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Biomedical subjects

R K Das

Publications and source records attributed to R K Das.

At least 19 recordsLinked to original sources

Validation of Monte Carlo dose calculations near 125I sources in the presence of bounded heterogeneities.

PURPOSE: Dose distributions around low energy (< 60 keV) brachytherapy sources, such as 125I, are known to be very sensitive to changes in tissue composition. Available 125I dosimetry data describe the effects of replacing the entire water medium by heterogeneous material. This work extends our knowledge of tissue heterogeneity effects to the domain of bounded tissue heterogeneities, simulating clinical situations. Our goals are three-fold: (a) to experimentally characterize the variation of dose rate as a function of location and dimensions of the heterogeneity, (b) to confirm the accuracy of Monte Carlo dose calculation methods in the presence of bounded tissue heterogeneities, and (c) to use the Monte Carlo method to characterize the dependence of heterogeneity correction factors (HCF) on the irradiation geometry. METHODS AND MATERIALS: Thermoluminescent dosimeters (TLD) were used to measure the deviations from the homogeneous dose distribution of an 125I seed due to cylindrical tissue heterogeneities. A solid water phantom was machined accurately to accommodate the long axis of the heterogeneous cylinder in the transverse plane of a 125I source. Profiles were obtained perpendicular to and along the cylinder axis, in the region downstream of the heterogeneity. Measurements were repeated at the corresponding points in homogeneous solid water. The measured heterogeneity correction factor (HCF) was defined as the ratio of the detector reading in the heterogeneous medium to that in the homogeneous medium at that point. The same ratio was simulated by a Monte Carlo photon transport (MCPT) code, using accurate modeling of the source, phantom, and detector geometry. In addition, Monte Carlo-based parametric studies were performed to identify the dependence of HCF on heterogeneity dimensions and distance from the source. RESULTS: Measured and calculated HCFs reveal excellent agreement (< or = 5% average) over a wide range of materials and geometries. HCFs downstream of 20 mm diameter by 10 mm thick hard bone cylinders vary from 0.12 to 0.30 with respect to distance, while for an inner bone cylinder of the same dimension, it varies from 0.72 to 0.83. For 6 mm diameter by 10 mm thick hard bone and inner bone cylinders, HCF varies 0.27-0.58 and 0.77-0.88, respectively. For lucite, fat, and air, the dependence of HCF on the 3D irradiation geometry was much less pronounced. CONCLUSION: Monte Carlo simulation is a powerful, convenient, and accurate tool for investigating the long neglected area of tissue composition heterogeneity corrections. Simple one dimensional dose calculation models that depend only on the heterogeneity thickness cannot accurately characterize 125I dose distributions in the presence of bone-like heterogeneities.

Iodine Radioisotopes

Accuracy of Monte Carlo photon transport simulation in characterizing brachytherapy dosimeter energy-response artefacts.

Practical dosimeters in brachytherapy, such as thermoluminescent dosimeters (TLD) and diodes, are usually calibrated against low-energy megavoltage beams. To measure absolute dose rate near a brachytherapy source, it is necessary to establish the energy response of the detector relative to that of the calibration energy. The purpose of this paper is to assess the accuracy of Monte Carlo photon transport (MCPT) simulation in modelling the absolute detector response as a function of detector geometry and photon energy. We have exposed two different sizes of TLD-100 (LiF chips) and p-type silicon diode detectors to calibrated 60Co, HDR source (192Ir) and superficial x-ray beams. For the Scanditronix electron-field diode, the relative detector response, defined as the measured detector readings per measured unit of air kerma, varied from 38.46 V cGy-1 (40 kVp beam) to 6.22 V cGy-1 (60Co beam). Similarly for the large and small chips the same quantity varied from 2.08-3.02 nC cGy-1 and 0.171-0.244 nC cGy-1, respectively. Monte Carlo simulation was used to calculate the absorbed dose to the active volume of the detector per unit air kerma. If the Monte Carlo simulation is accurate, then the absolute detector response, which is defined as the measured detector reading per unit dose absorbed by the active detector volume, and is calculated by Monte Carlo simulation, should be a constant. For the diode, the absolute response is 5.86 +/- 0.15 (V cGy-1). For TLDs of size 3 x 3 x 1 mm3 the absolute response is 2.47 +/- 0.07 (nC cGy-1) and for TLDs of 1 x 1 x 1 mm3 it is 0.201 +/- 0.008 (nC cGy-1). From the above results we can conclude that the absolute response function of detectors (TLDs and diodes) is directly proportional to absorbed dose by the active volume of the detector and is independent of beam quality.

Biophysical Phenomena

Micronucleus assay in pulmonary alveolar macrophages, a simple model to detect genotoxicity of environmental agents entering through the inhalation route.

A simple and short-term micronucleus (MN) test in pulmonary alveolar macrophages (PAMs) of rats has been developed to assess potential genotoxic effects of gaseous environmental agents. The protocol has been tested in model experiments with indoor air pollutants like mosquito coil smoke (MCS) and mosquito mat vapour (MMV). Smears of pulmonary lavage fluid collected in hypotonic (0.56%) KCl solution were fixed in absolute methanol and stained in Giemsa (10%). Characteristically the large size of the PAMs facilitates easy scoring of MN. An interval of 32 h post exposure seems to be suitable for MN preparation. A comparison of the concentration-response data on CAs (at 24 h post exposure) and MN (at 32 h post exposure) clearly reveals the validity of the MN assay in PAMs.

Air Pollutants

A secondary air kerma strength standard for Yb-169 interstitial brachytherapy sources.

Ytterbium-169 (169Yb) is a promising new intermediate low-energy isotope for interstitial implantation. To date, no air kerma strength (SK) standard for this source exists that can serve as a sound foundation for comparing various dose measurements and theoretical calculations. We have solved this problem by adapting the free air measurement technique of Goetsch et al, originally developed for 192Ir. Using a 100 cm3 spherical ion chamber with NIST traceable external beam calibrations in a free air geometry, we have measured the air kerma strength of six different source batches (two type 6 batches, three type 8 batches, and one experimental high-intensity source). Room scatter corrections, derived from an empirical fit to the data (following Goetsch et al) and/or directly by Monte Carlo simulation, yielded identical results with a reproducibility of 1%. The ratio [SK/Avendor] of measured SK to the vendor's contained activity assay averaged 1.554 cGy cm2 mCi-1 h-1 (0.0420 microGy m2 MBq-1 h-1), in conflict with the expected value of 1.34 (0.0362), derived from Monte Carlo calculations. The measured [SK/Avendor] for the type 8 seeds varies by as much as 10% whereas the SK/dose calibrator reading ratio varies by no more than 0.3%, suggesting that the reproducibility of Avendor is relatively poor. These discrepancies may help explain the variation (as large as 28%) in published dose rate constants for 169Yb.

Air

Experimental validation of Monte Carlo dose calculations about a high-intensity Ir-192 source for pulsed dose-rate brachytherapy.

Despite widespread use of high-intensity Ir-192 remotely afterloaded sources, no published measured or calculated dose-rate tables for currently used source designs are available. For a pulsed dose-rate Ir-192 source, both transverse axis (0.5-10 cm) and two-dimensional polar dose-rate profiles (1.5, 3, and 5 cm) were measured with thermoluminescent dosimetry in a solid water phantom. Dose rates were normalized to measured air-kerma strength, and the source geometry was verified by pinhole autoradiography and transmission radiography. At each measurement point, dose rates were calculated by a Monte Carlo photon transport (MCPT) code, which realistically modeled the experimental phantom, source, and detector geometry. Agreement between MCPT absolute dose-rate calculations and measurements averaged 3% and was less than 5%, demonstrating that Monte Carlo simulation is an accurate and powerful tool for two-dimensional dosimetric characterization of high activity Ir-192 sources.

Brachytherapy

Induction of chromosome aberrations and micronuclei in pulmonary alveolar macrophages of rats following inhalation of mosquito coil smoke.

The genotoxic potential of inhalation of mosquito coil (MC) smoke was evaluated by using metaphase chromosome aberration and micronucleus assays in pulmonary alveolar macrophages (PAMs) of rats following short-term as well as long-term whole body intermittent exposure. For short-term exposure, the animals were exposed for 15 min/h, 8 h/day to smoke collected for 1, 5 or 10 min, and they were killed 16 or 24 h after the final exposure. For long-term exposure, they were exposed for 15 min/h, 8 h/day, 7 days/week to smoke collected for 10 min and then they were killed 24 h after the final exposure. Each time before exposure, fresh smoke was collected by burning a mosquito coil. Pulmonary lavage was collected, and conventional flame-drying preparation was done for metaphase chromosome analysis and micronuclei (MN) were analyzed from smear preparations. Significantly higher frequencies of chromosome aberrations, including as well as excluding gaps, and micronucleated PAMs in smoke-exposed animals, compared to controls, indicated genotoxic capacity of MC smoke. The increases significantly correlated with the "concentration" of the gas. Mitotic indices also showed a significant and concentration-dependent increase. The frequencies of chromosome aberrations and MN following 7-day exposure were very similar to those for 1-day exposure. This was probably due to the transient nature of PAMs. A post-exposure gap of 24 h, compared to the 16-h gap, yielded a higher incidence of both mitoses and chromosome aberrations.

Animals

Reduction of clastogenic effect of clofazimine, an antileprosy drug, by vitamin A and vitamin C in bone marrow cells of mice.

Clofazimine (CLF), an antileprosy drug, has earlier been proved to be clastogenic in mice in vivo. It is an important constituent of the triple-drug regimen recommended by WHO for the treatment of leprosy. In this study the protective role of vitamins A and C (vit A and vit C) against the clastogenic effect of CLF in mouse bone marrow cells has been evaluated. Two doses (20 and 40 mg/kg) of vit C and two doses (2500 and 5000 IU/kg) of vit A were tested against a dose of 40 mg CLF/kg. The drug alone induced chromosomal aberrations of about 8 times the control value. Neither of the doses of vit C exhibited any clastogenic effect and, when administered simultaneously with CLF, both reduced the effect of CLF very significantly, the higher dose reducing chromosomal aberrations almost to the control value. Conversely, both doses of vit A, when administered alone, brought about significant increases in chromosome aberrations over the control value; the higher, but not the lower dose, given simultaneously with CLF, minimized the effect of CLF significantly but not as greatly as vit C. A scavenging effect of the vitamins, removing free radicals produced by CLF, is assumed to be responsible for modulation of the clastogenic effect of CLF.

Animals

Genotoxicity of 'gudakhu', a tobacco preparation. I. In mice in vivo.

'Gudakhu' is a paste-like tobacco preparation used widely in Orissa and neighbouring states of India. During use it is rubbed over the teeth and gum with a finger tip. Besides tobacco, it contains molasses, lime, red soil and water. The genotoxic potential of acetone extract of gudakhu was evaluated in mice in vivo using the chromosome aberration assay, micronucleus test and SCE analysis following single as well as long-term repeated treatment. The animals received an aqueous suspension of the extract via the oral route. Gudakhu extract induced significantly high frequencies, compared to controls, of chromosome aberrations, micronuclei (MN) and SCEs. Single treatment with different doses clearly revealed a distinct dose-dependent increase of the effects in all the assays. Analysis of MN in regenerated hepatocytes also indicated a significant positive correlation between time-course of chronic treatment and frequencies of micronucleated cells. But incidences of chromosome aberrations, MN and SCEs in bone marrow cells following repeated treatment for different periods did not differ greatly from each other; and these repeated treatment data, particularly in the MNT in bone marrow cells and the SCE assay, also did not differ markedly from the respective single treatment data for the same dose. This was probably due to the proliferative nature of the bone marrow cells.

Animals

Genotoxicity of 'gudakhu', a tobacco preparation. II. In habitual users.

The genotoxic potential of 'gudakhu', a paste-like tobacco preparation that is used widely in Orissa, India, was evaluated using the micronucleus test in exfoliated cells of the buccal mucosa. Cells from 120 habitual users and from 102 non-users were examined. The incidence of micronuclei (MN) was increased in the mucosa cells of users, and the increase was significant in those who had used gudakhu for more than 5 yr. The increased incidence of MN was significantly correlated with the period of use of gudakhu, as well as with the frequency of daily use. There were no significant differences between the results for men and women.

Administration, Buccal

Haematological and coagulation profile in acute falciparum malaria.

The haematological and coagulation profile of 30 cases of acute falciparum malaria were studied. Anaemia, mostly normocytic, normochromic, was observed in 86.7% of cases majority of whom had complications. Severe anaemia (HB < 6gm.) observed in 10% of cases was associated with 100% mortality. Leucocytosis and leucopenia were observed in 13.3% and 6.6% of cases respectively. 90% of cases had thrombocytopenia, the lowest count recorded being 26,000/- cmm. 16.7% of cases had evidence of intravascular coagulation but manifested as generalised bleeding in only one case. Bone marrow aspiration done in 10 cases revealed no abnormality, except for falciparum parasites observed in 2 cases.

Adult

Human cerebral malaria: characterization of malarial antibodies in cerebrospinal fluid.

Anti-malarial antibodies were quantified in cerebrospinal fluid (CSF) of 17 cases of cerebral malaria, 16 presumptive cases (no demonstrable parasitaemia in peripheral blood but responding to i.v. quinine therapy) of cerebral malaria, and 15 controls. A schizont-enriched Plasmodium knowlesi antigen was used in an ELISA. Anti-malarial antibodies of IgA and IgM isotypes were not detectable in most of the CSF samples analysed, although serum antibody titres were high. However, 88% of CSF from cerebral malaria and 56% of presumptive cerebral malaria cases had significant levels of IgG anti-malarial antibodies in comparison to control CSF. The antibody levels did not correlate with the severity of coma but correlated well with the duration of coma. The CSF malarial antibody titres were independent of degree of parasitaemia. The possible role of CSF anti-malarial antibodies in cerebral malaria in the light of recent demonstrations of intrathecal synthesis of immunoglobulins and deposition of immune complex in cerebral tissues is discussed.

Animals

Sonographic detection of foreign bodies of the extremities.

A prospective study to assess the accuracy of ultrasound in the detection and localization of foreign bodies of the extremities was undertaken. Forty-five patients with clinical suspicion of foreign bodies were included in the study. Among 20 patients with radio-opaque foreign bodies, ultrasonic detection of foreign bodies was achieved in 19 patients. In 25 patients, with no radiographic evidence of foreign body, ultrasonic detection of foreign bodies was made in seven patients and among these foreign bodies were confirmed and removed at surgery in five patients. Accurate pre-operative ultrasonic localization of foreign bodies was carried out in three patients.

Evaluation Studies as Topic

Evaluation of genotoxicity of clofazimine, an antileprosy drug, in mice in vivo. I. Chromosome analysis in bone marrow and spermatocytes.

Clofazimine, an antileprosy drug, was tested for its cytogenetic effect in mouse bone marrow and testis. Bone marrow metaphase analysis in adults treated directly for different periods (1, 2 and 4 weeks, 40 mg/kg/day) and with different doses (4, 20 and 40 mg/kg/day for 7 days) as well as in young animals exposed through lactation for different periods (2, 3, and 4 weeks) revealed significant increases in chromosomal aberrations over the controls. Analysis of diakinesis-metaphase I stages also exhibited a significantly elevated incidence of chromosome aberrations over controls after treatment for different periods. On the basis of the present result the drug may be considered a potential clastogen in mice.

Animals

Evaluation of genotoxicity of clofazimine, an antileprosy drug, in mice in vivo. II. Micronucleus test in bone marrow and hepatocytes.

The antileprosy drug, clofazimine, was tested for its possible genotoxicity using micronucleus (MN) tests in mice. A significantly higher incidence of MN in bone marrow erythrocytes, particularly in polychromatic erythrocytes, as well as in regenerated hepatocytes revealed a positive clastogenic effect of the drug. The drug also had a marked antimitotic effect as indicated by a negative correlation with the dose.

Animals

Spermatocyte chromosome alterations in mice inoculated with antirabies vaccine and tetanus toxoid separately and in combination.

The genotoxic potential of antirabies vaccine (ARV) and tetanus toxoid (TT) inoculated separately and in combination was evaluated by spermatocyte chromosome analysis in mice. Adult males were vaccinated with a dose of 1 ml/kg ARV once daily for 7 days, or with a dose of 1 ml/kg TT once only, or with both (TT being administered along with the last dose of ARV). Spermatocytes were analyzed over 1-6 post-vaccination weeks for numerical and structural changes as well as for univalent formation. Controls were age matched non-vaccinated males. Significantly high incidences of structural aberrations from wk 4 onwards and at wk 6 following inoculation of ARV and TT, respectively, suggested susceptibility of stem cells to the vaccines. Combined vaccination (ARV plus TT) showed an additive effect. Occurrence of univalents involving autosomes as well as sex chromosomes was very common in all the vaccinated groups, the sex chromosomes being prevalently involved. Structural aberrations showed a positive correlation with time, while univalent formation showed a negative correlation. It appears that factors for clastogenicity and univalent formation are different for both the vaccines.

Animals

Genotoxic potential of diethylcarbamazine, an antifilarial drug.

The mutagenic potential of diethylcarbamazine (DEC) was evaluated by metaphase chromosome analysis and the micronucleus test in bone marrow cells of mice. Both assay systems revealed clastogenicity, although not severe. The time-response study of metaphase chromosomes exhibited an early effect; at 72 h post-treatment the effect came down to the control level. The dose-response analysis showed significantly elevated frequencies of micronuclei (MN) for all the doses tested, but failed to show any influence of the dose on the induction of MN. Data on mitotic index (MI) indicated a lack of cell cycle inhibition. The decrease in aberration frequency with the lapse of time can be probably attributed to the elimination of the drug and its metabolites from the body.

Administration, Oral

A simplified method for micronucleus preparation from hepatic cells.

A simplified method for micronucleus preparation from regenerating hepatocytes has been developed. Small pieces of the regenerating portion of the liver are incubated in 1% sodium citrate solution containing collagenase Type 1A (final concentration 0.005% w/v) at 37 C for 10-15 min with occasional gentle agitation. The larger particles are discarded. Drops of the thick homogeneous citrate suspension of liver cells are put on the slides and drawn back immediately into the pipette, leaving only the drop marks. This simplified method, which gives good preparations with many intact hepatocytes, was validated in a model experiment using mitomycin C. The data revealed a distinct dose-response effect.

Animals