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Biomedical subjects

M D Mills

Publications and source records attributed to M D Mills.

At least 37 records · Page 2Linked to original sources

Growth and development of Haemonchus contortus in jirds, Meriones unguiculatus.

Growth and development of Haemonchus contortus were examined in jirds and were compared to these processes in lambs. Number, sex, size, and stage of development were determined for worms recovered at necropsy at various times postinoculation (PI) from immunosuppressed jirds inoculated with approximately 1,000 exsheathed infective larvae (L3) of H. contortus. In addition, gastric tissue samples from jirds were examined histologically. Parallel studies were done in lambs inoculated with approximately 7,500 L3. Typically, 5-30% of the inoculum established and survived in jirds at reasonably stable numbers to day 14 PI. By day 21 PI, worm numbers in jirds decreased dramatically. Although the parasite was similar in size and development on day 4 PI in jirds and lambs, from day 7 PI on, worms were significantly smaller and less developed in jirds. On histological examination, the parasite was found only in the glandular portion of the stomach of jirds (anatomically similar to its predilection site in the abomasum of lambs), and histological changes were consistent for both host species. Although growth and development of H. contortus are slower and incomplete in jirds, the parasite establishes, grows, and develops (at anatomically comparable sites in both hosts) in this model. Thus, the model appears to provide a useful laboratory host to study H. contortus.

Abomasum↗

Evaluation of a total scalp electron irradiation technique.

A dosimetric evaluation of a total scalp electron-beam irradiation technique that uses six stationary fields was performed. The initial treatment plan specified a) that there be a 3-mm gap between abutted fields and b) that the field junctions be shifted 1 cm after 50% of the prescribed dose had been delivered. Dosimetric measurements were made at the scalp surface, scalp-skull interface, and the skull-brain interface in an anthropomorphic head phantom using both film and thermoluminescent dosimeters (TLD-100). The measurements showed that the initial technique yields areas of increased and decreased dose ranging from -50% to +70% in the region of the field junctions. To reduce regions of nonuniform dose, the treatment protocol was changed by eliminating the gap between the coronal borders of abutted fields and by increasing the field shift from 1 cm to 2 cm for all borders. Subsequent measurements showed that these changes in treatment protocol resulted in a significantly more uniform dose to the scalp and decreased variation of doses near field junctions (-10% to +50%).

Electrons↗

Reliability of ultrasonographic formulary in the prediction of fetal weight and survival of very-low-birth-weight infants.

Antenatal management of very-low-birth-weight infants often requires difficult obstetric decisions. This study was designed to evaluate the predictive value for neonatal outcome of antenatally acquired estimation of gestational age and ultrasonographically estimated fetal weight or a combination of both in very-low-birth-weight infants. Sixty-seven fetuses with estimated gestational ages between 22 0/7 and 28 6/7 weeks were studied ultrasonographically to estimate fetal weight. A comparison of accuracy of estimated fetal weight with actual birth weight showed good correlation (r = 0.93). Neonatal outcome of these infants was analyzed by estimated gestational age and estimated fetal weight. Estimated gestational age and estimated fetal weight greater than 25 weeks and greater than 750 gm were associated with 50% survival, respectively. However, when both of these conditions were met survival reached 85%. This information may be useful to guide antepartum management decisions in this very-low-birth-weight group.

Birth Weight↗

Shielding considerations for an operating room based intraoperative electron radiotherapy unit.

The leakage radiation characteristics of a dedicated intraoperative radiotherapy linear accelerator have been measured on a machine designed to minimize the shielding required to allow it to be placed in an operating room suite. The scattering foil design was optimized to produce a flat beam for the field sizes employed while generating minimal bremsstrahlung contamination over the available energy range. More lead shielding was used in the treatment head than is used in conventional accelerators. A small amount of borated polyethylene shielding was also employed since neutron production was present at measurable levels. The room shielding installed in the operating room was demonstrated to be adequate to treat at least 20 patients each month to an average dose of 20 Gy. The worst case exposure was found to be 73% maximum permissible exposure. Administrative control was required for adjoining areas when calibrations and maintenance were performed.

Intraoperative Period↗

Spinal cord dose reduction using an anterior 13 MeV electron field situated between a split anterior 60Co supraclavicular field.

As part of the treatment for lymphoma, disease involving the supraclavicular region has been treated with megavoltage 60Co photons to a midline dose of 30 to 45 Gy through an anterior involved field and a supplementary posterior field when necessary. The spinal cord was shielded with a 5 cm lead block during treatment to the posterior field. A typical 40 Gy treatment results in a dose to the lower cervical and upper thoracic spinal cord in the range of 22 to 26 Gy, a level that could compromise subsequent mediastinal treatment in the event of a relapse. To reduce this cord dose, the midportion of the anterior supraclavicular 60Co To reduce this cord dose, the midportion of the anterior supraclavicular 60Co field was replaced with a high-energy (13 MeV) electron port, which reduces the dose to the cord to below 6 Gy in the average adult patient. This modification of the routine supraclavicular treatment allows greater flexibility in future treatment in the event of a mediastinal relapse.

Clavicle↗

Dosimetric evaluation of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction.

The accuracy of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction is demonstrated by comparing calculation with measurement. Ionization measurements have been made in a water phantom for a variety of non-standard geometries. Geometries to demonstrate the effect of an extended treatment distance, a sloping skin surface, and an irregular skin surface have been selected. Additionally, thermoluminescent dosimeters have been used to measure distributions in tissue-substitute phantoms, which were designed from individual patient computerized tomographic scans. Three patient scans have been selected: (1) diffuse hystiocytic lymphoma of the left buccal mucosa and retromolar trigone; (2) squamous cell carcinoma of the nose at the columnella ; and (3) carcinoma of the maxillary antrum. Results demonstrate the algorithm's ability to simultaneously account for the isodose shifting as a result of internal heterogeneities and for sidescatter non-equilibrium caused by lateral discontinuities of the skin surface and internal anatomy. The algorithm is shown to generally be accurate to within +/- 4% in the treatment volume or +/- 4 mm in regions of sharp dose gradients as found in the penumbra and distal edge of the beam. Examples of greater disagreement are shown and their physical interpretation discussed.

Carcinoma, Squamous Cell↗

Hyperthermic potentiation of unrejoined DNA strand breaks following irradiation.

Previous reports have suggested that the potentiation of cellular radiation sensitivity by hyperthermia may be due to its inhibition of the repair of single-strand breaks in DNA. Such inhibition could result in increased numbers of unrejoined breaks at long times following irradiation, lesions that are presumed to be lethal to the cell. As a test of this hypothesis, the amounts of residual strand-break damage in cells following combined hyperthermia and ionizing radiation were measured. The results show that hyperthermia does significantly enhance the relative number of unrejoined strand breaks as measured by the technique of alkaline elution and that the degree of enhancement is dependent on both the temperature and duration of the hyperthermia treatment. For example, compared to unheated cells, the proportion of unrejoined breaks measured 8 hr after irradiation was increased by a factor of 1.5 in cells that were treated for 30 min at 43 degrees C, by a factor of 6 for cells treated for 30 min at 45 degrees C, and by a factor of 4 for cells treated at 43 degrees C for 2 hr. In experiments in which the sequence of heat and irradiation were varied, a high degree of correlation was observed between the resulting level of cell killing and the relative numbers of unrejoined strand breaks. The greatest effects on both of these parameters were observed in those protocols in which the irradiation was delivered either during, just before, or just after the heat treatment.

Animals↗

Electron beam dose calculations.

Electron beam dose distributions in the presence of inhomogeneous tissue are calculated by an algorithm that sums the dose distribution of individual pencil beams. The off-axis dependence of the pencil beam dose distribution is described by the Fermi-Eyges theory of thick-target multiple Coulomb scattering. Measured square-field depth-dose data serve as input for the calculations. Air gap corrections are incorporated and use data from'in-air' measurements in the penumbra of the beam. The effective depth, used to evaluate depth-dose, and the sigma of the off-axis Gaussian spread against depth are calculated by recursion relations from a CT data matrix for the material underlying individual pencil beams. The correlation of CT number with relative linear stopping power and relative linear scattering power for various tissues is shown. The results of calculations are verified by comparison with measurements in a 17 MeV electron beam from the Therac 20 linear accelerator. Calculated isodose lines agree nominally to within 2 mm of measurements in a water phantom. Similar agreement is observed in cork slabs simulating lung. Calculations beneath a bone substitute illustrate a weakness in the calculation. Finally a case of carcinoma in the maxillary antrum is studied. The theory suggests an alternative method for the calculation of depth-dose of rectangular fields.

Electrons↗

Localization of fibronectin within the renal glomerulus and its production by cultured glomerular cells.

Fibronectin was shown in the kidney glomerulus by the use of the peroxidase-labeled antibody technique. At the ultrastructural level, fibronectin was present in greatest quantities along those cell surfaces that abut the capillary basement membrane, especially along the capillary epithelial cell foot process. Intracellular staining was also seen in the glomerulus, most notably in the mesangial cell. Fibronectin was present extracellularly in large amounts in glomerular cell culture and was also demonstrated on the cell membrane and intracellularly.

Animals↗

Culture of human glomerular cells.

Human glomeruli were routinely cultured in Waymouth's medium supplemented with insulin and conditioned medium. Three cell types were seen in the culture of both adult and infant kidneys, but the morphology of the glomerular cellular outgrowths depended on the age of the patient from which the kidney was obtained. Cultures of glomeruli from older individuals resulted in more "differentiated" cells, but both adult and infant glomerular cells rapidly became "dedifferentiated" as the length of time in culture increased. Outgrowths of cultured glomeruli did not contain fibroblasts or tubular cells. Finally, synthesis of basement membrane material by these cultured glomerular cells was demonstrated.

Adult↗

Electron beam therapy for eyelid carcinomas.

Forty-six (85%) basal cell and eight (15%) squamous cell carcinomas of the eyelids were treated with electron beams between 1963 and 1983. Lesion sizes ranged from microscopic to 4 cm, with 28 lesions larger than 1 cm. Thirty-eight lesions were treated with radiotherapy after incisional biopsy, and 16 were treated after excisional biopsy (specimens showed positive margins). Doses varied from 45 to 72 Gy, with daily fractions ranging from 2.12 to 4.0 Gy. There were six disease recurrences (10.9%): three in the treatment field and three at the treatment margin. Four of six recurrences were subsequently controlled by limited surgical excision and repair with preservation of the eye, whereas the other two required enucleation. Treatment sequelae such as skin atrophy, telangiectasis, and cosmetic results were evaluated in terms of radiotherapy parameters, pretreatment surgery, and size of the lesion. In 44 patients, the overall cosmetic result was judged as good to excellent, five patients had a mild to modest degree of deformity, and five had significant deformity. Such deformity was usually associated with tumor destruction or previous surgery. No major complications were noted.

Aged↗

Retinoblastoma in transgenic mice: models of hereditary retinoblastoma.

Retinoblastoma, the most common intraocular malignancy ill childhood, has served as a paradigm for the study of genetic mechanisms of oncogenesis. The retinoblastoma susceptibility gene RB1 was the first tumor suppressor gene to be cloned, and genetic and molecular biologic studies of this tumor have greatly expanded the understanding of the mechanics of tumorigenesis. Human retinoblastoma has essentially no naturally occuring animal counterpart. The development of transgenic murine models of retinoblastoma have created an experimental tool for manipulation of a tumor gene system in vivo. These models have also enabled studies of new therapeutic modalities. This review outlines the development of the transgenic murine models of retinoblastoma, together with the genetic mechanisms of retinoblastoma origin. Current therapeutic innovations developed by means of the transgenic models are described.

Animals↗

Prediction of electron beam output factors.

A method to predict square and rectangular field output factors from the measurement of selected fields of electron beams on the Therac 20 Saturne has been developed. A two parameter fit of the square field output factor data, based on the functional dependence as predicted by a pencil beam calculational model, has proven clinically acceptable. The pencil beam distributions are given by the Fermi-Eyges theory of multiple Coulomb scattering. For a rectangular field, the output factor can be calculated from the square root of the product of the two square field output factors wtih sides equal to those of the rectangular field. If however, there is a significant asymmetry between the X and Y collimator systems, then rectangular field output factors should be predicted from the product of the X and Y one-dimensional output factors. One-dimensional output factors are defined as output factors of rectangular fields where one side remains constant and equal to the side of the square reference field. Measured data indicate either of the two methods of determining rectangular field output factors to be clinically acceptable for the Therac 20, the use of one-dimensional output factors demonstrating greater accuracy. Data show agreement to within approximately 1.5% at electron energies of 6, 9, 13, and 17 MeV.

Electrons↗

Determination of electron beam output factors for a 20-MeV linear accelerator.

The demands of a busy clinic require that basic machine calculations be performed as accurately, rapidly, and simply as possible. For the electron beam of the Therac 20 Saturne linear accelerator, a method suitable for a programmable calculator is described to predict the dose output from the measurement of selected fields. One-dimensional output factors were measured; these are defined as output factors of rectangular fields where one side is always equal to the side of the square reference field. The output of an arbitrary rectangular field X, Y is given by the product of the output factors OF(X,Y) = OF(X,10) X OF(10,Y), where 10 is the side of the square reference field. The measured data indicate that the output of very large rectangular and square fields is underestimated using this method for the lower energies. A correction factor of the form CF = C X [(X - 10)(Y - 10)/(X - 10)(Y - 10) 1/2] results in agreement with measured data to within 1.5% for all energies.

Biophysical Phenomena↗

The exposure rate constant for a silver wire 125I seed.

The physical characteristics of the newer silver wire 125I seed were measured with a scintillation spectrometer to compare them with those of the original gold sphere 125I seed. The exposure rate constant was determined by converting the count rate from a scintillation spectrometer into the photon-fluence rate incident upon the detector, then calculating the exposure rate from the photon-fluence rate. The exposure rate constant measured perpendicular to the long axis of the seed is 1.361 R cm2/mCi h (1.192 cGy cm2/mCi h) +/- 3.7%, a value that compares favorably with the theoretical exposure rate constant of 1.354 R cm2/mCi h (1.186 cGy cm2/mCi h) calculated from the 125I emissions data. A value of 1.309 R cm2/mCi h was previously reported for the gold sphere 125I seed using the same technique. The angular intensity distribution and anisotropy factor of the silver wire 125I seed are shown to be very similar to those of the gold sphere 125I seed, leading to the conclusion that the clinical application of the two types of 125I seeds need not change.

Brachytherapy↗

The role of drug treatment in children with strabismus and amblyopia.

Strabismus, or misalignment of the eyes, is a common ophthalmic problem in childhood, affecting 2 to 5% of the preschool population. Amblyopia is an important cause of visual morbidity frequently associated with strabismus, and both conditions should be treated simultaneously. Pharmacological means for treating strabismus and amblyopia can be divided into 3 categories: paralytic agents (botulinum toxin) used directly on the extraocular muscles to affect eye movements; autonomic agents (atropine, miotics) used topically to manipulate the refractive status of the eye and thereby affect alignment, focus and amblyopia; and centrally acting agents, including levodopa and citicoline, which affect the central visual system abnormalities in amblyopia. Botulinum toxin, the paralytic agent that causes the clinical symptoms of botulism poisoning, can be injected in minute quantities to achieve controlled paralysis of the extraocular muscles. Although the role of botulinum toxin is established in adults with paralytic strabismus, its usefulness in the treatment of comitant childhood strabismus (primary esotropia and exotropia) is not universally accepted. Botulinum injections tend to be more effective with smaller degrees of strabismus, in patients with good binocular fusion, and in managing overcorrections or undercorrections after traditional muscle surgery. Inadvertent ptosis and paralysis of adjacent muscles, unpredictable responses and technical constraints of the injections limit its use in children. Miotic therapy, by altering the refractive state of the treated eye, offers an alternative to optical correction with bifocals in treating esotropia due to excessive accommodative convergence. It is also effective in treating residual esotropia following surgery. The ease of use of glasses restricts the wide application of miotics in these common strabismus syndromes. Atropine, an anticholinergic agent, paralyses the ability of the eye to focus or accommodate. In amblyopia therapy, atropine is used to blur vision in the non-amblyopic eye and offers a useful alternative to traditional occlusion therapy with patching, especially in older children who are not compliant with patching. The neurotransmitter precursor levodopa and the related compound citicoline have been demonstrated to improve vision in amblyopic eyes. The therapeutic role of these centrally acting agents in the clinical management of amblyopia remains unproven.

Amblyopia↗