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The development of pre-implantation mouse embryos was found to be prevented by exposure of the embryos to [35S]methionine, but not to [3H]methionine. Such embryos have also been shown to be highly sensitive to [3H]thymidine. These observations are discussed with reference to the path lengths and energies of electrons emitted from the different radioisotopes.
In addition to the usual parameters for haematologic an rheumatologic diseases folic acid, vitamin B12, and ferritin were investigated by radioisotope studies. In some groups folic acid was lower compared to controls, and it is possible that the disease causes the deficiency of folic acid absorption and distribution. Vitamin B12 was only slightly decreased, thus, the values may be assumed to be close to normals. Transferrin ankylosing spondylitis is similar to that of controls, however, transferrin increases in rheumatoid arthritis and in mixed groups containing patients various diseases. Finally, the deficiency of folic acid absorption can be assumed to be caused by the symptoms of the disease, whereas in the case of inflammatory diseases and in mixed group transferrin increased.
A double radioisotope derivative method was developed for the determination of clomipramine and desmethyl-clomipramine in plasma or urine. After addition of 14C-labeled clomipramine and desmethyl-clomipramine as internal standards and extractive isolation of both compounds, desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is separated from clomipramine by thin-layer chromatography and its radioactivity is measured. Clomipramine, extracted from the cilica gel, is reacted with trichloroethyl chloroformate. The urethane is saponified and decarboxylated. The resulting desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is purified by thin-layer chromatography and its radioactivity is measured. The sensitivity of the method is 15 mug/liter for clomipramine and 2 mug/liter for desmethyl-clomipramine. Its specificity was made sure by a cross-check with a gas chromatography-mass spectrometry technique.
The diagnostic value of the parallel investigations between the biochemical indices and radioisotope methods were followed up in the determination of the functional state of the thyroid gland. Ninety five patients were examined, subdivided into 5 nozological groups: 15 toxic adenomas with warm decompensated nodules; 20 mixed goiters with mainly warm nodules; 20 mixed goiters with typical sctintigraphic findings of the mixed goiter; 20 mixed goiters with cold nodules; 20 patients with Basedow's disease. The statistical assessment is according to the methods of variation correlation and alternation analysis. The correlation between the radiosiotope and biochemical methods is significant. Highest is the correlation coefficient between PBI and ETR in all groups discussed, especially in the group of toxic adenomas. The examination by capsules and medicamentosus treatment in advance diminishes the coefficient of correlation between. The importance of thyreoscintigraphic investigation is stressed upon as the basic topographic and functional method.
The radioisotope 195Aum because of its short halflife of 30 seconds and reduced radiation exposure allows routine first pass examinations in two oblique projections, i.e. right anterior and left anterior oblique. The value of the additional left anterior oblique projection has been examined in 30 patients after previous myocardial infarction by functional imaging in two oblique projections. The multicrystal gamma camera connected with a microprocessor and a contrast injector have been used. For assessment of left ventricular function the following functional images have been adopted: the regional ejection fractions (rEF), the regional ejection rates (rEJR) and the regional mean transit times (rMTT). The right anterior oblique view resulted diagnostic for miocardial infarction in 26 of 30 patients (86,6%). The left anterior oblique view was informative with respect of septal extension 17 times (58,6%), lateral extension 9 times (31%), septal and lateral extension 3 times. With regard of the different functional images the rMTT showed the severe dysfunction in the infarcted zones in all patients (100%), the rEJR in 29 patients (96,6%), the rEF in 28 cases (93,3%). In 4 cases dyskinesia was observed, twice in the left anterior oblique view and also twice in the right anterior oblique view. In patients with previous MI it is necessary to record the second left anterior oblique projection which can be done routinely by the use of 195Aum and first pass technique. On functional images, maximum information is obtained by the rMTT which visualizes the zones of severe dysfunction and its extension.
The results are reported from the radioisotope investigations of the regional blood supply, ventilation and difussion of 133 Xenon from four zones of both lungs in 78 patients with all stages of silicosis and 43 patients with chronic bronchitis--emphysema. Unsystemic and scattered focal disturbances of the separate respiration processes are established. They should be given consideration separately and together with the classical non-isotope investigations, with a view to the making of a precise functional diagnosis and occupational expertise, because they reflect the changes due to the basic disease as well as the other accompanying lung diseases as pneumosclerosis, chronic bronchitis, emphysema, tumors, etc. The complete safety, lack of unpleasant procedures for the patient and sufficient accuracy urge their wider application in practice, including as screening tests.
A survey of the use of radioisotopes for research into the vitreous and the zonule is presented. gamma-Rays emitting isotopes are useful for the investigation of transport and diffusion of substances, while 3H-thymidine is the substance of choice for the investigation of cell kinetics. The formation of the vitreous and the zonule during and after embryonal development can be studied by histoautoradiography using labelled precursors of collagen and aminoglycans. Cell kinetic investigations shows that the cells usually found in the vitreous are macrophages which have migrated into the eye. Therefore the existence of a specific vitreous cell is unlikely. The development of the zonule can be readily traced by histoautoradiography which shows that it is neither topographically nor temporally related to regression of the primary vitreous. The incorporation of cystine and glucose into the zonular fibers is of special interest. This suggests that the zonular fibers are not made up of normal collagen; they may consist of some sort of procollagen which is perhaps secreted by the ciliary epithelium.
Radioisotopic study of platelet kinetics can provide a preliminary orientation in the diagnosis of thrombocytopenia. A study of the platelet kinetics in thrombocytopenic and normal subjects using the Cr51 isologous platelet labelling technique and subsequent in vivo injection of the labelled platelets was conducted. The results obtained confirm the reliability and usefulness of the technique. The identification of the limitations involved and the recognition of their significance in processing data allows the hematologist and the general practitioner to allow the right amount of room for the study of platelet kinetics in the diagnosis of thrombocytopenia.
A technique is described in which the mean circulation (transit) time of each hemisphere is determined by means of an intravenous radioisotope technique. A sharp bolus of a rapidly excreted I131 labeled compound is released from an antecubital vein. The time of entrance into the brain blood pool of the densest portion of this bolus is determined by plotting the first derivative of the amount of isotope seen in the brain by a paired external collimation-detection system. The time of exit of the densest portion of the bolus is also similarly determined. The interval between the entrance and exit represents, we believe, the mean cerebral transit time. In 15 normal males transit times were obtained between 6.5 and 10 seconds. The test is virtually painless, repeatable, and exposes the patient to minimal radiation.
This report describes the results of a vitamin B12 study among ninety normal healthy school children using commercial radioisotopic dilution assay kits. Values obtained in this study are higher than those obtained in previous study by the microbiological assay using L. leichmannii as the test organism. These high values render the commercial kit unsuitable in its present form in the diagnostic process of liver and related diseases where serum vitamin B12 are significantly elevated. Some dilution of the serum will be essential if the commercial kits are to prove useful among populations with normal high vitamin B12 concentrations.
A radioisotope dilution (RID) method for the determination of vitamin B12 is presented. The method combines a standard extraction procedure (AOAC 43.108, 12th ed.) with a commercially available RID assay kit. The method was evaluated on a wide range of fortified and unfortified food products. Recovery studies on both groups yielded average recoveries of 98.1 and 95.8%, respectively. Reproducibility data generated from replicate analyses on both groups gave a relative standard deviation of 6.9% for the fortified group and 9.2% for the unfortified group. For the samples studied, the mean vitamin B12 content determined by the RID method was 8.01 micrograms/100 g vs a mean of 7.54 micrograms/100 g by the AOAC microbiological method; the correlation coefficient was r = 0.983.
An original radioisotopic method was employed in an investigation of the effect of sulpiride on extrahepatic bile duct motility. Stress is laid on the primarily hyposthenic effect of the drug, and the influence of various factors on the functional status of the gallbladder.
No single radioisotopic exploration is capable of detecting metastases of malignant melanomas, but the successive use of three different scintigraphic techniques (liver, bone and 67Ga citrate) has increased the detection rate from 55 to 68%. Since these metastases are small and may develop anywhere in the body, several methods must systematically be combined, particularly when one of them gives normal results. Experience has shown that 13% of metastases would have passed unnoticed if the three scintigraphic techniques had not been used.
Our study in unselected patients with diabetes was undertaken to determine the relation between glomerular filtration rate (GFR) and renal plasma flow (RPF) according to the patient's age. The diagnostic work-up was done with patients in unselected disease states because a classification of all systemic manifestations of the diabetes was not possible. The lack of selection may therefore reduce the value of our statistical results. From age 55 onwards, there was a reduction in GFR and, to a lesser extent, in RPF exceeding that which was age-dependent. It is, therefore, recommended to check the clearance in all patients with diabetes older than 55 years. The clearance with radioisotopically labeled substances, being a very sensitive method for the evaluation of restricted renal function, may permit an early recognition of diabetic nephropathy.
Radioisotope functional investigations of the thyroid gland were carried out with weaned lambs and pigs. The 131I captation capacity of the thyroid gland was studied to characterize the inorganic phase of iodine exchange. The evaluation of the hormone producing function of the thyroid gland required the determination of the level of the protein-bound 131I (PB 131I), T3-binding capacity of the thyroxin-binding globulin (TBG) and the ratio of the T3-binding capacity of TBG and the free thyroxin (T4) calculated as the FT-4 index. Established was the species peculiarity of the 131I captation capacity of the thyroid gland in weaned lambs and pigs in the early phases of investigation. At the 2nd hour the percent captation was calculated as 7.2 +/- 0.8 and 1.11 +/- 0.21 per cent, respectively. The values of PB 131I, T3-binding capacity of TBG and FT-4 of pigs varied within the limits of 1.20 +/- 0.05 per cent, 0.605 +/- 0.012, and 0.976 +/- 0.015 and of weaned lambs they were 0.954 +/- 0.009 per cent, 0.912 +/- 0.017 and 0.890 +/- 0.03. The differences in the investigated indices for the two animal species a L = 0.05 were statistically significant.
Immune response in WKA rats immunized with methylcholanthrene-induced KMT-17 tumor was measured by radioisotopic footpad assay. The assay was specific, quantitative, and objective compared with the ordinary method of measuring the thickness of footpads. The strongest footpad reaction was observed 24 hr after injection of the antigens. The reaction was transferred by lymphoid cells but not by serum. These results indicate that the footpad assay manifests delayed-type hypersensitivity to tumor antigens. In order to obtain more reliable antigen preparation for the footpad assay, antigens prepared by several methods were compared. Solubilized antigen extracted with sodium deoxycholate (DOC) showed the strongest reaction in the immunized host and weak reaction in the control non-immunized host. This marked difference between the immunized and control groups indicates that DOC-extracted antigen was better antigen than tumor cells treated with mitomycin-C (40 microgram/ml), formaldehyde solution (0.2%, 0.01%), X-irradiation (3,500, 10,000 rad), non-treated whole-cell antigen, crude membrane, cell homogenates, or antigens extracted by hypotonic sonication and 3M KCl method. The DOC-extracted antigen was well preserved at -20 degrees for 1 month.
The Japan Radioisotope Association (JRIA) is established as a nonprofit organization operated by the users with the purpose of facilitating the utilization of RI. Its major activities include academic activities, supplying RI, labeled compounds and radiopharmaceuticals, and collecting and treating radioactive wastes. All RI, 90% of which is radiopharmaceuticals, are distributed through JRIA. The growing rate of radiopharmaceuticals is now getting slow, and RIA has a tendency to be replaced by nonradioactive assays. Nishina Memorial Cyclotron Center is to be operated for cooperative research projects of all institutions in Japan. Kaya Memorial Takizawa Laboratory is established to treat all medical radioactive wastes.
The possibility that the unreliability of urinary excretion of radioactivity after the administration of oral 131I-triolein, as a measure of fat absorption, is due to variable renal clearance of iodide prompted investigation of a double-radioisotopic method. Intravenously administered radioiodide should be cleared identically with radioiodide split from absorbed fat and serve as an internal standard. Oral 131I-triolein was given in an 80 gm fat liquid meal; 125I-iodide was given intravenously; urine was collected fractionally for 72 hr. Accepted stool fat excretion data and stool radioactivity excretion data developed in this study were used to define groups of normals (less than 5.4 gm of fat or less than 7.8% 131I) and malabsorbers (greater than 5.4 gm of fat or greater than 7.8% 131I). In 26 normals urinary 131I ranged from 24.6% to 77.1% in 48 hr and 27.7% to 86.8% in 72 hr; in the malabsorbers these values lay between 0.6% and 62.8% in 48 hr and 1.0% and 66.8% in 72 hr, showing much overlap with normal. An index of the cumulative percentage of urinary 131I/125I X 100 at either 48 or 72 hr completely separated the groups, the index in normals ranging from 68.7 to 100 in 48 hr and 72.5 to 100 in 72 hr, whereas the malabsorbers varied between 2.0 and 64 in 48 hr and 2.2 and 67.5 in 72 hr.