Juvenile hypothyroidism among two populations exposed to radioiodine.

We found an epidemic of juvenile hypothyroidism among a population of self-defined "downwinders" living near the Hanford nuclear facility located in southeast Washington State. The episode followed massive releases of 131I. Self-reported data on 60 cases of juvenile hypothyroidism (<20 years of age) among a group of 801 Hanford downwinders are presented, as well as data concerning the thyroid status of approximately 160,000 children exposed to radioiodine before 10 years of age as a result of the 26 April 1986 Chernobyl explosion in the former Soviet Union. These children were residents of five regions near Chernobyl. They were examined by standardized screening protocols over a period of 5 years from 1991 to 1996. They are a well-defined group of 10 samples. Fifty-six cases of hypothyroidism were found among boys and 92 among girls. Body burdens of 137Cs have been correlated with hypothyroidism prevalence rates. On the other hand, the group of juvenile (<20 years of age) Hanford downwinders is not a representative sample. Most of the 77 cases of juvenile hypothyroidism in the Hanford group were diagnosed from 1945 to 1970. However, the ratio of reported cases to the county population under 20 years of age is roughly correlated with officially estimated mean levels of cumulative thyroid 131I uptake in these counties, providing evidence that juvenile hypothyroidism was associated with radioiodine exposures. Because even subtle hypothyroidism may be of clinical significance in childhood and can be treated, it may be useful to screen for the condition in populations exposed to radioiodine fallout. Although radiation exposure is associated with hypothyroidism, its excess among fallout-exposed children has not been previously quantified.

Somatic mutations at the glycophorin A (GPA) locus measured in red cells of Chernobyl liquidators who immigrated to Israel.

Glycophorin A (GPA) assays for human erythrocytes with gene expression loss and duplication phenotypes (NO, NN) were carried out on 15 Chernobyl clean-up workers (liquidators) who immigrated to Israel within the preceding 5 years, 19 local Israeli controls, and 14 Russian (nonliquidator) immigrants. GPA phenotype variants in red blood cells of the 15 liquidators showed values ranging from 1 to 101 events/10(6) cells, with a mean +/- SD of 25.6 +/- 7.0. In comparison, the 19 Israeli controls had values ranging from 0 to 13 GPA events per 10(6) cells, with a mean +/- SD of 3.9 +/- 0.8. The difference was highly significant (p < 0.001). Another group of 14 volunteer control subjects (nonliquidators) who had emigrated from the former Soviet Union to Israel during the past 5 years showed values ranging from 0.0 to 35.0 events per 10(6) cells, with a mean +/- SD of 6.1 +/- 2.7. The difference between this group and the liquidator group was significant at p < 0.01. The results are compatible with past exposure to radiation in the group identified as liquidators.

Thyroid-stimulating hormone levels in children from Chernobyl.

This study assesses parameters of thyroid function in persons who resided in Ukraine, Belarus, and southern Russia and exposed at 0 to 16 years of age to radioiodine contamination from the Chernobyl accident. Six to eight years after the accident a group of 300 young people who had immigrated to Israel were interviewed, underwent physical and ultrasound thyroid examination, and had their serum tested for thyroid-stimulating hormones (TSH), thyroid hormones, thyroglobulin, and antithyroid antibodies. Comparative groups came from areas with high (>1 Ci/km2) or low (< 1 Ci/km2) 137Cs ground contamination. Girls from high contamination areas, when compared to girls from areas with low ground contamination, showed significant upward shifts in levels of serum TSH (p = 0.023) although remaining within normal limits. Boys showed no significant differences. There was no evidence for differences in thyroid size or nodularity between the two groups of girls. A working hypothesis is proposed by which the shift in TSH levels in girls from high radiocontamination areas was associated with subclinical radiation damage from environmental radioiodine at the time of the accident.

Lessons learned from the study of immigrants to Israel from areas of Russia, Belarus, and Ukraine contaminated by the Chernobyl accident.

During the past 6 years, immigration to Israel of 700,000 persons from the former Soviet Union (FSU) included about 140,000 from radiocontaminated regions of Belarus, Ukraine, and Russia near Chernobyl. In Beer Sheva, a major center for immigrant absorption in Israel, a primary objective was to evaluate their health status and to refer them for care. 137Cs levels in 1228 men, women, and children were measured with a portable whole-body counter. Whole-body counts showed clear correlation with the degree of 137Cs ground contamination in previous regions of residence. The population could thus be sub-divided according to degree of exposure, based on previous regions of residence. The thyroid status of 300 local immigrant children was evaluated because of the increased risk of childhood thyroid cancer in the regions from which they came. This group was subdivided into comparative groups of children who came from less and more contaminated areas according to the International Atomic Energy Agency soil 137Cs contamination maps. Enlarged thyroids were found in about 40% of both groups. One 12-year-old girl from Gomel had a malignant papillary carcinoma. Thyroid-stimulating hormone levels, though within normal limits, were significantly greater (p < 0.02) for girls from high exposure regions. Liquidators showed significant increases in serum clastogenic factor and in the number of circulating glycophorin A-mutated red cells. In studies of over 700 people from both radiocontaminated and unaffected regions of the FSU, evidence for posttraumatic stress disorder was found more frequently in persons coming from the more contaminated areas.

Incidence of childhood disease in Belarus associated with the Chernobyl accident.

Study of the childhood incidence of cancer and other diseases in Belarus is of great importance because of the present unfavorable environmental situation. About 20% of the children in the republic were exposed in various degrees to radiation as a result of the Chernobyl accident. Since 1987 increases in the incidence of most classes of disease have been reported, including the development of thyroid cancer. From 1987 to 1995, thyroid cancer was diagnosed in 424 children; its incidence having increased from 0.2 to 4.0/10(5) in 1995. According to preliminary data for 1996, 81 childhood cancer cases were reported. During 1995 there also were increases in the incidence of endocrine and dermatologic diseases and mental disorders. During the period 1987 to 1995 significant increases in the incidences of all illnesses were observed for children listed in the Chernobyl registry. The highest incidence rates were found in evacuated children and those residing in contaminated areas. There also were increased incidences of thyroid and digestive organ diseases among these children and in addition, high prevalence of chronic tonsillitis and adenoiditis was observed. Since 1990 an increase of autoimmune thyroiditis has been observed. The highest rates of hematopoietic tissue diseases were found in children born after the accident to irradiated parents.

Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction.

BACKGROUND: The exact amount of drug deposited in the respiratory and gastrointestinal tract in children with airway obstruction, when delivered from a metered-dose inhaler (MDI) via a spacer with mask, and its distribution in children with airway obstruction, are unknown. METHODS: We studied 15 children, using salbutamol labeled with technetium 99m. Each patient was imaged with a gamma-camera immediately after one puff of labeled salbutamol was administered via a spacer with mask. Drug deposition was then analyzed to measure the distribution of the labeled spray in the oropharynx, the lungs, the stomach, and the spacer with mask (Aerochamber) itself. RESULTS: Fifteen infants and children (mean age, 21 months (range, 3 months to 5 years); mean weight, 9.3 kg (range, 3.2 to 15 kg)) were studied. Mean aerosol deposition was 1.97% +/- 1.4% in the lungs, 1.28% +/- 0.77% in the oropharynx, and 1.11% +/- 2.4% in the stomach. The remainder was trapped in the spacer. Lung imaging after inhalation from an MDI via a spacer showed widespread deposition of the drug in central and peripheral intrapulmonary airways. In two adult volunteers the deposition after one puff of the same radiolabeled drug, inhaled from an MDI via a spacer with a mouthpiece, was 19% in the lungs and 2% in the stomach. CONCLUSIONS: Infants and toddlers with obstructive lung disease can be reliably and safely treated with inhaled medication administered with an MDI via a spacer with mask. The doses of a drug given from an MDI to infants and toddlers when a spacer with mask is used are not yet well defined but should be higher than the currently recommended doses, perhaps as much as an adult dose.

Health effects in a casual sample of immigrants to Israel from areas contaminated by the Chernobyl explosion.

We analyzed questionnaire and physician examination data for 1560 new immigrants from the former USSR divided into three groups by potential exposure to Chernobyl radiation. Two groups were chosen according to soil contamination by cesium-137 at former residences, as confirmed by our findings in a 137Cs body burden study. The third group consisted of "liquidators," persons who worked at the Chernobyl site after the disaster. Liquidators had greater self-reported incidences of symptoms commonly accepted as acute effects of radiation exposure, increases in prevalence of hypertension, and more health complaints. Excesses of bronchial asthma and health complaints were reported in children from the more exposed communities. Asthma prevalence in children potentially exposed in utero appears to be increased eightfold. Older adults from more exposed areas had more hypertension as assessed by history and measurements. These findings suggest the possible association of radiation exposure with several nonmalignant effects.

Radiocesium body burdens in immigrants to Israel from areas of the Ukraine, Belarus and Russia near Chernobyl.

Of the 500,000 immigrants from the former Soviet Union who came to Israel during 1990-1993, about 100,000 are estimated to have come from radiocontaminated areas near Chernobyl. These people were subject to chronic uptake of environmental radiocesium over protracted periods. During October-November 1991, a joint Israeli-Canadian investigation measured radiocesium body burdens in immigrants to Israel from the Ukraine, Belarus, and the southern Russian republic in order to provide factual information on radiocesium levels to concerned immigrants and to relate the body burdens to the geographic area of residence before coming to Israel. Assessments were made of 137Cs body burdens in 1,228 volunteer men, women, and children. These measurements were accompanied by medical assessments based on clinical histories and examinations. Radiocesium levels were strongly dependent on the duration of residence in Israel, with the highest levels being found in the most recent immigrants. The maximum level, extrapolated back to the time of leaving the former Soviet Union, was estimated to be about 0.83 kBq (10.3 Bq kg-1). Of the most recent immigrants from the Kiev region (< 101 days in Israel), only 15% had back extrapolated body burdens > 50 Bq, whereas 53% of those coming from Gomel and other towns in the contaminated zones (> 3.7 x 10(10) Bq km-2 of radiocesium) had detectable levels > 50 Bq. People coming from the latter region had significantly higher body burdens as compared to those from the former, in accordance with the higher degree of ground radiocesium contamination reported for the latter region. Women and children showed considerably lower total radiocesium content in comparison to men. All radiocesium body burdens at the time of measurement were too low to be of health concern.

Localization of Tc-99m DTPA in a chordoma.

The authors report a patient with chordoma that was demonstrated as a photopenic region on Tc-99m MDP bone imaging but that localized Tc-99m DTPA intensely. An explanation for the discrepancy is discussed. Complementary Tc-99m DTPA imaging in the preoperative evaluation of sacral tumors is suggested.

Radionuclide imaging of soft tissue masses with Tc-99m DTPA.

A scintigraphic study was carried out on 48 patients presenting with palpable soft tissue masses. Imaging was carried out using Tc-99m DTPA in three phases (dynamic, blood pool after 5 minutes, followed by late scans after 2 hours). The resultant uptake of the agent was categorized as consistently positive (14 cases), initially positive but progressively negative (7 cases), initially negative but progressively positive (7 cases), and consistently negative (20 cases). Histopathologic examinations were carried out for all cases following biopsy. A variety of malignant and benign masses were found to localize DTPA, whereas all masses that did not concentrate the agent were proven to be lipomas. In order to determine whether the uptake of DTPA bore any relationship to blood flow, additional studies using Tc-99m labeled red cells were carried out on 15 patients with soft tissue tumors. There was no correlation between blood flow or pooling and the degree of Tc-99m DTPA uptake by the palpable masses. The sensitivity of DTPA uptake as indicative of nonlipomatous tissue was 100%, and its specificity was 91%. The predictive probability that a lesion was a liopoma if there was no DTPA uptake at any phase was 100%.

Tumour scanning with indium-111 dihaematoporphyrin ether.

Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection.

Suppression of lymphocyte activation by a soluble factor released from the human placental chorionic membrane: chemical analysis and functional characterization.

A heat-resistant factor that markedly and reversibly inhibits human lymphocyte activation was discovered in culture medium of human placental chorion. The chorionic factor inhibits lymphocyte proliferation in response to polyclonal mitogens and in the mixed leukocyte response. The inhibitory action is most effective if the factor is added during the first 24 h of lymphocyte culture and is reversible. The chorionic factor is sensitive to proteinase K, pepsin and bovine pancreatic protease; its activity is completely lost after papain digestion and following treatment with trichloracetic acid (TCA). The factor prevents the expression of IL-2 receptors and class II MHC glycoproteins (HLA-DR) on phytohemagglutinin-stimulated PBMC but does not affect the expression of MHC class I molecules. It inhibits the replication of IL-2-dependent CTLD cells but is without effect on the growth of various human or murine cell lines or acute leukemic cells. Human placental chorion is thus capable of releasing in vitro a nontoxic heat-resistant factor with protein characteristics that reversibly inhibits processes associated with the early stages of lymphoid cell triggering. This factor may play a role in an immunoregulatory mechanism that prevents maternally mediated immune rejection of the conceptus.

Radioimmunodetection of tumors with monoclonal antiplacental ferritin antibody: preliminary results.

Two mouse monoclonal antiferritin antibodies were employed to detect tumors. In the first case a solitary hepatoma was defined, while in the second one, mediastinal metastases of breast cancer were detected. In both cases serum ferritin levels were raised. The availability of monoclonal antiferritin antibodies offers certain advantages over polyclonal antibodies (ease of production, purification and reproducibility). These antiferritin antibodies may be found useful in diagnosis and therapy of certain tumors.

Hepatitis B infections in a chronic hemodialysis unit in a country where hepatitis B is endemic: a prospective study.

Hepatitis B markers were determined in patients with chronic renal failure and in staff members prior to entry into the hemodialysis unit of a hospital in southern Israel, an area in which hepatitis B is endemic. Patients and staff who were negative for hepatitis B markers were followed for a mean of 26.7 and 29.2 months, respectively, between November 1975 and May 1984. New infections occurred in 25.9% of the patients and 17.3% of the staff; the difference was not statistically significant. Hepatitis B markers were found in 26% of the staff and 41% of the patients (p less than 0.05) prior to their entry into the hemodialysis unit. Furthermore, in the patients, a relatively high rate of carriers was detected (7% compared with 2% in the general population), while no carriers were detected among the staff members. Within the staff group, nurses were at particularly high risk for new infections, accounting for seven of the nine (78%) events recorded. The high risk for the nursing staff is probably due to greater exposure to blood among nurses compared with other staff members.

Diagnosis of acute cholecystitis by 99mTc-iminodiacetic acid cholescintigraphy.

99mTc-iminodiacetic acid (IDA) compounds are concentrated by hepatocytes and excreted into the biliary system. The utility of 99mTc-IDA imaging in 116 patients with suspected acute cholecystitis was studied retrospectively over a 2-year period. Visualization of the gallbladder ruled out obstructed cystic duct and acute cholecystitis with a high degree of accuracy.

Alpha 1-antitrypsin in acute myocardial infarction.

Alpha 1-antitrypsin serum levels were measured in 48 patients with acute myocardial infarction and in 19 control patients either with coronary heart disease without necrosis, or with neither coronary disease nor inflammation. Alpha 1-antitrypsin was significantly raised in the group of patients with acute myocardial infarction. As some patients individually showed no change in alpha 1-antitrypsin levels, however, they were divided into two groups according to the maximum serum levels attained. Patients with non-increasing levels of alpha 1-antitrypsin showed increased mortality and a higher incidence of cardiogenic shock, whereas reinfarction occurred more frequently in the group with high alpha 1-antitrypsin levels. Our findings may suggest that the course of a myocardial infarction is determined not only by the severity of the ischaemic event, but also by the response of the "acute" phase reaction" mechanism. We conclude that a failure of alpha 1-antitrypsin levels to increase after myocardial infarction may be associated with a worse clinical course.

The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration.

We have quantified the effect of EGTA on K exodus and uptake in human blood lymphocytes. When lymphocytes were exposed to a medium containing an EGTA concentration that resulted in an ionized Calcium (Ca) of less than 10 microM, K exodus began to increase. This increase reached nearly threefold that of the control rate in a medium containing sufficient EGTA to reduce the ionized Ca concentration below 0.1 microM. When K exodus was increased, K uptake increased proportionately. This increase in K uptake represented active transport and was associated with an 80% increase in intracellular Na concentration from 15 to 27 mM. The addition of Ca to a medium containing EGTA reversed to normal the increased K exodus and uptake. Histidine, a potent chelator of divalent cations other than Ca, had no effect on K transport. These data indicate that extracellular Ca chelation leads to an increase in lymphocyte membrane permeability and cation leak. This increased leak is associated with an elevation of the cell Na and an increase in transport to a rate equivalent to that of the exodus rate. The compensatory increase in active transport maintains the cell monovalent cation concentration within 10 to 15 mM of unperturbed levels.

Immunological studies in angioimmunoblastic lymphadenopathy.

Immunological studies were carried out on two female patients with angioimmunoblastic lymphadenopathy (AIL). Both presented with fever, lymphadenopathy, hepatosplenomegaly, rash and apparent ampicillin hypersensitivity. During the active phase of the disease, cellular immunity was depressed and T cell blastogenesis induced by lectins was abnormal. In the first patient, a non-dialysable plasma factor was found that inhibited normal lymphocyte blastogenesis, the removal of which enhanced the activation of AIL lymphocytes. This inhibitory plasma factor was also observed in the second patient during relapse of the disease. The latter patient responded well to steroid and levamisole therapy, showing clinical remission and a return of in vivo and in vitro parameters of cellular immunity. Defective B cell regulation due to impaired suppressor function, followed by immunoglobulin overproduction, is suggested to occur in AIL.