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Analysis of labeling and clearance of lung surfactant phospholipids in rabbit. Evidence of bidirectional surfactant flux between lamellar bodies and alveolar lavage.

Turnover and clearance of lung surfactant phospholipids were studied with particular reference to myoinositol-induced perturbation in the acidic phospholipids. Administration of myoinositol decreased [(3)H]palmitate and [(32)P]phosphate incorporation into phosphatidylglycerol by 80-90% in whole lung, and by 94-99% in lamellar bodies and in alveolar lavage. The increased incorporation of radioactive isotopes into phosphatidylinositol following myoinositol, was inverse to the decrease in phosphatidyl-glycerol incorporation. Myoinositol treatment affected neither content nor labeling of phosphatidylcholine or disaturated phosphatidylcholine as studied within 50 h of administration. Phosphatidylglycerol was pulse labeled by intravenous [(32)P]phosphate and [(3)H]palmitate, followed by myoinositol. The biological half-lives of phosphatidylglycerol in the microsomal fraction, lamellar bodies, and alveolar lavage were 1.6, 4.6, 5.4 h (with (3)H), and 2.8, 6.5, 7.0 h (with (32)P), respectively.(32)P-labeled lung surfactant tracer was applied to the airways in saline suspension and the clearance of phospholipid radioactivity was measured in alveolar lavage, alveolar macrophages, lamellar bodies and lung homogenates. The clearance rates of phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylinositol as studied in whole lung over 6 h were 3.4-5.8% h. Only a small amount of phospholipid radioactivity was recovered in the alveolar macrophage fraction (including bis-[monoacylglycerol]phosphate). Phospholipid radioactivity in alveolar lavage fell to 40-70% of the maximum during the 1st h, and to 5-18% over the next 6 h. During 2 h after the application of phospholipids, the radioactivity in the lamellar body fraction increased, and the specific radioactivities approached those in alveolar lavage. The association of phosphatidylglycerol with lamellar bodies was unaffected by myoinositol. Phosphatidylinositol entered more slowly than did phosphatidylglycerol from microsomes to the alveolar lavage fraction, and from alveolar lavage to lamellar bodies. These differences may be of importance regarding the poor performance of phosphatidylinositol-containing surfactant at birth. Further investigations are needed to clarify the possible role for the postulated bidirectional surfactant flux between the lamellar body and alveolar lavage fractions in maintaining the activity of surfactant.

Animals↗

Frequency of Helicobacter pylori infection in children under 4 years of age.

The work aimed at establishment of frequency of Helicobacter pylori (Hp) infection in children under 4 years of age. One hundred ninety-eight children (6 month to 4 year) were tested using urea breath test (UBT) with the non-radioactive isotope (13)C (50 mg of urea). The air was collected before and in the 20(th) and 30(th) minute after standard meal. The results of measurements (mass spectrometry IRMS) were given as a quotient (13)CO(2)/CO(2) (delta), and a positive value was set at delta>3,5%. Parents of tested children were asked to fill in a questionnaire on a somatic development, the digestive tract symptoms of a child and family members as well as socioeconomic conditions. The data were analyzed to establish the risk factors in Hp infection in children. Hp infection was found in 18,38% of children. It was not related to child's sex nor age. The statistical significance was found in the occurrence of Hp infection among children whose family members had infection and among those attending créches or kindergartens. Non-radioactive (13)C UBT is very useful and easy method to use in epidemiological studies even in youngest children. The course of infection was asymptomatic and had no impact on their somatic development. Factors increasing the risk of Hp infection were occurrence of Hp among other family members and contact with other children in educational facilities.

Breath Tests↗

[Natural radioactivity of underground waters: surveying of alpha and beta global activity].

Two sets of measurements used in surveying of the alpha and beta global activity of drinking water drawn from 44 abyssal wells located in the Lódź cretaceous basin are discussed. The measurement method used involved the comparison between the activities of a model source and a prepared sample of water. Radioactive isotopes Am-241 were employed in alpha and K-40 in beta measurements. In order to detect radiation, a semiconducting radiation detector Si of high purity for registration of alpha molecules and a set of two G-M counters operating in the anticoincidence circuit for registration of beta radiation were used.

Fresh Water↗

15C-15F Charge symmetry and the 14C(n,gamma)15C reaction puzzle.

The low-energy reaction 14C(n,gamma)15C provides a rare opportunity to test indirect methods for the determination of neutron capture cross sections by radioactive isotopes versus direct measurements. It is also important for various astrophysical scenarios. Currently, puzzling disagreements exist between the 14C(n,gamma)15C cross sections measured directly, determined indirectly, and calculated theoretically. To solve this puzzle, we offer a strong test based on a novel idea that the amplitudes for the virtual 15C-->14C + n and the real 15F -->14O + p decays are related. Our study of this relation, performed in a microscopic model, shows that existing direct and some indirect measurements strongly contradict charge symmetry in the 15C and 15F mirror pair. This brings into question the experimental determinations of the astrophysically important (n,gamma) cross sections for short-lived radioactive targets.

Journal Article↗

[Henri Beckquerel's discovery of radioactivity, and history of nuclear medicine. 100 years in the shadow or on the shoulder of Röntgen].

In 1896 Henri Becquerel discovered that uranium emitted penetrating rays similar to X-rays. His finding started a series of discoveries that were rewarded with numerous Nobel prizes. Marie and Pierre Curie found that thorium was radioactive too, and discovered and described two new elements, polonium and radium. They also found that radioactive radiation could be separated into alpha, beta and gamma rays. In 1993 their daughter Irene Joliot-Curie and her husband Frederic Joliot managed to produce radioactivity artificially by bombarding atomic nuclei with alpha particles. Enrico Fermi did likewise, but bombarded the nuclei with neutrons. In the cyclotron invented by Ernest Lawrence, radioactive isotopes were produced by proton bombardment. The ability to produce radioisotopes of different elements initiated a variety of tracer studies in biology and medicine. The number of studies increased exponentially when the nuclear reactor in Oak Ridge, US, was opened for radionuclide production in 1946. This article summarises the history of the application of radionuclides in science and medicine internationally and in Norway until now.

History, 19th Century↗

Thyroid nodules and thyroid cancer: surgical aspects.

Patients with thyroid nodules must be treated selectively because these nodules develop far more frequently than does thyroid cancer. A thorough clinical history, family history and history of radiation, as well as an accurate physical examination, are very important in determining whether surgical treatment is indicated. Thyroid function tests, a radioactive isotope scan, a thyroid echogram and fine-needle biopsy are also useful. Although there is considerable debate concerning the amount of thyroid tissue that should be removed at operation, the minimal procedure for a "cold," solid thyroid nodule is a total thyroid lobectomy and isthmectomy. This is the treatment of choice for patients with occult papillary thyroid carcinoma. Partial lobectomy is to be discouraged. Near total or total thyroidectomy should be considered for all other patients with differentiated thyroid cancer. Many factors influence the prognosis of patients with thyroid cancer including age, sex, type of thyroid cancer, invasion, symptoms, lymph node metastasis, metastasis to distant sites, extent of the surgical procedure, and use of radioactive iodine and thyroid hormone. With adequate treatment, the prognosis for differentiated thyroid carcinoma is excellent.

Adolescent↗

Using the scanning electron microprobe and secondary ion mass spectrometry to locate 14C and 13C labelled plant residues within soil aggregates.

Increasing concentrations of CO2 in the atmosphere are placing emphasis on the necessity for sequestering carbon (C) into soil organic matter (SOM). By studying the interior parts of soil aggregates, a better understanding of the incorporation and sequestration of plant residue materials within these aggregates could be obtained. The location of newly added plant residues within soil aggregates may also assist in the investigation of the impact of these newly added plant materials on soil aggregation. This study investigated two different techniques for determining the location of newly added plant residues within soil aggregates by using plant materials labelled with 14C and 13C isotopes incorporated into two different soil types, Black Earth (Pellic Vertisol) and Red Clay (Chromic Vertisol). Both autoradiography combined with scanning electron microprobe analysis (14C) and secondary ion mass spectrometry (SIMS) (13C) were successfully used for detecting the presence and location of the newly added plant residues fragments within soil aggregates of both soil types. The use of labelled plant materials is essential for the study of the location of newly added plant materials within soil aggregates, and this has proven to be a useful tool for studying the impact of residue additions on soil aggregate formation. Furthermore, these methods have been shown to be useful for determining the incorporation and sequestration of C materials within soil aggregates. The development of the 13C SIMS technique could alleviate the necessity for the use of the radioactive isotope 14C in soil studies.

Carbon Isotopes↗

Using the scanning electron microprobe and secondary ion mass spectrometry to locate 14C- and 13C-labelled plant residues within soil aggregates.

Increasing concentrations of CO2 in the atmosphere are placing emphasis on the necessity for sequestering carbon (C) into soil organic matter (SOM). By studying the interior parts of soil aggregates, a better understanding of the incorporation and sequestration of plant residue materials within these aggregates could be obtained. The location of newly added plant residues within soil aggregates may also assist in the investigation of the impact of these newly added plant materials on soil aggregation. This study investigated two different techniques for determining the location of newly added plant residues within soil aggregates by using plant materials labelled with 14C and 13C isotopes incorporated into two different soil types, Black Earth (Pellic Vertisol) and Red Clay (Chromic Vertisol). Both autoradiography combined with scanning electron microprobe analysis (14C) and secondary ion mass spectrometry (SIMS) (13C) were successfully used for detecting the presence and location of the newly added plant residues fragments within soil aggregates of both soil types. The use of labelled plant materials is essential for the study of the location of newly added plant materials within soil aggregates, and this has proven to be a useful tool for studying the impact of residue additions on soil aggregate formation. Furthermore, these methods have been shown to be useful for determining the incorporation and sequestration of C materials within soil aggregates. The development of the 13C SIMS technique could alleviate the necessity for the use of the radioactive isotope 14C in soil studies.

Carbon Radioisotopes↗

Thyroid cancer morbidity in Opole province, Poland, after Czernobyl disaster.

The Czernobyl disaster caused an extensive pollution in Europe due to the release into the environment thousands of tons of radioactive isotopes affecting the elevated cancer morbidity in the continent. The authors used the data set on radiation in Opole province, Poland, to model thyroid cancer incidence in the 1994-1998 quinquennium. An increase in thyroid cancer morbidity in females was observed within the 137 + 134Cs elevated concentration areas. The changes of the cancer incidence in males were found not significant for the distinguished radiation levels in the region. The statistical modeling was performed via the BUGS software.

Environmental Exposure↗

Radionuclide therapy of cancer patients with bone metastases.

OBJECTIVES: We report our experience in the use of radionuclides in the treatment of bone metastases in patients with various primary cancers: breast cancer, prostate cancer, lung cancer, etc. MATERIAL AND METHODS: Eighty-seven patients (53 women, 34 men) with bone metastases were treated for pain relief with either 32-P (71 patients) or 89-Sr (16 patients). Fifty-three of the patients had breast cancer, 27--rostate cancer, 6--lung cancer and 1--kidney cancer. The patients were examined for side effects when 32-P was administered perorally and 89-Sr injected intravenously. We also studied the changes in the levels of hemoglobin, white blood cells (WBCs) count and platelets count. RESULTS: We found a significant decrease in the WBC and platelet count in the patients treated with 32-P (U = 2.20, P < 0.05 and U = 4.57, P < 0.001) one month after the therapy. These parameters showed no significant decrease in the group treated with 89-Sr. The pain, which was the rationale to use the radioactive isotopes, was relieved and the patients restored their previous mobility. DISCUSSION: The fact that 32-P alleviated the grave symptom of pain at the relatively weak radiation dose used (2 mCi) is a strong indication that this radiopharmaceutical can be used successfully for such a purpose, although some authors argue against its use in view of the myelosuppresion it causes. This myelosuppression, however, is mild and transient even without treatment and patients could benefit from this adjuvant treatment to manage the pain syndrome. 89-Sr administered intravenously in a dose of 4mCi also relieves pain efficiently but its use is limited by the cost of the quantity needed for 1 patient and for a single dose. The National Health Insurance Fund currently reimburses for a very limited quantity of this substance which makes the cost of the procedure 15 times as expensive as that using radioactive phosphorus. CONCLUSIONS: Using the radiopharmaceuticals 32-P and 89-Sr provides an additional, easy and efficacious means for palliation of cancer patients with bone metastases, especially those who are refractory to percutaneous irradiation.

Bone Neoplasms↗

[Radioisotopic diagnostic examination as a factor responsible for the Polish population exposure to ionizing radiation].

For the general population, in vivo radioisotopic radiological examinations are the second, after x-ray diagnostics, artificial source of ionizing radiation used for medical purposes. The 1981 survey was the first review of the radioisotopic examinations in Poland and revealed that 80,000 examinations are performed annually (2 examinations per 1,000 population on average). It was also found that 131 I was the most common isotope used during thyroid examinations very frequently performed at that time. According to the 1996 data published by the National Consultant on Nuclear Medicine, "In Poland there are 36 centers of nuclear medicine within the network of public health care services. Every year about 130,000 radioisotopic examinations are performed." In order to estimate real exposure of the Polish population resulting from radioisotopic diagnostic examinations it is necessary to gather detailed data on the age structure of patients, as well as on the type and activity of radiopharmaceutical be administered. The paper presents the preliminary results of the follow-up study on radioisotopic examinations in Poland carried out by the Department of Radiological Protection, Nofer Institute of Medicine, Łódź. The data have been collected according to the adopted schedule, taking account of the organ (system) examined, the type of administered radiopharmaceutical, the kind and activity of radioactive isotopes used to mark radiopharmaceutics, age and sex of examined patient. By the end of December 2000 the data on radioisotopic examinations performed in 12 centers of nuclear medicine (Warsaw--7; Kielce--2; Gdańsk, Łódź and Zgierz--one center in each city) had been collected. Thus far almost 40,000 radioisotopic examinations have been registered. According to the above mentioned procedure it was possible to collect data on all examinations performed in 1998. In addition, general numbers of examinations performed in the centers visited in 1999 were registered; the 2000 data are now being completed. It was finally established that the thyroid and musculoskeletal examinations constitute about 50% of the total number of examinations, which is in agreement with the data applying to the countries classified as those with the first level of health care. However, while an average effective dose per examination in those countries accounts for about 4 mSv, in the Polish centers the analogues indicator, estimated on the basis of the results collected thus far, is about 9 mSv, of this number, over 7 mSv is contributed by thyroid examinations with the use of iodine (131I). The obtained result is a strong stimulus to supplement and complete the data already gathered and to carry out a thorough analysis of radioisotopic examination in view of patients' exposure. Such an analysis would provide the subject matter arguments for the optimization of radiological protection in nuclear medicine in Poland.

Adult↗

[Lethal effect of the decay of 64Cu and 67Cu incorporated in mammalian cells].

A high lethal efficiency was observed when the decay of two radioactive isotopes of copper, 64Cu or 67Cu, occurred in mammalian cells. The lethal efficiency is of the same order for both isotopes in spite of their different decay processes. As the lethal event could be attributed to an injury inside the cellular DNA only, these results suggest that, even if present in the DNA in trace amounts solely, copper atoms are essential chromatin components. Their behaviour differs depending on whether the cell is a tumor or a non tumor cell because their lethal efficiencies are different (0.5 and 0.1 respectively).

Animals↗

Radiation.

The US Department of Homeland Security, and other state and federal agencies, continues to express concern over the potential use of radioactive isotopes as a weapon of terror. Few emergency medicine and critical care physicians are familiar with the care and treatment of an accidentally or intentionally irradiated patient who is contaminated externally or internally. This article reviews basic radiobiology and the variety of clinical signs and symptoms exhibited by victims exposed to radiation. Preparation for patient receipt and emergency care, followed by definitive diagnosis using biodosimetry is also presented. Therapeutic measures continue to evolve for externally and internally exposed victims, including those with combined injuries caused by burns and trauma.

Decontamination↗

Measuring total and regional lung deposition using inhaled radiotracers.

The delivery of an inhaled drug to the lungs can be measured by adding a gamma-emitting radiotracer to the formulation and using two-dimensional planar imaging or three-dimensional single photon emission computerized tomography (SPECT) to provide detailed information on lung deposition. The isotope most commonly used is the low energy (140 KeV) isotope, 99m technetium. Radiolabeling techniques have been successfully developed for use with nebulizers, pressurized metered dose inhalers (pMDIs), and dry powder inhaler formulations (DPI), and to investigate drug delivery to the respiratory tract for a variety of drug formulations and patient populations. However, for pMDIs and DPIs, the radiotracer is usually only physically associated with, rather than chemically bound, to the drug. Therefore, once deposited, the radiotracer may disassociate from the drug and cannot be used to track its subsequent fate; however, incorporation of a radiotracer directly into the drug molecule can overcome this. By using positron emitters such as 11carbon or 18fluorine it is possible to generate three-dimensional images of the drug in the lung using positron emission tomography (PET) scanning, which has a higher resolution and is more accurate than SPECT. Labeling drugs with PET emitters is more complex as the drug molecule must first be synthesized to contain the radioactive isotope before the drug is formulated for the inhaler. As with gamma-scintigraphy, PET scanning can be used to investigate physiological changes in the lung following therapeutic intervention, but as biological radiotracers are used, functional images (i.e., of the drug's uptake and metabolism) can also be obtained.

Administration, Inhalation↗

The ecosystem study on Rongelap Atoll.

During the 1950's and 1960's, the Laboratory of Radiation Biology at the University of Washington carried out an intensive study of this Atoll, which was contaminated with radioactive fallout from the "Bravo shot" in 1954. This study involved many aspects of the environment and the plant and animal life: soils, land plants, marine life, birds, geology and hydrology, and human diets as well. In much of the research, the fortuitiously present radioactive isotopes, especially 137Cs and 90Sr, were tracers. Although the term "ecosystem study" was not in vogue at that time, it is clear that this was an early use of the ecosystem approach. Soil types and their development, the distribution of mineral elements in plants and soils, including predominant radionuclides, distribution and growth of native terrestrial plants in relation to topography and salinity, some aspects of the human diets, micronutrient nutrition of the coconut palm, island and islet development and stability, were given attention in the studies. Some of the findings in the various areas of study will be presented and discussed.

Animals↗

Organ-specific measurements of protein turnover in man.

Methods that were originally developed for animal studies have now been modified for measuring tissue protein turnover in man with stable isotopes. Of the three techniques which have been discussed, only the arterio-venous difference method has the capacity to measure both the synthesis and degradation. This technique is, however, difficult to perform and has a number of potential sources of error, one of the most important being the assessment of precursor labelling. Constant infusion of a labelled amino acid with measurement of the incorporation into protein of a biopsy is a simpler and more precise technique for measuring synthesis in patients as well as volunteers, but the most appropriate means of assessing the precursor labelling still remains to be worked out. The flooding-dose procedure aims to minimize the difficulty of assessing precursor labelling and there is no evidence that the unphysiological dose of labelled amino acid given influences the synthesis rate which is measured. It is rapid to perform and is very well suited to measurements in patients, in whom a wide range of tissues can be studied. These advances in techniques have been facilitated particularly by improvements in mass spectrometry, which have allowed the use of stable in place of radioactive isotopes, and have enabled measurements of isotopic enrichments to be made in small samples of tissue. These techniques for assessing the dynamics of protein metabolism in individual tissues are now being used to answer nutritionally and clinically important questions in human volunteers and patients.

Amino Acids↗

Biological consequences of Chernobyl: 20 years on.

The disaster at the Chernobyl nuclear power plant in 1986 released 80 petabecquerel of radioactive caesium, strontium, plutonium and other radioactive isotopes into the atmosphere, polluting 200 000 km(2) of land in Europe. As we discuss here, several studies have since shown associations between high and low levels of radiation and the abundance, distribution, life history and mutation rates of plants and animals. However, this research is the consequence of investment by a few individuals rather than a concerted research effort by the international community, despite the fact that the effects of the disaster are continent-wide. A coordinated international research effort is therefore needed to further investigate the effects of the disaster, knowledge that could be beneficial if there are further nuclear accidents, including the threat of a "dirty bomb".

Animals↗

Brachytherapy of choroidal melanomas.

In the management of patients with primary malignant melanoma of the uvea, treatment techniques have included not only enucleation but also photocoagulation, cryotherapy, photoradiation, a limited resection, as well as circumstances indicating exenteration of the orbit. Surgical management has been the primary treatment program for over 100 years. In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including iridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques.

Brachytherapy↗