Search PubMed⌕ Search

Biomedical subjects

S Costa

Publications and source records attributed to S Costa.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Therapeutic strategy in advanced breast carcinoma].

Breast cancer metastastic to sites beyond regional axillary lymph nodes represents a historically incurable condition despite the judicious use of various hormonal manipulations and surgical and radiotherapeutic interventions, and the application of active cytotoxic chemotherapeutic agents for hormone-refractory disease. The systemic management of patients with hormone refractory breast cancer is classically characterized by the thoughtful, stepwise administration of cytotoxic chemotherapeutic agents. At various junctures in the continuum of care, a patient/physician analysis of the potential risks and benefits of chemotherapy may lead to the decision to proceed with subsequent systemic therapy, to consider an investigational strategy like new active agents or high dose therapy, or to opt for supportive care alone.

Breast Neoplasms↗
PubMed1998

Gluconeogenesis in isolated rat hepatocytes evaluated by gas chromatography/mass spectrometry using deuterated water.

Tritiated water and radioactive tracers have been used to monitor glucose production by primary cultures of hepatocytes. More recently, 3H2O has been replaced for by 2H2O in 'in vivo' studies addressed at the evaluation of the relative contribution of gluconeogenesis to total glucose production. In this work, the possibility of using 2H2O to determine the ratio between the glucogenic flux and the overall flux through glucose 6-phosphate in isolated liver cells in vitro was evaluated. For this purpose, hepatocytes from either fasted or fed rats were incubated with a medium containing 6, 12 and 25% of 2H2O in the presence of either 2 or 20 mM pyruvate. Isotopomer analysis of six different mass clusters (m/z 328, 314, 242, 212, 187 and 145) was carried out by gas chromatography/mass spectrometry (GC/MS) of glucose aldonitrile pentaacetate. For each cluster, ions at m/z +1, +2, +3 and +4 were monitored. From the combination of different clusters the enrichment at C-6 and C-2 of glucose was computed and the C-6/C-2 ratio was considered to represent the contribution of gluconeogenesis to total glucose production, as suggested previously. Based on the results obtained, conditions selected to be optimum for the use of the method in studies on the modulation of gluconeogenesis were as follows: incubation of hepatocytes with 20 mM pyruvate in 12% 2H2O followed GC/electron ionization MS analysis of the clusters of ions at m/z 328, 314 and 187 of the glucose derivative to calculate enrichment at the C-2 and C-6 positions of glucose.

Animals↗
PubMed1998

Cervicography and HPV DNA testing as triage criteria for patients with abnormal pap smear.

Cervicography and HPV DNA testing have been proposed as intermediate triage techniques for the management of patients with Pap smear showing minor-grade atypia. The aims of the present study of 221 patients with positive Pap smear (ages 16-65) were (1) to evaluate the association of cervicography and HPV DNA test with the probability of biopsy and final histology diagnosis of CIN2 or worse, (2) to identify the combinations of results on cervicography and HPV DNA test associated with the absence of such lesions, and (3) to estimate the cost of a potential triage protocol for patients with HPV-CIN1 smear. The probability of biopsy showed a univariate association with the severity of the smear result and the cervicography classification but not the HPV DNA test. In the multivariate analysis, only the cervicography result was a significant predictor of biopsy. The final histology diagnosis showed a univariate association with each of the three tests and a multivariate association with the degree of cytology positivity and the cervicography result. Among patients with HPV-CIN1 smears, only a negative cervicography (with any HPV DNA test result) was always associated with the absence of severe histologic lesions. This pattern accounted only for 7% of such patients. The additional costs of a potential triage protocol based on cervicography were estimated to exceed the savings resulting from the reduced colposcopy rate.

Adolescent↗
PubMed1998

Improvement of Pap smear sensitivity using a visual adjunctive procedure: a co-operative Italian study on speculoscopy (GISPE).

The present study evaluates whether speculoscopy, a magnified chemiluminescence examination, combined with Pap smear can improve the detection of cervical lesions, as compared with Pap smear alone. The investigation was a prospective practice-based research carried out as a multicentre cohort study throughout the Italian territory. The participants were 3,300 asymptomatic women age > or = 18 years undergoing routine pelvic and cytological screening. All participants were subjected to Pap smear, speculoscopy and colposcopy investigations in succession. The 646 women with positive colposcopy underwent biopsy. Of the 267 women with positive histology 25 were high-grade intraephitelial lesions (HGSIL) and 242 were low-grade intraephitelial lesions (LGSIL). The histological findings were correlated with the results of Pap smear and speculoscopy alone and combined (PPS). Pap smear alone detected 76% of HGSIL, speculoscopy alone identified 84% of HGSIL, and PPS indicated 100% HGSIL. Of the 242 women with LGSIL, Pap smear alone detected 37% of the cases, speculoscopy alone detected 54% of the cases, and PPS identified 91% of the cases. Together, the two tests missed 9% of the LGSIL. The combination PPS was found to increase sensitivity from 40% to 92%, but to lower specificity from 94% to 23%. Speculoscopy combined with Pap smear can yield a higher percentage of women with biopsy-confirmed cervical pathology than the use of Pap smear as a sole screening test. This is particularly true of patients with LGSIL. The mechanisms of pathological detection and the use of speculoscopy should be investigated further.

Adolescent↗
PubMed1997

Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells.

The integrin beta4 has a long cytodomain necessary for hemidesmosome formation. A yeast two-hybrid screen using beta4 cytodomain uncovered a protein called p27(BBP) that represents a beta4 interactor. Both in yeast and in vitro, p27(BBP) binds the two NH2-terminal fibronectin type III modules of beta4, a region required for signaling and hemidesmosome formation. Sequence analysis of p27(BBP) revealed that p27(BBP) was not previously known and has no homology with any isolated mammalian protein, but 85% identical to a yeast gene product of unknown function. Expression studies by Northern analysis and in situ hybridization showed that, in vivo, p27(BBP) mRNA is highly expressed in epithelia and proliferating embryonic epithelial cells. An antibody raised against p27(BBP) COOH-terminal domain showed that all beta4-containing epithelial cell lines expressed p27(BBP). The p27(BBP) protein is insoluble and present in the intermediate filament pool. Furthermore, subcellular fractionation indicated the presence of p27(BBP) both in the cytoplasm and in the nucleus. Confocal analysis of cultured cells showed that part of p27(BBP) immunoreactivity was both nuclear and in the membrane closely apposed to beta4. These results suggest that the p27(BBP) is an in vivo interactor of beta4, possibly linking beta4 to the intermediate filament cytoskeleton.

Amino Acid Sequence↗
PubMed1997

Androgen-receptor blockade does not impair bone mineral density in adolescent females.

The effect of peripheral androgen hypersensitivity on bone mineral density (BMD) was investigated in a group of adolescent women with idiopathic hirsutism (n = 17; mean age 17.0 +/- 1.7 years). The effect of long-term androgen-receptor blockade with flutamide (500 mg daily in two divided doses for 12 months) on BMD was assessed too. BMD was measured at lumbar spine (L2-L4) by a dual energy X-ray densitometer. Before flutamide treatment, patient BMD (1.14 +/- 0.07 g/cm2) was not significantly different from that of the control group (1.16 +/- 0.12 g/cm2, n = 22), and was normal for age and sex (BMD 0.14 +/- 0.69 SDS, P = NS vs. 0). After 12 months of treatment, absolute BMD in patients increased (1.18 +/- 0.08 g/cm2, P < 0.002), but SDS BMD did not change (0.21 +/- 0.72, P = NS vs. baseline). Flutamide treatment determined a clinical, marked improvement of androgen hypersensitivity (Ferriman-Gallwey score: before 22.0 +/- 6.2; 6 months: 13.2 +/- 6.4, P < 0.003; 12 months; 7.6 +/- 4.1, P < 0. 001; acne score: before 3.8 +/- 0.8; 3 months 0.8 +/- 0.5, P < 0. 001; later disappeared). The serum levels of 3alpha-androstenediol-glucoronide decreased (before: 8.6 +/- 1.1 microg/liter; 12 months: 7.2 +/- 1.0 microg/liter, P < 0.02), whereas the other endocrinological parameters did not change. No relationship was found between BMD and clinical or biochemical parameters of hyperandrogenism. We concluded that in adolescent women, peripheral hyperandrogenism is not associated with abnormal BMD; long-term treatment with flutamide, which blocks the androgen receptor, does not alter their BMD.

Absorptiometry, Photon↗
PubMed1997

Cloning and characterisation of a carrot cDNA coding for a WD repeat protein homologous to Drosophila fizzy, human p55CDC and yeast CDC20 proteins.

The present study describes the isolation of a cDNA coding for a carrot protein of 450 amino acids that contains WD repeats (DcWD1) and is homologous to Drosophila melanogaster fizzy protein, mammalian p55CDC and yeast Cdc20p. As for the known related proteins, sequence conservation concerned the majority of the polypeptide except the far N-terminus. Results of Southern blot analysis with genomic DNA under high stringency conditions showed the occurrence of a single gene. Northern blot analyses revealed the accumulation of DcWD1 mRNA in all tested tissues (leaves, petioles and hypocotyls, apical meristems, roots and suspension cultured cells), though at a different extent. Lack of induction of relevant transcripts in proliferating auxin-stimulated hypocotyls suggests a mode of expression not strictly related to the cell proliferation.

Amino Acid Sequence↗
PubMed1997

Absence in human milk of bovine beta-lactoglobulin ingested by the mother. Unreliability of ELISA measurements.

OBJECTIVES: To analyze the presence of bovine beta-LG in breast milk. METHODS: Human milk samples from 14 healthy non-atopic women on diets with different cow's milk contents were examined. The total concentration of beta-LG immuno-like proteins (beta-LGIP) was determined by enzyme linked immunosorbent assay (ELISA). Identification of antigens was done by N-terminal sequencing. RESULTS: beta-LGIP reactivity of the milk from subjects on different diets was not significantly different. Human lactoferrin, beta-casein and alpha-lactalbumin, were identified as cross-reacting antigens. CONCLUSIONS: False-positive results in ELISA determinations of bovine beta-LG in human milk might be due to cross-reactions between polyclonal antibodies and different protein antigens.

Animals↗
PubMed1997

Metallic ion release in artificial saliva of titanium oral implants coupled with different metal superstructures.

In this work the metallic ion release in oral implants with superstructures of different metals and alloys used in clinical dentistry has been determined. This study has been realized in a saliva environment at 37 degrees C. The measurements of the ion release were carried out by means of the Inductively Coupled Plasma Mass Spectrometry technique. The titanium oral implant coupled with a chromium-nickel alloy releases a high quantity of ions and the implant coupled with the titanium superstructure presents a low value of ion release.

Chromium Alloys↗
PubMed1997

Carboplatin plus paclitaxel as first-line chemotherapy in previously untreated advanced ovarian cancer. German AGO Study Group Ovarian Cancer. Arbeitsgemeinschaft Gynäkologische Onkologie.

Since publication of the results of the Gynecologic Oncology Group (GOG) III study, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been adopted widely as the new standard for treating advanced ovarian cancer. Further attempts to optimize first-line chemotherapy with platinum and taxanes include substituting carboplatin for cisplatin, individualizing the carboplatin dose by calculating it according to the area under the concentration-time curve, and reducing the length of the paclitaxel infusion. Attempts to optimize platinum/paclitaxel combinations have led to the initiation of several small phase I/II trials evaluating the carboplatin/paclitaxel combination. The promising results of these studies have prompted the initiation of three phase III trials comparing carboplatin/paclitaxel with the standard combination of cisplatin/paclitaxel. An interim analysis after 1 year's accrual to the prospectively randomized German Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study is presented. Treatment consists of paclitaxel 185 mg/m2 infused over 3 hours on day 1 followed directly by either cisplatin 75 mg/m2 (arm B) or carboplatin dosed to an area under the curve of 6 (arm A). Treatment is repeated every 3 weeks for six courses. Eligibility criteria are epithelial ovarian cancer International Federation of Gynecology and Obstetrics stage IIB through IV, age of consent, written informed consent, Eastern Cooperative Oncology Group performance status < or =2, life expectancy of more than 12 weeks, adequate bone marrow function defined as neutrophil count 1.5 x 10(9)/L and platelet count > or =100 x 10(9)/L, adequate renal function defined as glomerular filtration rate (GFR) > or =60 mL/min, and adequate liver function defined as serum bilirubin levels within 1.25 x upper limit of normal. From October 1995 to December 1996, 442 of 660 planned patients were recruited to the AGO study. The interim analysis is based on data from 353 patients who were enrolled within the first study year. These preliminary data indicate that hematologic toxicity occurred more frequently in arm A (carboplatin/paclitaxel), while nonhematologic toxicity occurred slightly more frequently in arm B. Dose-intensity analysis did not reveal cumulative dose reductions or increasing use of colony-stimulating factors over subsequent courses in either arm. In all, 44 patients with measurable disease following surgery completed chemotherapy and were evaluable for response. The data remain blinded at this time, and results are reported for the group as a whole. So far, there have been 18 (41%) complete responses and 15 (34%) partial responses, for an overall response rate of 75%. Retrospective comparison with the GOG results reveals no significant difference in response rates between patients in the cisplatin/paclitaxel arm of GOG III and those in the AGO study: the GOG study reported a 73% response rate, compared with a preliminary 75% response rate in the AGO study, resulting in a relative risk of 1.03 (95% confidence interval, 0.83 to 1.27). Overall, this interim analysis did not reveal any reason to terminate this study early. Accrual is ongoing and is expected to be completed in 1997.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Carboplatin/paclitaxel versus cisplatin/paclitaxel as first-line chemotherapy in advanced ovarian cancer: an interim analysis of a randomized phase III trial of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.

Since publication of the results of the Gynecologic Oncology Group III study, the combination of cisplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been widely adopted as standard treatment for advanced ovarian cancer. Further attempts to optimize first-line chemotherapy with platinum and taxanes include the substitution of cisplatin with carboplatin, individualization of the carboplatin dose by calculating it according to the area under the concentration-time curve, and reduction of paclitaxel infusion duration. These attempts have led to the initiation of several phase I/II trials evaluating the combination of carboplatin/paclitaxel. The promising results of these small studies have prompted the initiation of three phase III trials comparing carboplatin/paclitaxel with the standard combination of cisplatin/paclitaxel. The interim analysis after 15 months' accrual of the prospectively randomized German Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study is presented here. As of January 1997, 518 of 660 planned patients have been recruited. The interim analysis is based on data from 449 evaluable patients. The preliminary data indicate that hematologic toxicity occurred more frequently in arm A (carboplatin/paclitaxel), whereas nonhematologic toxicity occurred slightly more frequently in arm B (cisplatin/paclitaxel). Dose-intensity analysis did not reveal cumulative dose reductions or an increased need for colony-stimulating factors over subsequent courses in both arms. Forty-four patients with measurable disease following surgery completed chemotherapy and were evaluable for response, which remains blinded at this time and is reported for the group as a whole. So far, there have been 18 complete responses (41%) and 15 partial responses (34%), for an overall response rate of 75%. Retrospective comparison reveals no significant difference in response rates between patients in the cisplatin/paclitaxel arm of Gynecologic Oncology Group III and those in the Arbeitsgemeinschaft Gynäkologische Onkologie study. Overall, this interim analysis did not reveal any reason for an early termination of this study. Accrual is ongoing and is expected to be completed this year.

Antineoplastic Agents↗
PubMed1996

Allelic imbalance on chromosome 13q: evidence for the involvement of BRCA2 and RB1 in sporadic breast cancer.

Recently, the breast cancer susceptibility gene BRCA2 has been identified in chromosome 13q, a region that also contains the retinoblastoma gene RB1. To elucidate a possible role of BRCA2 and RB1 in sporadic breast tumorigenesis, allelic imbalance (AI) at 13q loci was examined in 78 primary sporadic breast tumors. AI was found in 52-63% of tumors. Nine tumors showed AI only in the BRCA2 region but not at RB1. Six tumors showed AI at RB1 but not in the BRCA2 region. AI in the BRCA2 region correlated significantly with aneuploidy (P = 0.032) and AI at RB1 with small tumor size (P = 0.025). Our data suggest that BRCA2 and RB1 may be both distinct target loci for AI on chromosome 13 in sporadic breast cancer.

Alleles↗
PubMed1996

Bone mineral density in adolescent females treated with L-thyroxine: a longitudinal study.

UNLABELLED: It has been suggested that chronic treatment with L-thyroxine (L-T4) could be implicated in reducing bone mineral density (BMD). The purpose of this longitudinal study was to determine whether appendicular and axial BMD is decreased by L-T4 treatment in adolescent girls. Thirteen adolescent girls with subclinical hypothyroidism caused by chronic lymphocytic thyroiditis were enrolled in the study at the median age of 13.4 years (range 9.2-18.1 years). L-T4 was administered in a single dose of 1-5 micrograms/kg daily. BMD was evaluated at the distal one-third of the non-dominant radius by single photon absorptiometry (SPA) and at the lumbar spine (L2-4) by dual energy X-ray densitometry (DEXA). Osteocalcin levels were measured to assess bone turnover before and during L-T4 treatment. Before the start of therapy, mean BMD at both the radial and lumbar level was not significantly different from that of a control group (median age 13.0 years; range 9.0-18.5 years). during L-T4 therapy for 2-5 years, BMD did not change at any site. Before treatment, osteocalcin levels were not significantly different from those of controls and did not change during follow up. CONCLUSION: Long-term L-T4 therapy in adolescent girls has no adverse effect on BMD and bone turnover. Our data indicate that attainment of peak bone mass is not impaired by L-T4 administration.

Absorptiometry, Photon↗
PubMed1996

Eprinomectin: a novel avermectin for use as a topical endectocide for cattle.

Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel avermectin selected for development as a topical endectocide for all cattle, including lactating dairy cows. Herein, we show its anthelmintic, insecticidal and miticidal activity. To determine its anthelmintic capabilities, eprinomectin was tested topically on Jersey calves at 0.08, 0.2, or 0.5 mg kg-1 in a probe formulation against experimental infections of adult Haemonchus placei, ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Dictyocaulus viviparus. Eprinomectin removed > or = 99% and > or = 98% of the adult stage of every species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The lowest dosage (0.08 mg kg-1) produced maximal or near maximal efficacy against most of the adult endoparasites with the exception of T. colubriformis (87%) and C. oncophora (88%). In a separate test, eprinomectin was evaluated topically against the immature stages of species at the same dosages. Results showed > or = 99% and > or = 98% removal of the immature stages of each species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The 0.08 mg kg-1 dosage maintained > or = 97% efficacy against 6 species with reduced activity against H. placei (42%) and N. helvetianus (66%). For ectoparasites, eprinomectin was tested topically at 0.16, 0.24, 0.32 or 0.5 mg kg-1 on mixed breed cattle naturally infested with the sucking louse, Linognathus vituli. Complete elimination of lice at all dosages was observed by day 14. Topical delivery of eprinomectin at 0.16, 0.24, 0.32 or 0.5 mg kg-1 to Holstein calves experimentally challenged with horn fly, Haematobia irritans, produced 100% efficacy to challenge by week 2 post-treatment in all dosages groups and 94% and 99% efficacy to challenge at the 0.32 and 0.5 mg kg-1 dosage groups, respectively, at week 4. Topical delivery of eprinomectin at 0.16, 0.24 or 0.5 mg kg-1 to Deutsches Fleckvieh cattle infested with mange mites, Chorioptes bovis, produced > or = 95% control at all dosages levels by day 14 post-treatment and was maintained at or near this efficacious level for the 6-week duration of the trial. No adverse reaction was observed in any animal in any of these tests. In summary, these experimental data indicate that eprinomectin is an excellent broad-spectrum endectocide for cattle and is suitable for topical delivery.

Administration, Topical↗
PubMed1996

Spatial expression of alpha and beta tubulin genes in the late embryogenesis of the sea urchin Paracentrotus lividus.

In Paracentrotus lividus sea urchin embryos, at blastula stage, there is an abrupt increase in the abundance of alpha and beta tubulin transcripts in particular of the PI beta 1, PI beta 2 and PI alpha 2 forms. In order to assign specific functions to the various embryonic tubulin genes, we have used whole-mount in situ hybridization to determine spatial patterns of expression of five different alpha and beta tubulin embryonic genes. The PI beta 3 transcripts, as previously shown for PI alpha 2, start to localize in a few founder cells from which the neurogenic territory differentiates. The other four embryonic tubulin mRNAs (PI beta 1/2 and PI alpha 1/10), are localized in the ciliated band- and gut-territory. These territories originate by morphogenetic processes, which occur in late embryogenesis in the sea urchin and depend on cellular interactions. In particular, the interactions between the oral and aboral ectoderm specify the position of the ciliated band, whereas the invagination of the vegetal plate forms the gut territory. We suppose that the increase in alpha and beta tubulin transcripts could be functionally related to these two morphogenetic events. Our results show in fact that specific tubulin isotypes, or a mix of them, are expressed in and mark the ciliated band and the neighboring oral/aboral ectoderm cells of the ciliated band, in addition to the cells of the gut territory. The same localization of all these tubulin transcripts has been confirmed by whole-mount in situ hybridization experiments performed on embryos treated with agents able to induce deciliation or exogastrulation. Furthermore a putative correlation of PI beta 2 with cilium formation has been shown by the results obtained on deciliated embryos.

Animals↗