PubMed Health⌕ Search

Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 19 recordsLinked to original sources
PubMed1997

Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.

BACKGROUND: Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. METHODS: In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumour site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held gamma-ray detector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. FINDINGS: From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97.5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1.5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. INTERPRETATION: In the large majority of patients with breast cancer, lymphoscintigraphy and gamma-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.

Adult↗
PubMed1997

Stimulation of corticotrophin-releasing hormone release by the obese (ob) gene product, leptin, from hypothalamic explants.

Recent data have suggested that adipocytes synthesize and secrete a 16 kDa peptide which acts centrally to regulate weight gain by suppressing appetite and activating the sympathetic nervous system. To exert such effects, it may function as an endogenous ligand in the CNS, since specific receptors (OB-R) have been recently reported to be widely distributed in the brain. We have speculated that this peptide, now known as leptin, may act centrally by stimulating the release of corticotrophin-releasing hormone (CRH), a recognized potent inhibitory modulator of appetite. We tested in vitro the effect of murine leptin on CRH secretion in the dose range of 0.1 pM-100 nM. The static rat hypothalamic incubation system used involved fresh hypothalamic explants maintained in EBSS with consecutive 20 min incubations, and estimation of CRH concentrations in the medium by a specific and sensitive radioimmunoassay. The effect of heat-denatured leptin at a dose of 1 nM and 10 nM, was also investigated. Any possible modulation of leptin effects by adrenergic pathways was then explored by coincubating hypothalami with leptin 10 nM and equimolar concentrations of the alpha 1-adrenergic antagonist prazosin or the beta-adrenergic antagonist propranolol. The active leptin, but not the heat-inactivated peptide, caused a dose-dependent stimulation of CRH release in vitro (p < 0.05- < 0.0001 vs control), with a plateau effect at a dose of 10 nM. The addition of either prazosin or propranolol was without effect on leptin-dependent CRH stimulation. These findings are consistent with the reported presence of leptin receptors in the rat brain, and suggest that leptin may act to regulate appetite at least in part by directly modulating the secretion of CRH from the hypothalamus. It would also appear that such effect occurs via a non-adrenergic mechanism.

Analysis of Variance↗
PubMed1997

Long-term effects of fenretinide on retinal function.

The long-term effects of the synthetic retinoid fenretinide (4-HPR) on retinal function were studied by electroretinogram (ERG) in 24 women treated for a median of 30.5 months and in 18 untreated controls belonging to a phase III intervention trial. The six outcome measures were: a wave implicit time, peak-to-peak amplitude and implicit time of b wave following both cone stimulation and maximal cone-rod stimulation in the dark-adapted eye. Multivariate analysis of covariance was applied to evaluate the joint effect on the whole set of ERG measures taking into account their inter-relationship. Predictive factors with a significant effect on ERG measures were: (1) a qualitative interaction between age and treatment duration and (2) the squared (parabolic) function of plasma retinol. Individually, the b wave implicit time following cone stimulation was the only ERG measure significantly influenced by the predictors, indicating a primary effect of 4-HPR on retinal photoreceptor sensitivity without significant alterations of the inner nuclear layer. Thus, in contrast to previous reports at higher dose, administration of 4-HPR at 200 mg/day seems to exert subtle alterations of retinal function as measured by ERG.

Age Factors↗
PubMed1997

In vivo characterization of the colonic prokinetic effect of erythromycin in the rabbit.

The motor effect of erythromycin was characterized in conscious rabbits chronically fitted with electrodes and strain-guage force transducers implanted along the proximal and distal colon. Fecal pellet output was also evaluated as an index of propulsive activity. In order to get an insight into the pathways involved in mediating the effect of erythromycin, the macrolide was also administered after pretreatment with atropine, nifedipine or ondansetron. Furthermore, in vitro experiments with erythromycin alone and in the presence of atropine, nifedipine, tetrodotoxin or ondansetron were carried out with circular muscle strips taken from rabbit distal colon. In vivo, erythromycin (0.087-5.6 mg/kg i.v. bolus) dose-dependently stimulated spike and mechanical activities at both colonic levels, with a more marked effect on the distal colon. Erythromycin also dose-dependently increased the number of aborally migrating long spike bursts and fecal pellet output. The reproducibility of the response to erythromycin was confirmed by experiments with the dose of 2.8 mg/kg i.v. bolus, repeated in five consecutive experiments at 48-hour intervals. Nifedipine, but not atropine or ondansetron, significantly reduced the colonic motor response to erythromycin. In vitro experiments gave results in line with the in vivo data: the concentration-dependent contractile effect of erythromycin was almost suppressed by nifedipine, but resistant to atropine, tetrodotoxin or ondansetron. In conclusion, this study provides evidence that: (1) erythromycin is a prokinetic drug at the colonic level in rabbits, and (2) both in vivo and in vitro, the effects of erythromycin are exerted at the smooth muscle level by mechanisms depending on influx of extracellular calcium, while muscarinic and 5-HT3 receptors are not involved, at least in this model.

Animals↗
PubMed1997

Cell proliferation-related markers in colorectal liver metastases: correlation with patient prognosis.

PURPOSE: We analyzed the relation between phenotypic (DNA ploidy) and functional markers (S-phase cell fraction, p53, and bcl-2 protein expression) and defined their relevance on clinical outcome on a retrospective series of radically resected liver metastases from colorectal cancer. PATIENTS AND METHODS: Among 104 patients with resectable liver metastases from colorectal cancer, DNA ploidy was determined by flow cytometry, 3H-thymidine labeling index (TLI) by autoradiography, and expression of p53 and bcl-2 by immunohistochemistry. RESULTS: TLI was a significant indicator for relapse at 4 years from radical surgery, DNA ploidy was a suggestive indicator of clinical outcome, and p53 and bcl-2 expression provided no clinical information. By multivariate analysis, cell proliferation rate and Dukes' stage remained independent prognostic parameters. In the most representative subgroup of patients with H1 liver lesions (86 cases), TLI was always associated with relapse, and DNA ploidy and p53 expression provided discriminant information within slowly proliferating liver lesions. CONCLUSION: Tumor-cell proliferation of liver lesions should be used with stage of the primary colorectal cancer for a more accurate prognosis in patients submitted to curative hepatic resection.

Adult↗
PubMed1996

Effect of ionizing radiation on cell-cycle progression and cyclin B1 expression in human melanoma cells.

In the present study we investigated the effect of gamma-irradiation (2.5 and 10 Gy) on cell-cycle progression of a human melanoma cell line, M14, characterized by a moderate radiosensitivity (SF2 = O.5). Flow cytometric analysis showed a dose-dependent S-phase accumulation, which was detectable 8 hr after treatment with 2 and 5 Gy and was still persistent at 12 hr after 10 Gy exposure. Such a delay in S-phase was paralleled or followed by an accumulation of cells in G2M, which was transient at the lowest radiation doses and still persistent at 72 hr after 10 Gy. Such an accumulation was, at least in part, due to a block in G2-M transition, as demonstrated by mitotic index analysis. Bivariate flow cytometric analysis of DNA content and cyclin B1 expression showed that, following 2 and 5 Gy, the fraction of cyclin B1-expressing cells was superimposable upon that of G2M cells. Conversely, in cells treated with 10 Gy, the fraction of cyclin B1-expressing cells was half the G2M cell fraction. Northern-blot analysis indicated that the radiation-induced decrease in cyclin B1 protein expression was accompanied by a reduced cyclin B mRNA level. On the whole, our results indicate a direct inhibitory effect of 10 Gy irradiation on cyclin B1 expression as a possible cause for the persistent G2 block in irradiated M14 cells.

Cell Cycle↗
PubMed1996

Glutathione S-transferase mu polymorphism and susceptibility to lung cancer in the Portuguese population.

Epidemiological studies have led to the suggestion that a genetic basis may exist in the individual variation in predisposition to cancer. Interindividual differences in human toxicological response to carcinogenic exposure have been attributed to heritable polymorphisms in metabolism, namely glutathione S-transferases (GSTs) coding for enzymes that are known to be detoxifiers of carcinogens. Within the human GST mu class, there is a specific isozyme that is frequently lacking. To check whether or not this association exists in the Portuguese population with lung cancer, we used polymerase chain reaction (PCR)-based genotyping to examine GSTM1 polymorphism (nulled and non-nulled) in 84 individuals as a control healthy population and a group of 98 lung cancer patients. In this study we were able to find a frequency of the GSTM1 phenotype among our healthy control subjects consistent with earlier genotyping studies in other Caucasoid populations. For the group of individuals with lung cancer as a whole, or in subsets of histological subtypes, our data for the Portuguese population did not show a positive correlation between the null allele and this neoplasm. In contrast, we found a slight increase in the frequency of the wild-type allele in our lung cancer group.

Carcinoma, Small Cell↗
PubMed1996

Glucocorticoid receptors immunoreactivity in tissue of human embryos.

The exact period when glucocorticoid receptors (GR) appear in human embryos is unknown, however their presence is acknowledged in target tissues before the fetal adrenal cortex secretes cortisol. Determining when GR develop could serve as an index of the importance of glucocorticoids in the morphological and functional development of tissues. The aim of this study was to determine time of onset of GR in human tissues using an immunohistochemical method. Results indicate GR are present in tissues of 8-10-week-old human embryos: in most tissues, the immune reaction was only or predominantly nuclear.

Embryo, Mammalian↗
PubMed1996

An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics.

Chronic alcohol consumption has been shown to be associated with abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in humans. However, conflicting data exist in the literature, with particular regard to studies performed in actively drinking or withdrawn alcoholics; in addition, the frequent presence of depressive disturbances in such patients may importantly affect the neuroendocrine findings. In this study, we investigated HPA function in 12 male alcoholics, in whom the presence of depression and other possible confounding factors was excluded, during the first and second weeks after cessation of ethanol intake. The plasma corticotropin (adrenocorticotropic hormone, ACTH) and cortisol levels in response to both a stimulation test with human corticotrophin-releasing hormone (CRH; 100 micrograms IV) and an insulin (0.15 UI/kg IV)-induced hypoglycaemia (ITT) were measured; the cortisol response to a standard overnight dexamethasone (1 mg) suppression test (DST) was also tested. While the mean baseline ACTH and cortisol levels, measured in the morning (0800-0830 h), were not different from those of controls, ACTH and cortisol responses to the CRH test were markedly reduced (area of secretion p < .01 and p < .05, compared to controls). Similarly, the patient group showed an almost absent ACTH and cortisol release following insulin infusion (area of secretion p < .01 compared to controls, in either case). In four patients, non-suppression of plasma cortisol levels was seen on the DST, but no significant difference from normal suppressors was noted as far as the clinical features were concerned. These findings suggest that impaired hypothalamic and pituitary responsiveness, unrelated to depressive disturbances, occurs in recently withdrawn chronic alcoholics. While the possible influence of the alcohol withdrawal syndrome should be taken into account, such a pattern may be due to increased activity of the HPA axis, even in the face of preserved basal adrenal secretion. Whether these findings reflect a direct effect of sustained ethanol exposure on the components of the HPA axis, or a non-specific marker of impaired adaptation in chronic alcoholics, deserves further investigation.

Adrenocorticotropic Hormone↗
PubMed1996

Continuing medical education in oncology in Europe.

A European Conference on Continuing Medical Education (CME) in Oncology was designed and organised in Dublin (Ireland), on 12th and 13th October 1995 by the European School of Oncology in collaboration with University College Dublin and with the financial support of the European Commission (Europe Against Cancer Programme). Two experts were invited from each Member State and all attended the Conference with the sole exception of the representatives of Luxembourg, who did not attend due to unexpected important commitments. Observers were invited to contribute to the discussion as representatives of organisations that were involved either directly or indirectly in CME. The Conference took the format of a plenary session coupled with the identification of five discussion groups formed to debate key areas in CME at a European level in oncology (Table 1). As a result of these discussions and subsequent consultations, an agreement was reached on the following statements: (a) Continuing Medical Education (CME) is an ethical duty and an individual responsibility for each doctor. Although CME should remain voluntary at the present time, it is nevertheless a professional obligation since almost 50% of medical knowledge becomes obsolete after ten years. It should be organised with clear guidelines for medical personnel working in hospitals, in primary health care and in private practice. (b) The CME system within the European Union (EU) should remain self-directed without the necessity for interval examinations: it should be interdisciplinary and must be driven and controlled by the profession itself. (c) A common concept and system within a CME framework may have a considerable impact on EU integration. It should certainly be developed, maintained and monitored at national level but on the basis of a common European model to ensure scientific and cultural interchange among Member States. (d) It was agree that a credit system is needed to help doctors keep track of their CME activities: the system should be based on the accumulation of credit points (one credit equalling one hour of continuing medical education) and monitored at a national level. Credit transfer among Member States is vital to facilitate exchange between Member States. (e) Oncology provides a very useful model of CME within which guidelines can be proposed and tested. Harmonisation of CME systems among the different European cancer organisations and scientific societies within this model system may represent a useful basis that other specialities can follow.

Education, Medical, Continuing↗
PubMed1996

P53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer.

The identification of biomarkers to complement pathological stage for a more accurate prognosis and help clinicians decide on treatment is still an open problem for patients with lung cancer. Expression of P53 protein was detected by an immunohistochemical approach using the monoclonal antibody PAb1801 on paraffin-embedded sections of tumours obtained surgically from 102 stage II - IIIa patients with non-small-cell lung cancer (52 squamous cell carcinomas, 50 adenocarcinomas). [3H]Thymidine labelling index, an indicator of the S-phase cell fraction, was evaluated on histological sections of [3H]thymidine-labelled tumour samples. DNA ploidy was defined by flow cytometric analysis on frozen tumour tissue. The biomarkers, histology and pathological stage were analysed in relation to relapse-free survival in univariate and multivariate analyses. Stage and interaction between [3H]thymidine labelling index and histology provided significant prognostic information for the overall series. [3H]thymidine labelling index was an independent prognostic indicator of 3 year relapse-free survival in patients with adenocarcinoma. The results indicate the importance of cell proliferation to complement prognostic information provided by pathological stage in patients with stage II-IIIa adenocarcinomas.

Biomarkers, Tumor↗
PubMed1996

N-acetylsuccinimidylglutamate, a cyclic imide form of the peptide N-acetylaspartylglutamate, is present in low micromolar concentrations in murine and bovine CNS.

N-Acetylsuccinimidylglutamate [(asu)NAAG], a cyclic form of the peptide N-acetylaspartylglutamate (NAAG) in which the aspartyl residue is linked to glutamate via the alpha- and beta-carboxylates, was identified and quantified by HPLC in the murine and bovine CNS. In the rat, the highest concentrations of (asu)NAAG were detected in the spinal cord (1.83 +/- 0.15 pmol/mg of wet tissue weight) and brainstem (1.16 +/- 0.08 pmol/mg wet weight), whereas the levels were below the limit of detection in cerebellum, hippocampus, and cerebral cortex. (Asu)NAAG was also detected in significant amount in the superior colliculus and lateral geniculate nucleus (1.17 +/- 0.05 and 0.82 +/- 0.13 pmol/mg we weight, respectively). Although the tissue content of (asu)NAAG was about three orders of magnitude lower than that of NAAG, levels of both peptides were positively correlated among different CNS regions (r=0.74, p<0.003). In the rat spinal cord, (asu)NAAG levels progressively increased from week 2 to month 12 after birth. In bovine spinal cord, the contents of (asu)NAAG and NAAG were comparable in gray and white matter as well as in the dorsal and ventral horns. These results suggest that NAAG and (asu)-NAAG are closely related metabolically and raise the question of the physiological significance of such a cyclic peptide.

Aging↗
PubMed1996

Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Aged↗
PubMed1996

Effect of tamoxifen on endometrial proliferation.

PURPOSE: An increase in the incidence of endometrial cancer and a potential increase in related mortality has been associated with the administration of 20 mg tamoxifen, the dose adopted in breast cancer chemoprevention trials, thus urging studies on intermediate markers of risk. PATIENTS AND METHODS: Thirty-three women who received 20 mg tamoxifen as adjuvant breast cancer treatment underwent endometrial biopsy. Samples were divided for histologic examination, including a quantitative analysis of stromal:epithelial ratio, and an assessment of DNA ploidy and proliferation by flow cytometry. Results were compared with 37 symptomatic subjects. RESULTS: All histograms were DNA diploid. Compared with controls, a significant increase in the risk of proliferation as measured by the hyperdiploid fraction was associated with tamoxifen duration (< or = 36 months: cumulative odds ratio = 16.5, 95% confidence interval, 1.85 to 146.5; > 36 months: cumulative odds ratio = 28.2, 95% confidence interval, 2.56 to 310.6, P for trend < .05). Tamoxifen-induced risk was significantly reduced by the extent of menopausal status. No cases of cancer or epithelial hyperplasia were observed in the tamoxifen group, whereas seven cases of epithelial hyperplasia without atypia were observed in the control group. The effect of tamoxifen on proliferation was associated with an increase in the stromal component. CONCLUSION: Tamoxifen at 20 mg/d exerts a time-dependent proliferative effect on the endometrium, particularly in premenopausal and early postmenopausal women. This effect appears to be mediated by the stromal component, which accounts for the discrepancy between flow cytometry and histology. Our study provides preliminary evidence that the DNA flow cytometric hyperdiploid fraction may be a useful tool for monitoring endometrial cell proliferation in women exposed to tamoxifen.

Adult↗