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Biomedical subjects

R C Miller

Publications and source records attributed to R C Miller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Impact of beam energy and field margin on penumbra at lung tumor-lung parenchyma interfaces.

PURPOSE: To determine the characteristics of the penumbra in the region of the lung tumor-lung parenchyma interfaces for various radiation beam energies and various field margins. METHODS AND MATERIALS: A phantom simulating the thoracic cavity with a tumor arising within the lung parenchyma was irradiated with opposed 6-, 10-, and 18-MV photon beams. Beam profiles were obtained at the tumor's surface and midplane using radiographic film. The field edge varied from 0.0 to 3.5 cm from the gross tumor volume. The effective penumbra (distance from 80 to 20% dose) and beam fringe (distance from 90 to 50% dose) were measured. Clinically acceptable beam profiles were defined as those in which no point of the planning target volume (gross tumor volume plus a 1-cm margin) received less than 95% of the central tumor dose. RESULTS: Mean effective penumbra and beam fringe were found to differ in a statistically significant manner with respect to energy, but not with distance from field edge to gross tumor volume. With the field edge < or = 1.5 cm from the gross tumor volume, no energy provided an acceptable dose distribution, as defined above. With the field edge 2 cm from the gross tumor volume, 6 and 10 MV provided acceptable dose distributions, but 18 MV did not. With the field edge > or = 2.5 cm from the gross tumor volume, all energies provided acceptable dose distributions. CONCLUSION: For irradiation of lung carcinomas in which the planning target volume includes a margin of normal lung tissue, 6- and 10-MV opposed beams yield a superior dose distribution with respect to penumbra at the tumor's surface and midplane, with the field edge placed 2 cm from the gross tumor volume. To achieve an equivalent distribution with 18-MV photons, a distance of 2.5 cm from field edge to the gross tumor volume is necessary, leading to an increase in normal lung tissue irradiated.

Humans↗
PubMed1998

Spinal cord localization in the treatment of lung cancer: use of radiographic landmarks.

PURPOSE: In the treatment of thoracic malignancies with radiotherapy, the critical dose-limiting structure is the spinal cord. Oblique fields typically are designed to exclude the spinal cord, and by convention, the field edge that shields the spinal cord is placed at the anterior border of the vertebral pedicles. Thus, the purpose of our study was to estimate the distance between the field edge and spinal cord in oblique fields that were designed by using the vertebral pedicle as a radiographic landmark. METHODS AND MATERIALS: The spinal cord of a cadaver was wrapped in wire, and oblique fields were simulated at 15 degree intervals. The distance from the spinal cord to a field edge placed at the anterior border of the pedicle was measured. In the second investigation, a three-dimensional treatment planning system was used to simulate hypothetical fields using actual patient data from computed tomography (n = 10), and measurements identical to those in the anatomical model were made (n = 1,100). RESULTS: The results of the anatomical and computed tomographic models were in close agreement (mean difference, 0.6 mm). The computed tomographic model predicted a mean field edge to spinal cord distance of 8.7 mm (95% confidence interval, 5.6-11.8 mm) for 30 degree/150 degree oblique fields and 8.0 mm (95% confidence interval, 4.7-11.7 mm) for 45 degree/135 degree oblique fields. This distance was greatest at levels T-1, T-2, and T-11 (8 to 20% greater). CONCLUSIONS: The mean distance from a field edge placed at the anterior border of a vertebral pedicle to the spinal cord for commonly used oblique angles constitutes a sufficient margin to account for expected differences in daily positional variations and mechanical uncertainties.

Cadaver↗
PubMed1998

Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis.

We have studied temporal mRNA expression patterns for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and transforming growth factor-beta1 (TGF-beta1) in two rat injury paradigms with very different cellular inflammatory reactions: contussion of the spinal cord and axotomy of the facial nerve. Our comparative analyses using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) show an early and robust upregulation of IL-1beta, TNF-alpha, IL-6, and M-CSF mRNAs in spinal cord after contusion injury. Peak expression of these mRNAs was transient and returned to control levels by 24 h postinjury. In contrast, expression of IL-1beta and TNF-alpha mRNAs in the axotomized facial nucleus was minimal and delayed, and levels of M-CSF mRNA remained unaltered. Similar to injured spinal cord, the axotomized nucleus showed a dramatic and early upregulation of IL-6 mRNA, but unlike spinal cord, IL-6 mRNA levels subsided only gradually. Both injury paradigms showed gradually increasing levels of TGF-beta1 mRNA which were maximal at 7 days postinjury. RT-PCR analyses were also performed on isolated blood-borne mononuclear cells and neutrophils. The results showed that these cells contain high levels of IL-1beta and M-CSF mRNAs, moderate levels of TGF-beta and TNF-alpha mRNAs, and minimal levels of IL-6 mRNA. The RT-PCR analyses together with histological observations indicate that expression of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 is short-lived and self-limited after contusion injury, and that it occurs primarily within endogenous glial cells. Transient expression of these molecules likely triggers secondary events which may be beneficial to wound repair and regeneration.

Animals↗
PubMed1998

Effect of track structure and radioprotectors on the induction of oncogenic transformation in murine fibroblasts by heavy ions.

The oncogenic potential of high-energy 56Fe particles (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at the Brookhaven National Laboratory was examined utilizing the mouse C3H 10T1/2 cell model. The dose-averaged LET for high-energy 56Fe is estimated to be 143 keV/micrometer with the exposure conditions used in this study. For 56Fe ions, the maximum relative biological effectiveness (RBEmax) values for cell survival and oncogenic transformation were 7.71 and 16.5 respectively. Compared to 150 keV/micrometer 4He nuclei, high-energy 56Fe nuclei were significantly less effective in cell killing and oncogenic induction. The prostaglandin E1 analog misoprostol, an effective oncoprotector of C3H 10T1/2 cells exposed to X rays, was evaluated for its potential as a radioprotector of oncogenic transformation with high-energy 56Fe. Exposure of cells to misoprostol did not alter 56Fe cytotoxicity or the rate of 56Fe-induced oncogenic transformation.

Animals↗
PubMed1998

'Best clinical practice': assessment of processes of care and of outcomes in the US Military Health Services System.

The National Quality Management Program of the Military Health Services System of the United States has undertaken a series of projects whose objective is the active, on-going monitoring and improvement of the effectiveness and efficiency of the care provided to a broad population that encompasses troops on active duty, retirees and dependents. The analytic activities consist of (1) identification by clinical panels of conditions and procedures of interest; (2) collection of data from electronic repositories and from charts to characterize the patients, how they are managed, the clinical outcomes they experience, the resource costs their care entails, and, from questionnaires, their functional status and level of satisfaction, and (3) generation of 'report cards' that inform organizational units down to the level of the hospital of the characteristics of their patients, their practices, and the risk-adjusted outcomes they achieve. The patterns of care employed by the hospitals that obtain the best risk-adjusted outcomes and resource utilization ('best clinical practice') are identified and made known. In addition, (4) a systematic process of developing outcomes-based practice guidelines has been devised. It intent is to serve as a decision-support tool for clinicians. Initial estimates have been obtained of the probable consequences of the application of this tool to operative interventions in childbirth. Use of the tool would result in a higher occurrence of elective Caesarean sections, a reduced rate of emergency Caesarean sections and much lower use of forceps, with an overall improvement in outcomes and lower resource costs. This program is currently in the early phases of implementation. The two principal requirements for the immediate future are (1) education of the clinical and administrative communities in the use of the data and the decision-support tools and (2) evaluation of the consequences of the use of the data by the clinical and administrative communities.

Benchmarking↗
PubMed1997

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors.

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.

Adolescent↗
PubMed1997

Neonatal effects and serum cortisol levels after multiple courses of maternal corticosteroids.

OBJECTIVE: To determine the effects of multiple courses of maternal betamethasone for fetal lung maturation on neonatal serum cortisol levels and clinical Cushing syndrome. METHODS: Seventy-nine mother-infant pairs delivered between 24 and 36 weeks' gestation were enrolled in the study. They were grouped according to the number of courses of betamethasone received between 24 and 34 weeks' gestation for fetal lung maturation: those receiving no courses, one course, and two or more courses. Physical examinations were performed and serum glucose, electrolyte, and cortisol levels were measured on days 1 and 3 of life. RESULTS: For those receiving multiple courses of betamethasone (n = 43), the mean (+/- standard error of the mean [SEM]) number of courses was 5.3 +/- 0.4, with a mean (+/-SEM) total dose of 125.0 +/- 10.7 mg. No neonates had findings suggestive of Cushing syndrome. Day 1 cortisol levels (pooled mean +/- SEM) were 12.6 +/- 2.4, 5.3 +/- 3.2, and 4.4 +/- 1.8 microg/dL in those receiving no courses, one course, and two or more courses, respectively (P = .03; no courses versus two or more courses, P = .03), but the differences were not significant when corrected for multiple variables. Differences among day 3 cortisol levels (pooled mean +/- SEM) were not significant: 8.3 +/- 1.6, 5.8 +/- 1.4, and 5.8 +/- 0.9 microg/dL in those receiving no courses, one course, and two or more courses, respectively. None of the neonates in the group receiving no courses of betamethasone had day 1 cortisol levels lower than normal, whereas 22% and 11% of the neonates receiving one and two or more courses, respectively, had day 1 levels lower than normal. On day 3, 15% of those receiving one course and 10% of those receiving two or more courses had serum cortisol levels lower than normal, whereas none of those who received no courses had a low cortisol level. Multivariate regression analysis could show no association between the number of courses or total dose of betamethasone and the day 1 or day 3 cortisol values. The day 1 cortisol level (log10) was most associated with the severity of respiratory distress syndrome (RDS) and day 3 cortisol level (log10) with race and severity of RDS. Only in neonates with absent or mild RDS did number of courses correlate with day 3 cortisol levels (log10), but this was a positive correlation. CONCLUSION: Serum cortisol levels either were independent of the number of courses or total dose of corticosteroids given or, in a subpopulation, were associated with increasing levels with increasing doses, suggesting that there is no suppressive effect with repeated dosing.

Betamethasone↗
PubMed1997

Aspirated safety pin requiring thoracotomy: report of a case and review.

Foreign body aspirations in children are relatively uncommon occurrences, but they can be a serious events, causing respiratory distress, atelectasis, chronic pulmonary infections, or death. Safety pins are not commonly aspirated objects and account for less than 3% of all foreign bodies found in the tracheobronchial tree. Fewer than 2% of patients require thoracotomy, and most aspirated materials can be removed by bronchoscopy, with low morbidity and mortality. A discussion of airway foreign bodies follows the presentation of a case of an older child who aspirated a safety pin, which required open thoracostomy for removal.

Bronchi↗
PubMed1996

The radiobiology of intravascular irradiation.

PURPOSE: There is increasing interest in the use of vascular irradiation, from an internally introduced radioactive source to control restenosis after balloon angioplasty. Both animal experiments and early clinical studies appear to show promising results in this regard. We consider various mechanistic interpretations of the experimental and clinical observations that doses of 12-20 Gy appear to be efficacious in preventing restenosis. We develop and investigate simple models, both experimental and theoretical, of the kinetics of radiation-induced smooth muscle cell (SMC) inactivation and regrowth, as a first step toward optimizing the design of clinical vascular irradiation. METHODS AND MATERIALS: Using in vitro models of human SMCs, we investigate the relative radiosensitivity of SMCs compared with endothelial cells and measure the dose-dependent ability of SMCs to repopulate a denuded region in a confluent layer of cells. We then use quantitative information on the number, radiation sensitivity, and growth rate of the potential arterial target cells to model the time course of the SMC population after irradiation. RESULTS AND CONCLUSION: Doses >20 Gy, which would be required to completely eliminate the SMC population which has the potential to cause restenosis, are too large to be practical because of the unacceptable risk of late complications. However, doses that can be practically given in vascular irradiation (<20 Gy) will certainly delay restenosis by 1-3 years, with larger doses producing longer delays. Whether such doses can avert restenosis permanently is unclear, as permanent prevention at realistic doses depends critically on the assumption that those SMCs which survive irradiation have a significantly limited capacity for proliferation. With regard to current animal model experiments, routine follow-up of <1 year, which is standard practice, is probably too short to address some of the key mechanistic question in intravascular radiation therapy.

Angioplasty, Balloon, Coronary↗
PubMed1996

Neoplastic transformation of mouse C3H10T1/2 cells following exposure to neutrons does not involve mutation of ras gene as analyzed by SSCP and cycle sequencing.

About 25% of human tumors contain a mutated member of the ras gene family. Neutron exposure is an occupational risk in several work places and while we know that cells exposed to neutrons can become transformed, the molecular basis of this process is not understood. To determine whether neutron-induced cellular transformation involves ras mutation, C3H10T1/2 cells were exposed to a single dose of 5.9 MeV neutrons. Type II and type III foci were isolated and established as cell lines. A total of 34 foci were selected and expanded for analysis of tumorigenicity, chromosomal aberrations and mutations in members of the ras gene family. The presence of mutations in genomic DNA in N-ras or K-ras of each focus was examined by either single-strand conformational polymorphism (SSCP) analysis or by asymmetric PCR coupled cell cycle sequence analysis. Although chromosomal aberrations were detected at metaphase, no alterations in either ras gene were detected. We conclude that in vitro neutron-induced transformation must occur through a mechanism other than ras mutation.

Animals↗
PubMed1996

The usefulness of a prenatal genetic questionnaire in genetic risk assessment.

OBJECTIVE: To evaluate a prenatal questionnaire as a genetic screen and as an aid in pre-amniocentesis genetic risk assessment. METHODS: In a retrospective cohort study, charts were reviewed for 158 consecutive women of advanced maternal age referred for genetic counseling. Genetic risks identified by use of a questionnaire completed by 79 consecutive patients were compared with those risks identified by the referring physician, those identified during subsequent three-generation pedigree analysis, and to genetic risks identified by pedigree evaluation of 79 consecutive individuals who underwent genetic counseling without the aid of a questionnaire (controls). RESULTS: Sixteen (20%) of the questionnaires revealed a previously unidentified genetic risk. The sensitivity and specificity of the questionnaire were determined to be 40.0 and 97.4%, respectively. Pedigree analysis alone (control group) identified significantly more at-risk pedigrees than did the questionnaire alone (34 versus 20%, P < .05), but identified significantly fewer at-risk pedigrees than obtained from the study group patients who completed a questionnaire and pedigree evaluation (34 versus 50.6%, P < .05). Of all 158 patients, 15.2% (n = 24) underwent additional testing on the basis of genetic risk assessment. There was no difference between the study and control groups in additional evaluations performed (P = 1.0). CONCLUSION: A three-generation pedigree is superior to a questionnaire in genetic risk assessment. The questionnaire was not sufficiently sensitive to serve independently as an adequate genetic screen or risk assessment tool and did not influence subsequent fetal evaluation. Assessment of the sensitivity and specificity of prenatal genetic questionnaires should be undertaken before their routine clinical use.

Adult↗
PubMed1996

The biological effectiveness of radon-progeny alpha particles. V. Comparison of oncogenic transformation by accelerator-produced monoenergetic alpha particles and by polyenergetic alpha particles from radon progeny.

Generation of estimates of risk caused by exposure to radon in the home, either from miner data or from A-bomb data, requires several scaling factors such as for dose, dose rate and radiation quality, and possible synergisms. Such scaling factors are best developed from laboratory-based studies. Two possible sources of alpha particles for such studies are (1) a polyenergetic spectrum, generated directly by radon and its progeny, or (2) a series of monoenergetic alpha particles. We compare here the results of oncogenic transformation from studies using both systems. At the Columbia University Radiological Research Accelerator Facility (RARAF), C3H 10T1/2 cells were irradiated with alpha particles of various energies, with defined LETs from 70 to 200 keV/mum. At Pacific Northwest Laboratory, cells from the same stock were exposed to alpha particles from radon gas and its progeny, which were in equilibrium with the culture medium. There was good agreement between the results of oncogenic transformation experiments using the two different exposure systems. Apart from the experimental transformation frequencies themselves, such a comparison requires (1) reliable dosimetry at both facilities and (2) estimated LET distributions for the polyenergetic alpha-particle irradiator. Thus this good agreement gives some confirmation to the technique which is used to fold together oncogenic transformation rates from monoenergetic alpha particles to yield a predicted rate for a spectrum of alpha particles.

Alpha Particles↗
PubMed1996

Bond strengths of fluoride-releasing restorative materials.

PURPOSE: To compare the shear bond strengths to dentin of four tooth-colored fluoride-releasing restorative materials that utilize different mechanisms of dentin-bonding. MATERIALS AND METHODS: Four materials were tested: a chemically-cured glass ionomer (Ketac-Fil); a light-cured resin-modified glass ionomer (Photac-Fil); a light-cured resin-modified glass ionomer in conjunction with a resin dentin-bonding agent (Vitremer); and a light-cured resin composite in conjunction with a resin dentin-bonding agent (Tetric). The enamel was removed from four sides of the twenty human noncarious extracted molars which had their roots embedded in acrylic blocks. Cylindrical samples of the materials were prepared in plastic molds and bonded to the dentin surface according to the manufacturers' instructions. After 24 hours of storage in a humidor, the samples were sheared with an Instron testing machine at a crosshead speed of 0.5 mm/minute. RESULTS: Statistical evaluation (ANOVA and Duncan's test) suggests that the fluoride-releasing resin composite material utilizing a resin dentin-bonding agent provided a significantly greater mean shear bond strength (16.5 MPa) after 24 hours storage than any of the selected glass ionomer materials. Of the three glass ionomer materials compared, the light-cured resin-modified material with a resin dentin-bonding agent provided a significantly greater mean shear bond strength (6.7 MPa) than the light-cured resin-modified material without a resin dentin-bonding agent (3.0 MPa) or the chemically-cured material (3.8 MPa).

Analysis of Variance↗
PubMed1995

Cellobiohydrolase B, a second exo-cellobiohydrolase from the cellulolytic bacterium Cellulomonas fimi.

The gene cbhB from the cellulolytic bacterium Cellulomonas fimi encodes a polypeptide of 1090 amino acids. Cellobiohydrolase B (CbhB) is 1037 amino acids long, with a calculated molecular mass of 109765 Da. The enzyme comprises five domains: an N-terminal catalytic domain of 643 amino acids, three fibronectin type III repeats of 97 amino acids each, and a C-terminal cellulose-binding domain of 104 amino acids. The catalytic domain belongs to family 48 of glycosyl hydrolases. CbhB has a very low activity on CM-cellulose. Viscometric analysis of CM-cellulose hydrolysis indicates that the enzyme is an exoglucanase. Cellobiose is the major product of hydrolysis of cellulose. In common with two other exoglycanases from C. fimi, CbhB has low but detectable endoglucanase activity. CbhB is the second exo-cellobiohydrolase found in C. fimi. Therefore, the cellulase system of C. fimi resembles those of fungi in comprising multiple endoglucanases and cellobiohydrolases.

Actinomycetales↗