Search

The rhombotin 2 gene was identified by its association with a recurrent chromosome translocation (11;14)(p13;q11), occurring in T-cell acute lymphoblastic leukaemias (ALLs). High levels of RBTN2 have been found in T-cell leukaemias carrying the translocation and in some T-cell ALLs that lack, by cytogenetic and molecular techniques, translocations involving 11p13. In normal murine tissues RBTN2 has been found to be widely expressed, with high levels present in brain and early B cells. Studies carried out in mice lacking RBTN2 have demonstrated the importance of this gene in erythropoiesis. We have investigated the expression of RBTN2 in human leukaemic cells, and in human and murine normal myeloid progenitor cells. RBTN2 is expressed in the leukaemic cells of patients with pre-B ALL, T-ALL and acute myeloblastic leukaemia (AML). By cytogenetic and molecular techniques no abnormalities were noted in 11p13. Using clonogenic assays and single cell PCR we found that RBTN2 is expressed strongly in the precursors of mixed erythrocyte/macrophage/mast, erythrocyte, megakaryocyte, neutrophil and macrophage colonies. In contrast, RBTN2 message was low to undetectable in the mature progeny. These findings indicate that RBTN2 is expressed in leukaemias of both the myeloid and lymphoid lineages. Further, these studies show that in normal myeloid and lymphoid cells the expression of RBTN2 is present in progenitor cells and is lost as the cells terminally differentiate. This latter finding further illustrates that the detection of a RNA in a population of cells should not be interpreted to mean that all of the cells in that population express the RNA.

Identification of genes that regulate clonogenicity of acute myelogenous leukemia (AML) cells is hindered by the difficulty of isolating pure populations of cells with defined proliferative abilities. By analyzing the growth of clonal siblings in low passage cultures of the cell line OCI/AML4 we resolved this heterogeneous population into strata of distinct clonogenic potential, permitting analysis of the transcriptional signature of single cells with defined proliferative abilities. By microarray analysis we showed that the expression of the orphan nuclear receptor EAR-2 (NR2F6) is greater in leukemia cells with extensive proliferative capacity than in those that have lost proliferative ability. EAR-2 is expressed highly in long-term hematopoietic stem cells, relative to short-term hematopoietic stem and progenitor cells, and is downregulated in AML cells after induction of differentiation. Exogenous expression of EAR-2 increased the growth of U937 cells and prevented the proliferative arrest associated with terminal differentiation, and blocked differentiation of U937 and 32Dcl3 cells. Conversely, silencing of EAR-2 by short-hairpin RNA initiated terminal differentiation of these cell lines. These data identify EAR-2 as an important factor in the regulation of clonogenicity and differentiation, and establish that analysis of clonal siblings allows the elucidation of differences in gene expression within the AML hierarchy.

Erythropoietin (Epo) regulates the growth and differentiation of erythroid cells by binding to a specific receptor. We characterized the native Epo receptor on erythroleukemia cell lines by ligand blotting. Solubilized cell membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose, and probed with 125I-Epo. Specificity was demonstrated by inhibition of 125I-Epo binding by unlabeled excess Epo but not other peptide growth factors and by the cellular distribution of the Epo binding protein. A single membrane protein of 61 Kd +/- 4 Kd was sufficient to bind 125I Epo in both human (OCIM2, K562) and murine (GM979, Rauscher, DA-1) cell lines. This finding is consistent with the predicted size of the Epo receptor from the murine cDNA clone. However, chemical crosslinking of 125I-Epo to its receptor has identified two Epo binding proteins of 105 Kd and 85 Kd. This difference may occur because the receptor is size fractionated before Epo binding in the ligand blot, but after Epo binding in crosslinking studies. Ligand blotting demonstrates that the native Epo receptor is composed of a single 61-Kd Epo binding protein, and suggests the presence of additional proteins of 20 to 25 Kd that associate with the receptor after Epo binding.

Current dosimetric models of the brain and head lack the anatomic detail needed to provide the physical data necessary for suborgan brain dosimetry. During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head for use in estimating regional absorbed dose within the brain and its adjacent structures.A new brain model has been developed that includes eight subregions: the caudate nuclei, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nuclei, the thalami, the third ventricle and the white matter. This brain model is incorporated within a total revision of the head model presented in MIRD Pamphlet No. 5 Revised. Modifications include the addition of the eyes, the teeth, the mandible, an upper facial region, a neck region and the cerebrospinal fluid within both the cranial and spinal regions.Absorbed fractions of energy for photon and electron sources located in 14 source regions within the new model were calculated using the EGS4 Monte Carlo radiation transport code for particles in the energy range 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for 24 radionuclides that are used in clinical or investigational studies of the brain, 12 radionuclides that localize within the cranium and spinal skeleton and 12 radionuclides that selectively localize in the thyroid gland.A substantial revision to the dosimetric model of the adult head and brain originally published in MIRD Pamphlet No. 5 Revised is presented. This revision supports suborgan brain dosimetry for a variety of radiopharmaceuticals used in neuroimaging. Dose calculations for the neuroimaging agent 1231-tropane provide an example of the new model and yield mean brain doses that are consistent with published values. However, the absorbed dose to subregions within the brain such as the caudate and lentiform nuclei may exceed the average brain dose by a factor of up to 5.

This continuing education article reviews radionuclide bone therapy agents that are available commercially and introduces agents that are being evaluated for future use. Currently these agents are used to provide pain palliation from metastases to bone. Future applications may include adjuvant therapy to surgery or external beam treatment. After reading this paper, the reader should be able to: (a) describe the desirable characteristics of radionuclide bone therapy agents; (b) compare and contrast radiopharmaceuticals available for bone therapy; and (c) state the clinical applications of radionuclide bone therapy agents.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with dosesor = 5.29 MBq/kg and 5 +/- 3 days with dosesor = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy.Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions.Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury.These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in patients with metastatic bone pain.Seventeen patients with bone pain due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229 microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic blood and daily urine samples were collected for 14 days to measure percent injected activity retained in blood and that excreted in urine. Simultaneous anterior and posterior view whole-body images were obtained under identical scan settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk postinjection. The total body retention was calculated using the geometric mean counts.After intravenous injection, the total body clearance of 117mSn(4+)DTPA shows two components: a soft-tissue component and a bone component. The soft-tissue component accounts for 22.4% of the dose and consists of four subcomponents with an average biologic clearance half-time of 1.45 days (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic lesions by 3-7 days. Pain palliation was observed with all three doses levels.Among the four potential bone pain palliation radionuclides, 117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other agents, but many features are different and unique and may make it an ideal bone pain palliation agent. Double-blind comparative studies are needed to determine its exact role in bone pain palliation.

Bone seeking radiopharmaceuticals consist of diagnostic (primarily single photon emitters) and therapeutic agents. The therapeutic radiopharmaceuticals are utilized on the basis of their particulate emissions (primarily beta-) and thus are treated differently than the single photon bone imaging agents. Lately, the therapeutic bone seekers have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients. However, there seems to be a paucity of published data on the pharmacokinetics of most of these agents. This paper will briefly review and summarize the presently available pharmacokinetic information on the various therapeutic bone seeking radiopharmaceuticals. Bone imaging agents based on single photon emitters will not be covered since they have been extensively discussed in the published literature.

During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region.A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions.Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV.S-values were calculated for five radionuclides used in brain imaging (11C, 15O, 18F, 99(m)Tc and 123I) and for three radionuclides showing selective uptake in the thyroid (99(m)Tc, 123I, and 131I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides.

The goal of this study was to determine the usefulness of radiolabeled aerosols in the assessment of regional ventilation in tracheotomized patients maintained on mechanical ventilation.Three commercially available radioaerosol nebulizer kits were studied on the bench to determine nebulizer efficiency and particle distribution of 99mTc-DTPA aerosols. We studied ventilated tracheotomized human subjects with a gamma camera and simultaneously measured regional ventilation with 81mKr gas and 99mTc-DTPA aerosol. Images were compared by analysis of radioactivity distributions in computer-generated regions of interest.The UltraVent nebulizing system produced the smallest particles with a mass median aerodynamic diameter of 0.9 micron compared to the AeroTech I and Venti-Scan II systems, which both produced aerosols of 1.3 microns. Despite relatively small particle sizes, 99mTc-DTPA deposition images with the UltraVent nebulizer did not accurately represent regional ventilation as measured by 81mKr equilibrium. Visual inspection of images revealed significant amounts of particle deposition in the region of the trachea which was diminished but not eliminated following replacement of the tracheotomy tube inner cannula. Based on regional analysis, correlation between radioactivity distributions of both isotopes was poor (r = 0.262, p = 0.162) with segmental analysis suggesting that the upper and middle lung regions were significantly affected by residual tracheal activity.The lungs of patients maintained on mechanical ventilation can be imaged after the inhalation of 99mTc-DTPA from commercially available delivery kits, but the correlation between aerosol deposition and regional ventilation is poor. Better definition of ventilated lung segments is obtained when using a gas such as 81mKr because tracheal activity with the radiolabeled gas is minimized.

The general dosimetry of 133Xe for human studies is well documented, but the resultant radiation exposure to tracheal tissue is poorly known. This organ is of central relevance because the tracer is primarily eliminated through exhalation.We report actual 133Xe concentrations in respiratory air during measurement of regional cerebral blood flow (rCBF), when the tracer is administered both by inhalation and intravenous injection. Data were collected from 102 patients, with equal gender representation and an age range of 18-82 yr. Most of the patients had subarachnoid hemorrhage or Alzheimer's disease or were normal control subjects. Average administered doses were 18 +/- 4 mCi by inhalation and 15 +/- 3 intravenously.We found average respiratory concentrations of about 1.80 mCi/liter during a 1-min inhalation and 0.74 mCi/liter following intravenous injection of standard doses. These activities drop rapidly: average respiratory concentrations during the second minute are 0.70 mCi/liter for inhalation and 0.19 mCi/liter for intravenous injection and reach negligible levels thereafter. We calculate that the tracheal absorbed dose from 133Xe procedures is approximately 28 mrad following inhalation and about 11 mrad following intravenous injection. These values reflect the full 11-min exposure, but most of the activity is only present initially.These values will agree with previous estimates and indicate an excellent safety margin.

The physical and biological attributes of 117mSn(4+)-DTPA indicate that it should be an effective agent for palliative therapy of painful bony metastatic disease. The aim of this study was to evaluate whether or not this agent could effectively reduce pain while sparing the hemopoietic marrow from adverse effects.Fifteen patients (10 males and 5 females) with painful bony metastases from various primary cancers were included in the study. Seven patients received 1.22 to 3.11 MBq/kg of 117mSn intravenously (Group 1) and eight patients received 4.85 to 5.77 MBq/kg (Group 2). All but one were treated as outpatients and followed for a minimum of 2 mo.In the first group, pain relief was non-assessable in four patients because of death or additional treatment of soft-tissue disease by another modality. One patient had no relief of pain, one had complete relief of pain and one had transient relief of pain. No myelotoxicity was observed. For Group 2, three patients achieved complete relief of pain, two good relief, two partial relief and one began to experience pain relief when he suffered a pathological fracture 2 mo post-treatment. None of these patients had myelotoxicity.Tin-117m(4+)-DTPA can reduce pain from metastatic disease to bone without inducing adverse reactions related to bone marrow. Further studies are needed to assess tolerance levels for the bone marrow and to evaluate response rates and duration of effect.

Stem cell factor (SCF) triggers cell growth by binding to cell surface c-kit receptors. Soluble forms of several cytokine receptors have been described and may play a role in the modulation of cytokine activity in vivo. For these reasons, we investigated whether human hematopoietic cells produce soluble c-kit receptors. The human leukemia cell lines OCIM1 and MO7e display approximately 80,000 and approximately 35,000 high-affinity cell surface c-kit receptors, respectively. Soluble c-kit receptors were detected by enzyme immunoassay in OCIM1 and MO7e culture supernatants. We determined the molecular weight and binding affinity of soluble c-kit receptor produced by OCIM1 cells, soluble c-kit receptor purified from human serum, and recombinant soluble c-kit receptor expressed in CHO cells. The three soluble c-kit receptors each have a molecular weight of 98 kD. Quantitative binding experiments with 125I-SCF indicate that the soluble c-kit receptors obtained from human serum or OCIM1 cells have binding affinities for SCF of approximately 200 to 300 pmol/L, in contrast to the recombinant form, which has a binding affinity of approximately 1.5 nmol/L. All three forms of the soluble c-kit receptor were able to compete with c-kit receptors on OCIM1 cells for 125I-SCF binding. Thus human hematopoietic cells can produce a soluble form of the c-kit receptor that retains high-affinity SCF binding activity. We speculate that the soluble c-kit receptor may bind SCF and function as a receptor antagonist in vivo.

The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented.System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm.The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals.The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.

The adaptive stencil concepts of ENO (Essentially Non-Oscillatory) methods are applied to the laminar Navier-Stokes equations to yield a high-order, time-accurate algorithm with a shock-capturing capability. The method targets problems in the areas of nonlinear acoustics, compressible transition, and turbulence which, due to the presence of shocks or complex geometries, are not easily solved by spectral methods. The present approach has been implemented and tested for the full three-dimensional Navier-Stokes equations in a transformed curvilinear coordinate system. Validation results are presented for a variety of problems which verify the method's accuracy properties and shock capturing capabilities, as well as demonstrate its use as a direct simulation tool.

A multi-block multigrid method for the solution of the three-dimensional Euler and Navier-Stokes equations is presented. The basic flow solver is a cell-vertex method which employs central-difference spatial approximations and Runge-Kutta time stepping. The use of local time stepping, implicit residual smoothing, multigrid techniques, and variable-coefficient numerical smoothing results in an efficient and robust scheme. The multi-block strategy places the block loop within the Runge-Kutta loop such that accuracy and convergence are not affected by block boundaries. This has been verified by comparing the results of one- and two-block calculations in which the two-block grid is generated by splitting the one-block grid. Results are presented for both Euler and Navier-Stokes computations of wings and wing-fuselage combinations.

Summary 99mTc-pertechnetate distribution studies were performed in rabbits and mice following pretreatment between 5—336 hours with various routinely used stannous complexes (HSA, MAA, GHT, DTPA, PYPs) containing different amounts of Sn++ (0.17 —15.0 μ mg/kg). Beyond a concentration of 0.26 mg/kg of Sn++ an alteration in 99mTc-pertechnetate distribution was observed. The red blood cell was found to be the most prominent target. An in-vivo reduction of 99mTc-pertechnetate apparently occurred by the presence of stannous ion within the red blood cell. Preloading time period between 5—24 hours did not alter the uptake of RBC/plasma ratio. Beyond that period it decreased slowly and still persisted up to 2 weeks following pretreatment. RBC/ plasma ratio of 99mTcO4 - increased with increased Sn++ content of various commercially available pharmaceutical kits.

A large survey of the sky has been undertaken in the near u.v. in two different steps by the Laboratoire d’Astronomie Spatiale du Centre National de la Recherche Scientifique: 1. A wide field camera 120 x 80° survey programme on rockets began in 1967 and was continued by the launch of the Janus camera in 1972. 2. A medium field (6 x 8°) programme due to the S 183 French experiment on Skylab. The map shows the distribution of the S 183 fields on the celestial sphere, superposed with the two wide fields of the Janus camera (figure 1). A complementary work in visible light (H a) using similar wide field (60°) optics and very selective interference filters has been made during the same period in order to obtain an idea of the penetration in interstellar space of radiation below 912 A owing to ionization of the interstellar hydrogen considered as evidence of this radiation. The full set of these experiments in u.v. and H a gives a good synthetic figure of the extreme population I extension in the Milky Way.

An implicit finite difference method with implicit boundary conditions is employed to solve the steady Euler equations for flows past arbitrary geometries/The resulting code is used to investigate in a systematic way various aspects of flow past airfoils at transonic speeds such as method of solution, boundary conditions, grid stretching and generation, shock and sonic point operators, the Kiitta condition, and smoothing. Results ob- tained are in good agreement with results of other codes. Moreover, it appears that the method of solution employed is such that Kutta's condition need not be invoked. This statement appears to be valid for other existing schemes employed in the solution of Euler equations. HE primitive variable form of the system of partial- differential equations governing the steady motion of an inviscid fluid (Euler equations) are first order and of mixed elliptic and hyperbolic type. Because of this, two approaches are used in obtaining steady-state solutions for subcritical and supercritical flows past bodies. The first seeks temporally asymptotic solutions of the time-dependent equations1'7 while the second exploits relaxation methods developed for the solution of second-order equations by embedding Euler equations in a second-order system8 or by using a stream function formulation.9 The purpose of this investigation is to develop an efficient algorithm for the steady Euler equations in primitive variable form and use it to carry out numerical experiments designed to investigate in a systematic way the various aspects of flows past airfoils at transonic speeds. These include method of solution, i.e., Peaceman-Rachford10 (PR) vs Douglas-Gunn1 1 (DG); boundary conditions; grid generation and stretching; shock and sonic point operators; smoothing; and the Kutta condition. The resulting algorithm solves the strong con- servation form of the Euler equations, with the energy equation replaced by the statement that the total enthalpy is constant, using an ADI finite difference scheme and implicit boundary conditions. To study arbitrary geometries, the algorithm is combined with the automatic grid solver (GRAPE) of Steger and Sorenson.12 With this capability, the code provides a general and efficient method for the solution of flowfields past arbitrary geometries for all speed ranges. The achieved efficiency of this code can be traced to two main reasons: the resulting block tridiagonal matrix for two- dimensional flows is 3 x 3 and not 4 x 4; moreover, the code incorporates a procedure that selects an optimum relaxation factor for each iteration. Formulation of the Problem

A new stream function formulation is presented for the solution of Euler equations in the transonic flow region. In this method the stream function and the density are the dependent variables. The governing equations for adiabatic flow are then the momentum equations which are solved in the strong conservation law form. The method differs from the recent formulation of Hafez and Lovell, which is based on Crocco's equation, in that it does not require knowledge of the vorticity. To study arbitrary geometries, the algorithm is combined with the automatic grid solver (GRAPE) of Steger and Sorenson. Results are presented for an NACA 0012 airfoil at various Mach numbers, angles of attack, and cylinders. Comparisons with other solutions of the Euler equations show good agreement.

Nonvisualization of the gallbladder is the primary finding in cholescintigraphy for acute cholecystitis. Recent investigators have described a useful secondary finding of increased pericholecystic hepatic activity (PCHA). A case of acute cholecystitis is presented in which the PCHA was round in configuration and appeared in the first 5 minutes of the study. This may be a source of diagnostic error if it is interpreted as visualization of the normal gallbladder. Appearance of the PCHA has not been previously described before 30 minutes. This case of early appearance raises the possibility that hyperemia may play a role as the cause in some forms of the PCHA. The phantom gallbladder was correctly identified as PCHA by observing the peak of activity of the PCHA occurring before the appearance of intrahepatic biliary radicals.

Work has been continued on the development of techniques for imaging spatial elemental distributions by means of differential absorption about the K-absorption edge of the particular element Z. A method to correct for spurious effects due to differential absorption in overlying absorber is described. Initial clinical studies of thyroid iodine images on patients are presented. Application of absorption edge transmission scanning to thin in-vitro samples of bone is also discussed.

The authors evaluate the performance of a large-area (50 cm2) germanium detector for rectilinear scanning by comparing both the modulation transfer function (MTF) and scan images with that of a standard NaI detector. The MTF was evaluated from the line-response function and compared with that observed with a conventional 7.6 × 5.1-cm NaI(Tl) detector using both full and upper half-peak energy windows of the 140 keY 99mTc gamma-ray peak. With the source in air, little difference was observed between the two, but with the Ge(Li) source surrounded by 12 cm of Lucite absorber, MTF improved significantly, as reflected in phantom scans of 99mTc activity.

A system of rectilinear scanning has been developed which senses the presence of particular elements by measuring the differential attenuation of x-ray photons about a specific absorption edge. A continuous x-ray spectrum generated from a side-window 50 kVcp tube is used and the transmitted beam is detected by an energy selective Ge(HP) semiconductor detector. Measurements on phantoms with absorbers up to 10 cm thick indicate sensitivity to middle Z elements such as iodine, down to the range of 1 mg/cm2 in reasonable scanning times. Little effect was seen by additional 1" absorbers, and the effects of in-line voids can be minimized. Scans were taken of rabbit kidneys and bileary tracts as an iodated contrast agent was infused, and of rabbit lungs while the animal breathed a xenon/oxygen mixture. Future directions for this technique of transmission scanning are discussed.

Interface thermal contact conductance between metals in vacuum studied for data on heat transfer mechanism

A fatty acid analog (15-p-iodophenyl)-3,3 dimethyl-pentadecanoic acid (DMIPP) was studied in cardiomyopathic (CM) and normal age-matched Syrian hamsters. Dual tracer quantitative wholebody autoradiography (QARG) with DMIPP and 2-[14C(U)]-2-deoxy-2-fluoro-D-glucose (FDG) or with FDG and 201Tl enabled comparison of the uptake of a fatty acid and a glucose analog with the blood flow. These comparisons were carried out at the onset and mid-stage of the disease before congestive failure developed. Groups of CM and normal animals were treated with verapamil from the age of 26 days, before the onset of the disease for 41 days. In CM hearts, areas of decreased DMIPP uptake were seen. These areas were much larger than the decrease in uptake of FDG or 201Tl. In early CM only minimal changes in FDG or 201Tl uptake were observed as compared to controls. Treatment of CM-prone animals with verapamil prevented any changes in DMIPP, FDG, or 201Tl uptake. DMIPP seems to be a more sensitive indicator of early cardiomyopathic changes as compared to 201Tl or FDG. The trial of DMIPP and SPECT in the diagnosis of human disease, as well as for monitoring the effects of drugs which may prevent it seems to be warranted.

201Tl-chloride and 204Tl-nitrate were similarly distributed in organs of mice 10 min and 60 min after intravenous injection. Autoradiographic studies were carried out with 204Tl-nitrate in rats (injected intraperitoneally) as well as in mice and dogs (injected intravenously). Thallium localized in the cells of proximal and distal convoluted tubules and collecting tubules of the kidney. In the intestines, it was distributed mostly in the cells of the smooth musculature and surface epithelium of the villi. Some silver grains were seen in the goblet cells and in the lumen as well. It localized in the sarcoplasm of the myocardium and the skeletal muscle cells. In thyroid, most of the thallium was seen in the colloidal part of the follicle. In testes, silver grains were seen in and around the cells of Sertoli and in the lumen of the seminiferous tubules. Some localized concentration in the interstitial cells of the testes was also observed.

Deferoxamine mesylate (DFO), given to rabbits 20 min after gallium-67 citrate, induces prompt and rapid urinary excretion of Ga-67 activity with concommitant decrease in blood and muscle activity. When DFO is given after 2 hr or later, the effect is smaller (15% decrease in blood activity compared with 50%). In abscess-bearing rats the same effect was observed: DFO accelerated the Ga-67 blood clearance by increasing urinary excretion. Tissue-distribution studies and direct counting of abscesses showed that DFO lowers Ga-67 activity in all organs as well as in the abscess if given 2 or 4 hr after Ga-67 citrate, but the abscess-to-blood ratio increases. At 24 hr after Ga-67 citrate, DFO administration causes an improvement in the ratios of abscess-to-blood and abscess-to-normal tissue. Thus, DFO could be used to decrease the radiation burden from Ga-67 citrate after imaging has been performed, and also to increase the target-to-nontarget ratio.

The long-term lung retention of 3.6-..mu..m-diameter polystyrene particles tagged with Sr-85 was measured in 5 healthy nonsmokers, 6 healthy ex-smokers, 8 smokers, and 6 persons with chronic obstructive lung disease (COLD). Normal long-term clearance was in two phases with half-times of 30 +- 23 days and 296 +- 98 days, respectively, 27 +- 13% clearing via the fast phase. Half-times and relative amounts clearing via the two temporal phases were independent of particle penetration, implying that they are associated with two different mechanisms clearing particles from the same anatomical compartment. A repeat study in one person was consistent with the first, showing that long-term clearance is a well-defined physiological function characteristic of an individual. Cigarette smoking supressed the fast clearance phase and increased the half-time of the slow phase by 14.7 +- 3.0 days (95% confidence limit) per pack-year of smoking. Healthy ex-smokers had normal long-term clearance, but the individuals with COLD had a significantly increased slow phase half-times.

A finite-volume method for solving the compressible laminar Navier-Stokes equation in two dimensions is assessed for use in the simulation of transitional flows. The method is second-order-accurate, uses alternating-direction-implicit time integration, and a total-variation-diminishing smoothing operator in the inviscid flux terms. The test problem was a free shear layer with a forced periodicity in x at a specified wavelength and with the parallel mean flow specified as a hyperbolic-tangent profile. A grid refinement investigation verified this method to be second-order-accurate with less than 4 percent error in the growth rate of isolated modes on a 32 by 64 grid. The interaction between modes of similar amplitude was small, less than 1 percent. However, in cases where there was a dominant mode, numerical phase error pumped energy into all other modes. This error results in nonphysical growth rate for modes whose energy content is several orders of magnitude below the dominant mode. In the case when the dominant mode saturates, the pumping action stops and the growth rate of the next largest growing mode regains physical significance.

Wir verwandten das Melanom des syrischen Goldhamsters als Laboratoriumsmodell, um eine mogliche Verwendbarkeit von radioaktiven Substanzen zur Melanomlokalisation zu prufen. Bioverteilungsdaten wurden ermittelt, und wo die Tumorhintergrundsverhaltnisse gunstig waren, wurden Szintigramme (scans) gemacht. Die untersuchten Wirkstoffe hinsichtlich ihrer %-Dosis/g-Aufnahme werden in einer Tabelle gezeigt. Die Scans waren von Nutzen bei Melanomen des Auges. Anderweitige Lokalisation von Melanomen hangen von der Organaufnahme im Gebiete des Tumors ab. Daher konnen wir nicht sagen, das alle Wirkstoffe gleich gut zur Lokalisationsdiagnostik geeignet sind; es scheint eher, das verschiedene radioaktive Substanzen fur die zu untersuchenden Bezirke ermittelt werden mussen. Klinische Studien mit Iodine-123, 4, 3 DMQ (4, 3 dimethylaminopropylamino-7-iodoquinoline) haben uns ermoglicht, zwei Aderhautmelanome und ein Hautmelanom zu lokalisieren. Negativstudien wurden in drei Fallen durchgefuhrt; alle hatten auch ein negatives Biopsieergebnis. Zur Lokalisation von Aderhautmelanomen waren spezielle Kollimatoren erforderlich.

The in vivo measurements of 127Xe and 79Kr clearance from the whole body indicate five components, with biologic half-times ranging from 13 sec to 17.04 h. The slowest component correlated highly with percent total-body fat, the half-time varying between 7.59 and 17.04 for xenon and between 4.20 and 9.62 h for krypton. The long-term retention was localized to regions of high fat content as determined by the coincidence mode of the whole-body counter and images obtained with the scintillation camera. The estimated dose based on the retention data of this study would indicate increased doses to body fat and gonads as compared with those previously calculated. These increased doses are due to the longer retention of noble gases in fat. After 10-min inhalations of a mixture of 127Xe and air and 79Kr and air, approximately one third of the total 127Xe and one fifth of the total 79Kr were transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, approximately 13% of the 127Xe and approximately 9% of the 79Kr were associated with the slowest component.

For the purpose of radiation dose estimates, organ assays and excretion measurements of the Tc-99m and In-111 complexes with DTPA were conducted in dogs at various time intervals up to 24 hr, and the results compared with available human data. The peak concentration of the Tc-99m complex, at 3 min after injection, was 5% of the administered dose for one kidney, 3.5% for the liver, and 3.5% for the small bowel. No organ system except the urinary tract reached a concentration higher than that in blood for several hours after the injection. The biliary excretion of these agents was extremely low, and their elimination in the feces was negligible. In man, it appears that the residual 4-5% of an administered dose not eliminated in the urine by 24 hr is widely distributed in various tissues. The distribution of the In-111 complex is similar but not identical to that of the Tc-99m complex.

Das strahlenaktive Iodine-125 hat eine Halbwertzeit von 60 Tagen, eine durchschnittliche Energie von 27 keV und eine durchschnittliche Tiefendosis von 18,0 mm (halbe Wasserdicke). Diese physikalischen Charakteristika sind fur eine radioaktive Quelle fur interstitielle Strahlentherapie geeignet. Wir haben einen neuen Trager fur die Iodine-125-Bestrahlung von Augentumoren entwickelt. Der Trager wurde so konstruiert, das normales Augengewebe und Orbitastrukturen von schadigenden Strahlen geschutzt werden, wahrend die Bestrahlung des Tumors gewahrleistet ist. Die ersten Trager waren aus Blei, danach aus rostfreiem Stahl, das eine nahezu vollstandige Absorption der Iodine-125-Strahlung ermoglicht. Ein Millimeter rostfreien Stahls absorbiert mehr als 97% der lodine-125-Strahlen, wahrend die Halbwertschicht von Cobalt-60 aus 12 mm Blei besteht. Der Trager erlaubt durch seine offene Vorderflache eine ungehinderte, ungeschwachte Iodine-125-Strahlung zum Tumor. Das Melanom wurde in den suprachorioidalen Raum transplantiert und dient als Modell. Die Tumoren werden mit Iodine-125-Tragern bestrahlt. Die Strahlenwirkungen auf das Auge werden durch histopathologische Untersuchungen bestimmt. Klinische Studien mit Iodine-125 mit Goldtragern sind im Gange. Diese Trager sind leicht herzustellen und ermoglichen eine gute Bestrahlung des Aderhautmelanoms, wahrend die vitalen Augenstrukturen geschutzt werden.

Nonvisualization of the gallbladder is the primary finding in cholescintigraphy for acute cholecystitis. Recent investigators have described a useful secondary finding of increased pericholecystic hepatic activity (PCHA). A case of acute cholecystitis is presented in which the PCHA was round in configuration and appeared in the first 5 minutes of the study. This may be a source of diagnostic error if it is interpreted as visualization of the normal gallbladder. Appearance of the PCHA has not been previously described before 30 minutes. This case of early appearance raises the possibility that hyperemia may play a role as the cause in some forms of the PCHA. The phantom gallbladder was correctly identified as PCHA by observing the peak of activity of the PCHA occurring before the appearance of intrahepatic biliary radicals.

Xenon-133 and xenon-127 were compared by performing ventilation studies with both radionuclides in 19 patients with a variety of lung diseases. Assessment of the counting rate over the chest, relative to the radioactivity in the lungs, permitted the evaluation of each isotope in terms of usable photons detected by a scintillation camera with a large field of view and appropriate collimation. A greater photon yield was obtained with Xe-127. Markedly improved resolution was shown by measurement of a line phantom, but was not apparent on subjective appraisal of scintiphotos except in the washout phase. Xenon-127 appears to be preferable to Xe-133 because of the higher counting rates, lower patient radiation dose, and longer shelf life. In addition, a prior perfusion study using a Tc-99m radiopharmaceutical does not affect the quality of a Xe-127 ventilation study. The use of Xe-127 therefore permits the selection for ventilation studies of only those patients with suspected pulmonary embolism, and eliminates unnecessary radiation exposure. A further improvement in image quality obtained with Xe-127 should be possible with certain modifications of the scintillation camera that would permit use of the 375-keV photopeak along with the 172- and 203-keV gamma energies. Charcoal traps designed for Xe-133 will require additional shielding and longer storage time when used for Xe-127. Xenon-127, however, might be used again after appropriate processing.