Search PubMed⌕ Search

Biomedical subjects

C Parmentier

Publications and source records attributed to C Parmentier.

At least 19 recordsLinked to original sources

Premature chromosome condensation associated with fluorescence in situ hybridisation detects cytogenetic abnormalities after a CT scan: evaluaton of the low-dose effect.

The purpose of this study was to assess the cytogenetic effects of the X ray irradiation used during a CT scan in order to estimate the mean absorbed dose in circulating lymphocytes. Chromosomal aberrations were scored in blood lymphocytes of ten patients undergoing CT scans, by applying fluorescence in situ hybridisation (FISH) to metaphase cells and premature chromosome condensation (PCC) with chromosomes 1, 3 and 4 painting probes immediately after exposure. This generated a dosimetric index that reflects the dose to the circulating lymphocytes. By using PCC a significant increase in the frequency of chromosomal fragment was observed immediately after a CT scan. However, no significant increase in chromosomal aberration was detected in metaphase cells. The mean dosimetric index immediately after exposure was 0.057 Gy (95% CI: 0.052-0.082 Gy). This dosimetric index depends essentially on the size of the examined and exposed blood volumes. This dose is in close agreement with the dose length product (DLP) (Gy cm) (R = 0.80). It should be kept in mind when justifying requests for diagnostic CT scan especially in young patients. The presence of chromosomal fragments after a CT scan indicated the cytogenetic effect of a low dose. PCC associated with chromosome painting is a method for detecting the cytogenetic effect of a low dose immediately after exposure.

Adult↗

Expression of tyrosine hydroxylase and vasopressin in magnocellular neurons of salt-loaded aged rats.

Tyrosine hydroxylase (TH) is expressed in catecholaminergic neurons. However, under certain conditions it is also ectopically expressed in magnocellular neurons of the hypothalamus. To test the hypothesis that this expression of TH is related to the cellular activation of these neurons and/or to the vasopressin (VP) expression, we studied the expression of both TH and VP in control and salt-loaded aged rats. Our results demonstrate that aged rats show a marked TH expression in VP cells which is further increased by osmotic stimulation in the absence of increase in VP synthesis in the supraoptic nucleus. The presence of TH-immunopositive dendritic swellings in the ventral part of this nucleus reveals the high state of plasticity of these neurons. Furthermore, the lack of several actors of catecholamine biosynthesis in these neurons suggests a different role for TH. This study further demonstrates an ectopic expression of TH in hypothalamic neurons of aged rats and a TH expression linked to the activation of VP neurons but unrelated to VP synthesis.

Adaptation, Physiological↗

Specific features of chronic astrocyte gliosis after experimental central nervous system (CNS) xenografting and in Wobbler neurological mutant CNS.

This study sets out to compare and contrast the astrocyte reaction in two unrelated experimental designs both resulting in marked chronic astrogliosis and natural motoneuron death in the wobbler mutant mouse and brain damage in the context of transplantation of xenogeneic embryonic CNS tissue into the striatum of newborn mice. The combined use of GFAP-labeling and confocal imaging allows the morphological comparison between these two different types of astrogliosis. Our findings demonstrate that, in mice, after tissue transplantation in the striatum, gliosis is not restricted to the regions of damage: it occurs not only near the site of transplantation, the striatum, but also in more distant regions of the CNS and particularly in the spinal cord. In the wobbler mutant mouse, a strong gliosis is observed in the spinal cord, site of motoneuronal cell loss. However, moderate astrocytic reaction (increased GFAP-immunoreactivity) can also be found in other wobbler CNS regions, remote from the spinal cord. In the wobbler ventral horn, where neurons degenerate, the hypertrophied reactive astrocytes exhibit a dramatic increase of glial fibrils and surround the motoneuron cell bodies, occupying most of the motoneuron environment. The striking and specific presence of hypertrophic astrocytes in wobbler mice accompanied by a dramatic increase of glial fibrils located in the vicinity of motoneuron cell bodies suggests that short astrogliosis fills the space left by degenerating motoneurons and interferes with their survival. In the spinal cord of xenografted mice, chronic astrogliosis is also observed, but only glial processes without hypertrophied cell bodies are found in the neuronal micro-environment. It is tempting to speculate that gliosis in the wobbler spinal cord, the local accumulation of astrocyte cell bodies, and high density of astrocytic processes may interfere with the diffusion of neuroactive substances in gliotic tissue, some of which are neurotoxic, and cooperate or even trigger neuronal death.

Animals↗

Dental device-associated problems: an analysis of FDA postmarket surveillance data.

BACKGROUND: The authors provide an analysis of dental device adverse event reports collected through the U.S. Food and Drug Administration's, or FDA's, mandatory and voluntary reporting programs between Aug. 1, 1996, and June 30, 1999. METHODS: This study includes an analysis of the total number of dental device adverse events reported during the study period and uses descriptive statistics to depict reporters' occupations, types of adverse events (deaths, injuries, malfunctions), device categories, device problems and patient problems. RESULTS: A total of 272,241 device reports were received during the 35-month study period, 28,555 (10.5 percent) of which involved dental devices. Within these reports, two deaths (0.007 percent), 18,406 injuries (64.4 percent) and 9,942 device malfunctions (34.8 percent) were reported. The most commonly reported dental devices were endosseous implants, which represented more than 90 percent of all dental device reports. Most reports (84.1 percent) provided the reporter's occupation, and the most frequently cited occupation was dentist (76.3 percent), followed by dental assistant (4.2 percent). CONCLUSIONS: Dentists and dental staff members are a vital link in the FDA's adverse event reporting system and are encouraged to report device problems to the FDA MedWatch program.

Data Collection↗

Biological dosimetry after total body irradiation (TBI) for hematologic malignancy patients.

PURPOSE: Biological dosimetry based on scoring chromosomal aberrations in peripheral lymphocytes was compared to physical dosimetry done for total body irradiation (TBI) before bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Fifteen patients undergoing TBI were included in the study. A total dose of 12 Gy in 2.5 days was fractionated into 2 or 3 daily doses of 1.8 Gy delivered by a 18 MV linear accelerator (dose rate: 15.8 cGy x min(-1)). Blood samples were obtained from patients before irradiation and after the first fraction of 1.8 Gy. A standard dose-effect curve was established by in vitro irradiation of healthy volunteer lymphocytes. Chromosomal aberrations were scored by the conventional cytogenetics (CCG) method for unstable anomalies and by fluorescent in situ hybridization (FISH) for stable anomalies. RESULTS: Healthy donor lymphocytes before irradiation yielded 0.1% dicentrics and 0.3% translocations of chromosome 4 (Chr. 4), that is 2.5% for the whole genome. Patients before irradiation had 2% of dicentrics and 1.1% of chromosome 4 translocations. The biologically estimated dose of the 15 patients after exposure to 1.8 Gy was 1.93 Gy (95% CI: 1.85-2.05) according to CCG, and 2.06 Gy (95% CI: 1.75-2.15) by FISH. CONCLUSION: The dose estimated by biological dosimetry, in this case of homogeneously distributed radiation of TBI agrees well with the absorbed radiation dose calculated by physical dosimetry.

Adult↗

Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay.

PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.

Adenoma↗

Simultaneous measurement of reactive oxygen species and reduced glutathione using capillary electrophoresis and laser-induced fluorescence detection in cultured cell lines.

A capillary zone electrophoretic (CZE) method coupled with laser-induced fluorescence (LIF) was developed for the simultaneous determination of two important intracellular parameters related to oxidative stress (i.e. reactive oxygen species, ROS, and reduced glutathione, GSH). This rapid and sensitive method was applied to the study of oxidative stress in cultured V79 fibroblast cells. The fluorogenic reagents selected were: (i) dihydrorhodamine-123 (DHR-123) which is converted intracellularly by ROS to the fluorescent rhodamine-123 dye (Rh-123), and (ii) naphthalene-2,3-dicarboxaldehyde (NDA), which reacts quickly with GSH in cell extracts to produce a fluorescent adduct. Separation of Rh-123, GSH-NDA and gamma-glutamylcysteine-NDA adducts was performed using an uncoated fused-silica capillary and a 100 mM borate buffer, pH 9.2, at 20 degrees C and at an applied voltage of 25 kV; LIF detection was operated using an argon laser. The cell line was also tested for its ability to alleviate oxidative stress induced by tert-butylhydroperoxide (t-BuOOH). Exposure to t-BuOOH (up to 3 mm for 2 h) did not affect the intracellular ROS and GSH concentrations. At higher (4-10 mM) t-BuOOH concentrations, an inverse relationship between the concentrations of ROS and GSH was obtained, showing that the present method can readily evaluate the gradual consumption of the primary cellular scavenger of ROS which occurs simultaneously with the increase of oxidative insult.

Animals↗

Determination of cellular thiols and glutathione-related enzyme activities: versatility of high-performance liquid chromatography-spectrofluorimetric detection.

A high-performance liquid chromatography (HPLC) method to determine the most important cellular thiols [reduced glutathione (GSH), cysteine, gamma-glutamylcysteine and cysteinylglycine] is described. Separation relies upon isocratic ion-pairing reversed-phase chromatography and detection is operated by spectrofluorimetry coupled with post-column derivatization reactions using either N-(1-pyrenyl)maleimide (NPM) or ortho-phthalaldehyde (OPA). When OPA is used without co-reagent, only GSH and gamma-glutamylcysteine are detected (heterobifunctional reaction). However, either the OPA reaction in the presence of glycine in the mobile phase (thiol-selective reaction) or NPM allows the detection of all the cited thiols. The HPLC system has been validated as concerning linearity, accuracy and precision. The low detection limits reached (in the pmol range for each thiol injected) allow the screening and the quantification of thiols (as NPM derivatives) in V79cl and V79HGGT cells as well as the measurement of two cytosolic enzymes related to the glutathione synthesis, using the heterobifunctional OPA reaction.

Animals↗

gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system.

In the presence of molecular oxygen and iron or copper ions, a number of antioxidants paradoxically generate reactive oxygen species (ROS) leading to free radical damage of nucleic acids and oxidative modification of lipids and proteins. The present work demonstrates that the combination of three components, which are often considered as part of an antioxidant protection system, can generate ROS. Purified human gamma-glutamyltransferase (GGT) in the presence of 2 mM glutathione (GSH) and 80 microM transferrin, as an iron source, at pH 7.4 generates ROS, as measured by chemiluminescence of luminol. Initiated by the addition of purified GGT, generation of ROS reached a maximal rate in the first 6 min. Intensity of the chemiluminescence was only slightly enhanced by addition of 200 microM hydrogen peroxide. Generation of ROS was also investigated in transfected V79 cells expressing human GGT. In comparison with GGT negative V79 cells, only recombinant cells expressing a high level of GGT on the cell membrane were able to generate ROS. Generation of ROS in these cells reached a maximum within 2 min and was enhanced by 200 microM hydrogen peroxide. We further confirmed the hypothesis that cysteinylglycine (CysGly), a product of GGT/GSH reaction, identified by high-performance liquid chromatography, but not GSH, was responsible for ROS formation initiated by the reductive release of iron from transferrin. These data clearly indicate that under physiological conditions, GGT is directly involved in ROS generation.

Animals↗

Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience.

BACKGROUND: Patients with thyroid microcarcinoma (TMC) have favorable long term prognoses. However, recurrences in the neck and distant metastases have been reported. The authors investigated independent factors associated with recurrence in an effort to define therapeutic guidelines. METHODS: Two hundred eighty-one patients (207 females, 74 males; mean age, 41.9 years) with a differentiated thyroid carcinoma < or = 1 cm in greatest dimension (mean size +/- standard deviation, 5.9+/-3.3 mm) were analyzed. The median follow-up time was 7.3 years. RESULTS: TMC diagnosis was incidental in 189 patients, and metastases were the first manifestation of the disease in the other 92 patients. Therapy included near-total thyroidectomy for 195 patients, lymph node dissection for 195, and therapeutic administration of radioiodine for 124. Eleven recurrences (3.9%) were observed 4.3+/-2.7 years (mean +/- standard deviation) after initial treatment: all had locoregional recurrence (4 in the thyroid bed and 7 in the lymph nodes), and in one of these the local recurrence was associated with lung metastases. Multivariate analysis showed that two parameters significantly influenced TMC recurrence, namely, the number of histologic foci (P < 0.002) and the extent of initial thyroid surgery (P < 0.01). Only 3.3% of patients with unifocal TMC treated with loboisthmusectomy had tumor recurrence. CONCLUSIONS: The recurrence rate for TMC appears to be low (3.9%). In the authors' view, loboisthmusectomy is the treatment of choice for patients with TMC when only one focus of cancer is found histologically, and total thyroidectomy is the optimal treatment for patients with multiple foci.

Adolescent↗

Combination of radioiodine (131I) and probe-guided surgery for persistent or recurrent thyroid carcinoma.

To improve the completeness of surgical excision of persistent or recurrent differentiated thyroid carcinoma, the following protocol was used for the treatment of 54 patients with functioning lymph node metastases: administration of 3.7 gigabecquerels (100 mCi) 131I; total body scintigraphy (TBS) on day 4; surgery on day 5, using an intraoperative probe (Gammed 2, Eurorad); and postoperative TBS with the remaining 131I activity on day 7. The 54 patients (35 women and 19 men presenting 47 papillary carcinomas, 2 well differentiated follicular carcinomas, and 5 poorly differentiated follicular carcinomas) had already undergone surgery for differentiated thyroid carcinoma: total thyroidectomy (51 patients) or lobectomy with isthmusectomy (3 patients), with lymph node dissection in 33. One to 7 131I treatments were performed before inclusion. Preoperative 131I-TBS with a high dose of 131I allowed accurate localization of previously suspected neoplastic foci and detection of yet unknown foci in 56%; it was the most sensitive tool for localizing neoplastic foci. The use of an intraoperative probe was considered decisive in 20 patients, as neoplastic foci were found inside sclerosis due to previous surgery (n = 9), at unusual sites behind vessels or in the mediastinum (n = 10), or both (n = 1). In 26 patients, it facilitated the preoperative detection of foci with 131I uptake already depicted at preoperative 131I-TBS. In all 46 patients, the completeness of excision was demonstrated by both the probe and the postoperative 131I-TBS and was confirmed during follow-up. Of note, lymph node metastases undetected by 131I-TBS or by the probe were found in 14 patients at histological examination. This clearly shows that en block dissection is the only recommended procedure. In four patients, no neoplastic foci were found and in four patients, uptake was either due to the thymus (in two) or to the salivary glands (in two).

Adenocarcinoma, Follicular↗

Biologic dosimetry in thyroid cancer patients after repeated treatments with iodine-131.

UNLABELLED: To estimate a cumulative dosimetric index that reflects the dose to the circulating lymphocytes after repeated treatments with 131I, biologic dosimetry was applied to 18 patients with differentiated thyroid carcinoma and neck relapse or lung metastases. METHODS: Chromosomal aberrations were scored in peripheral blood samples that were obtained before and 4 days after each administration of 3.7 GBq 131I according to two methods, conventional cytogenetics and chromosome 4 painting. RESULTS: The mean dosimetric index was equal to 0.5 Gy by both methods after the administration of 3.7 GBq 131I. Repeated administrations of 131I delivered the same dose each time, resulting in a cumulative dose from 1-3.5 Gy in the patients who had two to seven treatments. However, the estimated dose, based on the number of chromosomal aberrations on Day 4 and, above all, from the third treatment on, was considerably lower than the real dose absorbed by the lymphocytes. This may be linked to the phenomenon of apoptosis, which results in a loss of information during the course of repeated irradiation. CONCLUSION: Both chromosomal painting and conventional cytogenetics underestimate the cumulative dose after repeated 131I treatments. A complementary test measuring apoptosis may improve the dose estimates.

Apoptosis↗

Characterization and radiosensitivity at high or low dose rate of four cell lines derived from human thyroid tumors.

PURPOSE: This study attempted to establish cell lines derived from human differentiated thyroid tumors, and to characterize and evaluate the radiation dose-rate effect. METHODS AND MATERIALS: Two cell lines (K1 and K2) were derived from papillary carcinomas, one (K7) from a follicular less-differentiated carcinoma and one (A14) from a follicular adenoma. Cell-survival curves after irradiation were established by the in vitro colony method. Radiation doses were delivered either at a high (45.9 Gy/h) or low dose rate (0.6 Gy/h) by a 60Co source. The data were analyzed according to the linear quadratic and multitarget model of radiation action. RESULTS: Doubling times were around 24 h. All cell lines were positive for intracellular thyroglobulin. Cyclic adenosine monophosphate (cAMP) response to thyrotropin (TSH) was significant for the cell lines derived from the follicular adenoma and follicular carcinoma. The two cell lines derived from papillary carcinomas were tumorigenic after inoculation into nude mice. After high-dose-rate irradiation, the surviving fraction at 2 Gy (SF2) was not significantly different for the three malignant cell lines K1, K2, and K7, and ranged from 0.39 to 0.42. For the adenoma cell line A14, we found a higher radiosensitivity with a lower SF2 value and a higher alpha parameter. After low-dose-rate irradiation, only one cell line (K2) showed a significant low-dose-rate sparing with a dose reduction factor of 1.35. CONCLUSION: The major result of our study is the weak effect of the dose rate on the survival of thyroid cell lines.

Adenocarcinoma, Follicular↗

Leukaemias and cancers following iodine-131 administration for thyroid cancer.

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).

Adolescent↗

Digital superimposition of CT and positive SPECT tumor images. Phantom study and clinical applications.

Digital superimposition of SPECT and CT data was evaluated in a phantom and then applied to patient data. Seven patients were studied. Six patients had pheochromocytomas as evidenced by I-131 or I-123 MIBG localization and one had ovarian cancer imaged by In-111 OC125 MoAb. Anatomic or skin landmarks identified the level of each SPECT transaxial slice. Both SPECT and CT image data sets were transferred to a minicomputer connected to an image processor. Afterwards, a scaled, rotated and translated realignment was performed. Data for each modality were coded in different primary colors and then superimposed. Superimposition of phantom data was checked for the absence of distortion of pinpoint and large structures. For suspected tumor sites, superimposition of the patients' slices were allowed to check for matching SPECT and CT abnormalities to localize a SPECT abnormality without a corresponding CT lesion or to distinguish SPECT abnormalities from those seen on CT. In one case, the technique failed because of very low I-131 MIBG-tumor uptake. The superimposition decreases false positives in SPECT and both false negatives or false positives in CT.

Adolescent↗

Sequential biological dosimetry after a single treatment with iodine-131 for differentiated thyroid carcinoma.

UNLABELLED: To determine the cytogenetic and genotoxic risk associated with therapeutic exposure to 131I (3.7 GBq) in 50 patients with differentiated thyroid carcinoma, we estimated the dosimetric index that reflects the dose to the circulating lymphocytes on Day 4 and at several time intervals after exposure over a period of 2 yr. METHODS: Chromosomal aberrations were scored in peripheral lymphocytes obtained before and then 4 days, 3 mo, 6 mo, 1 yr and 2 yr after the first administration of 3.7 GBq 131I according to two methods: conventional cytogenetics and chromosome 4 painting. RESULTS: The dosimetric index was 0.52 Gy on Day 4, 0.49 Gy at 3 mo, 0.45 Gy at 6 mo, 0.44 Gy at 1 yr and 0.42 Gy at 2 yr by conventional cytogenetics and 0.47 Gy on Day 4, 0.45 Gy at 3 mo, 0.44 Gy at 6 mo, 0.43 Gy at 1 yr and 0.42 Gy at 2 yr by chromosome 4 painting. We found a decrease in the frequency of chromosomal aberrations between Day 4 and 3 mo after exposure. This may be due to the decrease of lymphocyte counts shortly after 131I administration, which will recover later on. In contrast, the number of anomalies remained constant starting 3 mo after 131I administration. CONCLUSION: These techniques permit retrospective biological dosimetry for up to 2 yr after therapeutic exposure to 131I.

Adult↗