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Biomedical subjects

B M Miller

Publications and source records attributed to B M Miller.

At least 19 recordsLinked to original sources
PubMed2002

Comparison of MRI pulse sequences in defining prostate volume after permanent implantation.

PURPOSE: To determine the relative value of three MRI pulse sequences in defining the prostate volume after permanent implantation. METHODS AND MATERIALS: A total of 45 patients who received a permanent 125I implant were studied. Two weeks after implantation, an axial CT scan (2 mm thickness) and T1-weighted, T1-weighted fat saturation, and T2-weighted axial MRI (3-mm) studies were obtained. The prostate volumes were compared with the initial ultrasound planning volumes, and subsequently the CT, T1-weighted, and T1-weighted fat saturation MRI volumes were compared with the T2-weighted volumes. Discrepancies in volume were evaluated by visual inspection of the registered axial images and the registration of axial volumes on the sagittal T2-weighted volumes. In a limited set of patients, pre- and postimplant CT and T2-weighted MRI studies were available for comparison to determine whether prostate volume changes after implant were dependent on the imaging modality. RESULTS: T1-weighted and T1-weighted fat saturation MRI and CT prostate volumes were consistently larger than the T2-weighted MRI prostate volumes, with a volume on average 1.33 (SD 0.24) times the T2-weighted volume. This discrepancy was due to the superiority of T2-weighted MRI for prostate definition at the following critical interfaces: membranous urethra, apex, and anterior base-bladder and posterior base-seminal vesicle interfaces. The differences in prostate definition in the anterior base region suggest that the commonly reported underdose may be due to overestimation of the prostate in this region by CT. The consistent difference in volumes suggests that the degree of swelling observed after implantation is in part a function of the imaging modality. In patients with pre- and postimplant CT and T2-weighted MRI images, swelling on the T2-weighted images was 1.1 times baseline and on CT was 1.3 times baseline, confirming the imaging modality dependence of prostate swelling. CONCLUSION: Postimplant T2-weighted MRI images provided superior prostate definition in all critical regions of the prostate compared with CT and the other MRI sequences tested. In addition to defining an optimal technique, these findings call two prior observations into question. Under dosing at the anterior base region may be overestimated because of poor definition of the prostate-bladder muscle interface. The swelling observed after implantation was lower on T2-weighted images as well, suggesting that a fraction of postimplant swelling is a function of the imaging modality. These findings have implications for preimplant planning and postimplant evaluation. As implant planning techniques become more conformal, and registration methods become more efficient, T2-weighted MRI after implantation will improve the accuracy of postimplant dosimetry.

Brachytherapy↗
PubMed2000

Compensation of x-ray beam penumbra in conformal radiotherapy.

In radiotherapy, the gross tumor volume is surrounded by a clinically defined margin to allow for the presence of undetected malignant cells. Additional margins are added to accommodate positioning uncertainties and organ motion, creating a planning target volume, or PTV. Finally, a margin is included in the beam apertures surrounding the PTV to account for the dose fall-off at the beam edges (i.e., the "penumbra"). For higher energy beams and for low density tissues adjacent to the PTV, the beam aperture margin should be increased to account for the increased range of scattered photons and electrons. However, increased margins also increase the volume of normal tissue irradiated. In this work, the beam aperture margin is reduced by using filters and multileaf collimator (MLC) techniques to create compensating rinds of increased beam intensity. These compensation techniques were evaluated for 6 and 18 MV x rays by calculating penumbral widths as a function of the increased beam intensity in the rind, the rind width, and tissue density. Dose calculations were performed using a 3D superposition algorithm, which includes an extrafocal source model. Calculations were validated experimentally with film dosimetry. Results show the distance between the 95%-50% isodose lines is reduced from 11 mm to 4 mm for 6 MV x rays in the lung phantom, when the beam intensity is increased by 20% in a 10 mm wide rind. At 18 MV, this distance is reduced from 16 mm to 6 mm with a 20% increase in rind intensity, but a 15 mm wide rind is required. In all cases, penumbra compensation did not result in any appreciable increase in scatter dose outside the field boundaries. These results suggest that penumbra compensation is a practical means of controlling the beam aperture margin.

Algorithms↗
PubMed2000

Monitor unit settings for intensity modulated beams delivered using a step-and-shoot approach.

Two linear accelerators have been commissioned for delivering IMRT treatments using a step-and-shoot approach. To assess beam startup stability for 6 and 18 MV x-ray beams, dose delivered per monitor unit (MU), beam flatness, and beam symmetry were measured as a function of the total number of MU delivered at a clinical dose rate of 400 MU per minute. Relative to a 100 MU exposure, the dose delivered per MU by both linear accelerators was found to be within +/-2% for exposures larger than 4 MU. Beam flatness and symmetry also met accepted quality assurance standards for a minimum exposure of 4 MU. We have found that the performance of the two machines under study is well suited to the delivery of step-and-shoot IMRT. A system of dose calculation has also been commissioned for applying head scatter corrections to fields as small as 1x1 cm2. The accuracy and precision of the relative output calculations in water was validated for small fields and fields offset from the axis of collimator rotation. For both 6 and 18 MV x-ray beams, the dose per MU calculated in a water phantom agrees with measured data to within 1% on average, with a maximum deviation of 2.5%. The largest output factor discrepancies were seen when the actual radiation field size deviated from the set field size. The measured output in water can vary by as much 16% for 1x1 cm2 fields, when the measured field size deviates from the set field size by 2 mm. For a 1 mm deviation, this discrepancy was reduced to 8%. Steps should be taken to ensure collimator precision is tightly controlled when using such small fields. If this is not possible, very small fields should not contribute to a significant portion of the treatment, or uncertainties in the collimator position may effect the accuracy of the dose delivered.

Particle Accelerators↗
PubMed1996

Analysis of the DNA content distribution of micronuclei using flow sorting and fluorescent in situ hybridization with a centromeric DNA probe.

The DNA content distributions of micronuclei induced in mouse 3T3 cells by ionizing radiation and chemicals was measured by flow cytometry. For a quantitative understanding of these distributions, micronuclei with increasing DNA contents were sorted and analysed for the presence of centromeric signals using fluorescent in situ hybridization (FISH) with a mouse centromeric gamma satellite probe. Radiation-induced micronuclei were found to be produced mainly by chromosome fragments, whereas micronuclei induced by the tear gas chlorobenzylidene malonitrile (CS) were found to be produced mainly by whole chromatids. In contrast, micronuclei induced by vinblastine (VBL) were, according to the shape of their DNA content distributions, produced mainly by whole chromosomes and by combinations of two or more whole chromosomes. With increasing DNA content, micronuclei induced by ionizing radiation also contained one or more whole chromosomes, whereas micronuclei induced by CS or VBL were found to contain several whole chromatids or chromosomes respectively. Computerized random breakage of chromosomes and random combination of chromosome fragments, whole chromatids and whole chromosomes were used according to the FISH results to simulate the measured DNA content distributions of micronuclei. A good agreement was obtained between measured and simulated distributions of micronuclei as well as between results of the measured frequency of micronuclei showing centromeric signals as a function of their DNA content and those predicted by the simulations. These results demonstrate the usefulness of flow cytometry and sorting combined with the FISH technique and computer simulations for producing a more detailed analysis of mechanisms of micronucleus induction.

3T3 Cells↗
PubMed1996

Fumonisins Veratox. A new rapid quantitative ELISA for determination of fumonisin in food and feed.

Polyclonal antibodies against fumonisin B1 were produced by immunizing sheep with fumonisin B1-keyhole limpet hemocyanin as an immunogen. A quantitative competitive enzyme-linked immunosorbent assay was developed whereby free fumonisins or sample extract containing fumonisins and enzyme-labelled fumonisin competed for binding to the solid phase-bound antibodies. The color intensity of wells, formed by substrate reaction with the enzyme, was inversely related to FB1 concentration. Detection limits for the assay were 0.1 ng/mL fumonisin B1 and concentrations of fumonisins B1, B2, and B3 required for 50% binding inhibition were 5.5, 23 and 18 ng/mL, respectively. For food and feed analyses, samples were extracted with 70% methanol and dilution of the extracts were used directly for ELISA. ELISA results were compared to HPLC analyses by a reference laboratory and the correlation (r value) between ELISA and HPLC was 0.967. The assay may be used to quantitate fumonisins in food and feed within 30 minutes.

Animal Feed↗
PubMed1995

Evaluation of the micronucleus test in vitro using Chinese hamster cells: results of four chemicals weakly positive in the in vivo micronucleus test.

A rapid and simple procedure for the micronucleus test (MNT) in vitro using Chinese hamster ovary (CHO) cells was established in our laboratory. The assay is intended to quickly screen chromosomal aberrations in vitro within the framework of industrial genotoxicity studies. To test the sensitivity of the assay in the experiments described here, four substances, classified as noncarcinogens but reported as weak inducers of micronuclei (MN) in bone-marrow cells of mice, were evaluated in the MNT in vitro. Of the four compounds, ascorbic acid, phenol, and 2,6-diaminotoluene proved to be genotoxic in the MNT in vitro. Titanium dioxide, which could not be dissolved in the culture medium, did not induce MN. The MNT in vitro proved to be quick and relatively simple and to yield highly reproducible results when testing the four chemicals.

Animals↗
PubMed1994

Diagnostic value of C-reactive protein in acute appendicitis.

Serum C-reactive protein was measured in 56 patients hospitalized with a suspected diagnosis of acute appendicitis. Based on these determinations, four groups of patients were defined: Group A = 26 patients with acute appendicitis who had a C-reactive protein level higher than 2.5 mg/dl. Group B = 4 patients with a C-reactive protein level lower than 2.5 mg/dl who, after surgery based on a presumed diagnosis of acute appendicitis, were found to have a normal appendix. Group C = 22 patients with nonspecific abdominal pain, 18 (72 percent) of whom had an elevated C-reactive protein level, although in only 4 (7.1 percent) were these levels higher than 2.5 percent mg/dl. Group D = 4 patients who had diseases other than acute appendicitis. It is concluded that an increase in C-reactive protein levels to more than 2.5 mg/dl is not a definite indicator of acute appendicitis. However, if the C-reactive protein level in blood drawn 12 hours after the onset of symptoms is less than 2.5 mg/dl, acute appendicitis can be excluded.

Acute Disease↗
PubMed1993

Analysis of micronuclei induced by 2-chlorobenzylidene malonitrile (CS) using fluorescence in situ hybridization with telomeric and centromeric DNA probes, and flow cytometry.

Micronuclei (MN) induced in NIH 3T3 cells by the tear gas 2-chlorobenzylidene malonitrile (CS) were studied in detail using fluorescence in situ hybridization (FISH). The chromosomal composition of CS-induced MN was analysed by simultaneous use of DNA probes for the telomeric hexamer repeat (TTAGGG) and for mouse major satellite DNA. The majority of CS-induced MN, 63-73% of all CS-induced MN at doses from 10 to 30 microM CS, revealed centromeric signals and several telomeric signals suggesting their origin from whole chromosomes. Almost 50% of all CS-induced MN showed one centromeric signal and were assumed to contain one single chromosome. Only 4.5% of all MN did not show any signal and 23-28% showed telomeric signals only, thus containing acentric fragments. Based on the experimental data from FISH the distribution of the DNA content of CS-induced MN was calculated assuming random breakage of chromosomes, and random combination of chromosomes and chromosome fragments. Good agreement between calculated MN distributions and distributions measured by flow cytometry was obtained. By sorting MN with distinct DNA content and hybridization of the sorted MN with the centromeric probe, regions in the MN distribution containing mainly MN with single whole chromosomes could be demonstrated.

3T3 Cells↗
PubMed1993

PCR cloning of a repeated DNA fragment from Chinese hamster ovary (CHO) cell X chromosomes and mapping by fluorescence in situ hybridization.

Hamster chromosome-specific DNA sequences were amplified by primer directed DNA amplification using mixed base oligonucleotides in an arbitrarily primed polymerase chain reaction (AP-PCR) protocol. The template DNA was comprised of approximately 3000 chinese hamster ovary cell (CHO) chromosomes enriched by flow sorting from a human x hamster hybrid cell line. Labeling of the PCR product pool and fluorescence in situ hybridization (FISH) demonstrated preferential binding to the distal long arm of the CHO X chromosome. The PCR products were cloned, labeled by PCR and hybridized to metaphase spreads. Clones containing highly reiterated DNA were identified by FISH and sequenced. Here, we present the sequence and chromosomal location of one of the repeat clones that maps close to the secondary constriction on the long arm of the CHO X chromosome, pCAT2066-24.

Animals↗
PubMed1992

Polyorchidism discovered as testicular torsion.

We report on a case of polyorchidism that presented as testicular torsion. A brief history and review of the literature is also presented. Of the 47 cases reported, this patient is the youngest.

Humans↗
PubMed1992

Factors influencing the DNA content of radiation-induced micronuclei.

The distribution of the DNA content of radiation-induced micronuclei was analysed in several cell lines (Chinese hamster, Syrian hamster and mouse NIH-3T3 cells) by flow cytometry. Frequency and DNA content of micronuclei were measured simultaneously using fluorescence and forward scatter signals of micronuclei and nuclei in suspension stained with ethidium bromide. Computerized random breakage of chromosomes and random combination of fragments was performed to compare the measured micronucleus distributions in synchronized cells irradiated during G1-phase with calculated distributions. The measured DNA distribution of radiation-induced micronuclei was found to be influenced by several factors: (1) the DNA distribution and the centromeric index of the chromosomes in the various cell lines; (2) the cell cycle phase at time of micronucleus measurement due to DNA synthesis in micronuclei; (3) the presence of chromosome fragments in micronuclei; and (4) the presence of whole chromosomes in micronuclei. These factors were shown to be responsible for the previously found large radiation-induced micronuclei which could not be explained by the classic assumption only that radiation-induced micronuclei are mainly produced by single acentric fragments.

3T3 Cells↗
PubMed1992

Aneuploidy induction in mouse spermatocytes.

Assays for aneuploidy are being developed within a coordinated research program sponsored by the Commission of the European Communities. The 10 known and suspect spindle poisons colchicine (COL), econazole (EZ), chloral hydrate (CH), hydroquinone (HQ), diazepam (DZ), thiabendazole (TB), cadmium chloride (CD), pyrimethamine (PY), thimerosal (TM) and vinblastine (VBL) were tested for aneuploidy induction in male germ cells. Two different criteria were used for the evaluation of slides from testicular material of (102/El x C3H/El)F1 mice at different times (6, 14 and 22 h) after treatment with different doses of each of the test chemicals. Secondary spermatocytes of mice were evaluated by chromosome counting to determine the induction of hyperploidy. The proportions of spermatogonial mitoses, first and second meiotic metaphases were determined in order to recognize an effect of the test chemicals on testicular cell proliferation. COL, EZ, CH, HQ and VBL clearly increased the frequencies of hyperploid secondary spermatocytes which indicated non-disjunction induction during the first meiotic division. DZ and CD were less effective but significantly positive (P less than 0.05). Concomitantly, COL, EZ, CH, HQ, DZ, CD and VBL induced meiotic delay in primary and/or secondary spermatocytes. It is concluded that meiotic delay may be indicative for aneuploidy induction and the evaluation of changes in testicular cell proliferation described here could serve as a prescreen and partially substitute the time-consuming counting of metaphase chromosomes in secondary spermatocytes.

Aneuploidy↗
PubMed1992

Analysis of radiation-induced micronuclei by fluorescence in situ hybridization (FISH) simultaneously using telomeric and centromeric DNA probes.

Fluorescence in situ hybridization using simultaneously a combination of DNA probes for the telomeric hexamer repeat (TTAGGG) and the centromerically repeated murine gamma-satellite DNA was applied to analyze the nature of radiation-induced micronuclei in mouse NIH 3T3 fibroblasts. After subtraction of spontaneously occurring micronuclei independent from the dose and time after irradiation, approximately 22% of the radiation-induced micronuclei did not reveal any hybridization signal. Approximately 17% showed one centromeric hybridization signal and about four telomeric signals, suggesting their origin from whole chromosomes. Almost 60% of radiation-induced micronuclei had telomeric signals only, suggesting their origin from acentric fragments. A fraction of micronuclei were found to contain two or more acentric fragments. Micronuclei derived from whole chromosomes or from multiple acentric fragments might, together with DNA synthesis in micronuclei, explain the occurrence of radiation-induced micronuclei with DNA contents greater than the largest chromosome arm.

Animals↗