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Biomedical subjects

M Zaider

Publications and source records attributed to M Zaider.

At least 55 records · Page 3Linked to original sources
PubMed1996

Dosimetric considerations for catheter-based beta and gamma emitters in the therapy of neointimal hyperplasia in human coronary arteries.

PURPOSE: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments. METHODS AND MATERIALS: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied. RESULTS: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored. CONCLUSIONS: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Brachytherapy↗
PubMed1996

Microdosimetric evaluation of relative biological effectiveness for 103Pd, 125I, 241Am, and 192Ir brachytherapy sources.

PURPOSE: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates. METHODS AND MATERIALS: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). RESULTS: Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir. CONCLUSIONS: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Americium↗
PubMed1996

Carcinogenic risk coefficients at environmental levels of radon exposures: a microdosimetric approach.

We report a microdosimetric-based evaluation of the effects of domestic exposure to radon. The risk coefficients obtained here are based on the microdosimetry of radon progeny alpha particles, on a function q(y) for in vivo radiogenic neoplasia, and on scaling A-bomb results (epidemiology + microdosimetry) to radon exposure. We do not use miner data, nor do we invoke such notions as quality factors, dose equivalent or equivalent dose. With basal cells as targets our estimated risk coefficients are in good agreement with the miner data, and thus a quality factor of about 20 (as suggested by ICRP 60) is not unreasonable. However, if we take as targets the secretory cells our risk coefficients are twice as large as those reported by BEIR-IV. The main uncertainty in these estimates remains the dosimetric model.

Carcinoma, Bronchogenic↗
PubMed1996

Microdosimetric-based risk factors for radiation received in space activities during a trip to Mars.

A system for evaluating quality factors, Q, based on the microdosimetric distribution of the radiation field of interest has been set up; it makes use of a specific quality function (SQF) to obtain--given microdosimetric spectra--values for Q. The advantages of a system based on lineal energy are well recognized. Furthermore, recent studies have shown that spectra in 1-microm diameter tissue-equivalent spherical volumes reproduce correctly (in the sense of this formalism) measured RBE values, and thus a proportional counter would be usable as a practical instrument for radiation protection. All specific quality functions, q(y), available to date have been calculated from in vitro cellular data. To extend this approach to radiations of interest in space activities we have recently obtained a new function q(y) for in vivo radiogenic neoplasia using data on the Harderian gland of the mouse. These data were obtained for charged particles and energies relevant to space exposures. Furthermore, we introduce a new procedure that allows one to obtain--here with the use of microdosimetric distributions for the Hiroshima-Nagasaki radiation fields--risk factors scaled from the A-bomb survivorship results. We apply these concepts to particles and energies representing the galactic spectrum. We estimate that for a trip to Mars (450 d) the excess lifetime cancer mortality due to galactic cosmic ray (GCR) radiation is 0.037. This is about 50% lower than the risk coefficient obtained with the aid of standard (LET-based) quality factors.

Aerospace Medicine↗
PubMed1996

The combined effects of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle. I. Survival probabilities after exposure to radiation.

An analytical model is presented that describes radiation-induced cellular inactivation in the presence of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle (the 3 Rs). The parameters of the model are measurable experimentally. Also taken into account are the initial age distribution of the cell population, the fact that subgroups of cells progress through the cycle at different speeds, the effects of a dose of radiation on the duration of the four phases of the cycle (G1, S, G2, M), the possibility that a certain fraction of the cells are quiescent, and cell loss and/or cell removal from the proliferating population. Survival probabilities are expressed as linear-quadratic functions of dose where the coefficient alpha and beta as well as the recovery constant (t0) are taken to depend on the position of the cell in the mitotic cycle. Explicit analytical expressions for inactivation probability are given for clonogenic cells exposed to continuous or fractionated radiation. Two model calculations are used to illustrate the formalism: in one, the redistribution of cells during fractionated therapy is examined. In the other calculation, it is shown that it is sufficient to take into account differences in proliferation rates and the change in the ratio alpha/beta within the generation cycle for cells that may have otherwise equal response to acute exposures to explain that in a fractionated treatment protocol late-responding cells are more sensitive to the dose per fraction than early-responding cells. It is not necessary to invoke differences in radiosensitivity between these two classes of cells.

Cell Cycle↗
PubMed1996

The combined effects of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle. II. The dependency of radiosensitivity parameters alpha, beta and t(0) on biological age for Chinese hamster V79 cells.

In this paper, an analytical formalism, designated the R3 model, is applied to the problem of understanding changes in cellular radiosensitivity as a function of the position of the cell in the generation cycle. The model describes the survival probability for cells exposed to ionizing radiation and incorporates the effects of sublethal damage repair, repopulation and redistribution in the cell cycle. The importance of this problem stems in part from the increasing reliance on in vitro, single-cell model systems to design optimal radiotherapy treatment protocols, and in particular from the fact that arguments used to justify newer methodologies often bear quite heavily on descriptors (e.g. alpha and beta) meant to be employed for cells homogeneous in radiosensitivity--a situation hardly applicable to tissues. From the analysis of two sets of data for Chinese hamster V79 cells (Sinclair and Morton, Nature 205, 247-250, 1964; Gillespie et al., Radiat. Res. 64, 353-364, 1975) the linear-quadratic parameters (alpha, beta) are obtained as a function of cell cycle age. The results indicate substantial variation of these parameters inside each phase of the cycle. Moreover, it is noticeable that alpha and beta show different patterns of variation during the cycle and therefore the ratio alpha/beta will also change. At the regions of the cycle where beta is large (the beginning of G1 phase, at the G1/S-phase border and during G2 phase) dose-rate effects would be expected to be important. The data for V79 cells are consistent with the view that sublethal damage repair occurs predominantly in S phase, with very little (if any) repair in the other phases of the cycle.

Animals↗
PubMed1995

Application of the HSEF to assessing radiation risks in the practice of radiation protection.

The primary risk coefficients upon which exposure limits for radiation protection purposes are currently based are derived almost exclusively from cancer-induction data obtained from human populations exposed to radiations of low linear energy transfer. The question of higher linear energy transfer radiations is handled by means of quality factors derived from values for relative biological effectiveness obtained from animal data. However, the advent of microdosimetry has made it possible to establish hit size effectiveness functions from single-cell systems, both in vitro and in vivo. This type of function can substitute completely for the concept of relative biological effectiveness, Q and equivalent dose. A common basis for risk coefficients and the hit size effectiveness function lies in the fact that human cancers are monoclonal and thus single cell in origin. The present communication utilizes this common base as a means of extending the present low-linear energy transfer based risk coefficients to include carcinogenic responses from exposure in radiation fields of any one or mixed qualities, extending from the smallest to the largest linear energy transfers of practical consequence. In doing so, risks from ionizing radiations of any linear energy transfer may be predicted more accurately than at present.

Biophysical Phenomena↗
PubMed1995

The effects of sublethal damage recovery and cell cycle progression on the survival probability of cells exposed to radioactive sources.

Cell progression through the mitotic cycle during low dose rate irradiation may alter notably the survival probability, particularly when a fraction of the dose is delivered during a sensitive phase of the cycle. In this paper we indicate that the consequences of this phenomenon, commonly believed to lead to an "inverse dose rate effect", may be significantly modulated (and even cancelled) as a result of (a) interactions among sublethal lesions produced in different phases of the mitotic cycle, and (b) variations in these lesions' production rates and repair ability from one phase of the cycle to another. The mathematical model presented (and accompanying numerical examples) takes into account the possibility of changes (e.g. radioactive decay) in the dose rate during exposure.

Brachytherapy↗
PubMed1994

Charged-particle transport in biomolecular media: the third generation.

We describe Monte Carlo codes that simulate, event by event, the interaction of energetic electrons with a double-stranded DNA molecule and with the condensed water surrounding it. Both direct and indirect effects are treated explicitly . The cross-sectional input necessary in the transport codes was obtained via quantum-mechanical calculations of the dielectric response function epsilon(q, omega), of polycytidine. For each inelastic event on DNA we score the energy deposited locally, the position of the event and the moiety that underwent that event. This information provides a detailed picture of the spatial disposition of molecular alterations for DNA exposed to ionizing radiation.

DNA↗
PubMed1994

An inductive assessment of radiation risks in space.

Procedures for the assessment of risks or vulnerabilities from radiation in space are evaluated in terms of model-independent inductive approaches. The reliability of risks calculated for space applications on the basis of accelerator-based physical and biological data is examined from a microdosimetric perspective. Probability distributions for energy deposition in biologically significant sites extend over several decades in lineal energy even for monoenergetic high-energy particles of relatively high atomic number. Because the response depends on a large number of variables and because of the difficulty of incorporating all such factors into calculations, a precise correlation between a physical descriptor of the field and observed effects in space is not feasible. For the same reasons, it is equally difficult to estimate the accuracies of such risk assessments. We use recently published microdosimetric spectra for HZE particles and biological weighting functions, including those derived from biological measurements with maximum entropy techniques, to illustrate some problems associated with the evaluations of risks from radiation fields in space.

Animals↗
PubMed1994

Prenatal cocaine exposure and the development of the human eye.

PURPOSE: The use of cocaine during pregnancy has been associated with congenital abnormalities of the developing eye. The authors report a prospective, controlled study of 40 cocaine-exposed and 40 nonexposed (control) preterm and full-term infants. METHODS: Detailed maternal and obstetric histories were obtained by chart review and interview. Infants with a positive urine toxicology screen for cocaine at birth or whose mothers tested positive for cocaine were recruited into the exposed group. Nonexposed infants were recruited at random from newborns admitted to the authors' nurseries. Mothers of these infants received routine prenatal care in the authors' clinics, and nonexposure was documented by maternal history and/or negative urine toxicologies that were available in 30% of these mother-infant pairs. General physical and ocular examinations, including measurement of axial length and intraocular pressure, were performed on all infants. RESULTS: Forty infants were recruited in each group, with gestational ages ranging from 25 to 42 weeks. Twenty-nine of the exposed infants and 26 of the control infants were full-term (gestational age, 37 weeks or older). A total of 160 eyes were examined. No differences were seen in the incidence of congenital anomalies, subconjunctival hemorrhages, retinal hemorrhages, or optic nerve abnormalities between the two groups. No differences in mean axial length (16.9 +/- 0.6 mm [exposed group] versus 17.1 +/- 0.7 mm [control group]) or intraocular pressure (15.4 +/- 3.8 mmHg [exposed group] versus 15.0 +/- 3.0 mmHg [control group]) were seen between full-term infants in both groups. Axial length correlated strongly with gestational age, birth weight, head circumference, and body length over the range of gestational ages evaluated in both groups. No effect of cocaine exposure on these correlations was demonstrated. The range of axial length was 12.1 to 18.0 mm in the exposed group and 12.4 to 18.6 mm in the control group. CONCLUSION: In this study group, no significant effect of prenatal cocaine exposure was seen on the infant eye. In both exposed and nonexposed groups, axial length measurements agreed closely with known statistical norms and correlated closely with other parameters of fetal growth.

Abnormalities, Drug-Induced↗
PubMed1994

Molecular damage induced directly and indirectly by ionizing radiation in DNA.

We describe the interaction of radiation with a double-stranded DNA molecule and with the structural water surrounding it. The results, which include a detailed picture of DNA molecular alterations, as well as their yield and spatial disposition, were obtained with the aid of Monte Carlo codes that simulate, event-by-event and simultaneously, direct and indirect effects. These calculations make use of explicit quantum-mechanical descriptions of the electronic structure of condensed water and of a homopolynucleotide chain. From these we obtain, via the dielectric response function of the two systems, epsilon (q, omega), the interaction probabilities necessary in the transport codes.

DNA↗
PubMed1994

Extracapsular cataract extraction and posterior-lip sclerectomy with viscoelastic.

A review of 15 cases suggests that posterior-lip sclerectomy can be performed safely with extracapsular cataract extraction (ECCE) and posterior chamber lens implantation. The anterior chamber was filled with viscoelastic at the end of each procedure; no case required reoperation for shallow chamber or hypotony. The mean intraocular pressure after 1 year was 12.1 mm Hg. The astigmatism induced by the triple procedure did not differ significantly from that caused by ECCE alone during the initial 2 postoperative years. A new mathematical model that describes the change over time of postoperative astigmatism associated with these procedures is described.

Aged↗
PubMed1994

A study of the excited states in cytosine and guanine stacks in the Hartree-Fock and exciton approximations.

We report calculated exciton energies for the cytosine and guanine stacks obtained in the ab initio Hartree-Fock crystal orbital and exciton approximation, which includes the excited electron-hole interaction. This interaction plays an important role in the description of excited electron spectra in the low-energy region. The stacks were chosen as examples of polymers with helical symmetry.

DNA↗
PubMed1993

A mathematical model for cell cycle progression under continuous low-dose-rate irradiation.

A mathematical model of the progression of cells through the mitotic cycle under continuous low-dose-rate irradiation is described. The model considers explicitly two special cases: (a) when a fraction of cells disintegrate and disappear after mitosis and (b) when a fraction of cells which have reached mitosis do not progress further but do not disintegrate either. We have established a relationship between the parameters of the model and dose and/or the age of the cell at exposure. This formalism is applied to studies of the effects of dose rate on HeLa cells (Mitchell, Bedford, and Bailey, Radiat. Res. 79, 520-536, 1979; 80, 186-197, 1979). Detailed information on the fraction of cells of a certain biological age at a given chronological time is needed because of the variation in the radioresponse of the cells as a function of age.

Cell Cycle↗