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Biomedical subjects

J Frühling

Publications and source records attributed to J Frühling.

At least 19 recordsLinked to original sources

[Nuclear accidents and iodine prophylaxis. Part 1: Risks due to irradiation of the thyroid gland].

In the frame of the emergency procedures in the case of an accident in a nuclear plant, this paper presents a survey of the information available on the risks related to the irradiation of the thyroid gland. Attention is focused on thyroid cancer resulting from an exposure to radioactive isotopes of iodine and especially and iodine-131. The consequences of the medical exposures as well as of the Hiroshima and Nagasaki irradiations are recalled first. Then the recently available informations on the effects on the populations exposed after the Tchernobyl accident are analysed more in details. Ten years after the accident, the most striking and the least questionable effects is a significant increase of the incidence of differentiated thyroid cancer in children, in the areas most exposed to the initial radioactive clouds. Young children are particularly vulnerable to this type of cancer which is of aggressive nature and shows a short latency period. These observations justify an iodine prophylaxis for the populations living in the vicinity of nuclear plants. Special attention should be paid to the protection of young children.

Adolescent↗

Tumor type and vascularity: important variables in infusional brachytherapy with colloidal 32P.

PURPOSE: This study investigated the role of histologic tumor characteristics, in comparison with a normal tissue, and of tumor vascularization on the uptake and retention of colloidal 32P used in infusional brachytherapy of solid cancers. The cytotoxicity of colloidal 32P was also evaluated for two tumors of different radiosensitivity, a melanoma, and a squamous cell carcinoma. METHODS AND MATERIALS: An in vitro analysis of colloidal 32P uptake was carried out on a human melanoma cell line, HBL, a human squamous cell carcinoma, SCC1, and normal fibroblasts, F-NBB. Tumor retention of colloidal 32P was studied in vivo for the HBL and the SCC1 tumors implanted subcutaneously in nude mice. Tumor vascular density was determined by microscopic study of Masson's trichrome slides of HBL and SCC1 tumors of about 1 cm diameter. RESULTS: In vitro studies showed that the time required for maximal cell uptake of colloidal 32P was only 10-20 min for the SCC1 and HBL tumors, while it took at least 60 min for the fibroblasts. After intratumoral injection of macroaggregated albumin (MAA), followed by 50 microCi of colloidal 32P, Bremsstrahlung imaging performed at 6 and 24 h showed that the activity remained in the HBL tumor while some of the radiocolloids leaked from the SCC1 tumor and was trapped in the reticuloendothelial system of the liver. Organ activity counting confirmed this finding: 32P activity was three to four times higher in the HBL than in the SCC1 tumor, whereas the activity in the liver, insignificant in the HBL mice (less than 0.1 microCi/g), was as high as 24 microCi/g in the SCC1 mice. This phenomenon may be explained by the difference in tumor vascular density, estimated for the HBL to be about four times less than that of the SCC1 tumor (5.7 vs. 21.4 blood vessels per mm2 for the HBL and the SCC1 tumors, respectively). CONCLUSION: Intratumoral infusion of colloidal 32P may be a useful complement of radiation therapy in the treatment of nonresectable but accessible solid tumors. Tumor vascularization must be taken into account for a successful vascular blockade by MAA prior to the infusion of colloidal 32P.

Animals↗

In vivo characterization by means of digital cell image analysis of early-induced fractionated radiotherapy effects on the MXT mouse mammary tumor.

PURPOSE: To study the cell kinetics and chromatin modifications occurring in function of the fractionated irradiation administered to the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: The MXT tumor cells were submitted to three fractions of a 4.8 Gy dose delivered at 24-h intervals. MXT tumor cells were collected by means of fine needle aspirations (between 5 and 10 samples were obtained after each irradiation) during treatment and submitted to the computer-assisted microscope analysis of Feulgen-stained specimens. Three groups of parameters has been described: i.e., the geometry of the nucleus, the nuclear DNA content, and the chromatin texture. Furthermore, cell cycle parameters were studied in the aim to know the distribution of the cells within the cell cycle. RESULTS: The mean values relating to geometric parameters (i.e., the nuclear area and its standard deviation) decreased during treatment. Variations in the nuclear DNA content appeared as being cyclical and could be explained in terms of the modifications in the distribution of the cells within the cell cycle. The quantitative analysis of the cell cycle parameters revealed that the percentage of S cells increased regularly after each irradiation. In contrast, the percentage of G2 cells decreased between each irradiation. The parameters describing nuclear texture showed regular variations between each irradiation. These variations consisted in two cycles constituted by a decrease in chromatin condensation, followed by an increase. CONCLUSIONS: The development of the geometric parameters indicates that fractionated radiotherapy leads to the emergence of a more homogeneous population. The effects of the radiotherapy on the distribution of the cells within the cell cycle could be explained through the phenomenon of repopulation and by the high degree of radiosensitivity of the G2 cells (decrease in the percentage of G2 cells). Last, the variations observed at chromatin pattern level could be explained through DNA repair processes.

Animals↗

Radioimaging of human breast carcinoma xenografts in mice by [123I]-labeled Z-17 alpha-iodovinyl-11 beta-chloromethyl-estradiol.

Z-17 alpha-iodovinyl-11 beta-chloromethyl-estradiol (Z-CMIV), a new selective estradiol derivative, can easily be labeled with high efficiency by radioactive iodine isotopes. Biodistribution studies and quantitative scintigraphic imaging of human breast carcinoma xenografts in mice demonstrated continuous and selective accumulation of the [123I]Z-CMIV, in estrogen receptor (ER)-positive target tumors, with significantly high target/nontarget ratio up to 48 h post-injection. A receptor-mediated mechanism of concentration of Z-CMIV in target tissues was confirmed by scintigraphic imaging and by biodistribution studies.

Adenocarcinoma↗

[Exposure to ionizing radiation: radiobiological and pathogenic effects (2)].

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radioinduced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low doses. The effects of irradiation on the gonads are also described.

Embryonic and Fetal Development↗

[Exposure to ionizing radiation: radiobiological effects and pathogenesis. 1].

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radio-induced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low-doses. The effects of irradiation on the gonads are also described.

Environmental Exposure↗

[Emergency measures in accidental exposure to ionizing radiation].

The present paper is intended to provide any physician with a basic information and recommendations on how to behave with individuals who have been irradiated and/or contaminated (or believed to have been exposed), either in the case of a broad nuclear accident or a limited accidental exposure (e.g. occupational). Emphasis is put on the emergency measures to be taken as well as on their relative priority. Information is also provided in order to allow any physician to assess the magnitude and the severity of the exposure on the basis of early clinical symptoms and reactions. This would enable him to sort out the patients and to orientate them towards the appropriate specialized centre, or on the other hand, to reassure the patients. The information and recommendations are presented, purposely, in a concise and schematic way in order to facilitate, when needed, a quick and easy reading.

Clinical Protocols↗

[Role of radioactive iodine in the treatment of differentiated thyroid cancer: physiopathological basis, results, considerations from the viewpoint of radioprotection].

Postoperative radioiodine treatment of differentiated thyroid cancer occupies a well determined place in the treatment policy of this disease. When the external exposure rate (EER) was determined at 1 m from the patient, 72 h after the administration of the high 131-I dosis, respectively 34 and 56 patients among 80 treated cases presented, and require external help for their daily life (+/- 90% of all cases). This value could be considered as the selective limit in order to authorize them to leave the hospital when favorable socio-economical conditions exist at home.

Adolescent↗

Metabolic changes in the rat brain after acute and chronic ethanol intoxication: a 31P NMR spectroscopy study.

In this work, 31P phosphorus NMR (31P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high-energy phosphates were observed: increase of phosphocreatinine (PCr)/beta AaTP and PCr/inorganic phosphate (Pi) in acute and long-term ethanol exposure, and decrease of Pi/beta ATP after acute ethanol administration. These changes in high-energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP+ H+ ATP+ Cr; ATP ADP+ Pi), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/beta ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism.

Adenosine Triphosphate↗

Monitoring of radiotherapy-induced morphonuclear modifications in the MXT mouse mammary carcinoma by means of digital cell image analysis.

The present work deals with the characterization of the morphological changes induced by ionizing radiation on MXT mouse mammary cancer cell nuclei. The monitoring of the radiotherapy-induced morphonuclear modifications was carried out by means of digital cell image analysis, which made it possible to compute morphometric (nuclear area), densitometric (nuclear DNA content) and textural (chromatin pattern characteristics) parameters assessed on Feulgen-stained nuclei. The biological material was obtained from serial fine needle-aspirations performed on control tumors and 2Gy and 8Gy irradiated tumors. Digital cell image analyses were assessed at the 7th, 18th, and 28th days-post irradiation. We showed that radiotherapy induced specific morphonuclear modifications that appeared in a dose-dependent and time-dependent manner. The 2Gy and 8Gy radiotherapy doses led to an increase in the mean nuclear area value, this feature being observed at both the 1st and the 4th week post-irradiation. The resultant effect on the chromatin pattern characteristics corresponded to a decrease in overall condensation level as compared to the control cell nuclei. Finally, the mean nuclear DNA content increased at the 1st week post-irradiation, but decreased at the 4th week post-irradiation as compared to the MXT control tumor. Computerized cell image analysis, therefore, appears to be a useful tool in helping to monitor the radiotherapy-induced effects that occur in neoplastic cell nuclei and which can be observed by means of optical microscopy.

Animals↗

Influence of hormono- and/or chemotherapy on the MXT mouse mammary tumor as monitored by 31P MRS.

We describe the early in vivo modifications that occurred in the MXT mouse hormone sensitive mammary tumor following various treatments which were monitored by 31P NMR spectroscopy. The MXT mouse mammary tumor was subjected to clinically relevant low-dose chemotherapy, i.e. seven cycles of 20 mg/kg cyclophosphamide (CPA) with or without an attempt at estrogenic cell recruitment prior to the CPA treatment. NMR measurements were begun at the end of the CPA treatment in order to evaluate the remaining 'long-term' chemotherapy-induced modifications within the MXT tumors. Statistical analyses performed on the 31P NMR parameters revealed that treatment had induced significant effects on bATP/PCr, Pi/PCr and PME/PDE only, with PCr being the most discriminating index. Its presence within MXT tumors was verified by means of an analysis of perchloric extracts. The results indicate a relative decrease of PME/PDE and a better conservation of PCr within the CPA-treated group as compared to the control one. This feature appeared even prior to any macroscopic modifications, as was the case within the group which contained tumors smaller than 120 mm2, and where no significant differences appeared between the mean sizes of the MXT cancers. In contrast, within the G2 group, which contained tumors equal to or larger than 120 mm2, CPA significantly slowed down tumor growth, while the administration of estradiol (E2) prior to CPA treatment antagonized the positive CPA-induced therapeutic effect. In conclusion, the non-invasive follow-up of the chemotherapeutic treatment of a clinically relevant mammary tumor model by 31P NMR spectroscopy backed up by statistical analyses revealed metabolic changes that appeared well before any modifications in histopathology or growth.

Animals↗

[Adoptive immunotherapy with interleukin 2. Initial results of a pilot study in 6 cancer patients].

Adoptive immunotherapy of cancer consists of using interleukin-2 to induce the formation of lymphokine-activated killer (LAK) cells which are toxic to tumoral cells. Six patients, 3 with hypernephroma and 3 with melanoma, were treated with interleukin-2. Drug toxicity consisted of capillary leakage syndrome in one case and reversible renal impairment in another. One patient showed an objective response; transient subjective improvement was observed in all patients.

Acute Kidney Injury↗

Bone marrow scintigraphy in breast cancer.

Bone marrow scintigrams (BMS) have been performed in 101 women with histologically proven breast cancer (36 stage IV among them at the time of the first investigation, follow-up examinations available in 41, disease evolution observed in 17). They have been compared to conventional bone scintigram (CBS) as well as to radiological, clinical, biological and follow-up data obtained in the same patients. Only three (7.4%) out of the 41 patients with radiologically or/and histologically proven skeletal metastasis had normal BMS and 33 had corresponding bone marrow scintigraphic defects (BMS ++). On the other hand, only three patients of the 32 with normal BMS had documented skeletal abnormalities. Abnormal bone marrow extension, observed in 61.4% of the patients (62/101), seems to represent a reaction of the reticulo-endothelial system to the disease dissemination - even microscopic - and, as such, to have prognostic implications. As BMS demonstrated skeletal invasion earlier or more precisely than CBS in ten cases, the technique appears of value and of interest in breast cancer management.

Adult↗