PubMed Health⌕ Search

Biomedical subjects

W T Millar

Publications and source records attributed to W T Millar.

18 recordsLinked to original sources
PubMed1994

Two components of repair in irradiated kidney colony forming cells.

Data describing the response of mouse kidney colony-forming cells to fractionated X-irradiation using different interfraction intervals were analysed in order to detect the presence of one or more components of repair. A two-component repair model gave a superior fit, with reference to a single-repair rate model, giving distinct repair halftimes of 0.15 (approximate 95% confidence limits: 0.0, 0.40) and 5.03 (1.23, 8.84) h. These values are the first reported for normal cells in vivo, and they are similar to values calculated for tissue responses in skin, lung and the spinal cord. The slow component of repair is important in radiotherapy, in particular regarding novel hyperfractionation regimens when interfraction intervals much less than 1 day are employed.

Animals↗
PubMed1993

Derivation and application of equations describing the effects of fractionated protracted irradiation, based on multiple and incomplete repair processes. Part I. Derivation of equations.

A general model is developed where the induction and interaction rates of sublethal radiation damage with subsequent irradiation are represented as polynomial functions of the dose-rate. The effect of incomplete multiple repair processes is also included. Equations are evaluated for fractionated protracted irradiation where the dose-rate is constant during each fraction. However, both the dose-rate and the fractional dose are permitted to change from fraction to fraction. The resultant equations show that the apparent alpha/beta ratio derived from the analysis of equivalent protocols may be protocol dependent. Also, the alpha/beta ratio calculated from experimental data, assuming a single repair half-life, will appear to be protocol dependent if in reality more than one repair process is involved in the repair of sublethal damage. It is possible that the effects due to the induction of sublethal damage or its subsequent interaction may be distinguished by designing experiments in which the dose-rate is not constant throughout the whole protocol; also that the underlying processes governing the conversion of sublethal damage may be analysed by fitting experimental data to the equations.

Clone Cells↗
PubMed1993

Derivation and application of equations describing the effects of fractionated protracted irradiation, based on multiple and incomplete repair processes. Part 2. Analysis of mouse lung data.

General equations for fractionated protracted irradiation have been applied to the analysis of mouse lung data derived from isoeffect protocols. The data were accrued from a spectrum of different protocols including different radiation qualities, interfraction times and dose-rates. This analysis, based upon two component repair rate processes, suggests that there are possibly two repair-rate processes involved in the repair of sublethal damage in the lung. The two repair half-lives were 0.32 and 1.92 h with a low dose-rate partitioning of 1:0.38 between the amount of lethal damage resulting from rapid and slow sublethal damage repair processes at low dose-rates. The analysis also indicates that there may be a dose-rate amplification of the amount of resultant lethal damage, deriving from sublethal damage, associated with the longer repair process. It is also shown that the alpha/beta ratio is probably independent of the radiation quality and that the ratios of multiple to single event damage for 240kVp X-rays and 60Co are almost identical. However, the absolute values of alpha and beta for 240 kVp X-rays may be greater than for 60Co.

Animals↗
PubMed1991

Application of the linear-quadratic model with incomplete repair to radionuclide directed therapy.

The linear-quadratic (LQ) model for fractionated external beam therapy has been modified by previous authors to include the effects due to an exponentially decaying dose rate. However, the LQ model has now been extended to include a general time varying dose rate profile, and the equations can be readily evaluated if an exponential radiation damage repair process is assumed. These equations are applicable to radionuclide directed therapy, including brachytherapy. Kinetic uptake data obtained during radionuclide directed therapy may therefore be used to determine the radiobiological dosimetry of the target and non-target tissues. Also, preliminary tracer studies may be used to pre-plan the radionuclide directed therapy, provided that tracer and therapeutic amounts of the radionuclide carrier are identically processed by the tissues. It is also shown that continuous radionuclide therapy will induce less damage in late-responding tissues than 2 Gy/fraction external beam therapy if the ratio of the maximum dose rate and the sublethal damage repair half-life in the tissue is less than 1.0 Gy. Similar inequalities may be derived for beta-particle radionuclide directed therapy. For example, it can be shown that radionuclide directed therapy will induce less damage to slowly repopulating tissue than 2 Gy/fraction external beam therapy for the same total dose if the maximum percentage initial uptake in tissue is less than 0.046%/g or 0.23%/g for an injected activity of 50 mCi of 90Y or 131I, respectively.

Brachytherapy↗
PubMed1990

Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid.

Although encouraging results have been obtained using systemic radioimmunotherapy in the treatment of cancer, it is likely that regional applications may prove more effective. One such strategy is the treatment of central nervous system leukemia in children by intrathecal instillation of targeting or nontargeting beta particle emitting radionuclide carriers. The beta particle dosimetry of the spine is assessed, assuming that the spinal cord and the cerebrospinal fluid compartment can be adequately represented by a cylindrical annulus. The radionuclides investigated were 90Y, 131I, 67Cu, and 199Au. It is shown that the radiation dose to the cord can be significantly reduced using short range beta particle emitters and that there is little advantage in using targeting carriers with these radionuclides. 199Au and 67Cu also have the advantage of having a suitable gamma emission for imaging, permitting pretherapy imaging and dosimetric calculations to be undertaken prior to therapy. If these methods prove successful, it may be possible to replace the external beam component used in the treatment of central nervous system leukemia in children by intrathecal radionuclide therapy, thus reducing or avoiding side effects such as growth and intellectual impairment.

Antibodies, Monoclonal↗
PubMed1990

Application of radiobiological dosimetry to radionuclide directed therapy.

The standard linear quadratic model, which has been used to assess the radiobiological damage to tissue by external beam fractionated radiotherapy, has been extended to encompass a general continuous time varying dose rate protocol such as radionuclide therapy. If the radionuclide clearance from the tissue is purely exponential, the effect is readily calculated. Otherwise, the effect can be evaluated by numerical integration if the dose rate time-1 profile is known. It can be shown that if the maximum percentage initial uptake g-1 uptake in normal or tumour tissue is less than 0.046 or 0.23 for an administered activity of 50 mCi of 90Y or 131I respectively, then the radiation-induced damage will certainly be less than for 2 Gy fraction-1 external beam therapy for the same total dose. Preliminary imaging and knowledge of the radionuclide kinetics using a non-therapeutic dose may be used to calculate the predicted radiation damage to tissues for a particular therapeutic dose provided the tracer and therapy doses have identical kinetics.

Models, Biological↗
PubMed1984

The rapid separation and assay of previously unreported plasminogen activators in human euglobulin fractions. The effect of venous occlusion.

Euglobulins were prepared from pre and post venous occlusion plasma by acidification and dilution at pH 5.9. It is shown by isoelectrofocussing that there are several plasminogen activators with differing pI's in euglobulin fractions. Activators with pI's 8.9/9.0, and 9.4 are the major activators responsible for the increase in post occlusion plasminogen activator activity. Fibrin was necessary for the induction of the vascular occlusion response.

Constriction↗
PubMed1983

Comparative study of different urokinase preparations.

Three different urokinase preparations were assayed for amidolytic and plasminogen activator activity. It was found that the preparation with the least amidolytic activity displayed a significantly greater plasminogen activator activity than the others. These results suggest that this particular preparation may be more effective clinically and that the use of assay systems for the comparison of urokinase preparations must be treated with caution.

Endopeptidases↗
PubMed1983

The comparison of solid phase and fibrin plate methods for the measurement of plasminogen activators.

A rapid and highly sensitive solid phase assay was compared with the fibrin plate method for the measurement of urokinase, streptokinase and the plasminogen activators in human euglobulin fractions. The solid phase assay was run using glu - or lys - plasminogen, and significant differences were observed in the activation of the plasminogens by urokinase and streptokinase. Plasminogen activator levels in euglobulin fractions were also measureable. Very good agreement was obtained between the fibrin plate and solid phase methods in all cases.

Endopeptidases↗
PubMed1975

Iodine organification defect following treatment of thyrotoxicosis with antithyroid drugs.

Two patients remained clinically euthyroid following treatment for thyrotoxicosis with antithyroid drugs in spite of persistently elevated thyroid radioiodine uptakes not suppressable by exogenous triiodothyronine. Perchlorate discharge tests showed a defect in the intrathyroidal organification of iodine. Circulating levels of thyroxine were normal. From our study of 105 patients treated for thyrotoxicosis with antithyroid drugs, apparent remission of thyrotoxicosis by this mechanism might occur in up to 2 percent of patients.

Carbimazole↗