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[Physical brachytherapy planning].

The treatment of prostate cancer, confined to the gland, with high conformal doses to the target volume and sparing of bladder, rectum and urethra at the same time can be achieved by interstitial brachytherapy. Close cooperation of urologist and radiologist, together with the physical treatment planning have improved the clinical results significantly. The ongoing development of new radioactive isotopes and of dedicated computerized treatment planning systems have resulted in a renaissance of the interstitial treatment. "Preplanning" i.e. preoperative treatment planning can be performed precisely and fast. Improved ultrasound techniques allow during the perineal template guided seed implantation a realtime dose calculation resulting in an improved seed placement. CT- or MRI based "postplanning" guarantees for early postoperative dose documentation and quality assurance. 2-dimensional as well as 3-dimensional dose distributions superposed to anatomical structures and dose volume histograms (DVH) allow for dose optimization and quality decision. 192Ir with high activity is used for the high dose rate (HDR) afterloading treatment as a boost after external radiotherapy. 125I and 103Pd as well are used as permanent implants to boost external irradiation. If fast growing low grade tumors should be treated with 103Pd permanent implant and slow growing tumors with 125I is discussed controversialy. About 50 to 100 seeds are implanted. The implanted patients are allowed to leave the hospital as there is sufficient shielding by the surrounding normal tissue. Postplanning is based on CT- or MRI for dose documentation and quality assurance. For 125I treatments the activity-dose-relation was redefined since 1995 (TG43 protocol). Similar corrections seem to be necessary for 103Pd treatments.

Brachytherapy↗

Protection of drinking water sources against modern pollutants.

One of the main tasks of hygiene necessitating urgent solution is the regulation, within the framework of governmental planning, of sanitary protection against modern pollutants of sources and water works supplying the human collectivities. Pollution by pesticides, surfactants, aromatic polycyclic hydrocarbons, oil waste products, phenolics, radioactive isotopes etc., is requiring particular concern. Cases of penetration of these chemical substances, especially of pesticides, oil residues and other kinds of industrial waste into ground waters have been recently observed with increasing frequency. Pollution of underground waters occurred either through the storage on the surface ground or into soil of waste products containing these substances or through their discharge into the water stream. The presence of these substances in most water supply systems the lowered effectivity of water-works in the removal of these substances, continual increase in the number of industries producing these pollutants, their participation in the origin or increased incidence of some chronic diseases characterizing the development of modern society make necessary scientific substantiation and urgent solution of the problem.

Ammonia↗

[Molecular cloning of the tumor associated antigen recognized by monoclonal antibody 3H11].

OBJECTIVE: Monoclonal antibody (McAb) 3H11 can specifically bind to different cancer cells from different tissues. Meanwhile, McAb 3H11 labeled with radioactive isotopes has been successfully applied to detect primary cancer and metastatic cancer in clinical imaging. Molecular cloning of the antigen recognized by McAb 3H11 will be significant for understanding tumor development. METHODS: Based on the fragment of the McAb 3H11 antigen cloned by Immunoscreening MGC803 cDNA expression library, the whole length of the cDNA molecule was gotten by RACE and nested PCR. RESULTS: Sequence data of the cDNA molecule indicates that there was no homologous gene in GenBank. Northern blot experiments showed that mRNA of McAb 3H11 antigen extensively distributes in different cancer cells and tissues but not in corresponding normal tissues. Moreover in producing antibodies of the antigen expressed prokaryotically, it was found that the immunogenicity of the antigen was quite low in mammalian. CONCLUSION: The antigen recognized by McAb 3H11 acts as a regulator in embryo cells and regains expression in tumor cells; and it may be associated with low differentiation and high proliferation.

Animals↗

Implementation of PET scan as a new service.

Positron emission tomography (PET) is a diagnostic test using injected radiopharmaceuticals (drugs or compounds tagged with radioactive isotopes) to obtain images of metabolic/physiologic processes. PET provides physiologic data rather than just anatomic data such as that provided by CT scan or MRI. Metabolic changes precede anatomic changes, hence the higher accuracy of PET. Scar tissue, necrosis and tumor mass may appear identical on CT and MRI, but markedly different on PET. PET may decrease unnecessary surgeries and improve treatment through greater specificity about the disease and may provide a better evaluation of recurrent disease.

Forms and Records Control↗

A new method for the diagnosis of pelvic pathologies Part II - interpretation of abnormal images.

The results presented are those presented are those obtained on the diagnosis of pelvic congestion by means of the use of radioactive isotopes, following an original method proposed by us and previously described. It has been carried out on 100 patients, of whom 6 were normal and 94 presented some gynecological pathology in the internal genitals. Laparatomy was carried out, proving the lesions visually in 51 cases. The diagnosis was correct in 98% of the cases. Finally the advantages which it presents over phlebography were analysed, and the possibilities of the method in gynecological practice suggested, since it can be used in a great number of genital diseases to carry out a diagnosis of vascular pathology.

Adolescent↗

The effect of stable strontium on the incorporation and metabolism of radioactive strontium in young and adult rabbit bones.

The experiments were performed on 5-, 8-, 12- and 14 months old rabbits. The effect of stable strontium enriched diet on the bone tissue formation (apposition) and on physiocochemical processes consisting in ion exchange were studied using radioactive isotopes: Sr-85 and Ra-226 and tetracycline. The results of kinetic and autoradiographic studies and micoscopical analysis of bone preparations suggest that stable strontium inhibits the mineralization of newly formed bone tissue without affecting the physico-chemical processes related to ion exchange.

Age Factors↗

Prognostic value of dobutamine-atropine stress (99m)Tc-tetrofosmin myocardial perfusion SPECT in patients with known or suspected coronary artery disease.

UNLABELLED: 99mTc-Tetrofosmin is a recently introduced radioactive isotope for the assessment of myocardial perfusion. Data regarding the prognostic value of stress imaging using this isotope are scarce. The aim of this study was to assess the prognostic value of dobutamine-atropine (99m)Tc-tetrofosmin SPECT for the prediction of late cardiac events in patients with known or suspected coronary artery disease. METHODS: A total of 721 consecutive patients with limited exercise capacity underwent dobutamine-atropine stress (99m)Tc-tetrofosmin SPECT. Follow-up was successful in 719 of 721 patients (99.7%). Twenty-eight patients who underwent early revascularization were excluded. RESULTS: Myocardial perfusion abnormalities were detected in 381 patients (55%) and included fixed defects in 190 patients (27%) and reversible defects 191 patients (28%). During a mean follow-up period of 37 +/- 17 mo, there were 150 deaths (22%), of which 62 (41%) were attributed to cardiac causes. Nonfatal myocardial infarction occurred in 23 patients (3%), and late (>3 mo) coronary revascularization was performed on 21 patients (3%). The cardiac death rate was 1%/y in patients with a normal scan and 5.1%/y in patients with an abnormal scan (P < 0.0001). In a multivariable Cox proportional-hazards model, the presence of abnormal perfusion was independently associated with an increased risk of cardiac death, after adjusting for clinical and stress test data (hazard ratio, 8.2; 95% confidence interval, 3.2-21). CONCLUSION: Dobutamine-atropine stress (99m)Tc-tetrofosmin SPECT is a useful imaging method for distinguishing patients at high and low risk of future cardiac events. The presence of perfusion abnormalities provides incremental prognostic information to clinical, stress electrocardiographic, and hemodynamic data.

Atropine↗

Study on the distribution of nodularin in tissues and cell level in mice.

OBJECTIVES: To study the tissue distribution of nodularin in mice and the cellular location of nodularin in the target organs. METHODS: The nodularin was labeled with radioactive isotope (125)I and then was given to mice via oral, intraperitoneal and intravenous administration. The distribution of nodularin in target organs and the cellular location of nodularin were studied by radioisotope and autoradiography techniques. RESULTS: The radioisotope study results showed that nodularin was mainly distributed in the kidney and liver in mice. Further autoradiography study indicated that nodularin was distributed in the renal cell nuclei and liver cell nuclei. CONCLUSION: The kidney and liver are the two main target organs for nodularin in mice.

Animals↗

[Treatment and development of thyroid carcinoma].

Reporting the results of a retrospective study on 101 cases of carcinoma of the thyroid gland, treated in our Service between 1979 and 1998. Analysis of the several anatomopathological variables found, the surgical treatment and also with radioactive isotopes, the complications and the condition evolution. Epidemiologically 82 percent of patients were women and men the 18 percent. Middle age 51 years. 12 percent of patients had familiar antecedents of thyroid pathology. The histological types found were: papillary carcinoma (74.26%), follicular carcinoma (14.85%), Hürthle's cellules carcinoma (3.96%) and anaplastic carcinoma (2.97%). In our Service elective treatment of thyroid gland carcinoma is total thyroidectomy with neck dissection in 18.3 percent of affected. The survival rate amount for 81.3 percent at five years. The aim of this article is to display the therapeutics and evolution of thyroid gland cancer, based in our own 18 years of experience acquired in the Service.

Aged↗

[Assessment of the status of biological health of the population of tundra Nentsy inhabiting northwestern Siberia from data on analysis of autoantibodies and lipoproteins from blood donors].

As a result of large-scale nuclear explosion on Novaya Zemlya test site (1955-62) the Tundra Nentsy population of Yamal-Nentsy autonomous region (YNAR) fell under constant influence of incorporated radioactive isotopes (137Cs and 90Sr). Therefore, it is very important to analyze a possible spectrum of diseases of Tundra Nentsy population. We have developed recently a new method for determination of concentrations of all main fraction and subfraction of lipoproteins (LP, 30 parameters) in human sera using small-angle X-ray scattering, and a general mathematical model to describe LP composition in human blood. The analysis of the 30 parameters characterizing fine spectrum of LPs in 374 YNAR natives showed that only approximately 10% of the donors are normal, while the indices for approximately 90% of the test subjects fall into the range of different pathologies (3-8% incidence in normal population, according to epidemiological studies). Moreover, we found that approximately 41% of European and approximately 56% of Tundra Nentsy have high level of autoantibodies to DNA and cardiolopine like the same for autoimmune diseases patients.

Autoantibodies↗

[cDNA libraries construction and screening in gene expression profiling of disease resistance in wheat].

A wheat line, Bai Nong 3217/Mardler BC5F4 with resistance to powdery mildew, was used to construct a conventional cDNA library and a suppression subtractive hybridization (SSH) cDNA library from wheat leaves inoculated by Erysiphe graminis DC. Three hundred and eighty-seven non-redundant ESTs from the conventional cDNA library and 760 ESTs from the SSH cDNA library were obtained, and the ESTs similarity analysis using BLASTn and BLASTx were conducted by comparing these ESTs with sequences in GenBank. The results showed that the redundancy of some kinds of genes such as photosynthesis related genes and ribosome related genes was higher in the conventional cDNA library but the varieties and quantities of disease resistance genes were less than those in the SSH cDNA library. The SSH cDNA library was found to have obvious advantages in gene expression profiling of disease resistance such as simple library construction procedure, rich specific DRR (disease-resistance-related) genes and decreased sequencing amount. To acquire genes that were involved in the powdery mildew resistance of wheat, hybridization with high-density dots membranes was used to screen the two libraries. The result showed that the method was relatively simple in operation, and the membranes could be used for many times. But some problems also existed with this screening method. For instance, a large amount of mRNA and radioactive isotope were needed and the hybridization procedure must be repeated several times to obtain stable hybridization results. About 54.1% function-known ESTs in the SSH cDNA library were identified to be DRR genes by screening. There were 247 clones of the SSH cDNA library that had positive signal in the repeated hybridizations with the pathogen uninfected probe. The identified DRR genes distributed in the whole procedure of powdery mildew resistance, but mainly focused on the SAR (systemic of acquired resistance).

Ascomycota↗

[Effect of protein kinase on endothelial cytoskeleton induced by septic shock].

OBJECTIVE: To study the effect of cGMP-dependent protein kinase (PKG) on the pathogenesis of septic shock. METHODS: Confluent endothelial cells were disintegrated and centrifugated to obtain cell lysates after being treated with LPS or PKG activator 8-Br-cGMP. PKG activity of lysates was measured with radioactive isotope label method in a reaction system of phosphorylation of specific substrate H2B by PKG, and the shape and the distribution of intracellular filamentous actin were detected by specific fluorescence staining. For the control study, the PKG specific inhibitor KT5823 was used to pretreat the endothelial cells before the administration of LPS or PKG activator 8-Br-cGMP. RESULTS: Exposure to LPS for 5, 10, 30 and 60 minutes led to a rapid time-dependent increase in endothelial PKG activity (P < 0.01 compared to the blank) and the polar distribution of intracellular filamentous actin and preincubation with KT5823 abolished these effects. 8-Br-cGMP was similar to LPS. CONCLUSIONS: The results suggested that LPS can mediate PKG activation and the stress variety of filamentous actin in the vascular endothelial cells, which probably induce the endothelial hyperpermeability after septic shock.

Capillary Permeability↗

Antibiotic penetration into bone in relation to the immediate management of open fractures: a review.

Bone is a vascular structure, which is capable of responding to changes in the systemic circulation. Antibiotics carried within the systemic circulation reach the capillaries in bone, and depending on molecular size, pass through the capillary walls to enter the fluid space. Following an open fracture, contamination with pathogenic organisms can occur both at the moment of injury, but also in the hospital, which is a particular problem in grade III fractures in which extensive soft tissue damage can occur in combination with an exposed wound. Antibiotics administered intravenously can be measured in bone by both bioassay and radioactive isotope techniques and are shown to reach bone in effective concentrations. It is apparent that short-course high-dose antibiotic therapy is appropriate for open fractures, and need not be continued as long as the normal fracture-healing process continues. However if infection in bone develops, further surgery is important to remove new dead tissue to allow adequate antibiotic penetration into bone. Thus antibiotics are useful when combined with effective surgical management, but do not on their own offer the only answer to management of the patient.

Anti-Bacterial Agents↗

[Effect of forskolin and quinacrine on leukocyte functions under the effect of low-dose radiation].

The adenylate cyclase and phospholipase A2 incorporation in the functional responses as well as lipid peroxidation processes and glutathione system homeostasis of animal leukocytes to small doses of ionizing radiation (1-100 mGy) have been estimated. The cells were irradiated by introduction of radioactive isotope 14C-leucine into the incubation medium. It is established that the ionizing radiation has different effects on the modification of cellular functions by the agents, which change adenylate cyclase and phospholipase A2 activity. Neutralization of stimulative irradiation effect on chemokinesis of polymorphonuclear leukocytes by quinacrine (the inhibitor of phospholipase A2) indicates for certain, that metabolism of eicosanoids takes immediate part in the cell response to ionizing radiation. Apparently, adenylate cyclase has no influence on this process, where at indicates the lack of influence of forskolin (the stimulator of adenylate cyclase) on the spontaneous motility, and on the radiation action on this leukocyte function. Rosette forming ability of lymphocytes is regulated by both enzymes because it is modified both by the inhibitor of phospholipase A2, and by the adenylate cyclase stimulant. In this case it is impossible to exclude the action of ionizing radiation both through the adenylate cyclase cascade, and through the eicosanoid metabolism. In all the concentration range the radionuclides do not affect the studied biochemical indexes of the cell, but change the action of the modifiers.

Adenylyl Cyclases↗

Significance of secondary ion mass spectrometry microscopy for technetium-99m mapping in leukocytes.

Secondary ion mass spectrometry (SIMS) microscopy is the only method potentially capable of mapping all the elements in the periodic table including stable and radioactive isotopes. We used this method to study 99mTc distribution by detecting and localizing of 99Tc, a daughter product which has the same mass and the same chemical properties. It was combined with albumin macroaggregates or with Hexamethylpropylene-amine oxime (HMPAO) in leukocytes. The efficiency of 99Tc ionization under Cs+ bombardment was higher than with an O2+ beam. By using high mass resolution we succeeded in detecting and localizing 99Tc in cell sections by eliminating polyatomic ions that arise from this biological matrix. The 99Tc specific signal was obtained with a mass resolution of 2000 for labeled albumin macroaggregates, and 5000 for HMPAO-labeled leukocytes. In the latter, the labeling varied from one cell to another and 99Tc was present in both the nucleus and the cytoplasm. The results indicate that SIMS microscopy can provide new insights into 99mTc dosimetry.

Humans↗

[Retinoblastoma--hereditary eye cancer in children].

BACKGROUND: Retinoblastoma is a malignant tumour of the retina that occurs in early childhood. The aim of this paper is to give an updated review of the disease. MATERIAL AND METHODS: A review is given based on literature published over the last few years and on the authors' own experience. RESULTS: The yearly incidence of retinoblastoma is approximately one per 14 000 live births, which gives four new cases of retinoblastoma per year in Norway. The only known risk factor is heritage. Symptoms of retinoblastoma are strabismus, reduced visual acuity and red eye, but the absolutely most important sign is leukokoria (white pupillary reflex). Important diagnostic tools are ophthalmoscopy, ultrasonography, CT and MRI. The goal of treatment is to destroy all tumour tissue, but not the surrounding tissue. Treatment options are enucleation, chemotherapy, external beam radiation, radioactive isotope plaques, cryotherapy, photocoagulation, or a combination of these depending upon the size and location of the tumour. INTERPRETATION: The overall results in the treatment of retinoblastoma are favourable and have improved over the last few years because of better treatment modalities. The survival rate is approximately 95%. It is important that physicians bear in mind the signs of retinoblastoma and especially the alarming sign of leukokoria and acute strabismus in a child.

Child↗

Susceptibility of the human pathogenic fungi Cryptococcus neoformans and Histoplasma capsulatum to gamma-radiation versus radioimmunotherapy with alpha- and beta-emitting radioisotopes.

UNLABELLED: Fungal diseases are difficult to treat in immunosuppressed patients and, consequently, new approaches to therapy are urgently needed. One novel strategy is to use radioimmunotherapy (RIT) with fungal-binding monoclonal antibodies (mAbs) labeled with radionuclides. However, many fungi manifest extreme resistance to gamma-radiation, such that the doses of several thousand gray are required for 90% cell killing, whereas for mammalian cells the lethal dose is only a few gray. We compared the susceptibility of human pathogenic fungi Cryptococcus neoformans (CN) and Histoplasma capsulatum (HC) to external gamma-radiation and to the organism-specific mAbs 18B7 and 9C7, respectively, conjugated to (213)Bi and (188)Re radionuclides. METHODS: CN and HC cells were irradiated with up to 8,000 Gy ((137)Cs source, 30 Gy/min). RIT of CN with (213)Bi- and (188)Re-labeled specific mAb and of HC with (188)Re-labeled specific mAb used 0-1.2 MBq per 10(5) microbial cells. After irradiation or RIT, the cells were plated for colony-forming units (CFUs). Cellular dosimetry calculations were performed, and the pathway of cell death after irradiation was evaluated by flow cytometry. RESULTS: Both CN and HC proved to be extremely resistant to gamma-radiation such that significant killing was observed only for doses of >4,000 Gy. In contrast, these cells were much more susceptible to killing by radiation delivered with a specific mAb, such that a 2-logarithm reduction in colony numbers was achieved by incubating them with (213)Bi- and (188)Re-labeled mAb 18B7 or with (188)Re-9C7 mAb. Dosimetry calculations showed that RIT was approximately 1,000-fold more efficient in killing CN and approximately 100-fold more efficient in killing HC than gamma-radiation. Both gamma-radiation and RIT caused cell death via an apoptotic-like pathway with a higher percentage of apoptosis observed in RIT-treated cells. CONCLUSION: Conjugating a radioactive isotope to a fungal-specific antibody converted an immunoglobulin with no antifungal activity into a microbicidal molecule. RIT of fungal cells using specific antibodies labeled with alpha- and beta-emitting radioisotopes was significantly more efficient in killing CN and HC than gamma-radiation when based on the mean absorbed dose to the cell. These results strongly support the concept of using RIT as an antimicrobial modality.

Antibodies, Monoclonal↗