Adenovirus-mediated transfer of HST-1/FGF-4 gene protects mice from lethal irradiation.

Intraperitoneal injection of a replication-deficient adenovirus containing the HST-1 (FGF-4) gene (Adex1HST-1) increased peripheral platelet counts in mice, and also effectively prevented experimentally induced thrombocytopenia. Here, we report the therapeutic potential of Adex1HST-1 on severely injured mice after exposure to otherwise lethal irradiation. Eighteen out of 20 mice that received Adex1HST-1 prior to gamma-irradiation (9 Gy) survived, while all the 20 mice with prior administration of control adenoviruses died after irradiation (P<0.0001). Hematological and histopathological analyses revealed that Adex1HST-1 acts as a potent protector against lethal irradiation, which causes injury of intestinal tract as well as myelosuppression in the bone marrow and spleen. These data demonstrate that the protective effects of administration of Adex1HST-1 against irradiation are superior to any other protective effects of cytokines against a lethal dose of irradiation, and that the pre-administration of Adex1HST-1 may be useful for lessening the side effects of currently used chemo- and radio-therapy against cancer.

Prediction of hematologic toxicity after radioimmunotherapy with (131)I-labeled anticarcinoembryonic antigen monoclonal antibodies.

UNLABELLED: This study was undertaken to determine the factors affecting myelotoxicity after radioimmunotherapy (RAIT) with 131I-labeled anticarcinoembryonic antigen (anti-CEA) monoclonal antibodies (MAbs). METHODS: Ninety-nine patients who received 131I-labeled MN-14 or NP-4 anti-CEA MAbs for the treatment of CEA-producing cancers were assessed for platelet and white blood cell (WBC) toxicity based on the common Radiation Therapy Oncology Group (RTOG) criteria. Univariate and multivariate regression analyses were used to identify the statistically significant factors affecting toxicity among the following variables: red marrow dose, baseline platelet and WBC counts, bone or marrow (or both) metastases, prior chemo- or radiotherapy, timing of prior chemo- or radiotherapy in relation to RAIT, type and number of prior chemotherapeutic regimens, age, sex, antibody form and cancer type. RESULTS: Red marrow dose, baseline platelet or WBC counts and multiple bone or marrow (or both) metastases were the only significant factors affecting hematologic toxicity according to both univariate and multivariate analyses, whereas chemotherapy, 3-6 mo before RAIT, was significant according to multivariate analysis. In this retrospective study, the multivariate regression equations using these four variables provided an exact fit for postRAIT platelet toxicity grade (PltGr) and WBC toxicity grade (WBCGr) in 40% and 46%, respectively, of the 99 patients included in the analysis. Moreover, severe (grade 3 or 4) PltGr and WBCGr could be classified accurately in all cases, whereas nonsevere (grade 0, 1, or 2) PltGr and WBCGr could be classified accurately in all but 6 of 13 cases of grade 2 toxicity, in which a severe toxicity grade was estimated using the regression equations. CONCLUSION: Red marrow dose, baseline blood counts, multiple bone or marrow (or both) metastases and recent chemotherapy are the most important factors related to hematologic toxicity after RAIT. This study provides a simple model for predicting myelotoxicity with reasonable accuracy in most patients. In addition, the identification of bone or marrow (or both) metastases and recent chemotherapy as significant factors for myelotoxicity may be important in the future design of clinical trials.

[The use of cycloferon in experimental radiotherapy of tumors]. / Primenenie tsikloferona pri éksperimental'noi luchevoi terapii opukholei.

The biological activity of cycloferon (CF) used in interferon manufacture has been investigated for its therapeutic and prophylactic properties which may be used for radiotherapy of glioma. It was demonstrated in experiments on rats that use of CF is most effective at an early stage of irradiation due to decrease in tumor mass which does not occur in case of irradiation alone. When used at a later stage, CF caused certain hematological indices of immunity to rise. CF did not produce an antitumor effect of its own. It successfully competed with Leukomax when used to bring blood indices in irradiated tumor-bearing animals back to normal.

Biochemical indicators of whole-body gamma-radiation effects in the pig.

PURPOSE: Validation of the pig as an experimental animal model for dose assessment after ionizing irradiation. MATERIALS AND METHODS: The evolution of haematological and biochemical parameters was followed for up to 7 days after irradiation in pigs exposed to whole-body 60Co gamma-radiation at doses between O and 6 Gy. RESULTS: Some biochemical indicators showed significant variations: amylase, LDH, alkaline and acid phosphatases, ALT and iron. None of the studied parameters alone presents a reliable dose-effect relationship; however, there was evidence that the combination of lymphocyte and neutrophil counts and the determination of LDH, ALT, AST and urea levels allowed some dose determination, independent of time, if blood samples were taken within 7 days post-irradiation. CONCLUSION: The results confirm the main problems of biochemical dosimetry. However, the pig model could represent a useful alternative to the non-human primate in radiobiology research, especially in the case of partial-body exposure. A multiparametric approach to dose assessment seems to be possible in the pig model. Confirmation should be carried out using blood samples from patients undergoing radiotherapy treatment.

Thrombopoietin promotes hematopoietic recovery and survival after high-dose whole body irradiation.

PURPOSE: The therapeutic potential of thrombopoietin (TPO), the major regulator of platelet production, was evaluated for hematopoietic recovery and survival in mice following lethal and supralethal total body irradiation (TBI). METHODS AND MATERIALS: Hematopoietic recovery was studied in C57BL6/J mice after 8 Gy TBI (gamma-rays). Survival experiments were performed with C57BL6/J and BCBA F1 mice. Two protocols of TPO administration were evaluated: treatment for 7 consecutive days (7 x 0.3 microg/mice) beginning 2 h after exposure, or a single dose (0.3 microg/mice) administered 2 h after irradiation. RESULTS: TPO improved the platelet nadir and accelerated the platelet reconstitution of irradiated mice in comparison to placebo-treated mice. Recovery of neutrophils and erythrocytes was stimulated as well. TPO induced an accelerated recovery of hematopoietic progenitors and immature multilineage progenitors in bone marrow and spleen. In addition, TPO administration induced approximately 90% survival of 8 Gy irradiated C57BL6/J mice, a TBI dose which resulted in 100% mortality within 30 days for placebo-treated mice. Single TPO administration was as effective as repeated injections for hematopoietic recovery and prevention of mortality. Dose-effect survival experiments were performed in BCBA F1 mice and demonstrated that TPO shifted the LD50/30 from approximately 9.5 Gy to 10.5 Gy TBI given as a single dose, and from 14 Gy to as high as 17 Gy when TBI was given in three equal doses, each separated by 24 h. CONCLUSION: These results demonstrate that the multilineage hematopoietic effects of TPO may be advantageously used to protect against lethal bone marrow failure following high dose TBI.

Relative efficacy of 32P and 89Sr in palliation in skeletal metastases.

UNLABELLED: 32p and 89Sr have been shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. Clinically significant pancytopenia has not been reported in doses up to 12 mCi (444 MBq) of either radionuclide. To date, no reports comparing the relative efficacy and toxicity of the two radionuclides in comparable patient populations have been available. Although a cure has not been reported, both treatments have achieved substantial pain relief. However, several studies have used semiquantitative measures such as "slight," "fair," "partial" and "dramatic" responses, which lend themselves to subjective bias. This report examines the responses to treatment with 32P or 89Sr by attempting a quantification of pain relief and quality of life using the patients as their own controls and compares toxicity in terms of hematological parameters. METHODS: Thirty-one patients with skeletal metastases were treated for pain relief with either 32P (16 patients) or 89Sr (15 patients). Inclusion criteria were pain from bone scan-positive sites above a subjective score of 5 of 10 despite analgesic therapy with narcotic or non-narcotic medication, limitation of movement related to the performance of routine daily activity and a predicted life expectancy of at least 4 mo. The patients had not had chemotherapy or radiotherapy during the previous 6 wk and had normal serum creatinine, white cell and platelet counts. 32P was given orally as a 12 mCi dose, and 89Sr was given intravenously as a 4 mCi (148 MBq) dose. The patients were monitored for 4 mo. RESULTS: Complete absence of pain was seen in 7 of 16 patients who were given 32P and in 7 of 15 patients who were given 89Sr. Pain scores fell by at least 50% of the pretreatment score in 14 of 16 patients who were given 32P and 14 of 15 patients who were given 89Sr. Mean duration of pain relief was 9.6 wk with 32P and 10 wk with 89Sr. Analgesic scores fell along with the drop in pain scores. A fall in total white cell, absolute granulocyte and platelet counts occurred in all patients. Subnormal values of white cells and platelets were seen in 5 and 7 patients, respectively, with 32P, and in 0 and 4 patients, respectively, after 89Sr therapy. The decrease in platelet count (but not absolute granulocyte count) was statistically significant when 32P patients were compared with 89Sr patients. However, in no instance did the fall in blood counts require treatment. Absolute granulocyte counts did not fall below 1000 in any patient. There was no significant difference between the two treatments in terms of either efficacy or toxicity. CONCLUSION: No justification has been found in this study for the recommendation of 89Sr over the considerably less expensive oral 32P for the palliation of skeletal pain from metastases of advanced cancer.

Radiation-induced chromosomal aberrations and haematological alterations in hospital workers.

Long-term exposure to low doses of ionizing radiation may affect cells and tissues and result in various adverse health effects. The purpose of this study was to investigate whether chromosome aberrations and haematological alterations could be used as biomarkers of possible radiation injury in workers exposed to ionizing radiation. Groups totalling 323 medical professionals handling X-ray equipment and 160 control subjects were examined for incidence of chromosome aberrations and changes in leukocyte, lymphocyte and thrombocyte counts. The incidence of all types of chromosome aberrations was higher in the exposed groups than in controls, yet no significant difference was found between the exposed groups. A many-fold increase in chromosome aberration frequency in all exposed groups was not followed by a corresponding haematological depression. This suggests that chromosome aberrations are a significantly more sensitive indicator of changes caused by low doses of ionizing radiation than haematological alterations.

The utility of serial complete blood count monitoring in patients receiving radiation therapy for localized prostate cancer.

PURPOSE: It is standard practice in our department to monitor weekly complete blood counts (CBCs) in patients receiving definitive radiation therapy for prostate cancer. The clinical utility and cost effectiveness of this practice has not been analyzed. METHODS AND MATERIALS: The charts of all prostate cancer patients treated with radiation therapy between January 1994 and July 1996 at the Veterans Administration Hospital, Philadelphia, PA were reviewed. CBC values were available for 89 patients. Patients received a median dose of 68 Gy using a four-field box technique and megavoltage photons. Whole-pelvic radiotherapy followed by a conedown to the prostate was administered to 29 patients. Fifty-nine patients received radiation to the prostate alone or prostate and seminal vesicles. Fifty-seven patients received concurrent hormonal therapy which included luteinizing hormone-releasing hormone (LHRH) agonist, antiandrogens, or both. RESULTS: No patient experienced a drop in their hemoglobin, white blood cells (WBCs), or platelets below critical nadirs (defined as WBC < 2 counts x 1000/mm(3), hemoglobin < 8 g/dl, platelet < 50 counts x 1000/mm(3) 2 in WBCs. In the urban area surrounding the Philadelphia Veterans Administration Medical Center, the cost of obtaining a CBC is approximately $30. However, if staff time is considered, the cost of obtaining a weekly CBC during prostate cancer radiotherapy approached $400 per patient. CONCLUSION: These results suggest that weekly monitoring of CBCs in prostate cancer patients undergoing definitive radiotherapy may not be necessary. We recommend a baseline CBC be performed, and if normal, no other monitoring unless clinically indicated. This strategy would result in a cost savings approaching $30,000 per 100 treated patients. Further research on the cost effectiveness and utility of serial blood tests in patients receiving partial body radiation therapy is needed.

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma.

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

Blood cell damage after in vitro irradiation of fresh whole blood with 630 nm laser light.

A study on blood cell damage after irradiation of fresh whole blood with 630 nm laser light was carried out in vitro. Various fluence rates of laser light were used with and without cooling of blood. Damage to the blood was assessed by blood cell counts, osmotic fragility measurements and examination of blood films. Exposure of a 1 mm blood layer to 630 nm laser light without cooling led to changes in blood counts first detected at fluence rates of 130 mW/cm2. Changes in osmotic fragility first became evident at 210 mW/cm2. Increasing cell damage with increasing fluence rates was evident in blood films. Using the cooling device changes in whole blood after irradiation first occurred at a fluence rate of 293 mW/cm2. Measurement of the fluence rates at which cell damage begins is important in laser induced fluorescence diagnostics and photodynamic therapy applications in blood or blood products using photosensitizers.

Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation.

PURPOSE: To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT). PATIENTS AND MATERIALS: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored. RESULTS: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV1) was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died. Features suggestive of a positive response to TLI included longer interval from transplant to RT, higher FEV1 at initiation of RT, and absence of preexisting pulmonary infection. CONCLUSION: Total lymphoid irradiation for chronic allograft rejection refractory to conventional medical management following BLT was tolerable. A subset of patients experienced durable preservation of pulmonary function and decreased immunosuppressive requirements. Patients with rapidly progressive allograft rejection, low FEV1, or preexisting infection were least likely to benefit from irradiation. Early initiation of TLI for patients experiencing chronic allograft rejection following BLT may be warranted.

[The criteria of disorders in body antitumor resistance in subjects with dyshemopoiesis]. / Kriterii narushenii protivoopukholevoi rezistentnosti organizma u lits s disgemopoézom.

A complex of methods is proposed adapted to practices common in clinical and diagnostic laboratories that enables the state of bodily antitumoral resistance to be properly assessed. A diagnostic system of disturbances in the antineoplastic resistance of the organism, which makes for detection of endogenous factors marking a high risk for the development of oncohemopathology is suggested.

[Evaluation of individual radiation resistance of rats based on reactions to non-radiation testing]. / Otsenka individual'noi radiorezistentnosti krys po reaktsiiam na testiruiushchee neradiatsionnoe vozdeistvie.

Presented are the data on radiation sensitivity of various groups of animals preliminary differentiated by their tolerance of acute hypoxia. The processes of blood forming system impairment and reparation are detailed. As was shown, highly resistant to hypoxia rats are distinguished by the best radiation resistance. Survivability of these rats was significantly higher as compared with other groups of animals. Recovery of blood formation by both the red and white chits following exposure to [symbol: see text] of the mean lethal dose proceeded more rapidly in the radiation resistant rats.

Phenotype of the engrafting stem cell in mice.

The present data on engraftment into non-myeloablated mice strongly suggest that engraftment is determined by host-donor ratios as opposed to opening space. Theoretically, if the ratios of donor to host stem cells could be altered, especially without causing toxicity to the host animal, then the phenotypic readout could be increased in a clinically applicable manner. To research this further, we investigated low-dose irradiation (100 cGy) for its effects on marrow, spleen and peripheral blood counts, as well as engrafting stem cell levels. We found a transient but significant depression in the white blood cell and platelet counts in the peripheral blood which returned to normal by two weeks, with no apparent deleterious effect on the animals. However, the same irradiation dose after two months impaired marrow repopulation and reduced engraftment potential to less than 20% capacity. These results suggested that we could obtain much higher phenotypic readouts after engraftment with this model; thus, we assessed the engraftment of 40 million male BALB/c marrow cells into female hosts exposed to 100 cGy at two, five and eight months after cell infusion. The resultant high levels of chimerism, reaching 100% in many cases, strongly suggest that the key to engraftment in these models is host-donor stem cell ratios. One important issue relative to the above finding is whether cytokine-stimulated proliferating stem cells have irreversibly lost engraftment capacity or whether changes in the engraftment capacity are of a plastic nature, possibly related to cell cycle transit. A number of experiments following engraftment have shown that the engraftment defect is reversible and can be repeatedly lost and regained during the initial portions of a cytokine-stimulated culture. The above results suggest that, at least at the more primitive stem cell level, hematopoietic stem cell regulation may in part be based on a cell cycle model rather than a hierarchical system.

Estudo histológico e morfométrico da reparaçäo de feridas cutâneas, provocadas em ratos, submetidas à radiaçäo beta do estrôncio-90 / Histologic and morphometric study on the healing of skin wounds in rats subwitted to Beta irradiation of Stroncium-90

O objetivo deste trabalho foi investigar os efeitos da radiaçäo Beta do Estrôncio-90 no processo de reparaçäo tecidual de feridas provocadas em ratos. Utilizamos 24 animais da linhagem EPM-1 Wistar distribuídos em 4 grupos. Receberam a radiaçäo em dias alternados e sua análise foi feita aos 3, 7, 14 e 21 dias de pós-operátorio. Realizou-se duas incisöes no dorso de cada animal, suturou-se em seguida, sendo que a de situaçäo cranial foi irradiada e a caudal serviu para controle. Nas àreas determinadas, as feridas controle e irradiada foram observadas macroscopicamente e retiradas para preparo do estudo histológico comparativo ao microscópio óptico. Realizou-se, em seguida, análise morfométrica para contagem de leucócitos, fibroblastos e fibras colágenas, submetidas a estudo estatístico. Da análise dos resultados, pode-se concluir que, em geral, a radiaçäo Beta do Estrôncio-90 provocou um aumento no número de leucócitos, uma diminuiçäo no número de fibroblastos e näo alterou o número de fibras colágenas, quando comparou-se a ferida irradiada à controle nos tempos do experimento

Prediction of myelotoxicity using semi-quantitative marrow image scores.

UNLABELLED: Marrow radiation with resultant myelosuppression is usually dose-limiting in radioimmunotherapy (RIT). This study evaluated the relationship between a semiquantitative score of radiolabeled antibody marrow uptake obtained by imaging and subsequent decrease in peripheral blood cell counts in a patient population in whom marrow malignancy is common. METHODS: Semiquantitative scores were assigned to lumbar marrow images of 18 patients acquired 0, 6, 24 and 48 hr after the first therapy dose of 131I-Lym-1. Scores were adjusted for injected dose (GBq) and body surface area (m2), and correlated with post-therapy blood counts. A well-defined scale, where 0 and 4 represented least to highest marrow uptake when compared to background, was used to assign marrow image scores. Injected doses of 131I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). RESULTS: Linear regression of summed marrow scores (0-24 hr after injection) versus decrease in cell counts produced correlation coefficients of 0.76, 0.44, 0.58 and 0.46 for platelets, granulocytes, white blood cells (WBC) and hematocrit, respectively. Scores for individual and other combinations of images obtained immediately up to 24 hr after injection were also predictive.

Prediction of myelotoxicity using radiation doses to marrow from body, blood and marrow sources.

UNLABELLED: Bone marrow is generally the dose-limiting organ in radioimmunotherapy (RIT). Although radiation doses to marrow estimated from tracer doses have been shown to be comparable to those from therapy doses of radionuclide, the correlation of marrow radiation dose and myelotoxicity has not been well documented. The purpose of this study was to evaluate the relationship between radiation dose to marrow and subsequent changes in peripheral blood cell counts. METHODS: Radiation doses to marrow from three sources, body, blood and marrow targeting, were compared with changes in blood counts after the first therapy dose of (131)I-Lym-1 in 16 patients. Doses of (131)I-Lym-1 ranged from 1.1-8.2 GBq (29-222 mCi). Cumulated radioactivity in the body and marrow were obtained using sequential, quantitative images of the body and lumbar vertebrae, respectively, and that in blood using activity in blood samples. The individual and sum of radiation doses from penetrating radiations in the body, and nonpenetrating radiations in the blood and marrow, were compared with blood counts. RESULTS: In this group of patients, median radiation doses were 15.1, 15.4 and 42.1 cGy from body, blood and marrow targeting, respectively. Linear regression of radiation doses from body and blood versus fractional decreases in blood counts produced correlation coefficients of 0.38, 0.06, 0.22 and less than 0.01 for platelets, granulocytes, white blood cells (WBCs) and hematocrit, respectively. Linear regression of targeted marrow radiation doses versus fractional decreases in blood counts produced correlation coefficients 0.61, 0.31, 0.54 and 0.20 for platelets, granulocytes, WBCs and hematocrit. The closest association was found between radiation dose to marrow from marrow targeting and change in platelet count (r = 0.61). CONCLUSION: In patients, such as those with non-Hodgkin's lymphoma (NHL), likely to have marrow targeting, prediction of myelotoxicity by conventional body and blood contributions to marrow is substantially improved by the use of radiation dose to marrow estimated from images.

Historical events associated with fallout from Bravo Shot--Operation Castle and 25 Y of medical findings.

The events prior to Bravo Shot-Operation Castle that led to a decision not to evacuate the Marshallese prior to testing the thermonuclear bombs are presented as are the actions taken after the fallout incident in evacuating the exposed Marshallese and the military personnel. The initial medical effects (findings during first 6 wk after exposure) are briefly described and are followed by description of long term effects, namely, induction of one case of fatal acute myeloid leukemia and a large number of thyroid tumors (benign and malignant) in addition to hypothyroidism in adults and children and two cases of cretinism. The hypothyroidism and cretinism responded well to administration of oral thyroxine. During the first 25 y, there was also much unrest and political agitation initiated by exposed and unexposed Marshallese who were very unhappy as a result of relocation and inability to return to their homelands and feeling that all illness and deaths were due to the mysterious radiation, which they understandably did not understand. The difficulties in part were ameliorated by financial aid from the U.S. Congress. In view of one of us (EPC), no one agency or person in the U.S. Government was willing to take the responsibility for care of the Marshallese and its financing. The exposed and nonexposed Marshallese had their lifestyle changed, some of their homelands made uninhabitable for several years and could aptly be called "nuclear nomads," an expression coined by others.

Treatment of lymphoid cell malignancy with In-114m labelled autologous lymphocytes.

This paper is a preliminary report of a clinical trial for the treatment of patients with refractory chronic lymphocytic leukaemia, using autologous In-114m-labelled lymphocytes. Fourteen patients have been treated so far with doses ranging from 69 to 211 MBq. All patients had progressive low grade NHL, resistant to chemotherapy and conventional radiotherapy. Following the intravenous administration of radiolabelled autologous lymphocytes 53% (range 33-92%) of the activity accumulated in the spleen, 35% (21-64%) in the liver and 5% in the bone marrow. The initial response in all patients was a rapid decrease in lymphocyte count in peripheral blood. 10 of the 14 (72%) patients showed a response to the treatment. In 2 patients, there was a complete response which lasted 24 and 36 months respectively, 8 patients showed a partial response of 2 to 17 months duration. None of the patients experienced any subjective toxicity although myelosuppression was seen in all patients. This is a novel concept for the administration of therapeutic radiation in a selective way for the treatment of lymphoid cell malignancy and has produced significant antitumour effect in patients with highly resistant disease. The trial is ongoing and a full report will be published on its completion.

[Changes in the content of ribonucleic acid in the blood cells and plasma compared to the hematological indicators of a radiation-induced lesion in rats]. / Izmeneniia soderzhaniia ribonukleinovoi kisloty v kletkakh i plazme krovi v sopostavlenii s gematologicheskimi indikatorami radiatsionno-indutsirovannogo porazheniia u krys.

A whole-body gamma irradiation of rats with a dose of 8.5 Gy caused a significant decrease in the RNA concentration in the blood. The original level of concentration was restored within 3 weeks after irradiation and exceeded by the 21st day after irradiation. The changes were studied in terms of the haematological indices of a radiation-induced damage.