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Biomedical subjects

B Franc

Publications and source records attributed to B Franc.

At least 37 records · Page 2Linked to original sources
PubMed1999

Medullary thyroid microcarcinoma: a clinicopathologic retrospective study of 38 patients with no prior familial disease.

Thirty-eight patients (25 women, 13 men; mean age, 57.8 [32 to 91]) showing one or more medullary thyroid microcarcinomas (ie, < 1 cm), with no prior MEN II or medullary thyroid carcinoma history in their family, were reviewed. Follow-up was available for 29 patients (mean, 53.6 months [1 to 147]). 21 patients (72.4%) are alive and free of disease, four patients (13.8%) died during follow-up without disease, 2 patients are alive with disease (local recurrence and persistent hypercalcitoninemia) after 80 and 99 months, respectively, and 2 patients died of disease after 24 and 46 months. Most tumors were incidental pathological findings (19 of 38) or were discovered by systematic blood calcitonin measurement for a nodular thyroid disease (15 of 38). Only the four patients who had an unfavorable outcome were symptomatic cases (palpable micro-MTC, diarrhea, cervical lymph node metastasis and pulmonary metastatic disease). The two patients with metastatic disease at diagnosis died during follow-up. In univariate analysis, a symptomatic medullary thyroid carcinoma was a strong predictor of an unfavourable outcome (p < .00008), as were the preoperative calcitonin level (P = .007) and an elevated postoperative calcitonin level (P = .004). Among 30 histopathological criteria, only the presence of amyloid correlated with an unfavorable outcome (P = .018).

Adult↗
PubMed1999

Graves-Basedow disease goiter: a model of Bax-Bcl2 regulated apoptosis.

This study demonstrates the involvement of a Bax-Bcl2-dependent apoptotic process in Graves-Basedow thyroid disease, a pathological condition known for its spontaneously oscillating evolution. A continuous series of 86 cases of surgically treated Graves' thyroid was evaluated for apoptotic cell content identified by histological criteria and confirmed by terminal desoxynucleotidyl transferase-mediated desoxyuridine triphosphate nick end-labeling (TUNEL). A significant correlation was found between tissue features of Graves' disease (epithelial hyperplasia, cellular hypertrophy, colloid content) and the amount of apoptotic cells. No correlation was found with lymphocytic infiltrates. Significantly, 11 cases (about 12% of the series) with high-level apoptosis displayed the typical features of active Graves' disease over all tissue sections. In contrast, cases with no detectable apoptosis exhibited regressive tissue features of Graves' disease. An intermediate group of cases was characterized by tissue heterogeneity with hyperactive foci, rich in apoptosis, alternating with regressive areas lacking apoptosis. In this group the participation of apoptosis to the remodeling of Graves' thyroid parenchyma, in a tight balance with cell proliferation, was best illustrated. Moreover, the thyroid follicle by accumulating apoptotic cells and bodies, allowed a tentative chronological ordering of apoptosis steps in correlation with Bax-Bcl2 tissue distribution and cellular pattern. Our observations suggest that the initiation of apoptosis corresponds to a loss of cellular cohesion, a drop in Bcl2 expression, and a delocalization of Bax from a putative Golgi storage location to a mitochondrial distribution.

Adult↗
PubMed1999

Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules.

Although ultrasound (US)-guided fine needle aspiration biopsy (FNAB) is widely prescribed in nonpalpable thyroid nodules, the goal of this study was to define precisely the indications and limits of US-FNAB in a series of 450 nonpalpable nodules. Among 94 surgically controlled cases, 20 (8 infracentimetric and 12 centimetric or supracentimetric) carcinomas were diagnosed. The diagnosis of malignancy was successfully made by US-FNAB in 16 of 20 carcinomas, 3 were missed because of insufficient cytological material, and 1 was misdiagnosed. US-FNAB sensitivity and specificity were 94% and 63%, respectively. A logistic model indicated that nodule size (P < 0.6) was not associated with histological diagnosis, but that solid hypoechoic features were more likely to be malignant (P < 0.0003), with US sensitivity and specificity for malignancy of 80% and 70%, respectively. Logistic regression indicated that adequate cytological material significantly increased with nodule size (P < 0.0001). This result outlined the limits of US-FNAB in small nodules. Hence, indication of US-FNAB appears judicious in centimetric or supracentimetric nodules or in solid and hypoechoic ones. Such a management would allow the discovery of 15 of 20 carcinomas and would avoid 16% of unnecessary biopsies.

Adolescent↗
PubMed1999

[112 cases of sporadic and genetically determined pheochromocytoma: a comparative pathologic study].

The aim of this study was to compare 64 genetically determined pheochromocytomas (PH) (49 MEN IIa, 3 MEN IIb, 6 Von Recklinghausen diseases, 1 von Hippel-Lindau disease, 5 familial pheochromocytomas) and 48 sporadic PH. Genetically determined PH were more often observed among men and more frequently bilateral and multicentric than sporadic PH. Sporadic tumors had more often adrenal capsular invasion, necrosis and pseudocysts. Genetically determined PH were more differentiated with an insular pattern, hyaline globules and a higher percentage of polyhedric cells. Sporadic tumors were less differentiated with more frequently a diffuse pattern and small cells. Adrenal medullar hyperplasia was significantly associated with genetically determined PH. Adrenal cortical hyperplasia was not associated with a particular type of PH. The PS100 and chromogranin immunodetection was equivalent in both groups.

Adrenal Cortex↗
PubMed1998

Dorsal medullary 5-HT3 receptors and sympathetic premotor neurones in the rat.

1. Our aim was to determine whether the cardiovascular neurones in the rostro-ventrolateral medulla (CV-RVLM neurones) were involved in the sympathoexcitation induced by stimulation of 5-HT3 receptors in the region of the nucleus tractus solitarii (NTS). Experiments were performed in pentobarbitone-anaesthetized rats, artificially ventilated and paralysed with pancuronium bromide. 2. Using extracellular recordings, different types of RVLM neurones were characterized: cardiovascular (CV), ventilation-related and baroreflex-insensitive (unidentified) neurones. The CV-RVLM cells were further subdivided into three populations according to their axonal conduction velocities: A (1.2 +/- 0.1 m s-1), B (2.5 +/- 0.2 m s-1) and C (6.8 +/- 1.1 m s-1). 3. Only the CV-RVLM neurones of the A and B categories were partially inhibited (-30 %) by a hypotensive dose (2.5 microg kg-1 i.v.) of clonidine. 4. Microinjections into the region of the commissural NTS of 1-(m-chlorophenyl)-biguanide (CPBG, 2 nmol), a selective 5-HT3 receptor agonist, elicited an increase in both lumbar sympathetic nerve discharge (SND) and arterial pressure. In addition, this treatment produced a marked excitation of CV-RVLM neurones of the A and B categories, without affecting those of the C type, as well as ventilation-related and unidentified RVLM cells. 5. The activity of the CV neurones in the caudo-ventrolateral part of the medulla oblongata (CV-CVLM) was not modified by 5-HT3 receptor stimulation in the NTS. 6. Prior intra-NTS microinjections of ondansetron (300 pmol, a selective 5-HT3 receptor antagonist) into the region of the commissural NTS prevented the excitation of A and B CV-RVLM neurones induced by CPBG. 7. Intracarotid administration of saline saturated with CO2 (chemoreceptor activation) elicited both an increase in the SND and an excitation of the clonidine-insensitive CV-RVLM neurones of the C type, without affecting A and B neurones. 8. In conclusion, the sympathoexcitation elicited following 5-HT3 receptor stimulation in the region of the commissural NTS of pentobarbitone-anaesthetized rats seems to result from the excitation of two different pools of clonidine-sensitive CV-RVLM neurones. These neurones are apparently not involved in the sympathetic component of the chemoreceptor reflex.

Action Potentials↗
PubMed1998

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

Adolescent↗
PubMed1998

Sporadic medullary microcarcinoma of the thyroid: a retrospective analysis of eighty cases.

Clinical characteristics and prognosis of 80 patients (53 women and 27 men) with sporadic medullary thyroid carcinomas (MTC), less than 1 cm in size (micro-MTC), operated on between 1971 and 1996 are reported (73 total and 7 partial thyroidectomies). These patients, obtained from a national database of 899 patients with MTC, were compared with 357 cases of sporadic MTC greater than 1 cm and 149 subjects with familial MTC less than 1 cm (familial micro-MTC). Median age at surgery was 52.5 years, a distribution similar to larger sporadic MTC. Micro-MTC was identified due to elevated calcitonin (47.5%), clinically identified lymph node (10.0%), distant metastases (6.3%) or pathologic finding at surgery (36.2%). Diarrhea and/or flushing were observed in 6 patients including 4 with clinically identified lymph node. Among patients who had lymph node dissection at surgery (68.8%), lymph node involvement with tumor was observed in 30.9%, and was significantly more frequent in multifocal (7/11) than in unifocal micro-MTC (p < 0.03). All sporadic micro-MTC were unilateral. Survival rate was 93.9% +/- 4.4% (SE) at 10 years, greater than that observed in sporadic macro-MTC (p = 0.04). Normal postoperative basal calcitonin (CT) was obtained in 71.1% of micro-MTC patients versus 33.6% in sporadic macro-MTC (p < 0.01). Sporadic micro-MTC is much more frequent than expected, 15% of MTC in our series. Although specific survival rate and percentage of biological cure in micro-MTC are significantly better than for larger tumors, the frequency of lymph node involvement, however, justifies an aggressive surgical approach including total thyroidectomy and bilateral central lymph node dissection.

Adolescent↗
PubMed1998

[Management of 29 children with thyroid cancer following the Chernobyl accident].

As a consequence of the Chernobyl nuclear power plant accident, a considerable increase of thyroid cancer among contaminated children has been reported in Ukraine, Belarus and Russia. A group of 29 children aged from 5 months to 10 years (mean 4.7 years) at the time of the accident, with a papillary thyroid cancer, have been examined at the Pitié-Salpêtrière hospital in Paris. The cancer was discovered by systematic ultrasonography in only 25% of cases. No reliable dosimetric estimation was achieved. The initial surgical treatment was performed in Ukraine. Cervical lymph node and pulmonary metastases were present in 24 and 11 cases respectively. A complementary surgical treatment was necessary for 9 children and one to four radioiodine treatments were given to 24 children. With a mean delay of 7 years after the cancer discovery, an apparent cure or a remission was obtained for 20 children, 6 children have cervical lymph node metastases requiring a surgical treatment and 3 have evolving lung metastases. The management of the great number of foreseeable cases of thyroid cancer requires an improved systematic screening, a large number of rooms dedicated to high activity radioiodine treatments, funds for disposable material and training missions.

Child↗
PubMed1998

[Transgenic mouse models. Their interest in thyroid tumors].

Mouse transgenic models that develop thyroid diseases were generated. All transgenes were driven by the thyroid specific promoter of the thyroglobulin gene. The tissue specificity of the promoter was investigated by using the bacterial chloramphenicol acetyltransferase gene as reporter. The expression of the adenosine A2a receptor resulted in the permanent activation of the cAMP cascade. As a consequence, transgenic mice developed severe hyperthyroidism and a large goiter, demonstrating in vivo the role of the cAMP cascade in the promotion of both function and proliferation of the thyroid cell. These mice constitute a model for autonomous hyperfunctional adenoma and non autoimmune familial hyperthyroidism, where mutant of thyrotropin receptors stimulate the cAMP cascade constitutively. The expression of a mutant of the alpha 1B adrenergic receptor resulted in the constitutive activation of both the cAMP and IP3-CA++ cascades, growth stimulation, hyperfunction, cell degeneracy attributed to the overproduction of free radicals, and development of malignancies. The expression of the SV40 large T antigen promoted the development of aggressive undifferentiated tumors mimicking the phenotype of human anaplastic carcinomas and embryonal tumors. In another transgenic model, the function of the retinoblastoma susceptibility gene product RB1 (and of related proteins) was inhibited by expressing the E7 oncoprotein of human papillomavirus type 16. The result was the development of a differentiated and normofunctional colloid goiter, with progressive development of differentiated malignant lesions. This model suggests the essential role of RB1 and related proteins in the negative control of proliferation that characterizes thyroid cells in the adult. Other transgenic models of thyroid diseases are discussed.

Adenoma↗
PubMed1998

[Thyroid insular carcinoma].

This review article illustrates the several histological and immunohistochemical patterns of thyroid insular carcinoma and their associated disease. Differential diagnosis are also discussed. Poorly differentiated thyroid carcinomas are overviewed. The interest of transgenic mice models is presented.

Animals↗
PubMed1998

[Medullary thyroid carcinoma: evolution of concepts].

This article analyses in a large overview several of the actual problems encountered by pathologist in the management of MTC whatever the diagnostic circumstances. We insist on difficulties upon C cell hyperplasia and early detected disease. Unusual MTC cases are discussed. The need for large multidisciplinary group in studying such tumors is underlined with reference to the French GETC (Groupe d'Etude des Tumeurs à Calcitonine).

Carcinoma, Medullary↗
PubMed1998

[Fine needle aspiration of the thyroid].

This article precises the technical conditions of fine-needle aspiration, elements of microscopical analyses which establish the diagnostic, complementary technics, specially immunocytochemistry that could enhance the performance. Limits and worrisome histologic changes following fine needle aspiration are also discussed. Fine needle aspiration results are discussed. The text is fully illustrated.

Biopsy, Needle↗
PubMed1997

Vasoactive intestinal polypeptide microinjections into the oral pontine tegmentum enhance rapid eye movement sleep in the rat.

Rapid eye movement sleep can be elicited in the rat by microinjection of the cholinergic agonist carbachol into the oral pontine reticular nucleus. Intracerebroventricular administration, during the light period, of vasoactive intestinal peptide enhances rapid eye movement sleep in several species. Since this peptide is co-localized with acetylcholine in many neurons in the central nervous system, it was assumed that the oral pontine tegmentum could also be one target for vasoactive intestinal peptide to induce rapid eye movement sleep. This hypothesis was tested by recording the sleep-wakefulness cycle in freely-moving rats injected with vasoactive intestinal peptide or its fragments (1-12 and 10-28) directly into the oral pontine reticular nucleus. when administered into the posterior part of this nucleus, vasoactive intestinal peptide at 1 and 10 ng (in 0.1 microliter of saline), but not its fragments, induced a 2-fold enhancement of rapid eye movement sleep during 4 h, at the expense of wakefulness. At the dose of 10 ng, a significant increase in rapid eye movement sleep persisted for up to 8 h. Moreover, when the peptide was injected into the centre of the positive zone, rapid eye movement sleep was enhanced during three to eight consecutive days. These data provide the first evidence that rapid eye movement sleep can be elicited at both short- and long-term by a single intracerebral microinjection of vasoactive intestinal peptide. Peptidergic mechanisms, possibly in association with cholinergic mechanisms, within the caudal part of the oral pontine reticular nucleus may play a critical role in the long-term regulation of rapid eye movement sleep in rats.

Animals↗
PubMed1997

Hashimoto's thyroiditis associated with Riedel's thyroiditis and retroperitoneal fibrosis.

This article describe the case of a 38-year-old woman with simultaneous involvement of the thyroid by Hashimoto's thyroiditis and Riedels's disease, associated with retroperitoneal fibrosis and lipidic endarteritis. According to a large review of the literature on the occurrence of this rare condition the difficulty in sharply defining the two thyroid processes is discussed. The chronology of the events is analyzed, and etiopathogenic hypotheses are listed with emphasis on the relationship between the vascular lesions and the onset of the fibrosing process.

Adult↗
PubMed1997

MUC1 mucin gene, transcripts, and protein in adenomas and papillary carcinomas of the thyroid.

MUC1 mucin is found in a variety of epithelial tissues and is overexpressed in several epithelial cancers. This molecule could modulate cellular adhesion and thereby influence tumor invasion and metastasis. Little is known of MUC1 gene expression in thyroid tissues. We investigated whether MUC1 mucin gene alteration and/or expression correlated with thyroid tumor progression by studying 21 fresh thyroid tissue specimens comprising 10 macrofollicular adenomas and 11 papillary carcinomas. Normal adjacent tissue from the same patients was also studied. To determine the integrity and expression of the MUC1 mucin gene, a complementary DNA (cDNA) probe was used for Southern blot analysis of DNA and Northern blot analysis of RNA. A detailed immunohistochemical analysis of MUC1 protein expression was performed with DF3 monoclonal antibody, and was compared with other tumor characteristics and clinical manifestations at diagnosis. Of the 14 tumors informative (heterozygous) with the pMUC10 polymorphic probe, 2 (14%) showed loss of heterozygosity (1 adenoma and 1 carcinoma). Overexpression of MUC1 RNA, compared with normal thyroid tissue, was observed in 6 of the 11 papillary carcinomas and in none of the 10 adenomas. Immunostaining of the corresponding formalin-fixed paraffin-embedded tissue sections detected MUC1 mucin protein at the apical domain of follicular cells. Most of the lining was thin in normal tissue and follicular adenomas, but the protein was more irregularly and less strongly expressed in adenomas. In carcinomas the epithelial mucin produced by the MUC1 gene was present irregularly as a thin and/or thick lining at the apical domain of tumor cells. In addition, 5 of the 6 samples with MUC1 mRNA overexpression showed intracytoplasmic staining. Moreover, intracytoplasmic MUC1 mucin staining was found in 75% of "high-risk" papillary thyroid carcinoma (PTC) (PTC with extrathyroid extension at initial diagnosis and/or lymph node involvement), and in only 28.5% of "low-risk" PTC (purely intrathyroidal carcinomas).

Adenoma↗
PubMed1997

Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study.

We report a prospective quantitative image analysis study of C cells in 57 normal autopsy thyroid glands, serially sectioned and wholly embedded in paraffin; all slides were immunohistochemically stained for calcitonin. Computerized quantitative image analysis was performed on 47 cases to measure C cell surface area and parenchymatous surface area after immunoperoxidase staining for calcitonin. The method was time-effective, with a good reproducibility. C cells were mainly found in the middle third of each lobe. Important inter-individual variations were observed; the maximum C cell surface area in a section (Amax) ranged from 28 x 10(3) to 470 x 10(3) microns2 (mean, 167 x 10(3) microns2) among 42 adults. Of particular interest was the important difference observed between sexes; Amax was twice as high in men (mean, 201 x 10(3) microns2) as in women (mean, 91 x 10(3) microns2; P = 0.0009). Moreover, 14 (33%) adult subjects [2 women (15%) and 12 men (41%)] fulfilled C cell hyperplasia criteria, i.e. at least 3 fields at x 100 magnification containing more than 50 C cells, suggesting that a substantial part of the normal adult population could have C cell hyperplasia.

Adult↗