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[An empirical model for calculating electron dose distributions].

Dose-distributions in radiation fields are calculated for purpose of irradiation planning from measured depth dose and cross-distributions predominantly. Especially in electron fields the measuring effort is high to this, because these distributions have to be measured for all occurring irradiation parameters and in many different tissue depths. At the very least it can be shown for the 6...10 MeV electron radiation of the linear accelerator Neptun 10p that all required distributions can be calculated from each separately measured depth dose and cross-distribution. For this depth dose distribution and the measured border decrease of cross-distribution are tabulated and the abscissas are submitted to a linear transformation x' = k.x. In case of depth dose distribution the transformation factor k is dependent on electron energy only and in cross-distribution on tissue depth and source-surface-distance additionally.

Electrons↗

Total body irradiation techniques and dosimetry.

Irradiation techniques and dosimetric methods used for total body irradiation (TBI) performed at Institut Gustave Roussy (Villejuif) are presented. TBI are performed in a 5,6 MV X-ray beam produced by a linear accelerator Neptune. The patient, lying laterally on a couch at 4.20 m from the target, is irradiated by a horizontal beam with a mean nominal dose rate at the abdomen mid-plane of about 9 cGy per minute. The procedure used for TBI consists of three parts in order to deliver 8 Gy in the whole body except for lungs which are protected with a lead screen during a part of irradiation and receive a dose of 4 Gy. We have preferred using "in vivo" measurements methods rather than calculations to determine the doses at different points of the patients. Two kinds of detectors are placed on the patient's skin all along the total body irradiation : two sets of five Therados semi conductors probes permit to control the irradiation and lithium fluoride thermoluminescent dosimeters are used like reference detectors. The dosimetric results obtained during the TBI performed at IGR are discussed.

Abdomen↗

Comparison between experimental measurements and calculated transport simulation for electron dose distributions inside homogeneous phantoms.

Comparison is made between dosimetric results measured on electron beams delivered by the three medical accelerators Sagittaire, Saturne and Neptune built by CGR MeV with the results simulated by a Monte Carlo method. In depth, the differences are small for moderate energies with scanned electron beams. In the penumbra region, the differences are small in all cases.

Electrons↗

Primary lung cancer surgery in stage II and stage III.

We reviewed 100 operations performed on 95 consecutive patients with stage II (n = 7) and stage III (n = 88) primary lung cancer. The five-year survival of patients with N1 involvement was 58% and with N2 disease was 21%. Of 13 patients with Pancoast or chest wall involvement, 58% survived five years. The entire group had a 34% five-year survival and a median survival of 32 months. Preoperative and/or postoperative radiotherapy, in the presence of nodal disease, appears to improve local control, but an effective chemotherapy program is needed for unrecognized visceral metastases. In the absence of contraindications, surgical excision offers the best likelihood of survival and quality of life.

Adenocarcinoma↗

Short-term and subchronic repeated exposure studies with 5-ethylidene-2-norbornene vapor in the rat.

5-Ethylidene-2-norbornene (ENB) is an industrial chemical whose physical properties indicate a likelihood for vapor exposure to humans. The potential for target organ or cumulative toxicity was investigated in rats exposed for 6 h per day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4- week recovery animals were added to the 14-week study. Mean analytically measured ENB vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2 ppm for the 9-day study and 4.9 +/- 0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the subchronic study. There were no mortalities, and clinical signs were limited to periocular swelling and/or encrustation, and urogenital area wetness. Body weight gain was decreased in the 9-day 359 ppm females and in the subchronic 24.8 and 149 ppm males. A minimal macrocytic anemia was present in subchronically exposed males, which resolved during the recovery period. In the 9-day study increased liver weight was associated with minimal centrilobular hepatocytomegaly and cytoplasmic basophilia with no degenerative or serum biochemical liver function changes, suggesting an adaptive response. Only relative liver weights were increased in the subchronic 149 ppm males, and no histopathological findings were observed. Principal target organ effects were to the thyroid gland, which showed an exposure concentration-related, but not exposure time-related, depletion of follicular colloid that resolved during the recovery period, together with light microscopic evidence for a hypertrophic and hyperplastic response in the follicular epithelium that resolved more slowly. The thyroid colloid depletion was a graded effect without a clear no-effect concentration, but was not accompanied by any clinical or clear biochemical evidence for thyroid dysfunction. A no-effect concentration of 4.9 ppm was established for the follicular cytological effects.

Administration, Inhalation↗

An aggressive approach to marginally resectable lung cancer.

Between July 1968 and December 1974, 53 patients with lung cancer were planned for preoperative irradiation and surgery. All patients were considered clinically marginally resectable because of advanced local disease, 4 Stage II patients, with limited pulmonary reserve and 49 Stage III patients. Most patients received 3000 to 4000 rad followed in two weeks by thoracotomy. Forty-six patients were explored and 38 were resectable. Twelve patients are alive with a median follow-up of 48 months. The cumulative 5-year survival of all resectable patients is 27%. The survival of patients with marginally resectable lung cancer treated by accelerated radiotherapy followed by aggressive surgery approaches the survival experience of patients with primary resectable lung cancer and is superior to such patients treated with radiation therapy alone.

Bronchial Fistula↗

Concomitant 5-fluorouracil infusion and high-dose radiation for stage III non-small cell lung cancer.

Thirty patients with Stage III non-small cell lung cancer were entered on a trial to evaluate the feasibility of combined radiation and concomitant 5-fluorouracil infusion. Patients had received prior debulking surgery (nine), induction chemotherapy (16), or no therapy (five). Radiation employed standard fractionation (180-200 rad/day) administered to a median cumulative dose of 5500 rad (range, 4500-6200 rad). 5-Fluorouracil was infused 24 hours per day throughout the period of radiation at a dose of 300 mg/m2/day for a median of 42 days (range, 28-56 days). Radiation complications included pneumonitis three of 30 (10%) and esophagitis (27%). Chemotherapy complications included stomatitis, two of 27 (7%), and hand-foot syndrome, three of 30 (10%). Treatment interruptions were necessary in six of 30 (20%) and four of 30 required parenteral nutrition. At a median follow-up of 12 months 26/30 (87%) maintained local control and eight had distant metastases (three of whom presented with Stage IV disease). 5-Fluorouracil delivered continuously throughout standard fractionation radiation to high cumulative doses is feasible and practical. Comparative clinical trials of the various combined radiation and chemotherapy schedules employed are in order. One additional clinical observation was the identification of six of 30 (20%) with brain metastases at presentation or after 12 months, all of whom had adenocarcinoma histologic subtype.

Aged↗

Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development.

The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that is known to be a site of viral attachment and entry, but its physiologic functions are undefined. CAR expression is maximal in neonates and wanes rapidly after birth in organs such as heart, muscle, and brain, suggesting that CAR plays a role in the development of these tissues. Here, we show that CAR deficiency resulted in an embryonic lethal condition associated with cardiac defects. Specifically, commencing approximately 10.5 days postconception (dpc), CAR-/- cardiomyocytes exhibited regional apoptosis evidenced by both histopathologic features of cell death and positive staining for the apoptotic marker cleaved caspase 3. CAR-/- fetuses invariably suffered from degeneration of the myocardial wall and thoracic hemorrhaging, leading to death by 11.5 dpc. These findings are consistent with the view that CAR provides positive survival signals to cardiomyocytes that are essential for normal heart development.

Animals↗

Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice.

The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.

1-Propanol↗

Chemical investigation of Titan and Triton tholins.

We report chromatographic and spectroscopic analyses of both Titan and Triton tholins, organic solids made from the plasma irradiation of 0.9:0.1 and 0.999:0.001 N2/CH4 gas mixtures, respectively. The lower CH4 mixing ratio leads to a nitrogen-richer tholin (N/C > 1), probably including nitrogen heterocyclic compounds. Unlike Titan tholin, bulk Triton tholin is poor in nitriles. From high-pressure liquid chromatography, ultraviolet and infrared spectroscopy, and molecular weight estimation by gel filtration chromatography, we conclude that (1) several H2O-soluble fractions, each with distinct UV and IR spectral signatures, are present, (2) these fractions are not identical in the two tholins, (3) the H2O-soluble fractions of Titan tholins do not contain significant amounts of nitriles, despite the major role of nitriles in bulk Titan tholin, and (4) the H2O-soluble fractions of both tholins are mainly molecules containing about 10 to 50 (C + N) atoms. We report yields of amino acids upon hydrolysis of Titan and Triton tholins. Titan tholin is largely insoluble in the putative hydrocarbon lakes or oceans on Titan, but can yield the H2O-soluble species investigated here upon contact with transient (e.g., impact-generated) liquid water.

Amino Acids↗

Infrared spectroscopy of Triton and Pluto ice analogs: the case for saturated hydrocarbons.

The infrared transmission spectra and photochemical behavior of various organic compounds isolated in solid N2 ices, appropriate for applications to Triton and Pluto, are presented. It is shown that excess absorption in the surface spectra of Triton and Pluto, i.e., absorption not explained by present models incorporating molecules already identified on these bodies (N2, CH4, CO, and CO2), that starts near 4450 cm-1 (2.25 micrometers) and extends to lower frequencies, may be due to alkanes (C(n)H2n+2) and related molecules frozen in the nitrogen. Branched and linear alkanes may be responsible. Experiments in which the photochemistry of N2:CH4 and N(2):CH4:CO ices was explored demonstrate that the surface ices of Triton and Pluto may contain a wide variety of additional species containing H, C, O, and N. Of these, the reactive molecule diazomethane, CH2N2, is particularly important since it may be largely responsible for the synthesis of larger alkanes from CH4 and other small alkanes. Diazomethane would also be expected to drive chemical reactions involving organics in the surface ices of Triton and Pluto toward saturation, i.e., to reduce multiple CC bonds. The positions and intrinsic strengths (A values) of many of the infrared absorption bands of N2 matrix-isolated molecules of relevance to Triton and Pluto have also been determined. These can be used to aid in their search and to place constraints on their abundances. For example, using these A values the abundance ratios CH4/N2 approximately 1.3 x 10(-3), C2H4/N2 < or = 9.5 x 10(-7) and H2CO/N2 < or = 7.8 x 10(-7) are deduced for Triton and CH4/N2 approximately 3.1 x 10(-3), C2H4/N2 < or = 4.1 x 10(-6), and H2CO/N2 < or = 5.2 x 10(-6) deduced for Pluto. The small amounts of C2H4 and H2CO in the surface ices of these bodies are in disagreement with the large abundances expected from many theoretical models.

Alkanes↗

The Titan haze revisited: magnetospheric energy sources and quantitative tholin yields.

We present laboratory measurements of the radiation yields of complex organic solids produced from N2/CH4 gas mixtures containing 10 or 0.1% CH4. These tholins are thought to resemble organic aerosols produced in the atmospheres of Titan, Pluto, and Triton. The tholin yields are large compared to the total yield of gaseous products: nominally, 13 (C + N)/100 eV for Titan tholin and 2.1 (C + N)/100 eV for Triton tholin. High-energy magnetospheric electrons responsible for tholin production represent a class distinct from the plasma electrons considered in models of Titan's airglow. Electrons with E > 20 keV provide an energy flux approximately 1 x 10(-2) erg cm-2 sec-1, implying from our measured tholin yields a mass flux of 0.5 to 4.0 x 10(-14) g cm-2 sec-1 of tholin. (The corresponding thickness of the tholin sedimentary column accumulated over 4 Gyr on Titan's surface is 4 to 30 m.) This figure is in agreement with required mass fluxes computed from recent radiative transfer and sedimentation models. If, however, these results, derived from experiments at approximately 2 mb, are applied to lower pressure levels toward peak auroral electron energy deposition and scaled with pressure as the gas-phase organic yields, the derived tholin mass flux is at least an order of magnitude less. We attribute this difference to the fact that tholin synthesis occurs well below the level of maximum electron energy deposition and to possible contributions to tholins from UV-derived C2-hydrocarbons. We conclude that Titan tholin, produced by magnetospheric electrons, is alone sufficient to supply at least a significant fraction of Titan's haze--a result consistent with the fact that the optical properties of Titan tholin, among all proposed materials, are best at reproducing Titan's geometric albedo spectrum from near UV to mid-IR in light-scattering models.

Aerosols↗

Temperature of nitrogen ice on Pluto and its implications for flux measurements.

Previous work by K.A. Tryka et al. (Science 261, 751-754, 1993) has shown that the profile of the 2.148-micrometers band of solid nitrogen can be used as a "thermometer" and determined the temperature of nitrogen ice on Triton to be 38(+2)-1 K. Here we reevaluate that data and refine the temperature value to 38 +/- 1 K. Applying the same technique to Pluto we determine that the temperature of the N2 ice on that body is 40 +/- 2 K. Using this result we have created a nonisothermal flux model of the Pluto-Charon system. The model treats Pluto as a body with symmetric N2 polar caps and an equatorial region devoid of N2. Comparison with the infrared and millimeter flux measurements shows that the published fluxes are consistent with models incorporating extensive N2 polar caps (down to +/- 15 degrees or +/- 20 degrees latitude) and an equatorial region with a bolometric albedo < or = 0.2.

Astronomical Phenomena↗