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PubMed1975

[Study of the pathogenesis of toxoplasmosis by means of tagged atoms].

The authors' investigations showed a principal possibility of labeling toxoplasma with radioactive isotopes on condition of the administration of the latter in vivo into the donor animals infected with toxoplasmosis. The labeled atom method could be used for studying the pathogenesis of toxoplasmosis in the experimental animals, particularly at the early periods of the infectious process. The use of the labeled atom method permitted not only to confirm the results obtained by parasitological and pathomorphological studies, but also to reveal the fact of a primary parasitemia, later confirmed by biopsy. In combination with other methods of study the labeled atom method can be used for studying various aspects of the problem of toxoplasmosis, particularly of the mechanisms of transmission of the infection.

Animals↗

PubMed1990

Use of a new gas chromatograph isotope ratio mass spectrometer to trace exogenous 13C labelled glucose at a very low level of enrichment in man.

The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4 +/- 0.7 mg.kg-1.min-1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1 +/- 1.1 mg.kg-1.min-1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g.kg.-1,1 g.kg.-1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97 +/- 0.04 g.kg.-1 and 1.2 +/- 0.04 g.kg.-1, exogenous glucose appearance was 0.51 +/- 0.02 g.kg.-1 and 0.84 +/- 0.04 g.kg.-1, endogenous glucose production was 0.44 +/- 0.04 g.kg.-1 and 0.35 +/- 0.06 g.kg.-1 after the 0.5 and 1 g.kg.-1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Gas chromatography/mass spectrometry analyses of [2,3,3-d3] serine, [2,3,3-d3] cysteine and [3-13 C] cysteine in plasma and skin protein: measurement of transsulphuration in young sheep.

A new procedure using stable isotope labelled serine (L-[2,3,3-d3] serine) and cysteine (L[13-3-13 C] cysteine) and analysis by gas chromatography/mass spectrometry (GC/MS) has been developed to measure transsulphuration in sheep. The enrichments of the tracers in plasma and skin biopsy samples were measured by GC/electron impact MS analysis of the t-butyldimethylsilyl derivatives. The measured recoveries of the standards enriched with [3-13 C] cysteine from 0.1% to 8%, or with [2,3,3-d3] serine from 0.14% to 14% were greater than 99% of the theoretical values, and the variation coefficients were less than 3% when the enrichment was higher than 0.5%. The use of dithiothreitold (DTT) as a reducing agent before deproteinization of the sample and during the derivatizations successfully increased the cysteine peak area and significantly improved reproducibility in the analysis. The cysteine residues in protein from the skin biopsy were also during the protein hydrolysis with DTT in 6 n HCI. The method was applied to measure transsulphuration of methionine in young sheep. The amount of cysteine derived from transsulphuration accounted for 17% to 21% of the irreversible loss rate of cysteine, depending on the substrate supplies. The results are consistent with other reports. Compared with conventional methods of measuring transsulphuration using radioactive isotopes, the processes of animal experimentation was sample analysis were simple, and there were no radiation hazards. The method should prove useful in studies on the metabolism of methionine and cysteine in human and animals.

Amino Acids, Sulfur↗

PubMed2000

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

OBJECTIVE: To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. DESIGN: Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. PARTICIPANTS: Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. MAIN OUTCOME MEASURES: Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). RESULTS: Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. CONCLUSIONS: Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Adolescent↗

PubMed2001

Sentinel lymph node detection in patients with cervical cancer.

PURPOSE: We investigated the validity of sentinel lymph node (SLN) detection after radioactive isotope and/or blue dye injection in patients with cervical cancer. PATIENTS AND METHODS: Between December 1998 and May 2000, 50 patients (mean age 44 years) with cervical cancer FIGO stage I (n = 32), stage II (n = 16), or stage IV (n = 2) underwent SLN detection during primary operation (radical laparoscopic-vaginal or abdominal hysterectomy, exenteration). The day before surgery 1 ml of Albu-Res labeled with 50 MBq Technetium 99m was applied into the cervix at 3(00), 6(00), 9(00), and 12(00). Blue dye injection (Patentblue) occurred intraoperatively into the cervix at the same locations. RESULTS: The detection rate of SLN was 78%. Ten patients (20.0%) were diagnosed with lymph node metastases. No SLN was detected in 10 patients, of which 4 patients had positive lymph nodes. Sensitivity and negative predictive value were 83.3 and 97.1%, respectively. The false-negative rate was 16.6% (1 of 6 patients). After the combined injection, the detection rate, sensitivity, and negative predictive values were 100%. A mean of 2.7 pelvic and 2.6 para-aortic SLNs were detected. Para-aortic SLNs were located in the paracaval region in 66.6%, whereas pelvic SLNs were detected in 25.7% at the origin of the uterine artery and in 24.7% at the division of the common iliac artery. CONCLUSION: A combination of radioactively labeled albumin with blue dye allows successful detection of SLN in patients with cervical cancer. The clinical validity of this technique must be evaluated prospectively.

Adult↗

PubMed2004

Strontium biokinetics in humans: influence of alginate on the uptake of ingested strontium.

Radioactive isotopes of strontium, mainly 90Sr, released into the environment due to nuclear accidents may contribute significantly to the internal radiation exposure of members of the public after ingestion of strontium with contaminated foodstuffs. The committed radiation dose is significantly dependent on the fraction of the ingested activity that crossed the gut wall (f1 value). In tracer kinetic investigations, the effect of sodium alginate on the gastrointestinal absorption of strontium was studied in human subjects. Sodium alginate was proven to be a potent agent for reducing strontium absorption with high efficiency and virtually no toxicity. The data obtained show that the uptake of ingested strontium from milk was reduced by a factor of nine when alginate was added to milk. It is concluded that alginate preparations are a suitable antidote against radiostrontium.

Administration, Oral↗

PubMed2002

Early reproductive success of western bluebirds and ash-throated flycatchers: a landscape-contaminant perspective.

Eggshell quality, clutch size, sex ratio, and hatching success of western bluebirds (Sialia mexicana) and ash-throated flycatchers (Myiarchus cinerascens) were studied on a landscape-soil contaminant gradient at Los Alamos National Laboratory (LANL) in New Mexico from 1997 to 1999. A variety of contaminants (heavy metals, chemicals, insecticides, polychlorinated biphenyls (PCBs), organochlorines, and radioactive isotopes) range across different spatial scales and concentrations on LANL land. This study is an example of a monitoring program over a large area with varying degree of contamination that is used to highlight locations of concern for future research. There were two locations where the flycatcher had a lower hatching success. The bluebirds at Sandia wetland, a location of concern for PCBs. had a thinner eggshell thickness index (RATCLIFFE) and the eggs were smaller than at other locations. The flycatcher had thinner eggshells than bluebirds, which could add to sensitivity to exposure to contaminants. There was no variation in clutch size or sex ratio between locations or areas closer to contaminant release sites for both species. Percent females in the clutch ranged from 0 to 100% in the WEBL and from 33 to 67% for ATFL.

Animals↗

PubMed1999

Iodine prophylaxis and nuclear accidents.

Due to high volatility and environmental mobility, radioactive isotopes of iodine pose a serious risk in the acute phases of a nuclear accident. The critical organ for iodine is the thyroid. A number of studies dealing with thyroid protection from exposure to radioiodine have shown that radioiodine uptake by the thyroid can be effectively blocked by administration of stable iodine, usually in the form of potassium iodide (KI) pills. However, unless perfectly timed, this protective action may be counterproductive. The International Atomic Energy Agency recommends potassium iodide prophylaxis in cases when an avertable thyroid dose by protective action exceeds 100 mGy. This paper reviews experiences and practices with potassium iodide in the thyroid protection. This kind of information should serve as the basis for discussion and decision making on KI prophylactic programmes in nuclear emergency situations in Croatia. If Croatia adopts such programme, it will still have to develop the most effective way of KI stockpiling and distribution or predistribution.

Humans↗

PubMed2006

Well water radioactivity and risk of cancers of the urinary organs.

Water from bedrock frequently contains higher concentrations of natural radionuclides than water from other sources. Bladder and kidneys receive a radiation dose when radioactive isotopes are excreted into urine. The subjects for this case-cohort study were selected from all drilled wells users in Finland. The study comprised 61 bladder cancer and 51 kidney cancer cases diagnosed between 1981 and 1995, as well as a random sample of 274 reference persons, stratified by age and sex. The median activity concentrations of radon in drilled wells used by bladder and kidney cancer cases and the reference cohort were 170, 140, and 130 Bq/L, respectively. The radium concentration was 0.01 Bq/L for all groups and the uranium concentrations were 0.08, 0.07, and 0.06 Bq/L, respectively. The bladder cancer risks associated with radon, radium, and uranium activity concentrations in drinking water were 1.02 (0.68-1.54) per log(100 Bq of radon/L), 0.73 (0.21-2.50) per log(0.1 Bq of radium/L), and 0.77 (0.32-1.89) per log(1 Bq of uranium/L). The corresponding figures for kidney cancer were 0.81 (0.47-1.37), 0.12 (0.01-1.10), and 0.92 (0.36-2.35), respectively. In conclusion, even though ingested radionuclides from drilled wells are a source of radiation exposure, they are not associated with a substantially increased risk of bladder or kidney cancers in concentrations occurring in drilled wells.

Case-Control Studies↗

PubMed2002

Studies of strontium biokinetics in humans. Part 2: uptake of strontium from aqueous solutions and labelled foodstuffs.

The accidental release of radioactive isotopes of strontium, mainly (90)Sr, into the environment and its transfer into the biosphere results in an internal radiation exposure of the affected population. In order to obtain reliable estimates of the committed dose due to an intake of Sr radionuclides, reliable information on its metabolic behaviour inside the human body is needed, i.e. biokinetic data on fractional uptake from contaminated foodstuffs, distribution to and retention in different organs and tissues of the human body. Such information can be obtained by tracer kinetic investigations. The committed effective dose is dependent on the fractional intestinal absorption of the ingested activity (f(1) value). The International Commission on Radiological Protection in its publication ICRP 67 adopted an f(1) value of 0.3 for adults. This study is aimed at investigating if the value corresponds with the actual uptake from contaminated foodstuffs. Aqueous solutions and contaminated vegetables, i.e. cress and salad (lettuce) were used as test materials. For this purpose, the methodology for intrinsic labelling of foodstuffs described in part 1 was applied. For aqueous solutions, a mean f(1) value of 0.63+/-0.14 (mean +/- SD) was obtained by administering 1 mg of strontium. The uptake of Sr from cress intrinsically labelled with about 1 mg Sr almost corresponds to that from aqueous solutions (f(1)=0.62+/-0.10), but from lettuce it is reduced by a factor of 2 (f(1)=0.27+/-0.08).

Adult↗

PubMed2006

Transport and fate of radionuclides in aquatic environments--the use of ecosystem modelling for exposure assessments of nuclear facilities.

In safety assessments of nuclear facilities, a wide range of radioactive isotopes and their potential hazard to a large assortment of organisms and ecosystem types over long time scales need to be considered. Models used for these purposes have typically employed approaches based on generic reference organisms, stylised environments and transfer functions for biological uptake exclusively based on bioconcentration factors (BCFs). These models are of non-mechanistic nature and involve no understanding of uptake and transport processes in the environment, which is a severe limitation when assessing real ecosystems. In this paper, ecosystem models are suggested as a method to include site-specific data and to facilitate the modelling of dynamic systems. An aquatic ecosystem model for the environmental transport of radionuclides is presented and discussed. With this model, driven and constrained by site-specific carbon dynamics and three radionuclide specific mechanisms: (i) radionuclide uptake by plants, (ii) excretion by animals, and (iii) adsorption to organic surfaces, it was possible to estimate the radionuclide concentrations in all components of the modelled ecosystem with only two radionuclide specific input parameters (BCF for plants and Kd). The importance of radionuclide specific mechanisms for the exposure to organisms was examined, and probabilistic and sensitivity analyses to assess the uncertainties related to ecosystem input parameters were performed. Verification of the model suggests that this model produces analogous results to empirically derived data for more than 20 different radionuclides.

Adsorption↗

PubMed2002

Mechanisms of desorption of 134Cs and 85Sr aerosols deposited on urban surfaces.

The radioactive isotopes of cesium and strontium may be deposited on urban surfaces in the case of an accidental atmospheric discharge from a nuclear facility and thus imply a health hazard. In order to handle the decontamination of these surfaces, we have carried out experiments under controlled conditions on tiles and concrete and we have studied.the physical and chemical mechanisms at the solid-liquid interface. The deposition of radionuclides was carried out in the form of aerosols indicating an accidental source term. Their desorption by rainwater is low in all cases, of the order of 5-6% for cesium for any material and 29 and 12% for strontium on tile and concrete, respectively. The low desorption values of cesium may be explained by the strong bonding that occurs with the silicates constituting the tile due to virtually irreversible processes of exchange of ions and by the formation of insoluble complexes with the C--S-H gel of concrete. The strontium-tile bonds are weaker, while strontium precipitates with the carbonates of concrete in the form of SrCO3. In view of these characteristics, washing solutions with high concentrations of chloride and oxalate of ammonium chosen for their ion-exchanging and sequestering properties were tested on these surfaces. The desorption of cesium improved strongly since it reached 70% on tile and 90% on concrete after 24h of contact, which is consistent with our knowledge of the; bonds between this element and the surfaces. Strontium, given the greater complexity of physical and chemical forms that it may take is less well desorbed. The ammonium chloride improves the desorption (50% and 40%, for tile and concrete, respectively) but the oxalate, while it does not affect desorption on the tiles, decreases that on the concrete since by strongly etching the concrete, it causes the release of carbonate ions that precipitate with strontium.

Adsorption↗

PubMed1985

Hepatobiliary scintigraphy for cholestasis in congenital hepatic fibrosis. Diagnosis and treatment.

A 9-year-old child with congenital hepatic fibrosis had dilated intrahepatic bile ducts and recurrent cholangitis. Choleretic agents were administered to prevent recurrent cholangitis. Response to treatment was monitored with serum bile acid concentrations and computer-assisted technetium Tc 99m iprofenin (Pipida) scintigraphy. Dehydrocholic acid with meals improved hepatobiliary excretion of the radioactive isotope and lowered serum bile acid levels but did not prevent cholangitic attacks when used alone. Sulfamethoxazole and trimethoprim used alone prevented infection, but a steady rise in serum bile acid concentrations suggested increasing cholestasis. During combined drug treatment, the patient remained free of cholangitis for at least two years. Optimal therapy of congenital hepatic fibrosis with cholestasis but without mechanical biliary obstruction may involve the combined use of a choleretic such as dehydrocholic acid plus a suppressive antibiotic.

Bile Ducts, Intrahepatic↗

PubMed1980

Pheochromocytoma. A persistently problematic and still potentially lethal disease.

Fifty patients with pheochromocytomas have had their conditions diagnosed and have been treated by these authors during a 13-year peneod. Three patients died in the postoperative period, for an overall mortality of 6%. Thirty-two patients underwent primary excision without fatality. Eighteen patients had more complicated illnesses associated with recurrences, notable other disease, acute catecholamine crisis, and/or pregnancy. All three postoperative deaths occurred in this group. Diagnosis was made by urinary catecholamine analysis of epinephrine, norepinephrine, metanephrine, and normetanephrine. Localization was done by plain films, ultrasonograms, computerized tomograms, radioactive isotope scans, intravenous pyelograms, caval samples, venograms, and arteriograms. Management of these complicated cases requires prompt and accurate diagnosis, availability of sophisticated methods of tumor localization, and thoughtful awareness of the potential outcome by an experienced team of surgeons and anesthesiologists.

Acute Disease↗

PubMed1997

Interstitial implantation techniques in prostate cancer.

Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance.

Aged↗

PubMed1998

Brachytherapy in lung cancer.

Brachytherapy, the direct application of a radioactive isotope into the tumor bed, delivers a high dose to the tumor as compared to the surrounding normal tissue. Interstitial brachytherapy, the placement of the isotope into a tumor bed where no lumen exists, has been described but is utilized infrequently in clinical practice. Endobronchial brachytherapy, the placement of the source within the airway lumen, as a boost to conventional external beam radiation has not yet demonstrated improved local tumor control or overall survival as compared to external beam alone in the definitive treatment of inoperable lung cancer. In the palliative setting, brachytherapy can provide prompt relief of obstructive symptoms and hemoptysis in the majority of patients.

Brachytherapy↗

PubMed1996

Prostate specific antigen findings and biopsy results following interactive ultrasound guided transperineal brachytherapy for early stage prostate carcinoma.

BACKGROUND: Interactive, transrectal, ultrasound-guided transperineal implantation is a new technique for performing permanent brachytherapy implants of the prostate. Prostate specific antigen (PSA) findings, biopsy results, and morbidity are examined to demonstrate its efficacy and safety in treating early stage prostate carcinoma. METHODS: Ninety-seven patients underwent permanent implants for classifications T1 to T2 adenocarcinoma of the prostate gland with a median follow-up of 18 months (range: 6-51 months). Seventy-nine patients had negative laparoscopic pelvic lymph node dissections prior to implantation. Patients with positive lymph nodes were not implanted. The radioactive isotope used was I-125 in 71 patients and Pd-103 in 26 patients. RESULTS: PSA failure was defined as two consecutive increases in PSA above the nadir level. The actuarial freedom from PSA failure (FFPF) at 2 years was 76% for the entire group. Stage significantly affected FFPF. Patients classified as T1b to T2a (35) had a FFPF of 91% at 2 years compared with 68.5% for patients classified as T2b to T2c (62) (P = 0.04). The pre-treatment PSA also significantly affected FFPF. Patients with PSA values of < or = 10 ng/mL (44) had a FFPF of 83% at 2 years. A similar rate of 82% was found in patients with PSA values of 10.1 to 20 ng/mL (29). Patients with PSA values > 20 ng/mL (24) had a significantly poorer FFPF at 2 years of 58% (P = 0.02). The PSA values of patients free from a PSA failure (82) ranged from 0.1 to 12.9 ng/mL with a median of 0.8 ng/mL. Transrectal prostate biopsies were performed 18 to 36 months posttreatment in 39 patients. Negative biopsies were found in 74% (29/39) of cases. The procedure was associated with an actuarial preservation of erectile function rate and sexual potency at 2 years of 96% and 79%, respectively. There were no cases of urinary incontinence or radiation cystitis. Associated morbidity included urinary retention requiring catheterization in 4% of the patients, outlet obstruction requiring a transurethral resection of the prostate in 2% and Grade 2 rectal complications in 1%. CONCLUSIONS: Interactive, ultrasound-guided transperineal brachytherapy results in a low PSA failure rate, high negative biopsy rate, and is associated with low morbidity and preservation of erectile function.

Adenocarcinoma↗

PubMed1998

Snapback SSCP analysis: engineered conformation changes for the rapid typing of known mutations.

Several approaches may be applied to detect known mutations, including restriction enzyme cleavage, allele-specific oligonucleotide (ASO) hybridization or amplification, dideoxy fingerprinting, and direct DNA sequencing. All these approaches require several extra steps after PCR and may involve radioactive isotopes, time-consuming hybridization, template purification, or digestion steps. The ease and simplicity of the SSCP test make it a popular choice for mutation detection, but a significant limitation is that some DNA changes will not alter the overall conformation of either single strand and are thus not amenable to SSCP typing. We describe Snapback SSCP to genotype normal and mdx mice (an animal model of Duchenne muscular dystrophy) that previously could not be differentiated by conventional SSCP analysis. A snapback primer was designed with additional bases at the 5' terminus, which were complementary to the normal sequence flanking the mdx mutation and used under the original amplification conditions. Each single strand of these snapback PCR products now had one terminus capable of re-annealing or "snapping back" to the normal sequence but not the mdx mutation. In this manner, a conformation change was engineered into the normal strand that could be readily distinguished from the mdx allele on a SSCP gel. This approach could be applied to the routine screening of other known mutations that are not amenable to detection by simple SSCP analysis.

Animals↗