aged↗
PubMed2001

European School of Oncology: 20 years of cancer education and a contribution to European Guidelines of Oncology.

Since its creation in 1982, the European School of Oncology (ESO) not only looks back on two successful decades of cancer education and active promotion of knowledge and provision of oncology training in almost all parts of the world, but also the establishment of the State-of-the-Art (START) European oncology guidelines, a free, Internet-based, and readily accessible program of evidence-based medicine. In addition, ESO has been at the forefront of various activities which have led to the evolution of a common Continuing Medical Education system in Europe. A special framework to support the training of health care providers in underdeveloped countries was also launched by ESO. On the occasion of its 20th anniversary, ESO reflects on the past, defines the status quo and presents its future prospects.

Decision Support Techniques↗
PubMed2001

[Two case reports of cerebral autosomal dominant arteriophaty with subcortical infarctions and leukoencephalopathy (CADASIL)].

Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) was first reported in European families and since 1993 it has been observed in America, Africa and Asia, suggesting that today the disease probably still remains largely underdiagnosed. CADASIL appears to be essentially a disorder of the arteries linked to single missense mutations in the Notch3 gene locus on chromosome 19; the aberrant dimerisation of Notch3, due to abnormal disulphide bridging with another Notch3 molecule or with another protein, may be involved in the pathogenesis of the disorder. It is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseudobulbar palsy and dementia, caused by multiple lacunar infarctions with ischemic and diffuse white matter abnormalities on neuroimaging. Migraine with aura, epileptic seizures and affective disorders are frequent additional symptoms of CADASIL. It is usually observed in the 3rd decade, but some individuals remain asymptomatic close to the age of 60. MRI displays a marked leukoencephalopathy in affected individuals as early as in the age of 20. The authors emphasize the role of a direct DNA test for gene mutation to make a differential diagnosis between CADASIL and other forms of vascular leukoencephalopathy as Alzheimer's dementia, multiple sclerosis and Binswanger's subcortical arteriopathic encephalopathy where CADASIL's arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits.

Adult↗
PubMed2001

The specific-word frequency effect: implications for the representation of homophones in speech production.

In a series of experiments, the authors investigated whether naming latencies for homophones (e.g., /nlambdan/) are a function of specific-word frequency (i.e., the frequency of nun) or a function of cumulative-homophone frequency (i.e., the sum of the frequencies of nun and none). Specific-word but not cumulative-homophone frequency affected picture-naming latencies. This result was obtained in 2 languages (English and Chinese). An analogous finding was obtained in a translation task, where bilingual speakers produced the English names of visually presented Spanish words. Control experiments ruled out that these results are an artifact of orthographic or articulatory factors, or of visual recognition. The results argue against the hypothesis that homophones share a common word-form representation, and support instead a model in which homophones have fully independent representations.

Adult↗