PubMed Health⌕ Search

Biomedical subjects

A Gonçalves

Publications and source records attributed to A Gonçalves.

At least 19 recordsLinked to original sources
PubMed2006

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy.

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

Adult↗
PubMed2006

Post-operative sequential high-dose chemotherapy with haematopoietic stem cell support as front-line treatment in advanced ovarian cancer: a phase II multicentre study.

In spite of multimodal management including aggressive surgery and chemotherapy, the prognosis of advanced ovarian cancer (AOC) remains poor. Multicycle high-dose chemotherapy (HDC) with haematopoietic stem cell (HSC) support has been shown to be a promising procedure in various cancers including AOC. We conducted a phase II multicentre study to evaluate feasibility, toxicity and efficacy of post-operative front-line sequential HDC with HSC support in AOC. Thirty four patients with stage IIIC/IV received a post-operative sequential combination of high-dose cyclophosphamide/epirubicin (D1, D21) with HSC harvesting, high-dose carboplatin (D42, D98) followed by HSC infusion, and dose-dense paclitaxel (D63, D77, D119, D133). Rh-G-CSF (filgrastim) was administered following all cycles. Primary endpoint was pathological complete response rate (pCR). Thirty patients received at least 7 of the scheduled 8 cycles. Haematological toxicity was significant but manageable. Grade 3/4 extra-haematopoietic toxicities were relatively uncommon and reversible. No toxicity-related death was observed. The observed pCR was 37% and did not reach the initial endpoint. Post-operative front-line sequential HDC in AOC is feasible and safe in a multicentre setting. The observed pCR does not support a clear advantage over conventional treatment. This approach remains an experimental strategy to further optimise and validate.

Adult↗
PubMed2006

Milk intake is inversely related to obesity in men and in young women: data from the Portuguese Health Interview Survey 1998-1999.

OBJECTIVE: To assess the relationships between milk intake and body mass index (BMI) in a representative sample of the mainland Portuguese population. DESIGN: Cross-sectional study. SETTING: National Health Interview Survey 1998-1999. Average daily milk intake was calculated by a frequency questionnaire that also assessed the average volume of one serving. BMI was derived from the subject's reported height and weight. SUBJECTS: A total of 17,771 men and 19 742 women aged > or =18 y. RESULTS: In men, milk intake was inversely related to BMI (r = -0.10, P < 0.001), whereas the relationship in women was weaker (r = -0.06, P < 0.001). In men, prevalence of milk consumers was lower in obese (62%) and in overweight (68%) than in normal weight subjects (71%, P < 0.001). After adjusting for age, region, physical activity, smoking, number of meals and educational level, milk intake decreased with increasing BMI (adjusted mean +/- s.e.: 280 +/- 5, 266 +/- 5 and 246 +/- 7 ml/day for normal, overweight and obese subjects, respectively, P < 0.001), even after excluding subjects who did not consume milk (368 +/- 5, 353 +/- 6 and 346 +/- 8 ml/day, P < 0.02). In women, prevalence of milk consumers was lower in obese (71%) and in overweight (72%) than in normal weight subjects (76%, P < 0.001). In women younger than 55 y, milk intake decreased with increased BMI categories (291 +/- 9, 271 +/- 10 and 269 +/- 11 ml/day for normal, overweight and obese subjects, respectively, P < 0.001), whereas no relationship was found in the older group. CONCLUSIONS: Increased calcium intake is slightly but significantly negatively related with BMI in men and premenopausal women. The lack of relationship in older women might be due to the hormonal status, but awaits further investigation.

Adult↗
PubMed2005

[Genetic epidemiology: epidemiology, genetics or none of them?].

In an attempt to contribute to a better understanding of the identity of Genetic Epidemiology, we review its conception, its field of influence, its appropriate methods and techniques and, at last, some of its applications. Genetic Epidemiology involves the study of genetic factors acting on diseases and on their environmental interactions. These includes two major areas: a descriptive one, related to the distribution of such conditions in families and populations, to the epidemiologic surveillance and to the study of determinants; and another characterized by intervention, which is related to preventive measures. Because of the difficulty in considering all possible situations, especial attention is given to review some converging epidemiological and genetical methods and techniques. Among them, we stress the case studies on lab methodologies, as dermatoglyphics, and on quantitative procedures, as path analysis. Some studies are taken as examples for application, since they have been object of research in our country: leprosy, hydrargyrism and schizophrenia.

English Abstract↗
PubMed2005

Late outcome of Senning and Mustard procedures for correction of transposition of the great arteries.

OBJECTIVES: To evaluate late mortality and morbidity after an atrial switch procedure for correction of transposition of the great arteries (TGA) and to assess predictive factors for adverse outcome. SETTING: Tertiary referral centre. DESIGN AND PATIENTS: Retrospective follow up study of 137 patients surviving hospitalisation for TGA atrial switch procedure (Mustard or Senning) in a single institution and divided into two groups (simple and complex) depending on presurgical anatomy. Several surgical and follow up factors were evaluated during 16.7 (5.6) years' follow up. RESULTS: Late mortality was 5.1% (95% confidence interval 1.37% to 8.84%) with sudden death as the most common cause. No significant difference was found between Mustard and Senning procedures and between the complex and simple groups in terms of mortality. Independent predictive factors for late mortality were a history of supraventricular tachyarrhythmias and advanced New York Heart Association (NYHA) functional class during follow up. A very common finding was development of sinus node dysfunction (47.6%), which had no influence on mortality. There was little need for reintervention (5.1%) and relatively few cases of right ventricular systolic dysfunction (14.6%). During follow up, most patients (96.2%) were in NYHA functional class I-II. CONCLUSIONS: Overall long term outcomes of patients with atrial repair of TGA in the present era are encouraging in terms of late mortality and quality of life. Nevertheless, better outcomes may be offered through improved diagnostic methods for right ventricular function and better management of supraventricular tachyarrhythmias.

Adolescent↗
PubMed2004

[Molecular alterations in breast cancer: clinical implications and new analytical tools].

PURPOSE: Breast cancer is a complex and heterogeneous disease resulting from various molecular alterations, the identification of which should have profound impact on the management of patients. CURRENT KNOWLEDGE AND KEY POINTS: The discovery of germline mutations within breast cancer susceptibility genes, such as BRCA1 and BRCA2, which are associated with a major risk of breast cancer during lifetime, has improved the assessment of the individual risk toward the disease, allowing appropriate strategies of screening and prevention. The identification of key molecular actors in the mammary oncogenesis may help to better assess the prognosis of the disease, while providing new therapeutic targets. Large-scale molecular technologies, which allow simultaneous assessment of a high number of molecular parameters in a single assay, should provide new tools to tackle complexity and heterogeneity of breast cancer. Hence, by examining transcriptional profiles of breast cancer using DNA microarrays, it was possible to reveal new prognostic tumor subgroups, previously indistinguishable. Further improvements are awaited with the recent development of high throughput and large-scale technologies investigating the tumor proteome. PROSPECTS AND PROJECTS: Precise knowledge of molecular alterations involved in each individual breast cancer will allow more effective and less toxic, tailored therapies.

Breast Neoplasms↗
PubMed2004

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.

The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.

Adult↗
PubMed2003

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy.

The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.

Adult↗
PubMed2003

Docetaxel and radiotherapy and pancreatic cancer.

PURPOSE: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of weekly docetaxel delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Thirteen patients with histologically proven locally non-resectable advanced adenocarcinoma of the pancreas were enrolled in this study. Patients received 4 weekly doses of docetaxel by 1-hour intravenous (IV) infusion with 40 Gy of external beam radiation therapy during 4 weeks. Patients who were stabilized or in response, received 2 additional cycles of docetaxel with a 10 Gy boost of radiotherapy. Doses were escalated at 10 mg/m2 increments in successive cohorts of 3 new patients until MTD was observed. RESULTS: Four patients received docetaxel at 20 mg/m2/week, 3 at 25 mg/m2/week, 3 at 30 mg/m2/week, and 3 at 35 mg/m2/week. All patients, except 2, were given the treatment in its integrity. The most common toxicities were nausea, vomiting, asthenia, and abdominal pains. Except for 1 patient, all toxicity was reversible and did not exceed grade 3. Hematologic toxicity was mild and has not required treatment interruption. 28% of the patients had to be rehospitalized. A total of 73 cycles was administered with a mean of 4 cycles per patient (2-6). CONCLUSION: Even the MTD was not reached, dose escalation was stopped at 35 mg/m2/week. This dose is comparable to the ones previously published using docetaxel in combination with radiotherapy in other tumors. Three patients achieved stable disease and 1 patient an objective response. This combination of weekly docetaxel and radiotherapy shows a feasible and well-tolerated regimen, with, nonetheless, a significant rate of rehospitalization, for patients with locally advanced pancreatic cancer.

Adenocarcinoma↗
PubMed2002

Dens invaginatus type III: report of a case and 10-year radiographic follow-up.

AIM: The purpose of this article is to report the 10-year follow-up of a right mandibular central incisor with 'dens invaginatus' that was root filled. SUMMARY: 'Dens invaginatus' is a rare malformation of teeth, probably resulting from an infolding of the dental papilla during tooth development. It has alternatively been called 'dens in dente' and 'dilated composite odontome'. Radiographic examination may clearly demonstrate this feature, although no signs may be recognized clinically. If no entrance to the invagination can be detected and there are no signs of pulp pathosis, then no treatment is required other than fissure sealing of the invagination. In deep invaginations, it is likely that root-canal treatment may be required. Occasionally, when the tooth has an immature root, apexification is necessary. Root-canal treatment of a right mandibular central incisor with 'dens invaginatus' is described along with 10-year follow-up. KEY LEARNING POINTS: Both clinical and radiographic examinations are necessary to determine morphological features of teeth before root-canal treatment. Sensibility testing to determine the pulp condition is critical prior to treatment.

Child↗
PubMed2002

[Percutaneous closure of a mid-muscular residual ventricular septal defect using the Amplatzer(TM) device].

We present the case of a 6-year old boy with a mid-muscular residual ventricular septal defect (VSD) of difficult surgical access, who underwent transcatheter closure using the Amplatzer(TM) VSD occluder. Transcatheter closure was guided by transthoracic echocardiography and successful closure was achieved with a 12 mm diameter VSD occluder, with no complications. Chest radiography showed a considerable decrease in cardiomegaly and normalization of pulmonary vascular markings before 24 hours, and echocardiography showed correct positioning of the Amplatzer(TM) VSD device without residual shunt through the device and minimal residual shunt in an apical VSD. After a 3-month follow-up, the patient was asymptomatic and echocardiography showed that the device was correctly positioned with minimal residual apical shunt.

Cardiac Catheterization↗
PubMed2001

Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics.

Microtubule dynamics are crucial for mitotic spindle assembly and chromosome movement. Suppression of dynamics by Taxol appears responsible for the drug's potent ability to inhibit mitosis and cell proliferation. Although Taxol is an important chemotherapeutic agent, development of resistance limits its efficacy. To examine the role of microtubule dynamics in Taxol resistance, we measured the dynamic instability of individual rhodamine-labeled microtubules in Taxol-sensitive and -resistant living human cancer cells. Taxol-resistant A549-T12 and -T24 cell lines were selected from a human lung carcinoma cell line, A549. They are, respectively, 9- and 17-fold resistant to Taxol and require low concentrations of Taxol for proliferation. We found that microtubule dynamic instability was significantly increased in the Taxol-resistant cells. For example, with A549-T12 cells in the absence of added Taxol, microtubule dynamicity increased 57% as compared with A549 cells. The length and rate of shortening excursions increased 75 and 59%, respectively. These parameters were further increased in A549-T24 cells, with overall dynamicity increasing by 167% compared with parental cells. Thus, the decreased Taxol-sensitivity of these cells can be explained by their increased microtubule dynamics. When grown without Taxol, A549-T12 cells were blocked at the metaphase/anaphase transition and displayed abnormal mitotic spindles with uncongressed chromosomes. In the presence of 2-12 nM Taxol, the cells grew normally, suggesting that mitotic block resulted from excessive microtubule dynamics. These results indicate that microtubule dynamics play an important role in Taxol resistance, and that both excessively rapid dynamics and suppressed dynamics impair mitotic spindle function and inhibit proliferation.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer cells (HT29-D4).

Antimicrotubule agent-induced apoptosis was examined in the proliferating human colon cancer cell line HT29-D4. G2/M arrest and subsequent apoptosis were dose-dependent, both observed with 100 nM paclitaxel or docetaxel and 10 nM vinorelbine. Bcl-x(L) phosphorylation was observed simultaneously with mitotic block, then caspase-3 cleavage and poly(ADP-ribose) polymerase degradation were detected 48 hr later. By using both enzymatic assay and immunoblot detection of cleaved fragments, we showed that caspase-8, a central component of the CD95-induced apoptotic pathway, was significantly activated during paclitaxel exposure, contemporary to apoptosis occurrence. Caspase-8 activation and apoptosis were independent of CD95 ligation and evidenced only for concentrations inducing Bcl-x(L) phosphorylation and a decrease in mitochondria permeability. Similar results were obtained with docetaxel and vinca alkaloids. Thus, antimitotic drugs may induce apoptosis via caspase-8 activation independently of CD95/CD95-L. Caspase-8 may be a common mediator of anticancer drug-induced apoptosis that could represent a promising target for future therapies.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells'.

Paclitaxel is an antimicrotubule agent that induces mitotic block and apoptosis. We show for the first time that paclitaxel acts directly or mitochondria isolated from human cancer cells. In isolated yeast mito chondria, paclitaxel (15 microM) induced an 18% increase in the respiration rate, with no concomitant release of cytochrome c. In isolated neuroblas toma mitochondria, paclitaxel (10-100 microM) induced a 27-72% release o cytochrome c. Release was prevented by cyclosporin A, suggesting the involvement of the permeability transition pore. Doxorubicin did no induce cytochrome c release, whereas vinorelbine, another antimicrotu bule agent, did. Thus, antimicrotubule agents can directly affect mito chondria to induce apoptosis.

Antibiotics, Antineoplastic↗
PubMed2000

[Total anomalous pulmonary venous return in children: importance of echocardiographic diagnosis and early surgery].

OBJECTIVE: We studied patients who underwent surgical repair for total anomalous pulmonary venous return at our hospital. We report the importance of diagnosis by echocardiographic imaging before surgical treatment. METHODS: Within the period of 1990-1999, fourteen patients underwent surgical repair of this cardiopathy in our hospital. The type of anomalous drainage was supracardiac in 6 patients, infracardiac in 4, to the coronary sinus in 1, and mixed-type in 3 patients. Eleven cases were diagnosed with an echo-Doppler study, the findings being confirmed intraoperatively. RESULTS: There were 2 early deaths: one occurred in the operating room in a patient with a small left ventricle, and the second one was 35 days postoperatively as a result of a septic complication. Early in the postoperative period our primary goal has steadily been the control and treatment of pulmonary hypertension. After a mean follow-up time of 50 months, only 1 patient needed to be reoperated on and the remainder are symptomless. CONCLUSIONS: That sufficient diagnostic data on total anomalous pulmonary venous return can reliably be obtained by ultrasound scanning so that surgery can be promptly undertaken, and that its surgical risk is currently low and mid-term post-repair outcome is fairly good.

Child↗
PubMed1999

Differentiation of human colon cancer cells changes the expression of beta-tubulin isotypes and MAPs.

The human colon adenocarcinoma HT29-D4 cell line is an interesting model for studies on epithelial cell differentiation. Undifferentiated cells are malignant proliferating cells, whereas differentiated cells act like epithelial polarized cells. In the present study, we first characterized the action of taxoids on the microtubular network of HT29-D4 cells according to the state of differentiation. Microtubular bundles were found in undifferentiated cells but not in differentiated cells, even with 500-fold higher taxoid concentrations for 96 h. This finding led us to study changes in microtubules according to the polarity status of the cell. E-MAP-115 was expressed only in differentiated cells; expression of beta-tubulin isotypes was altered in them relative to undifferentiated cells. Classes I, II, III, IVa and IVb isotypes were expressed in both phenotypes; however, differentiated epithelial cells displayed a specific increase in class III beta-tubulin. Thus, the increase in expression of this beta-tubulin isotype in differentiated cells is not restricted to neuronal cells. Moreover, these expression changes may reflect a higher stability of microtubular network in differentiated cells, which may explain the lower activity of anti-microtubule agents, independently of the mitotic process. These results indicate that the composition of microtubules should be considered as one of the criteria involved in the response of tumour cells to chemotherapy with anti-microtubule agents.

Antineoplastic Agents, Phytogenic↗
PubMed1999

[Evolution of the weight-height and weight-age relationship in children 3-6 years of age receiving preschool care in Sorocaba (SP), Brazil].

The nutritional status of Brazilians has improved over the last three decades. Still, little is known about the role played by nutritional assistance programs that public institutions and philanthropic organizations provide for low-income preschool children, who face greater nutritional risk. Therefore, we carried out a quasi-experimental study to evaluate the nutritional impact of the municipal preschool nutritional assistance program in the city of Sorocaba, São Paulo, Brazil. Over the course of a year, we performed quarterly measurements of weight and height on 444 children, whose ages ranged from 3 months to 6 years. In this population, 164 children were assisted by the preschool nutritional program (intervention group), and 280 children were not (nonintervention group). The children in the nonintervention group were identified by a special census for that purpose; they did not attend the preschool but lived nearby. After obtaining informed consent and carrying out a pretest, professionals and university students interviewed the mothers of the participating children, following standard techniques and conditions. Anthropometric measurements were done by teams of two interviewers, one of whom was a permanent member of the team, using equipment calibrated by the appropriate regional technical organization. The correspondence between the first measurement and subsequent measurements was evaluated by stratifying the population into three groups by z scores for weight-for-age and for weight-for-height, using U.S. National Center for Health Statistics reference curves. The z score groupings were established at the beginning of the study for three different age groups: younger than 24 months, 24-36 months, and older than 36 months. The two study groups (intervention and nonintervention) were similar sociodemographically, with the following exceptions: maternal employment (more of the mothers of children in the intervention group had jobs outside the home); age (children in the intervention group were significantly older); nutritional status (it was worse in the intervention group); and prevalence of hospital admittance (it was higher in the intervention group). After just the first three months of the study, 32% of the children in the intervention group had moved to a higher nutritional stratum, whereas only 13% of children in the nonintervention group had shown improved nutritional status. The difference in favor of the intervention group increased with the length of the intervention and was higher among older children. These results show that the preschool nutritional assistance program helped to improve the assisted children's nutritional status.

Age Factors↗