Pattern of Tubercular Uveitis in Active Pulmonary Tuberculosis.

Ocular tuberculosis is an extra-pulmonary form of systemic Tuberculosis (TB). It is rarely found concomitant with active pulmonary tuberculosis (PTB). The aim of this prospective observational study was to evaluate the pattern of tubercular uveitis (TBU) in the patients with active PTB who attended in our Uvea clinic at NIO&H from July 2018 to December 2020. Active PTB patients who had uveitis consistent with TBU and TBU patients who were confirmed as active lung lesion were included in the study. Chest X-ray, TST, IGRA (QuantiFERON-TB Gold Test), RT PCR of aqueous fluid for tubercular bacillus, Gene Xpert TB test of sputum were done to confirm the diagnosis of ocular and primary TB. If the induration is 15 mm of TST was considered patient in this study. Among 33 patients of active PTB, 4 had TBU (12.12%). Among 48 patients of TBU, 5 had active PTB (10.41%). 13 eyes of 9 patients were affected. Mean age at presentation was 41.8 years. There were anterior uveitis in 23.00% eyes, posterior uveitis in 69% eyes and panuveitis in 7.00% eyes. Choroidal granuloma was the most common presentation of posterior uveitis (46.00%). There were more than 4 times chance to develop choroidal granuloma in patients with active PTB than extrapulmonary TB (Χ²=4.53, <0.05), TBU patients with choroidal granuloma should be evaluated meticulously for active PTB and active PTB patients should be evaluated routinely by ophthalmologist for the search of TBU.

Monte Carlo simulation of a multi-leaf collimator design for telecobalt machine using BEAMnrc code.

This investigation aims to design a practical multi-leaf collimator (MLC) system for the cobalt teletherapy machine and check its radiation properties using the Monte Carlo (MC) method. The cobalt machine was modeled using the BEAMnrc Omega-Beam MC system, which could be freely downloaded from the website of the National Research Council (NRC), Canada. Comparison with standard depth dose data tables and the theoretically modeled beam showed good agreement within 2%. An MLC design with low melting point alloy (LMPA) was tested for leakage properties of leaves. The LMPA leaves with a width of 7 mm and height of 6 cm, with tongue and groove of size 2 mm wide by 4 cm height, produced only 4% extra leakage compared to 10 cm height tungsten leaves. With finite (60)Co source size, the interleaf leakage was insignificant. This analysis helped to design a prototype MLC as an accessory mount on a cobalt machine. The complete details of the simulation process and analysis of results are discussed.

Oncogenic transformation of mammalian cells by ultrasoft X-rays and alpha particles.

For a better understanding of oncogenic cell transformation by ionizing radiation, we conducted experiments with ultrasoft X rays and low energy alpha particles. Confluent C3H10T1/2 cells were irradiated by Al-K (1.5 keV) X rays or alpha particles from plutonium through a thin mylar sheet, on which the cells attached and grew. Our results indicated that Al-K X rays were more effective in causing cell inactivation and oncogenic transformation than 60Co gamma rays but less effective than 1.0 and 3.7 MeV alpha particles. There was no significant difference between 1.0 and 3.7 MeV alpha particles in transforming cells although the latter were slightly more effective than the former in producing lethal effect. These results indicated that track structure is important in causing biological effects by ionizing radiation.

High-LET radiotherapy and experiences in improving rural health care in India.

A brief back ground of high-LET radiotherapy developments and its current status will be presented. In addition, based on my experience in developing a program on cancer prevention and early detection in rural India, the gulf between sophisticated developments in cancer diagnosis and treatment and the basic needs in the developing world will be presented with some possible solutions.

Radiobiology of ultrasoft X rays. V. Modification of cell inactivation by dimethyl sulfoxide.

The effects of the radioprotector dimethyl sulfoxide (DMSO) were investigated for carbon-K (0.28 keV) and aluminum-K (1.47 keV) X rays compared with 60Co gamma rays for inactivation of mouse C3H 10T1/2 cells. The protection factor for 2 M DMSO was found to be 2.8 for both of the ultrasoft X-ray energies, which is not significantly different from the protection factor of 2.6 found for gamma rays. The results indicate that the proportion of scavengeable lethal damage from gamma and X rays does not depend on the proportion of the total energy that is deposited by low-energy electrons of relatively high ionization density.

Particle radiotherapy: historical developments and current status.

The current status of particle radiotherapy from a historical perspective is presented. This is done with a personal view and contains personal references and memories during the development of particle radiotherapy. The particles covered are fast neutrons, neutron capture therapy, protons, helium ions, pions and heavy ions. International cooperation in the development of the field of particle therapy, its impact on radiobiology and conventional radiotherapy, and some personal reflections and conclusions are also presented briefly.

Proton radiobiology, radiosurgery and radiotherapy.

This review briefly traces the historical developments of proton radiobiology, radiosurgery and radiotherapy for the benefit of young researchers and clinicians entering into this field. In preparing to use protons in radiosurgery and radiotherapy, radiobiological effects of protons were studied extensively by various groups, including the University of California at Berkeley, the University of Uppsala, Massachusetts General Hospital, and the Harvard Cyclotron Laboratory. Considerable work on proton radiobiology was also done because protons are a major component of the radiation environment in space. The biological effects of proton beams were found to be quantitatively and qualitatively similar to conventional radiations used in radiotherapy. The relative biological effectiveness (RBE) of protons suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally in the range 1.0-1.25, and remains the same with depth of penetration, except for the descending portion of the depth-dose curve. Also, unlike other heavier charged particles and neutrons, the RBE of high-energy protons, which are suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally found to be independent of the fraction size in in vivo experiments. The oxygen enhancement ratio for high-energy protons is not significantly different from that of X-rays. An RBE = 1.1, compared with 60Co gamma-rays, is generally used in the clinical application of protons; however, the radiobiological data on mouse, rat, rabbit and primate suggest that the gastrointestinal tissues may be relatively more sensitive to protons. About 13,000 patients have been treated with protons at about 15 facilities around the world. Nearly half of these patients were neurosurgical patients treated with stereotactic radiosurgery. The pioneering efforts at the Harvard Cyclotron in collaboration with the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary were responsible for the development of proton treatment for choroidal melanoma and for the tumours of the skull base and spine. There has been extensive confirmation of these results by other groups, especially the groups at Lawrence Berkeley Laboratory and Paul Scherrer Institute. The first medically dedicated proton facility is in operation at Loma Linda University in California. The construction in the USA of another proton treatment facility at Massachusetts General Hospital has been decided upon, and there are plans for many more worldwide.

Radiobiology of alpha particles. IV. Cell inactivation by alpha particles of energies 0.4-3.5 MeV.

In this report the effectiveness of low-energy alpha particles in the range 0.4 to 3.5 MeV for cell killing is investigated. Four cell lines of different nuclear dimensions (AG1522, C3H 10T1/2, CHO-10B, and HS-23) are studied. Monte Carlo simulations are carried out to interpret the experimental results. They are presented as a function of dose to the nucleus, the total track length of alpha particles in the nucleus, and other parameters. It is found that the effectiveness of alpha particles for cell killing decreases with decreasing alpha-particle energy. The maximum RBE value is found to extend to LET values as high as 180 keV/microns. Although the LET might be the same, the effectiveness of alpha particles for cell killing is higher in the ascending part of the Bragg curve compared to descending part of the Bragg curve. The terminal tracks of alpha particles are observed to be less effective for cell killing.

Radiobiology of alpha particles. II. Dosimetry of low-energy alpha particles using parallel-plate ionization chambers and a surface barrier detector.

Three small parallel-plate ionization chambers were developed for measuring dose rates, of primarily low-energy alpha particles in the energy range 0.4-3.5 MeV, at a defined cell-Mylar interface. Spectral energy distributions of these alpha particles were also measured at the same position using a specially designed small-area silicon surface barrier detector. Dose rates were derived from the spectral distributions and compared with those derived from the ionization chambers. Different alpha-particle energies were obtained using a 144-MBq 238Pu collimated source and a variety of Mylar moderator foils of different thicknesses. These measurements, extended to mean alpha-particle energies as low as 0.4 MeV, will enable us to correlate radiobiological data with effects of alpha particles terminating in different regions of cell nuclei.

Radiobiology of alpha particles. III. Cell inactivation by alpha-particle traversals of the cell nucleus.

Cell inactivation after exposure to collimated 3.5-MeV alpha particles in three hamster cell lines, V79, CHO-10B, and HS-23, one mouse cell line, C3H 10T1/2, and a human skin fibroblast cell line were studied. Several parameters were investigated for each cell line. Theoretical calculations were performed to find the distribution of energy deposited in the nuclear volume for each cell line. The mean number of alpha-particle traversals required to induce a lethal lesion varied between two for HS-23 cells and six for C3H 10T1/2 cells. The number of traversals per unit area and the total track length of alpha particles that inactivated a cell were found to be nearly constant for the hamster and mouse cell lines. These quantities were found to be lower for the human skin fibroblast cell line. The RBE values for all cell lines were found to be about 3.8 at 10% survival. Thus cell lines that are more sensitive to alpha radiation are also more sensitive to gamma radiation. The average number of alpha-particle traversals producing a single lethal lesion is greater than one. The passages of alpha particles through the cell nucleus that do not kill the cell may lead to carcinogenic effects.

Oxygen enhancement ratio as a function of dose and cell cycle phase for radiation-resistant and sensitive CHO cells.

There is still controversy over whether the oxygen enhancement ratio (OER) varies as a function of dose and cell cycle phase. In the present study, the OER has been measured as a function of survival level and cell cycle phase using volume flow cell sorting. This method allows both the separation of cells in different stages of the cycle from an asynchronously growing population, and the precise plating of cells for accurate measurements at high survival levels. We have developed a cell suspension gassing and sampling system which maintained an oxygen tension less than 20 ppm throughout a series of sequential radiation doses. For both radiation-resistant cells (CHO-K1) and a radiation-sensitive clone (CHO-xrs6), we could separate relatively pure populations of G1-phase, G1/S-boundary, S-, and G2-phase cells. Each cell line showed a typical age response, with cells at the G1/S-phase boundary being 4 (CHO-K1) to 12 (CHO-xrs6) times more sensitive than cells in the late S phase. For both cell lines, G1-phase cells had an OER of 2.3-2.4, compared to an OER of 2.8-2.9 for S-phase and 2.6-2.7 for G2-phase cells. None of these age fractions showed a dependence of OER on survival level. Asynchronously growing cells or cells at the G1/S-phase boundary had an OER similar to that of G1-phase cells at high survival levels, but the OER increased with decreasing survival level to a value near that of S-phase cells. These results suggest that the decrease in OER at high survival levels for asynchronous cells may be due to differences in the OERs of the inherent cell age subpopulations. For cells in one cell cycle stage, oxygen appears to have a purely dose-modifying effect.

Response of X-ray-sensitive CHO mutant cells (xrs-6c) to radiation. II. Relationship between cell survival and the induction of chromosomal damage with low doses of alpha particles.

The induction of cytotoxicity, chromosomal aberrations, and sister chromatid exchanges (SCEs) was measured in CHO K-1c cells and in isogenic X-ray-sensitive mutant xrs-6c cells that had been irradiated with X rays and alpha particles in isoleucine-deficient alpha-minimal essential medium in G1 phase of the cell cycle. There was a noticeable shoulder region on the survival curve for CHO K-1c cells irradiated with very low doses of alpha particles, whereas this feature was absent for xrs-6c cells with alpha-particle doses as low as 0.5 cGy. Higher frequencies of chromatid-type aberrations were induced in G1-phase xrs-6c cells than in G1-phase CHO K-1c cells by both gamma- and alpha-particle irradiation. Induction of nonlethal chromosomal aberrations was observed following exposure to 2-6 cGy of alpha particles, doses yielding 97-100% cell survival. Irradiation with 0.5 cGy of alpha particles induced SCE; nearly 60% of irradiated cells contained significantly increased levels of SCE. However, only 3% of the nuclei of cells exposed to 0.5 cGy of alpha-particle radiation were actually traversed by an alpha particle. The observation that a large fraction of cells apparently survive exposure to very low doses of alpha-particle radiation with persistent genetic damage manifested by both chromosomal aberrations and SCEs may have important implications for the carcinogenic hazards of high-LET radiation.

Radiobiology of alpha particles. I. Exposure system and dosimetry.

A 238Pu alpha-particle exposure apparatus was designed and constructed for use in radiobiological studies with cultured cell systems. The system provides a wide dynamic range of absorbed doses and a uniform radiation field. Average dose rate in air was measured with a small-volume ionization chamber. Estimates of dose rate at the cell surface were obtained from measurements taken with a silicon surface barrier detector. Particle fluence uniformity and fluence rate were measured using track etch procedures. The design and dosimetric characterization of the apparatus are discussed.

Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells.

CHO K-1 cells were irradiated during the G1 phase with 0.5-6 rad of alpha particles. There was no appreciable cell killing in this low dose range. Significantly increased frequencies of sister-chromatid exchanges were induced by doses as low as 0.5 rad of alpha-particle irradiation, whereas increased numbers of chromosomal aberrations were observed following exposure to 2 rad. These results suggest that very low doses of alpha radiation may lead to radiation-induced genetic alterations.

Radiobiology of pions in comparison with other heavy particles.

Our recent data on late effects of pions in spinal cord, lung and rectum in rodents is presented with reference to other high-LET radiations. Unlike high-LET radiations such as neutrons and neon ions, the RBE for late effects of pions (up to 1.5) is not found to be significantly different from acute effects. Because of the potential of matching treatment volume (especially by using dynamic treatments) to the target volume by using pions and heavy ions, it is of utmost importance to study the tolerance of normal tissues to late effects as a function of volume. Such knowledge combined with pion and heavy ion dynamic treatment could lead to a further step in heavy particle radiotherapy.

Measurement of the G-value for 1.5 keV X-rays.

Although there are several theoretical predictions of the dependence of the G-value on X-ray energy, measurements have not been made below approximately equal to 7 keV. Using a ferrous sulfate solution modified by the addition of benzoic acid, we have measured the relative G-values for Alk characteristic X-rays (1.5 keV), 238Pu alpha-particles (3.7 MeV), 60Co (1.17 MeV) and 137Cs (0.66 MeV) gamma-rays. This modified ferrous sulfate solution gave a 4-fold increase in sensitivity relative to the conventional solution, making measurements with the Alk X-rays feasible. The relative ferrous-to-ferric conversions as a function of dose were similar for the two gamma-ray energies, yielding G-values of 1.62 and 1.59 mumol J-1 for the 60Co and 137Cs radiations, respectively. The alpha-particle G-value was 0.52 mumol J-1, or 31 per cent of that for the 60Co gamma-rays, in good agreement with previous measurements. The Alk X-rays had a G-value of 0.92 mumol J-1 or 57 per cent of that of the 60Co radiation. This G-value for the 1.5 keV X-rays is within 20 per cent of the values predicted by current theories, and theoretical values are within the error range of our measurement. The consistency between the experimental value reported here and theoretical G-values for ultrasoft X-rays should be valuable for models of radiation action on biological systems.

Radiobiology of ultrasoft X rays. III. Normal human fibroblasts and the significance of terminal track structure in cell inactivation.

Ultrasoft characteristic X rays from carbon (0.28 keV) are severely attenuated as they pass through biological material, causing a nonuniform distribution of dose to cell nuclei. Complications of studying ultrasoft X rays can be minimized in this context by using cells with very thin cytoplasm and nuclei (e.g., less than the attenuation length of the X rays), and which exhibit a more nearly exponential dose response to cell killing, such as normal human fibroblasts compared with V79 cells. Using this cell system, we report the relative biological effectiveness (RBE) of A1-K and C-K X rays to be near unity. Previous studies of cell inactivation by characteristic carbon X rays gave RBEs of 3 to 4, supporting the idea that localized energy depositions from secondary electrons and primary track ends represent the principal mode of biological action for other low-LET radiations. In part, the reported high RBEs result from the use of mean dose to describe energy deposited within the cell nuclei by these poorly penetrating radiations. Implicit in the use of mean dose is that cellular damage varies linearly with dose within a critical target(s), an assumption that is of questionable validity for cells that exhibit pronounced curvilinear dose responses. The simplest interpretation of the present findings is that most energy depositions caused by track-end effects are not necessarily more damaging than the sparsely ionizing component.