Joseph Sternberg

Radiation and pregnancy.

Irradiation during pregnancy may occur either as the result of radioactive pollution of the environment, or during a medical procedure using x-rays or radionuclides. While the former is usually unforeseeable, the latter is known and accepted by both physician and patient.

Metabolic studies with seleniated compounds: I—Kinetic studies with Se75O3 in rats☆☆☆

Abstract Trace amounts of Se 75 O 3 Na 2 were injected intravenously into adult female rats and the blood dynamics, excretion pattern, body burden and distribution in the subcellular fractions of the liver were examined between 15 min and 75 hr after injection. In blood, selenite is very rapidly bound to the plasma proteins, which act as carriers of the trace element as well as final products of the metabolic incorporation of the isotope. The albumin-bound Se 75 prevails in the carrier phase, while during the elaboration phase the isotope is chiefly bound to the α and γ globulins. The binding in the carrier phase seems to be of the anionic selenite-basic endings of the serum proteins and can be reproduced in vitro , although to a lesser extent than in vivo . A significant amount of Se 75 is exhaled through the lungs during the first 30 min after injection; this is related to the transmethylation of selenite and the formation of the volatile compound Se(CH 3 ) 2 . The phenomenon takes place chiefly within the liver microsomes, and could be taken as an index the of liver function, since experimental modification of the liver capacity result in a modification of the rate of lung excretion of di-methyl selenide. The kidney is the most important excretion route for selenite; there is little faecal excretion only during the first 24 hr after injection. The biliary excretion of selenite is also less important than the urinary elimination; the isotope does not seem to be bound to the common biliary salts. There is little resecretion of selenite through the digestive tube. In the subcellular fractions of the liver, selenite is equally distributed among nuclei, mitochondria and microsomes; the largest fraction remains in the soluble liver compounds and is rapidly excreted through the kidney; the soluble Se 75 in the liver is not bound to the proteins.

Metabolic studies with seleniated compounds—III. Lung excretion of selenium 75 and liver function☆

Abstract Lung excretion of volatile seleniated compounds is linked with the transmethylation process and the subsequent binding of methyl groups to selenium, in order to form dimethyl selenide; this occurs with selenite but not with selenomethionine or selenocystine. Intravenous injection of selenite is followed by rapid exhalation of dimethyl selenide; the excretion curve is diphasic, with an initial rapid phase followed by a slower component. The amount of exhaled compound is not influenced by administration of methyl donors, but increases after a high protein diet; sub-total hepatectomy induces a slowing down of the first phase of excretion, but the phenomenon disappears rapidly with regeneration of the liver. Stimulation of liver enzymes by phenobarbital produces an increase of lung excretion of dimethyl selenide, while neither inhibition of ribosomal enzymes (by SKF-525 A) nor administration of ethionine influences the rate of exhalation. Administration of toxic doses of selenite results in a diversion of the methyl groups to meet the metabolic challenge and to provoke a considerable acceleration of the liver transmethylation process, at least with regard to the organification of selenite; stimulation with phenobarbital results in a further acceleration, while administration of ethionine is followed by a marked slowing down of the phenomenon. These findings suggest a shift in the transmethylation process in cases of metabolic emergencies; it is not known whether the shift occurs at the expense of the other pathways of transmethylation, especially the proteins and phospholipids. The procedure could be developed into a clinical test of the lipotropic function of the liver, provided that a less toxic compound is employed.

Metabolic studies with seleniated compounds: II—Turnover studies with Se75-methionine in rats☆☆☆

Abstract Tracer amounts of Se75-methionine were injected intravenously into adult female rat and the turnover of labeled plasma proteins as well as the distribution of the isotope in subcellular fractions of the liver were studied between 5 min and 6 hr after administration. Plasma proteins incorporate rapidly the labeled amino-acid; the largest amount of Se75 was found in the α globulin, followed by the γ globulin. The rate of incorporation remains unchanged in animals with sub-total hepatectomy, and even in those with total hepatectomy; moreover, a small proportion of seleno-methionine is bound to plasma proteins after incubation in vitro with total blood. These results suggest that the biosynthesis of plasma proteins can take place by transpeptidation between the circulating proteins and the free amino-acids; this does not preclude the template assembly of amino-acids on the ribosome, but offers the possibility of both mechanisms acting simultaneously in some cases. Supplementary evidence is offered by the fact that the microsomal fraction of the liver did not exhibit any significant increase of Se75 during the period of time when the amino-acid is supposed to be bound to the ribosome, but not yet released into the circulation. It is not established whether the mechanism of transpeptidation is quantitatively important, and also whether it is peculiar to selenomethionine or a more generalized phenomenon. There is no pulmonary excretion of Se75 after intravenous injection of Se75-methionine, in contrast to the significant lung excretion of isotope after administration of selenite; the main excretion route of seleno-methionine is the kidney; fecal and biliary excretion are lower during the first 6 hr after administration. The highest differentiation between pancreas and liver is obtained in rat at 3 hr after injection of Se75-methionine, while the highest difference between pancreas and blood occurs at 1 hr after injection. Thus, if animal results can be extrapolated to humans, it might be advisable to make an early scanning in cases of severe pancreas congestion.

Effect of tetracyclines on the turnover of calcium-45 in young rats.

Abstract Trace amounts of Ca 45 were administered parenterally to young rats, and the turnover of bone calcium was determined in control animals as well as in animals treated with an antibiotic of the tetracycline family. In tibias of control animals, the pool of rapidly exchangeable calcium represents 12.36 percent of the total calcium; the accretion and the resorption rate average 6.79 mg/day and 5.86 mg/day respectively, with a net growth of 0.94 mg/day for the duration of the experiment. Administration of antibiotic in therapeutic or in higher doses, for short or long periods, remained without any detectable effect on the kinetics of Ca 45 , or on the distribution pattern of the isotope in the tissues and fluids of the animals. The amount of calcium incorporated into the accreted bone in combination with the antibiotic represents only 0.1 percent of the total calcium turned over in 24 hr by the same organ. This insignificant proportion does not offer any biochemical evidence to the clinical reports of inhibition of bone growth in infants treated with tetracyclines.

Studies in placental permeability. Transmission of poliomyelitis antibodies, lipoproteins, and cholesterol in single and twin newborn infants.

I N PKE VI0 U s papers, we have compared the electrophoretic pattern in parturient and cord blood in normal and in pathological pregnancies1 There is a significant increase of the relative level of fetal y globulin as compared to the maternal y globulin level. This relative hypergammaglobulinemia of the newborn has been considered as an indication of its physiologic maturity. Transfer of the maternal y globulin to the fetus starts toward the sixth month of the pregnancy; its rate is different from that of the other serum proteins. Indeed, whereas the albumin and the other fractions are transferred at approximately the same rate throughout the last trimester, the rate of transfer of the y fraction is very low at the beginning (16 to 20 per cent of the maternal value), but it increases sharply and reaches the maternal level during the eighth month; the fetal level then exceeds the maternal level, so that at term the ratio of fetal/maternal y globulin is 1.35-1.50.

Irradiation and radiocontamination during pregnancy.

THE IN J u RI E s provoked by ionizing radiation during the early stages of life have been extensively studied; it is not within the scope of this review to repeat these wellknown facts. Our chief purpose is to familiarize the practicing obstetrician with the incidences and the consequences of a voluntary or inadvertent application of a radiation procedure to a pregnant woman. With the spectacular development of nuclear medicine, these instances are bound to occur more frequently in the near future; also, the widespread use of nuclear energy for industrial purposes will lead to situations in which pregnant women will be exposed to accidental environmental radiocontamination.

Radiocontamination of the environment and its effects on the mother and fetus: I—Classification of fission products and neutron-activated elements according to their rate of placental transfer☆

Abstract Intra-uterine irradiation of the fetus can be an important factor in the pathogenesis of embryopathies. Fetal irradiation occurs either by direct action of electromagnetic radiations on both mother and fetus, or by internal contamination of the mother, followed by systemic distribution of the radiocontaminant and subsequent placental transfer and fetal uptake. Fission products or activated elements can be divided into different categories, according to their respective rate of placental transfer: there is free transfer for natural metabolites and probably for inert gases and perhaps some discrimination for the periodic relatives of natural metabolites. The colloidal forms of rare earths do not cross the placenta. A large proportion of fission products is constituted by non-metabolites, whose metabolic fate and placental transfer are unknown. Fetal uptake of fission products is presently limited, especially the variation of tissular concentration in function of the age of the embryo. There is no evidence that, for a given radiocontaminant, embryo and fetus have the same critical organs as adult tissues. The damaging effect of the radiocontaminant in embryonic tissues is probably different from that produced by the same amount of radioactive element in adult tissue, due to the difference in radiosensitivity and also to the different metabolic profile of the cells. The study of the effects of radiocontaminants on fetus is an urgent problem, in view of the impending development of peaceful uses of nuclear energy. An indirect method of approach is the determination of the retention of radiocontaminants by human placentas, obtained from deliveries in different geographic areas of the world. Cesium-137 is the first contaminant of interest; in placentas obtained from normal deliveries of the Montreal area, preliminary measurement indicated a retention of Cs 137 in the placentas similar to that calculated from the total-body burden obtained in the literature. No determination was made on placentas of inhabitants of Canadian northern regions. Further studies are needed in this direction, chiefly a world-wide determination of placental retention of Cs 137 , related to the dietary habits and chiefly to the degree of radiocontamination of the geographic area where the placentas were obtained.

Radiocontamination of the environment and its effects on the mother and fetus—III: Part I—Retention of cesium 137 during pregnancy: An inter-laboratories study☆

Abstract The determination of cesium 137 and strontium 90 in human placments was carried out in different laboratories in Japan and Canada, in order to standardize the radioassay procedures. Placentas from normal term deliveries were collected and measured for a period of 12–16 months in the Tokyo and Osaka areas in Japan and in the Montreal area in Canada. Two procedures required the ashing of the entire placenta prior to radioassay. In the Tokyo group, the ashed organ was placed in a two NaI crystal system, in an almost 4π geometry, and the γ radiation was measured. The Osaka group continues the chemical separation of cesium by precipitation with chloroplatinate; the β radiation is then further measured with an anticoincidence system. These procedures are not adequate for a large series of measurements, since the ashing of the placenta is time-consuming and frequently leads to errors due to loss of material during the ashing. Another procedure avoids the ashing and compresses the fresh placentas to a semi-dry cake; the method is more rapid and avoids losses of radionuclides or radiocontamination during the manipulation. The samples are then measured in a two NaI crystal system, with a geometry close to 4π. The average content of cesium 137 is closely similar in Japanese and Canadian placentas, regardless of the differences in the dietary habits and potassium intake in the two racial groups. However, some organs exhibit a markedly higher level, sometimes 3–4 times the average of 23–24 μμCi/kg tissue; even at this concentration, the total amount of placental cesium 137 accounts for only a small fraction of the irridiation produced by potassium 40 in the same organ. The amount of absorbed energy produced by both radionuclides is well below the danger level. These data compare well with the former measurements in placentas obtained from women of the Hiroshima region, some of whom had been in that city during the war.

Teaching nuclear medicine. An educational experiment at the University of Montreal

Abstract Nuclear Medicine has been introduced in the curriculum of the Faculty of Medicine of Canadian and American universities; the presence of a chair is necessary, but that of a department is not compulsory; fundamental notions and technical data are being offered within the framework of other departments, chiefly within the basic sciences. Graduate studies lead to the obtention of an M.Sc. or Ph.D. degree in Nuclear Medicine, with an intensive program; however, the post-graduate teaching is the most stringent need at present, until the new generations of physicians will start to practice.