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Biomedical subjects

C Parmentier

Publications and source records attributed to C Parmentier.

At least 55 records · Page 3Linked to original sources

Haematopoietic growth factors in the treatment of therapeutic and accidental irradiation-induced bone marrow aplasia.

Bone marrow aplasia is one of the main syndromes following a high dose accidental exposure of ionizing radiation. Although both transfusion and bone marrow transplantation have been used with some success since the first treatments of patients, other therapeutic strategies are needed. The strategies involving haematopoietic growth factors for the treatment of radiation victims have been explored in vivo mainly in animal models and it is hoped that new therapeutic regimens will be elucidated from such approaches. The growth factors stimulate proliferation and/or differentiation of haematopoietic progenitor cells and possible stem cells. Furthermore, they act on the functions of mature cells. They now have specific uses in haematology, related to their role in the regulation of growth and differentiation of haematopoietic progenitor cells. The results of the clinical trials, performed with numerous patients and often randomized bring important clues about what to expect from growth factor therapy. Other factors are only entering the preclinical or clinical trials now. Although numerous in vitro or in vivo experiments suggest a benefit from their effects, their possible uses in therapy are still questionable. Some growth factors have already been used for the treatment of accidental radiation-induced aplasia and lessons have been learned from their medical management and follow-up.

Accidents↗

Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: After intravenous administration of a radiolabeled somatostatin analog (octreotide), an image of the thyroid gland is frequently observed; few data are available, however, on somatostatin receptors in epithelial thyroid cells assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of 110 MBq of 111In-pentetreotide. The results were compared to data obtained with other imaging modalities, including scintigraphy performed after administration of a therapeutic dose of 131I. RESULTS: There were positive foci in distant metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was positive in two patients with an "insular" form of DTC, one of whom had a positive (faintly) 131I scan. Of the other two patients with papillary DTC without radioiodine uptake, only one exhibited a certain degree of pentetreotide scintigraphy positivity in distant metastases. CONCLUSION: These results show promise for exploration of insular thyroid carcinoma and suggest that these carcinomas may possess functional differentiation features, including somatostatin receptors.

Bone Neoplasms↗

Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma.

METHODS: The results of in vivo somatostatin scintigraphy were correlated with those of MIBG from 14 patients, aged 22-66 yr, with metastatic pheochromocytoma (10 patients), malignant paraganglioma (3 patients) and metastatic ganglioneuroblastoma (1 patient). Twelve patients had elevated catecholamine excretion. A dynamic study and serial whole-body scans (4-48 hr) were obtained after injection of 130-187 MBq of 111In-DTPA-Phe-1-octreotide. When indicated, SPECT imaging was done. The results were compared to MIBG scans obtained after a diagnostic or a therapeutic dose. RESULTS: Three patients with more than 20 tumor sites on MIBG scans had only 1-9 sites on 111In-octreotide scintigraphy. Two patients had no MIBG uptake but one had lung uptake on octreotide scintigraphy. In the other 9 patients with a total of 41 foci of MIBG uptake, 33 sites of 111In-octreotide uptake are found. All positive images with octreotide scintigraphy were seen at or before 4 hr, but the contrast improved at 24 hr. Uptake intensity was lower with 111In-octreotide than MIBG and the number of tumor sites was higher with MIBG. However, seven foci were positive only on octreotide scintigraphy and six of them could not be confirmed by other imaging modalities. CONCLUSION: Use of octreotide to identify somatostatin receptors seems promising, especially when results from MIBG scans are negative. Moreover octreotide images could aid in determining a treatment regimen as well as establishing the extent of disease and prognosis.

3-Iodobenzylguanidine↗

Upper clavicular and cardiac meta-[123I]iodobenzylguanidine uptake in children.

In order to clarify some of the particularities and pitfalls of the MIBG thoracic scan, we report our experience with 5 children with Stage III or IV neuroblastoma who presented equivocal scans. The physiological thoracic distribution of MIBG in children differs from that in adults and has to be taken in account in the accurate interpretation of the scans.

3-Iodobenzylguanidine↗

Somatostatin receptor imaging: a preliminary experience in forty-nine patients.

We report our experience with the 111In-pentetreotide scanning of 47 adult patients presenting with neuroendocrine tumors (n = 38) or malignant pheochromocytomas or related tumors (n = 9), and 2 children with metastatic neuroblastomas. A dynamic study was performed after i.v. administration of 50-190 MBq of 111In-pentetreotide followed by a whole body scan at 1.5-4 hours and at 24 hours. Where indicated, tomoscintigraphy or a dual isotope bone, liver or kidney scan was performed in order to improve the anatomical definition. Lesions were visualized in the earliest phases of the examination but contrast was enhanced on delayed images due to an improved signal to background ratio. In 9/49 patients, octreotide scan (OS) detected unknown tumors sites. On the other hand, the lesion uptake of 111In-pentetreotide varied, and not all the sites shown by other imaging modalities were visualised, probably due to differences in membrane receptor expression. In conclusion, OS can be useful in the diagnosis, follow-up and therapeutic management of neuro-endocrine tumors. Further investigations are required to assess the role of OS in other pathologies. Short title: Somatostatin receptor imaging.

Adolescent↗

Negative 123-meta-iodobenzyl-guanidine imaging in Ewing's sarcoma of bone.

The role of radiolabeled meta-iodobenzyl-guanidine (mIBG) is established in the detection and the staging of neuroblastoma. We designed a study of mIBG scanning for patients with Ewing's sarcoma, a tumor for which a neuroectodermic origin has been proposed. We explored 15 children with round cell sarcoma of bone by a whole body scan carried out 24 hours after injection of 123-I mIBG. No patient demonstrated significant uptake either at the site of the primary or at the sites of metastases. These results suggest that despite its neural histogenesis Ewing's sarcoma is a member of the nonneuroblastoma neural crest tumors, which does not produce or store adrenergic metabolites.

3-Iodobenzylguanidine↗

Screening for adrenal medullary disease in patients with medullary thyroid carcinoma.

Adrenal medullary disease (AMD) is clinically silent in most patients with medullary thyroid carcinoma (MTC). It was screened yearly by urinary measurements of catecholamines and derivates, and by abdominal ultrasonography (US) in a series of 174 patients with MTC. In cases with suspicion of AMD, abdominal computerized tomography and scintigraphy with meta-iodobenzylguanidine were also performed. AMD was discovered in 10 patients (one adrenal medullary hyperplasia and 9 pheochromocytomas). Three patients were already known to belong to a type II multiple endocrine neoplasia (MEN-2a) family and two had a MEN-2b syndrome. In 5 patients previously considered as having either a sporadic (4 cases) or a familial type of isolated MTC (one case), the occurrence of AMD led to diagnose a MEN-2a syndrome. The diagnostic values of the tests were evaluated by a case-control study. Urinary metanephrine plus normetanephrine (MN+N) had an acceptable sensitivity (0.8) and specificity (0.8). The other urinary tests had a high specificity (range: 0.8 to 1) but a poor sensitivity (range: 0.1 to 0.5). US had a high sensitivity (0.8) and a specificity of one. MN+N and US performed yearly constitute a simple and efficient strategy to screen for AMD in patients with MTC.

Adolescent↗

Selective venous sampling catheterisation for localisation of persisting medullary thyroid carcinoma.

Selective venous sampling catheterisation was performed in 19 patients with medullary thyroid carcinoma without known distant metastases for persistent hypercalcitoninaemia after surgery. Calcitonin (CT) gradients were found in the neck and/or the mediastinum in 18 patients and in five patients at distant sites also. After venous catheterisation, 13 patients were subjected to repeat surgery. Neck and/or mediastinal tumour foci were found in 12 patients at the sites of the CT gradients. Of these, nine patients had only cervicomediastinal CT gradients: after reoperation, the serum CT level normalised in one, significantly decreased in five, and did not change in three, and no neck relapse occurred after a mean follow-up of 5.3 years. Distant metastases emerged clinically in all five patients with distant gradients and in only one of the 14 patients with no distant gradient. In conclusion, selective venous catheterisation is the most sensitive tool for the localisation of residual disease and for the early detection of distant metastases. However, in patients with only local disease, biochemical cure is rarely obtained after reoperation.

Adolescent↗

Processing by factor analysis of dynamic dual isotope studies using 99Tcm and 201Tl within a middle energy band. Evaluation in thyroid nodule malignancy.

Simultaneous investigations with two isotopes are currently restricted because of spectral overlap. The factor analysis of spectral and dynamic structures (FASDS) method is shown to achieve accurate spectral separation. In addition, it estimates underlying dynamic mechanisms. Twenty-six patients were injected simultaneously with 99Tcm-pertechnetate and 201Tl-chloride to assess the malignancy of solitary thyroid nodules. List-mode acquisition of spectral, temporal and spatial coordinates of events allows the reconstruction of an image sequence indexed by time and energy. FASDS proceeds in two steps. First it yields both dynamic and spatial information related to each isotope (99Tcm and 201Tl) and partially removes the scatter component. Then it estimates the underlying kinetics and associated spatial distributions of each isotope. Using the 201Tl component, an index was derived from the uptake ratio between nodules and normal thyroid tissue. Concerning the detection of malignant nodules the method indicated no false negative in our limited group of 26 patients. One false positive result was found which could not be classified by the investigation of the 201Tl dynamic components contained in the reconstructed 201Tl factor sequence.

Factor Analysis, Statistical↗

The use of 32 phosphorus (32P) in the treatment of polycythemia vera.

The treatment of polycythemia vera with 32phosphorus (32P) raises two problems: 1) what is its therapeutic efficacity? 2) Does the use of 32P increase the risk of acute leukemia? The large series of treated patients have shown the remarkable efficacy of 32P. This is particularly evident when comparing the recent series of patients treated with 32P with those of Videbaek whose patients were treated by phlebotomies only. Patients are treated one time with 3.7 x 10(6) mBq (0.1 mCi) of 33P per kg of body weight. Granulocytes and platelets are rapidly affected, whereas red cells show a response 3 months later due to their longer survival. Remission lasts from a few months to three years. If the result is not satisfactory, another dose can be given 3 months after the first one. Resistance to 32P may arise but may be reversible after a course of chemotherapy. The clear therapeutic effect of 32P renders it especially valuable for patients with a high vascular risk. Some authors have claimed that polycythemia vera evolves towards acute leukemia, but Modan's study has demonstrated that 32P is indeed responsible for the occurrence of acute leukemia; this has been largely confirmed by others. The dose to the bone marrow is not negligible and the leukemic incidence following the treatment is a factor which limits its indication. Trials were conducted to search for therapies with alkylating agents, such as Chlorambucil or Busulphan, which would be less leukemogenic. The Polycythemia Vera Study Group found that Chlorambucil was at least 2.3 fold more leukemogenic than 32P. The EORTC compared the leukemogenic effect of 32P with that of Busulphan.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Intrinsic radiosensitivity and chromosome aberration analysis using fluorescence in situ hybridization in cells of two human tumor cell lines.

The survival curves for cells of two human tumor cell lines, HT29 and MeWo, have been defined using a Dynamic Microscopic Imaging Processing Scanner (DMIPS). There are two major differences between these two cell lines: (a) HT29 is more radioresistant than MeWo (surviving fraction at 2 Gy of 74 and 27%, respectively) and (b) HT29 presents a marked multiphasic survival curve with hypersensitivity at low doses (< 0.5 Gy) followed by an increase in radioresistance at higher doses which we have interpreted as "induced radioresistance"; this phenomenon is much less pronounced for the more radiosensitive cell line MeWo. We have now measured in these two cell lines the stable chromosomal aberrations and fragments, with the method of fluorescence in situ hybridization (FISH). We have analyzed chromosome 4, which does not have spontaneous translocations in either of these two cell lines. A dose-effect relationship was studied for radiation doses up to 5 Gy. At all doses, both translocations and breaks are more frequent in the radiosensitive cell line MeWo compared to the radioresistant cell line HT29. The correlation between survival and translocations is different for HT29 and MeWo, thus indicating that another factor(s) may be involved in cell killing in these lines.

Cell Survival↗

Refining interpretation of MIBG scans in children.

UNLABELLED: In pediatrics, the distribution of radioiodinated metaiodobenzylguanidine (MIBG) has been studied primarily in neuroblastoma. However, normal patterns in children show a number of particularities and pitfalls related to the context of pediatric oncology which must be identified. METHODS: We report on 28 equivocal scans in 24 children. In all cases, two experienced observers judged the scans to be equivocal and the definite interpretations were confirmed by follow-up. RESULTS: Difficulties in interpreting the scans were observed at the level of the thorax (15 patients), the abdomen (5 patients), the head (4 patients) or elsewhere (4 patients). The final interpretation of the scans was attributed to an unusual physiological pattern linked to age (9 patients), tumoral context (17 patients) or artifacts (2 patients). CONCLUSIONS: A number of important physiological areas of uptake in soft tissues can lead to false-positive interpretations of normal scans, such as the physiological upper thoracic uptake which has never been previously described. Numerous technical and physiological possibilities exist and those pitfalls must be ruled out. A precise knowledge of these technical difficulties and physiological variants can reduce the number of equivocal MIBG scans.

3-Iodobenzylguanidine↗

Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing bone metastases of differentiated thyroid carcinoma.

Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated thyroid carcinoma (DTC), but precise localization may be difficult, especially in the thorax, due to the quality of image resolution with 131I and the lack of anatomical landmarks. When bone metastases do not show radioiodine uptake bone scintigraphy can be used to detect them. We studied two groups of patients. In group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq 131I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740 MBq) was injected and a whole-body scan with simultaneous acquisition of 131I and 99mTc-HMDP images was carried out using a large field of view gamma camera fitted with a high-energy collimator. Technetium uptake was abnormal in 47 of 63 localizations, being increased in 29 foci, decreased in 7 and heterogeneous in 11. The superimposition of 131I and 99mTc-HMDP scans permitted an accurate localization in 80% of spine metastases and in 46% of osseous thoracic localizations, even in the presence of lung metastases. In group 2, 9 patients, who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC bone metastases without iodine uptake. They received a diagnostic dose of 99mTc-HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with a low-energy collimator. Technetium uptake was abnormal in 37 of 38 localizations, being increased in 34 foci and decreased in 3. One false-negative was found in a skull metastasis. In both groups of patients, 99mTc-HMDP scans were useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗

Factor analysis as a means of determining response to chemotherapy in patients with osteogenic sarcoma.

The prognosis of localized osteogenic sarcoma (OS) has improved considerably since the introduction of neoadjuvant chemotherapy. However, there is a subset of patients who do not show full benefit from neoadjuvant chemotherapy because of chemoresistance. The early identification of poor responders to chemotherapy during neoadjuvant therapy remains difficult. In order to evaluate the role of bone scintigraphy we report our experience of dynamic technetium-99m hydroxymethylene diphosphonate bone scintigraphy in 19 cases of paediatric osteogenic sarcomas. Before the beginning of chemotherapy, a dynamic scan was recorded during 30 min followed by static images at 3 h. The procedure was repeated halfway through the course of chemotherapy (6th week). Histological grading of the response to chemotherapy was carried out in the 12th week, showing nine good responses and ten poor responses. Factor analysis of dynamic structures (FADS) applied to dynamic scans allowed us to identify three factors termed vascular, "soft tissue" and osseous factors. The effect of chemotherapy on each factor was evaluated. Using FADS we were able to detect all the poor histological responders with the combination of vascular and osseous factors. Six out of nine good histological responders were also classified as scintigraphic responders. FADS applied to dynamic bone scans allowed us to identify at an early stage all the poor histological responders to neoadjuvant chemotherapy. This method may have clinical relevance for the therapeutic strategy in patients with OS.

Adolescent↗

Intraoperative detection of pheochromocytoma with iodine-125 labelled meta-iodobenzylguanidine: a feasibility study.

We evaluated the feasibility of intraoperative detection of pheochromocytoma sites after injection of meta-iodobenzylguanidine labelled with iodine-125. Six patients with multiple or recurrent pheochromocytoma were injected for intraoperative detection. During surgery, all count rates were recorded using a CdTe detector diode. Tumour foci were found in all cases. Tumour count rates ranged from 50 to 1000 counts per second (mean approximately 400). Blood activity, used as a reference level, ranged from 10 to 50 counts per second (mean approximately 35). In all patients, the intraoperative probe was helpful to the surgeon and facilitated the discovery of the pathological foci even when they were small (< or = 1 cm). Complete resection under probe control was correlated with postoperative normalization of urinary normetanephrine excretion. The use of a probe designed to detect low-energy gamma-ray radionuclides bound to a highly specific molecule provides an accurate detection tool which is well adapted for ectopic localizations and for small foci.

3-Iodobenzylguanidine↗

Cytogenetic characterization of a new human papillary thyroid carcinoma permanent cell line (GLAG-66).

A new permanent cell line (GLAG-66) has been established from the metastases of a papillary thyroid carcinoma in a male patient. Herein are reported the cytogenetic characteristics of this new cell line, which is tumorigenic in athymic mice. An aneuploid chromosomal pattern was observed (48 chromosomes) with various chromosomal abnormalities. The karyotype was: 48,XY,der(1)t(9;1;9), +der(8)t(1;8),der(9)t(1;9),der(9)t(1;9), +14. This cell line should prove to be of great value in the study of the biology of human papillary thyroid carcinomas.

Aneuploidy↗

Long-term effects on the thyroid of irradiation for skin angiomas in childhood.

Thyroid morphological and functional tests were carried out on 396 patients who were recalled because their thyroid gland had been exposed during hemangioma irradiation in childhood 11-43 years before (median, 22 years). The irradiations have been classified into two categories based on their duration: short duration, from a few seconds to a few minutes (90S and X rays), and long duration, from 30 min to several hours (336Ra, 192Ir, and 32P). The risk of a thyroid nodule increased significantly with the total dose received by the thyroid; it was linked to the dose delivered in the short duration (excess relative risk per Gy = 10), but not to that delivered in the long duration. The risk of a simple diffuse goiter, which also increased with the dose received by the thyroid, did not depend on the duration of the irradiation. In conclusion, this study emphasizes the role of the dose rate in the risk of thyroid nodule, the detection of which does not appear to be improved by plasma thyroid marker determination.

Child↗