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The identification of the folate conjugates found in rat liver 48 h after the administration of radioactively labelled folate tracers.

About 70% of the radioactivity retained in the livers of rats dosed 48 h earlier with radioactively labelled folate was incorporated into two folate conjugates. The major derivative was purified and isolated by Sephadex G-15, DEAE-cellulose and DEAE-Sephadex ion-exchange column chromatography and paper chromatography. It was identified as 10-formylpteroylpentaglutamate by a combination of spectral, microbiological, chemical and chromatographic techniques. The minor conjugate, though less well characterized, exhibited similar properties and was assigned the structure 10-formylpteroyltetraglutamate. 10-Formylpteroylpentaglutamate (2.0nmol/g) and 10-formylpteroyltetraglutamate (0.25nmol/g) comprised about 20% of the total endogenous hepatic folate as determined by microbiological assay (Lactobacillus casei after conjugase treatment.

Animals↗

The measurement of calcium absorption and absorption rate with an external arm radioactivity counter.

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.

Absorption↗

Assessment of glucose turnover in normal man with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer.

1. Glucose kinetics were assessed in seven normal adult male subjects by an intravenous bolus technique with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer. Tracer enrichment in plasma was assessed by gas chromatography-mass spectrometry. For comparison five subjects also received a simultaneous intravenous bolus of [6-3H]glucose and kinetics were assessed by conventional means. 2. Administration of [6,6-2H]glucose did not alter circulating glucose or insulin concentrations. 3. Glucose turnover, assessed by the use of [6,6-2H]glucose, was 11.4 (+/- 0.9) micromol min-1 kg-1 and 11.6 (+/- 0.5) micromol min-1 kg-1 with rate of glucose was 2.3 (+/- 0.3) ml min-1 kg-1 with both isotopically labelled tracers. Estimates of mean residence time, glucose pool and glucose space were also similar by each technique. 4. [6,6-2H]Glucose is therefore an effective tracer and allows investigation of glucose kinetics without administration of a radioactive label.

Adult↗

Mutation analysis by a non-radioactive single-strand conformation polymorphism assay in nine families with X-linked severe combined immunodeficiency (SCIDX1).

X-linked severe combined immunodeficiency (SCIDX1) is an inherited disease characterized by profound abnormalities of cell-mediated and humoral immunity. Patients with SCIDX1 have defects in the common cytokine receptor gamma chain gene (IL2RG) that encodes a shared, essential component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9 and IL-15. We have characterized nine SCIDX1 families by using a DNA-based, non-radioactive screening method and DNA sequencing. Nine different mutations were found, scattered from exon 1 to exon 5 of the IL2RG gene. Two of these mutations have been previously identified in other unrelated patients; the other seven are novel mutations that differ from all of the 95 already reported in the IL2RG mutation data base. In addition to describing novel mutations in the IL2RG gene, this study shows that the knowledge of the genetic defect and the use of an efficient, non-radioactive, and rapid screening approach have important implications for prenatal and postnatal diagnosis, carrier female identification, and possibly prenatal therapy.

DNA Mutational Analysis↗

The effect of propylthiouracil on subsequent radioactive iodine therapy in Graves' disease.

OBJECTIVE: Antithyroidal drugs (ATD) are used in the management of Graves' disease either as primary therapy for several months while awaiting remission of the disease or as pretreatment for several weeks prior to definitive radioactive iodine therapy (RAI). We have reported previously that pretreatment with propylthiouracil (PTU) before definitive RAI therapy is associated with a higher RAI treatment failure rate than RAI therapy alone. The objectives of the current study were 2-fold. First, to verify the results of our prior study regarding the effect of PTU used as pretreatment before RAI in a cohort of patients from a different institution and, secondly, to better define the relationship between the number of days off PTU before RAI therapy and therapeutic efficacy of RAI dosing. DESIGN: A retrospective review of Graves' disease patients treated from 1980 to 1994. PATIENTS: Study patients had to meet the following inclusion criteria: radionuclide studies and thyroid hormone values consistent with Graves' disease, at least 1 year of follow-up data available and discontinuation of the ATD at least 4 days before RAI administration. Exclusion criteria included therapy with any ATD other than PTU or ATD therapy during or following RAI dosing. MEASUREMENTS: Effectiveness of RAI therapy, days on PTU, days off PTU and calculated RAI dose to the thyroid were recorded for each subject. We compared the efficacy of RAI therapy in patients treated with PTU (used either as pretreatment in preparation for RAI therapy or as primary long-term therapy) before RAI administrations to those treated with RAI alone with special attention to the number of days on and off PTU before RAI dosing. Patients were considered RAI treatment failures if a second dose of RAI was required to achieve a euthyroid or hypothyroid state. RESULTS: One hundred and sixteen patients met our study criteria. Forty patients received PTU therapy for a mean of 221 +/- 59 days. The PTU was discontinued for a mean of 60 +/- 25 days before RAI dosing. Persistent hyperthyroidism was seen in 9% (7/76) of patients treated with RAI alone. The failure rate of a single dose of radioactive iodine was significantly increased when PTU was discontinued between 4 and 7 days before the administration of RAI (29% vs 9% for RAI alone, P = 0.039). PTU discontinued for at least 1 week before RAI dosing was associated with a nearly 2-fold increase in failure rate, but this difference did not achieve significance (17% vs 9% for RAI alone, P = 0.24). Examining only those patients receiving PTU, patients who had successful single dose RAI therapy tended to receive a higher dose of RAI than patients failing RAI therapy (480 +/- 30 vs 410 +/- 40 MBq administered dose, P = 0.18; and 8.0 +/- 0.9 vs 5.5 +/- 1.1 MBq/g thyroid tissue calculated dose, P = 0.21). Furthermore, total serum thyroxine at diagnosis was significantly higher in patients failing RAI therapy after PTU administration than in patients successfully treated with RAI after receiving PTU (316 +/- 40 vs 225 +/- 13 nmol/L, P = 0.03). CONCLUSIONS: Propylthiouracil discontinued 4-7 days before radioiodine dosing is associated with a significant increase in the failure rate of a single dose of radioiodine. Discontinuation of the propylthiouracil for at least a week before radioiodine administration is associated with a higher, although not statistically significant, radioiodine failure rate. In patients that require treatment with propylthiouracil before radioiodine therapy, a higher total serum thyroxine level at diagnosis is associated with an increased rate of radioiodine failure. Consideration should be given to increasing empirically the dose of radioiodine administered to Graves' disease patients that have received propylthiouracil within a week of radioiodine administration in an effort to decrease the radioiodine failure rate to an acceptable level.

Adult↗

Preparation for radioactive iodine administration in differentiated thyroid cancer patients.

OBJECTIVE: Because in recent years the practice of TSH suppression has changed, and thyroxine doses have been reduced significantly in the treatment of patients with low-risk differentiated thyroid cancer, the goal of this study was to determine the time needed to attain a target TSH level (of 30 mIU/l) following levothyroxine withdrawal in patients treated with thyroxine according to current guidelines, in anticipation of radioactive iodine (RAI) administration. DESIGN: Observational study. PATIENTS: Thirteen consecutive patients with differentiated thyroid cancer on suppressive doses of levothyroxine planned for RAI administration. Five of the patients received cholestyramine in an attempt to facilitate TSH recovery. MEASUREMENTS: Serum TSH, free-T3 and free-T4, at 3-4-day intervals. RESULTS: In 13 patients on suppressive doses of thyroxine, on 15 separate occasions, baseline TSH levels were between 0.01 and 0.4 mIU/l. The mean interval required to reach the target TSH concentration of at least 30 mIU/l was 17 days (95% CI 15-19; range 11-28 days). Cholestyramine had no effect on the rate of TSH recovery. Once TSH concentration became detectable, it increased exponentially; and once it reached the upper limit of normal, it rarely took more than 10 days to attain target level. CONCLUSIONS: Attaining target TSH level before radioactive iodine administration requires a considerably shorter time than is currently recommended. Reducing preparation time might improve patients' acceptance of the procedure.

Adult↗

Estimation of anti-D IgG in red blood cell eluates using the specific radioactivity of 125I-labeled IgG: effect of unlabeled, cytophilic IgG.

The specific radioactivity of conventionally prepared 125I IgG anti-D eluates is significantly less (from 1/5 to 1/20) than that of the 125I IgG fraction used to prepare the eluate. This discrepancy is due to the release of unlabeled, cytophilic IgG from normal red blood cells during eluate preparation and does not represent an underestimation of the eluate anti-D IgG content. Cytophilic IgG content of eluates plays an important role in reducing the nonimmunologic binding of labeled antibody IgG. The results justify the assumption used in numerous studies that the specific radioactivity of 125I IgG fractions can be used to provide a valid estimate of the anti-D IgG content of eluates.

Cytotoxicity, Immunologic↗

Comparison between radioactive aerosol, technegas and krypton for ventilation imaging in healthy calves.

The use of lung scintigraphy in calves necessitates the validation of a ventilation (V) imaging agent compatible with clinical applications. This study aimed at defining the value of an inhaled radioactive aerosol (99mTc-DTPA) and a 'pseudogas' (Technegas) in the assessment of regional V in healthy conscious calves by comparing 99mTc-DTPA and Technegas deposition (D) images to V(V) images obtained from the steady-state inhalation of the short half-life krypton 81 (81mKr) gas. Images were compared by analysis of radioactivity distribution in computer-generated regions of interest within the right lung and D to V ratio images were generated in order to highlight areas of mismatching between 99mTc-DTPA or Technegas and 81mKr distributions. Results of this analysis showed that the 99mTc-DTPA aerosol droplets were unable to reach the lung parenchyma because of significant particle impaction in the major conducting airways. Better definition of the ventilated lung was obtained when using Technegas because of minimal deposition in conducting airways. Furthermore, the Technegas and 81mKr distribution patterns were highly equivalent.

Aerosols↗

Intra-arterial embolization of head-and-neck cancer with radioactive holmium-166 poly(L-lactic acid) microspheres: an experimental study in rabbits.

A total of 22 NZW rabbits with VX2 squamous cell carcinomas transplanted into the auricles were intra-arterially (i.a.) embolized with radioactive or inactive holmium-labelled poly(L-lactic acid) (HoPLA) microspheres with a mean diameter of 38-80 microm. The effects on tumour growth, the efficiency of i.a. infusion, the efficacy of retention of microspheres in the primary tumour and the excretion of free holmium-166 were analyzed. Complete tumour remissions were obtained in 79% and 86% following embolization with radioactive and inactive microspheres, respectively. Over 95% of the microspheres were retained in the tumour and the leaching of holmium-166 in urine and faeces was less than 0.1% in 2 days. The injection efficiency was not optimal, as 40% of the microspheres were retained in the cannulation system. Arterio-arteriolar connections should be detected and closed prior to embolization to prevent stray emboli from entering the brain. It is concluded that 166HoPLA microspheres are promising candidates for further studies on radio-embolization of unresectable head-and-neck cancer.

Animals↗

[Monitoring of post-operative prevention of thrombosis by low dosage heparin with the radioactive iodine fibrinogen test (author's transl)].

In a prospective study low dosage subcutaneous heparin was administered to 148 patients after major gynaecological operations. The preventive effect on deep vein thrombosis was monitored by the radioactive iodine fibrinogen test. In 10.1% (15) of the cases higher than normal activity of the radioiodine fibrinogen test was detected. Only 4 patients (2.7%) had clinical signs of deep vein thrombosis. Because of the early occurrence of silent signs of deep vein thrombosis in the radioactive iodine fibrinogen test the onset of the subcutaneous heparin prophylaxis of thrombosis was shifted from the post-operative period to the pre-operative administration.

Adult↗

[Distribution of radioactively labeled digitalis in the eye].

Twenty-four hours after instillation of radioactively labeled digoxin into the conjunctival sac the radioactivity is concentrated in the various ocular tissues. A fourfold enrichment was observed in highly vascularized tissues such as the iris, ciliary body, and retina, as opposed to tissues with minimal vascularization such as the sclera. No concentration of digoxin was observed in the untreated control eye. Only in the sclerae was there a slight enrichment, corresponding to that found in the blood. Values in the untreated control tissues (skeletal muscle and skin) were minimal. These experiments show that the retina, ciliary body, and iris have a selective affinity for locally administered digoxin.

Animals↗

Intrasomatic injection of radioactive precursors for studying transmitter synthesis in identified neurons of Aplysia californica.

We introduced radioactive precursors directly into identified neurons of Aplysia californica. [(3)H]-Choline and L-[(3)H]tryptophan were injected with pressure into nerve cell bodies to study synthesis of acetylcholine and serotonin. We confirmed the cholinergic nature of R2, L10, and L11, identified neurons of the abdominal ganglion. Cells in the LD cluster (which contains motor neurons to the heart and gill) also converted most of the injected choline into acetylcholine. Neurons in the RB cluster (which contains an excitatory motor neuron to the heart) and the two metacerebral cells of the cerebral ganglion converted injected tryptophan to serotonin. No cell studied could convert both choline to acetylcholine and tryptophan to serotonin. Pressure permits rapid injection of precursors, from small amounts to amounts large enough to saturate intracellular synthetic pathways. In contrast to the results with injection, we found far less synthesis of acetylcholine and serotonin in identified nerve cell bodies when ganglia were incubated in the presence of the radioactive precursors.

Acetylcholine↗

The radioactivity of atmospheric krypton in 1949-1950.

The chemical element krypton, whose principal source is the atmosphere, had a long-lived radioactive content, in the mid-1940s, of less than 5 dpm per liter of krypton. In the late 1940s, this content had risen to values in the range of 100 dpm per liter. It is now some hundred times higher than the late 1940 values. This radioactivity is the result of the dissolving of nuclear fuel for military and civilian purposes, and the release thereby of the fission product krypton-85 (half-life = 10.71 years, fission yield = 0.2%). The present largest emitter of krypton-85 is the French reprocessing plant at Cap-de-la-Hague.

Journal Article↗

[Effect of application of a herbicide propyzamide into the soil by study of mineralization of glucose 14C(U) and distribution of radioactivity in various fractions of the soil (laboratory and open field tests)].

The effects of the herbicide PROPYZAMIDE are studied in laboratory and field conditions. The modifications involved are characterized by measurement of 14C-glucose mineralization and radioactivity incorporation into the soil fractions. In laboratory conditions, temperature and moisture are kept stable and the experiment is performed during less than 24 hours. In these conditions, Kerb 50 (commercial formulation of propyzamide) and the emulsifier (material used in propyzamide formulation) exert little effect on 14CO2 evolution. In field conditions, propyzamide andKerb 50 are applied once at two different doses: at field rate (1,5 kg/ha) and twentyfold this rate. Essays are duplicated. The herbicide (propyzamide in Celanol and Kerb 50) and the emulsifiers alone (Celanol and the material used in propyzamide formulation) are applied on the soil surface (application date: 3.02.81). Two weeks later and then every month during four months, samples are taken to the depth of about 5 cm (Propyzamide migrates very slowly in the first centimeters of the soil). The characterization experiment is performed on 10 g soil samples by 14C-glucose incubation at 28 degrees C during two hours. 14CO2 evolved is measured after incubation and acidification with HCl. Then radioactivity distribution in the soil is counted after chemical fractionation of soil. This distribution is about 10-16.5% as 14CO2, 22-37% in the acid-soluble fraction, 10-25% in the alkali-soluble fraction and 15-45% in the human fraction (measured as 14CO2 evolved after combustion). This distribution is little modified by the herbicides or the emulsifiers but its evolution is significantly related to environmental conditions (temperature). Nevertheless a few modifications are observed. They can be due to the herbicide propyzamide itself but the emulsifiers and the degradation products of propyzamide can also influence the measurement (After forty days in the soil, 70-95% of the starting active ingredient have disappeared). They can also be a result of the initial effects of the products (modification of the microflora and of the environment).

Benzamides↗

Bioevaluation of radioactive bandages in a murine model of melanoma.

PURPOSE: To study the effectiveness of a radioactive bandage incorporating a beta(-) emitter for the treatment of superficial tumours like melanoma. MATERIALS AND METHODS: (188)Re tin particles were immobilized on a bandage patch ((188)Re bandage). The effectiveness of the (188)Re bandage for controlling tumour growth was tested in C57BL/6 mice bearing BL6/FIO melanoma. The effect of the single dose delivered, two-dose treatment and time of contact of bandages on the skin was studied by following tumour size. RESULTS: Tumour growth was delayed significantly in treated animals compared with controls. Complete tumour regression was observed with some doses of radiation. Histology studies and dose-rate calculations were also carried out to evaluate the effectiveness of (188)Re bandages. CONCLUSIONS: Radioactive bandages could be a promising modality for the treatment of skin cancers.

Animals↗

Natural radioactivity levels for selected kinds of Egyptian sand.

The monitoring and evaluation of natural radioactivity content of sixty-five different samples of sand used in building materials, black sand and its components, and therapy sand collected from different locations in Egypt have been investigated. The specific radioactivity concentration of 238U, 232Th series, and 40K were measured by gamma-ray spectrometer using a shielded HPGe. The obtained results of 238U and 232Th series as well as 40K are discussed. The absorbed dose rate of gamma radiation ranged from 15.1 to 64.1, 9.3 to 109, 751, and 32.9 to 63.4 nGy h(-1) for sand used in building materials, black sand with its components, and therapy sand samples, respectively. The representative external hazard index (H ex) for the corresponding values are also estimated and tabulated. The present results are compared with other data previously obtained from different sand areas in both Egyptian and foreign locations.

Desert Climate↗

[Characterization of radioactivity distribution in the organism during constant intravenous infusion of tracer amino acids and calculation of the rate of tissue protein synthesis in rats].

Male wistar rats (100 g live mass) were given infusions into the tail vein of 14C-leucine and 14C-lysine simultaneously for 0.5; 1.0; 2.0; 3.0; 4.5; 6.0 and 7.0 hours. At the end of the infusion the specific radioactivity of the free leucine and lysine in the blood plasma, liver, M. gastrocnemius, small intestines and colon were ascertained as well as after the 6-and-7-hour infusion that of the protein-bound leucine and lysine. In all tested tissues the specific radioactivity of the free amino acids attained a plateau during the 6-and-7-hour infusion. The rate constants for the increase were calculated for each organ tested. The two amino acids used are suitable for the calculation of the fractional rate of protein synthesis in tissues. The values of the fractional rate of protein synthesis calculated on the basis of the 6-and-7-hour infusion were: 54 +/- 7.7%/day for the liver, 9.4 +/- 1.2%/day for muscles, 89 +/- 12.2%/day for the small intestines and 42 +/- 5.9%/day for the colon. The simultaneous application of two tracer amino acids is recommendable for the estimation of the precursor pool for protein synthesis and the more accurate calculation of the rate of protein synthesis.

Amino Acids↗

A non-radioactive sensitive assay to measure 5-fluorouracil incorporation into DNA of solid tumors.

A non-radioactive method to determine 5-Fluorouracil (5FU) incorporation into DNA has been developed. Isolated DNA was enzymatically degraded to bases and the resulting 5FU was measured with standard gas-chromatography coupled to mass spectrometry (GC-MS) and compared with that of radioactive 5FU in a cell line. Incorporation into DNA of the murine Colon 26-B tumor treated with maximal tolerated doses of 5FU and fluorodeoxyuridine (FUdR) was maximal after 2 hour and was 15.4 and 71.0 fmol/microg DNA, respectively. After a plateau for about 3 days a decrease was observed to +/- 2 fmol/microg DNA after 10 days. The assay is very sensitive and reproducible and can be used in a clinical setting.

Animals↗