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E Fonseca

Publications and source records attributed to E Fonseca.

At least 73 records · Page 4Linked to original sources

Expression of stratified epithelial-type cytokeratins in hyalinizing trabecular adenomas supports their relationship with papillary carcinomas of the thyroid.

AIM: To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas. METHODS AND RESULTS: This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas. CONCLUSION: Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma.

Adenoma↗

Evaluation of an immunoenzymometric assay (IEMA) using automated system for determination of luteinizing hormone and follicle stimulating hormone.

It has been proposed that automated systems for immunoenzymometric assay (IEMA) may substitute traditional radioimmunoassay (RIA) for measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood due to the advantage of being more rapid, higher sensitivity, lower cost and not requiring radioactive reagents. The study was designed to evaluate both systems using serum samples to determine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. The automatic system (ES-300) for IEMA utilized two monoclonal antibodies, one of them on the solid phase was the specific extractant for the antigen, and the other was a peroxidase labeled antibody which recognizes a different epitope in the antigen molecule, specifically bound in linear proportion to the antigen concentration. Blood samples were obtained from patients who were treated at the hospital for various clinical problems ("problem group") as well as blood samples from patients in whom FSH and LH concentrations were already known ("high", "medium" and "low" levels) by previous RIA ("control group"). IEMA showed a higher sensitivity, 0.42 and 0.96 mIU/ml for FSH and LH, respectively, whereas RIA was 1.95 mIU/ml for both hormones. Intra- and interassay coefficient of variation were below 10% within the range of 15-150 mIU/ml for FSH and 5-100 mIU/ml for LH; however, the coefficient of variation was 15-25% at lower concentrations of FSH and LH. Accuracy of IEMA was evaluated by recovery percentage, thus when high and medium concentrations of FSH and LH were analyzed the recovery was between 99-104%. On the other hand, the recovery was 110% when low levels of FSH and LH were used. In conclusion, IEMA resulted reliable when FSH and LH concentrations are in the middle and high range; likewise, the detection limit of IEMA was lower than RIA, particularly for FSH. On the bases of these results, IEMA showed several advantages over RIA, but its reliability diminishes when serum samples contain low FSH and LH concentrations. It is important to extend these studies to steroid assays and elaborate a database in each laboratory.

Adult↗

[Sequential chemotherapy and radiotherapy in the treatment of locally advanced carcinoma of the head and neck].

In patients with non-resectable carcinoma of the head and neck, radiotherapy produces an average survival of 12 months. Neoadjuvant chemotherapy followed by radiotherapy has been shown to prolong survival and preserve organ structure and function, and to reduce systemic relapses in patients with advanced, resectable disease. An analysis was made of 35 patients treated with sequential chemotherapy and radiotherapy, 20 with non-resectable disease and 15 with resectable disease who refused surgery. Treatment consisted of 4 cycles of cisplatin + 5-fluoruracil in a 96-h continuous intravenous infusion in 16 patients, and the same treatment with leucovorin in 19 patients. After chemotherapy, the patients underwent cobalt irradiation of the primary tumor and neck. Chemotherapy produced a complete response rate of 46% and a partial response rate of 28%, yielding an overall rate of 74%. After radiotherapy, the CR increased to 63%. After 92 months of maximum follow-up, overall survival was 20% and median survival was 25 months. Locoregional relapses were the main cause of treatment failure. Our results suggest that sequential chemo-radiotherapy achieved encouraging CR rates with no significant increase in toxicity, prolonged survival in non-resectable patients, and enabled organ preservation in patients with resectable disease.

Adult↗

[Postmenopausal metabolic effects of a synthetic estrogen (tibolone) with a characteristic estrogenic action].

Life expectancy in women has nearly reached 80 yr old, therefore the postmenopausal period is considered very important, particularly regarding the benefits of hormone replacement therapy. At the present there are several therapeutic options in order to protect against the long term complications resulting from chronic hypoestrogenism and avoiding some of the side effects associated with estrogens medication, tibolone is a synthetic steroid possessing mild estrogenic effect and some progestagenic and androgenic actions; moreover this steroid does not require to be converted to estradiol. We studied the effect of administering tibolone 2.5 mg daily orally during six months to 11 postmenopausal women in order to analyze any changes on several biochemical markers. Estradiol concentrations were not modified although FSH, total cholesterol, low density lipoproteins and triglycerides levels decreased. Collaterally there was observed an increment in high density lipoproteins and sexual hormone binding globulin. It is concluded that tibolone exerts its effect directly on specific receptor tissues without being converted to estradiol so that this finding may help to understand some of the clinical effects, particularly upon mammary gland, endometrium and body weight.

Aged↗

Prognostic factors in thyroid carcinomas.

The AA review the so-called prognostic factors in thyroid carcinoma taking in consideration four of the five major histotypes of thyroid tumours: Papillary ca. (5-year-survival -91%), follicular ca. (73%), poorly differentiated ca. (48%) and undifferentiated ca. (0%), with an emphasis on papillary carcinoma. The prognostic factors are described in two major groups: Clinicopathologic factors comprising the classic clinicopathologic features--age, gender, size, extrathyroidal extension, vascular invasion, nodal metastization and distant metastization--and Biologic factors, comprising a group of heterogeneous and less classic features such as DNA content and proliferation markers, oncogenes and tumour-suppressor genes, growth factors and growth factor receptors, pro- and anti-apoptotic genes, mucin and histo-blood group antigens, cytoskeletal filaments, adhesion molecules, and so forth. Finally, the AA address briefly a third group of (prognostic) factors that reflect the interaction between the neoplastic cells and their microenvironment: extracellular matrix and proteolytic enzymes (laminin, collagen IV, fibronectin, collagenases, alpha-1 anti-trypsin) and lymphocytic infiltration (S-100 positive cells, IGF-I and IGF-I receptor).

Adenocarcinoma, Follicular↗

[Cytogenetic changes in benign thyroid gland hyperplasias and adenomas correlated with histology].

In order to elucidate cytogenetic changes associated with the development of benign growth of follicular epithelial cells of the thyroid, cytogenetic analyses were performed on 340 follicular thyroid adenomas and goiters after short-term culture. Clonal chromosome changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases). Other recurrent numerical changes were loss of chromosome 22 (4 cases) and the second X or the Y chromosome (5 cases). Translocations involving 19q13 (12 cases) were frequent structural chromosome changes. After a histopathological classification of all cases, we have correlated the cytogenetic findings with the histology of the tumors. Only 8.4% of the goiters showed clonal abnormalities whereas 44.9% of the adenomas revealed clonal abnormalities. Furthermore, simple clonal changes were predominantly found in goiters and complex changes in adenomas. The most impressive correlation was found in the group of lesions with trisomy 7: Whereas all but one lesion with one or two additional trisomies were goiters, those having three or more additional trisomies were all adenomas or adenomatous goiters.

Adenoma↗

Mediastinal mass following chemotherapy in patients with Ewing sarcoma and osteosarcoma.

Thymic hyperplasia following combination chemotherapy for malignant disease is very uncommon in adolescents and adults. Our experience includes a thymic enlargement noted on the sequential computed tomography (CT) in three patients who were disease-free after chemotherapy for Ewing sarcoma (2) and osteosarcoma (1). The development of an anterior mediastinal mass after successful chemotherapy does not always imply relapse of malignant disease. To prevent inappropriate treatment, the possibility of benign aetiology must be considered.

Adolescent↗

Gastrin levels in mothers and neonates at delivery in various perinatal conditions.

BACKGROUND: This study was designed to assess the variations of gastrin (Ga) serum levels in mothers and newborns at birth in some perinatal disorders. MATERIALS AND METHODS: Ga levels were measured by RIA in maternal serum, amniotic fluid and cord sera of newborns in 55 cases with the following conditions: normal pregnancy and eutocic vaginal delivery (n = 8), repeat cesarean section (n = 10), and cardiotogographic register suggestive of fetal compromise (n = 15), cephalopelvic disproportion (n = 8), preeclampsia (n = 7) and postdate pregnancy (n = 7). Statistical analysis was performed by Mann-Whitney U test. RESULTS: Ga levels in cord sera of newborn and amniotic fluid in normal pregnancy and eutocic delivery were significantly higher (p < 0.02 and p < 0.01, respectively) than those found in patients with repeat cesarean operation. Serum Ga concentrations in women with postterm pregnancy were significantly higher (p < 0.02) than in women with prior cesarean section. Ga levels in amniotic fluid samples in the presence of suspected fetal compromise and postdate pregnancy were significantly higher (p < 0.001) than those observed in women who had repeat cesarean operation. CONCLUSION: Vaginal delivery and perinatal pathology may induce hypergastrinemia in both mother and neonate at birth.

Adult↗

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Adult↗

Elevation of activity of creatine phosphokinase (CK) and its isoenzymes in the newborn is associated with fetal asphyxia and risk at birth.

OBJECTIVE: To investigate the relationship of creatine phosphokinase and its isoenzymes with fetal asphyxia and risk at birth. METHODS: Thirty-five pregnant women with high-risk pregnancy were studied. RESULTS: In 21 patients, fetal distress was diagnosed by interpretation of the fetal heart rate tracing (FHR). The remaining 14 women, having normal fetal cardiotocography, were considered as the control group. Total CK and its isoenzymes activity was measured in cord sera and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and CK-BB) exhibited higher values in asphyxiated infants as compared to normal neonates. Electrocardiographic ischemia occurred in seven newborns who had elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum. Chromatographic study showed in normal neonates that the predominant isoenzyme was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS: Antepartum fetal distress is associated with release of CK-BB, and particularly CK-MB; therefore, these biochemical markers may indicate either brain or myocardial damage.

Asphyxia Neonatorum↗

Diagnostic problems in differentiated carcinomas of the thyroid.

In this review article we consecutively address the following issues: differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas, with a special emphasis on the hyalinizing trabecular tumours; differential diagnosis of benign and malignant papillary lesions; individualization of the variants of papillary carcinoma that carry a guarded prognosis; differential diagnosis of differentiated thyroid carcinomas exhibiting foci of other types of thyroid carcinoma, namely mucoepidermoid and poorly differentiated carcinoma; and, finally, the diagnostic problems raised by the so-called mixed medullary-follicular carcinomas.

Diagnosis, Differential↗

p53 protein expression in viral warts from patients with epidermodysplasia verruciformis.

The p53 protein is the product of a tumour suppressor gene, which is implicated in many human malignancies. p53 expression was investigated by immunohistochemistry in a series of viral warts (n = 12) from five patients with epidermodysplasia verruciformis (EV), using a monoclonal anti-p53 antibody (DO7). p53 expression was also investigated in a series of common warts (n = 8), flat warts (n = 8), and penile bowenoid papulosis (n = 6) from non-EV patients. Immunostaining was positive in 11 of 12 (92%) EV warts, whereas p53 reactivity was negative in most cases of warts from non-EV patients. Exons 5-8 of the p53 gene were screened by the polymerase chain reaction-single strand conformation polymorphism technique in four EV warts, which were strongly stained for p53, and p53 mutations were not detected. These results suggest an association between p53 accumulation (probably of wild type) and EV warts.

Epidermodysplasia Verruciformis↗

Rothmund-Thomson syndrome and Addison disease.

We report an 18-year-old man with the unusual combination of Rothmund-Thomson syndrome (RTS) and Addison disease. He was admitted when he was 26 months old because of short stature, dehydration, metabolic acidosis, hyperpigmentation, and typical skin lesions. Because his growth remained delayed, at age 10 years he was given a trial of recombinant growth hormone. After six years of treatment no improvement in height, bone, or sexual maturation was observed. This fact may be related to a defect in connective tissue metabolism. Chromosomal analysis of peripheral blood lymphocytes revealed increased numbers of breaks and gaps. Fibroblasts cultured from affected skin did not grow. Patients with RTS are prone to developing cancer, but no malignant disease was found in our patient. Early diagnosis and treatment of both endocrinologic and malignant complications are essential for survival of patients with this rare syndrome.

Acidosis↗

Detection of numerical alterations for chromosomes 7 and 12 in benign thyroid lesions by in situ hybridization. Histological implications.

Polysomies of chromosomes 7 and 12 have been frequently observed by conventional cytogenetics in a subgroup of thyroid follicular adenomas and in some cases of thyroid goiters. To further study possible cytogenetic similarities between these two types of thyroid lesions, we have used fluorescence in situ hybridization (FISH) to detect polysomies of chromosomes 7 and/or 12 in isolated nuclei from frozen and paraffin-embedded material of goiters and thyroid follicular adenomas and compared results with previous ones obtained by flow cytometry and conventional cytogenetics. With a set of two alpha-satellite DNA probes specific for the centromeric regions of chromosomes 7 and 12, used either separately (single-target fluorescence in situ hybridization) or simultaneously (double-target fluorescence in situ hybridization), we detected polysomies of chromosome 7 in 35.7% of the thyroid follicular adenomas and in 10.7% of the goiters. Polysomies of chromosome 12 were detected in 29.6% of the thyroid follicular adenomas and 6.7% of the goiters. The significantly higher frequency of adenomas with numerical alterations for chromosomes 7 and/or 12 supports the idea of a biological continuum and karyotypic evolution between both lesions. It is also noteworthy that polysomies of chromosomes 7 and/or 12 were observed only in lesions with an exclusive (or predominant) microfollicular histological component, as detected by enzymatic in situ hybridization on frozen sections.

Adenoma↗

Four days' continuous infusion of cisplatin-5-fluorouracil and short daily infusion of high-dose leucovorin as induction chemotherapy for locally advanced head and neck cancer.

Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Patients with TSH-secreting pituitary tumor possess different TSH molecular isoforms.

The objective of the study was to demonstrate if TSH secreted by a pituitary tumor correlates with particular molecular forms of TSH. Aliquots of sera from two hyperthyroid patients with TSH-secreting pituitary tumor were subjected to gel filtration chromatography to be assayed for TSH. The assay was repeated in one case after transsphenoidal adenomectomy. Sera from two additional patients with long-lasting primary hypothyroidism, and from two subjects with normal thyroid function were also chromatographed. Molecular weight (mol wt) of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, mol wt, and partition coefficient. Chromatographic profile of the two cases with TSH-secreting pituitary tumor exhibited mainly two peaks of TSH immunoreactivity. The major component of immunoreactivity eluted as a peak corresponding with the alpha-subunit of the glycoprotein. This pattern was different from that obtained in sera from two women with hypothyroidism, which was heterogeneous and presented a predominance of molecular variants corresponding with mol wt of 22 and 29 kD, and no alpha-subunit was present. In cases of normal thyroid function the chromatographic profile showed that the major proportion of TSH eluted simultaneously with the labeled standard and 22 kD marker. These results demonstrate that TSH secreted by pituitary tumors is composed of various molecular forms and the alpha-subunit is the major component. This chromatographic profile is different from that observed in other cases with elevated concentrations of TSH as it occurs in primary hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗