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Biomedical subjects

D L Wilson

Publications and source records attributed to D L Wilson.

At least 55 records · Page 3Linked to original sources

Experiences of cancer in children and adolescents.

In an effort to understand the effect of cancer diagnosis and treatment in children and adolescents, and to identify issues that should be addressed with newly diagnosed patients, 85 patients with Ewing's sarcoma family tumors (ESFT) were interviewed about their experience of having cancer. This represents 90% of all eligible patients who survived at least 3 years since their diagnosis and who were treated for ESFT at the National Cancer Institute (NCI) from 1965-1993. The mean age of patients at the time of diagnosis was 15.8 +/- 5.3 years, and mean time since diagnosis was 13.6 +/- 6.4 years. Patients from this cohort had a disease usually related to poor outcome. Patients answered five open-ended written questions. Negative experiences that they described included transient and permanent discomfort and disabilities related to cancer; disruption of life or relationships; and emotional aspects of cancer diagnosis or treatment. Positive aspects of having cancer included changed attitudes about self and life, improved relationships with others, or better job performance. Advice for newly diagnosed patients most often dealt with the emotional aspects of cancer. The importance of patient-to-patient support was frequently described. Overall, having cancer was not an entirely negative experience, and it may result in introspection and improved relationships with others.

Adaptation, Psychological↗

How to screen for 222Rn in large buildings.

222Rn measurements have been made in over 10,000 ground-contact rooms in 908 federal buildings. These data were examined statistically to compare parametric distributions that might be useful in the design and execution of future surveys of indoor 222Rn in large buildings. In 152 of the 365 buildings with the most measurements per building, the log-normal distribution was acceptable. Many other distributions were observed in the other 213 buildings, including bi- and tri-modal distributions. In contrast, when data from entire facilities were examined, the data were usually described by a lognormal distribution. Because of the above observations, we propose that any future surveys of indoor 222Rn in large buildings be done in two phases, screening and assessment. During the screening phase, all facilities may be surveyed with a comparatively low sampling density, perhaps, one measurement per 465 m2 (5,000 ft2) of floor space. Based on the results presented here, it is expected that statistical analysis of the screening data will reveal any facilities with substantial evidence of a high incidence of rooms with elevated indoor 222Rn concentrations (e.g., above 150 Bq m-3). In the assessment phase, the identified facilities will be surveyed with a sampling density of one measurement for every ground-contact room or about one per 84 m2 (900 ft2). Using numerical simulation techniques, we have tested the proposed screening phase protocol against data from sixteen facilities. The results of the simulated screenings support the feasibility of a two-phased approach to the task of identifying facilities having rooms with elevated 222Rn concentrations.

Air Pollution, Indoor↗

Pulsed fluoroscopy detectability from interspersed adaptive forced-choice measurements.

Using a new reference/test, adaptive forced-choice method, we investigated detectability of low contrast disks in simulated x-ray fluoroscopy image sequences. The method minimized effects of undesirable variables, such as changes in subject attention level by alternating conventional fluoroscopy (reference) and low acquisition rate fluoroscopy (test) presentations. To compare absolute target detectability and x-ray dose requirements of reference and test presentations, the contrast of the test presentation was set equal to that of the reference presentation, and the dose of the test presentation was adapted to give equivalent detectability of disk targets. Comparing pulsed fluoroscopy at 15 acq/s (pulsed-15) and 7.5 acq/s (pulsed-7.5) with conventional fluoroscopy at 30 acq/s (pulsed-30), dose savings were found in 22 of 24 experiments. When averaged over 3 disk sizes and 4 subjects, savings were 22% and 26% for pulsed-15 and pulsed-7.5, respectively. In most experiments, the subject was given an unlimited time to view presentations. With unlimited display times, subjects took slightly longer to respond for pulsed-15 or pulsed-7.5 than for pulsed-30. In other experiments, display times were limited. As the restricted display time increased, absolute target detectability increased while the x-ray dose for equivalent detectability was unchanged. The number of frames, N, in a repeating loop was also varied. Absolute detectability increased as N increased from 1 to 30 but changed little as more frames were added up to 150. The new experimental paradigm gives efficient, robust comparisons of image data and is applicable to a wide variety of medical image perception problems.

Adult↗

Mumps outbreak in a highly vaccinated school population. Evidence for large-scale vaccination failure.

OBJECTIVES: To describe an outbreak and to identify risk factors for mumps occurring in a highly vaccinated high school population. (Note: Highly vaccinated means a population in which more than 95% have been vaccinated.) DESIGN AND PARTICIPANTS: Survey and cohort study of 307 (97%) of 318 students. OUTCOME MEASURES: Mumps was defined as an illness with 2 or more days of parotid swelling. Serologic confirmation of infection was obtained in eight cases, seven of which were evaluated for presence of IgM antibody using immunofluorescent antibodies. Vaccination records were verified for 297 (97%) students. RESULTS: Between October 3 and November 23, 1990, clinical mumps developed in 54 students (attack rate, 18%), 53 of whom had been vaccinated. Most cases (40 [77%] of 52) occurred 12 to 20 days after a school-wide pep rally. Immunofluorescent antibody testing of all seven specimens demonstrated IgM antibody to mumps. Risk factors for clinical mumps identified in multivariate analyses included female gender (odds ratio, 3.0; 95% confidence interval, 1.6 to 5.7) and source of vaccination other than the local public health clinic (students vaccinated by private providers [odds ratio, 3.0; 95% confidence interval, 1.3 to 5.2] or in other districts [odds ratio, 2.4; 95% confidence interval, 1.1 to 5.3]). CONCLUSIONS: The overall attack rate is the highest reported to date (and to our knowledge) for a population demonstrating virtually complete mumps vaccine coverage. Even verified documentation of vaccination may not be an accurate indicator of an individual's protection against mumps. Vaccination failure may play an important role in contemporary mumps outbreaks. We found no evidence to indicate that waning immunity (secondary vaccine failure) contributed significantly to this outbreak. A second dose of mumps vaccine, as recommended using measles-mumps-rubella vaccine, could potentially prevent similar outbreaks in secondary school populations in the future.

Adolescent↗

The influence of pregnancy on the biotransformation and urinary excretion of methoxyphenamine in mice.

(i) The urinary elimination of methoxyphenamine (MPA) and its metabolites in underivatized samples was examined after single and multiple oral administration to pregnant and non-pregnant mice by GLC and GLC-MS. (ii) The major metabolite O-desmethylmethoxyphenamine (ODMP), along with lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (2OH), were the only metabolites detected in urine extracts of pregnant and non-pregnant mice. 5-Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not increase the recovery of either substrate or metabolites in either the pregnant or non-pregnant animals. The results show that MPA metabolism in the Swiss-Webster mouse is distinctly different from that seen in man and other laboratory animals. (iii) The mean MPA:ODMP ratio in day-6 urine from pregnant mice after a single dose was 0.31 +/- 0.04. The NDMP:ODMP ratios were less than 0.10 in all samples. Non-pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2OH after multiple dosing. (iv) While multiple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in the MPA:ODMP ratio during gestation. (v) MPA was extensively metabolized to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightly higher than that observed in the pregnant and non-pregnant females.

Animals↗

On the reduction of error in alpha track detector measurements of indoor 222Rn.

Small plastic chambers containing alpha track detectors are often used for measuring indoor concentrations of 222Rn. This paper reports an experimental assessment of sources of error in measurements made with alpha track detector-containing chambers. The results demonstrate the feasibility of a nondestructive test for the identification of alpha track detector-containing chambers that are packaged in a way that does not effectively prevent ambient 222Rn from inducing tracks prior to field exposure. Results also indicate that there is statistically significant variation among manufacturing lots and among chemical processing batches. Error from these sources can be avoided or compensated if appropriate control measures are implemented as part of a quality assurance program during any survey using alpha track detector-containing chambers.

Air Pollutants, Radioactive↗

Metabolism of methoxyphenamine and 2-methoxyamphetamine in P4502D6-transfected cells and cell preparations.

1. Control and P4502D6-transfected human B-lymphoblastoid cell lines (cHol and h2D6v2 respectively) were used to study 2D6-mediated metabolism of methoxyphenamine (MPA) and 2-methoxyamphetamine (2MA). The main metabolites were products of O-dealkylation and aromatic hydroxylation at the 5-position. In addition, N-desmethyl-methoxyphenamine (NDMP) was also identified as a minor metabolite of MPA in extracts of these cells, confirming previous reports of 2D6-mediated N-demethylation of MPA. 2. An additional ring-hydroxylated metabolite of MPA and 2MA has been tentatively identified as the corresponding 3-hydroxy-2-methoxy derivative. 3. MPA metabolism in whole cells was time dependent, with approximately 30% of the MPA metabolized after 72 h. A 35% conversion of MPA was achieved on average with cell lysates. Only 18% 2MA was metabolized. By contrast, control cells (cHol) showed no evidence of any MPA or 2MA metabolites even after 96-h incubation. 4. Continuous presence of haemin/dimethylsulphoxide (DMSO) throughout the 4-day incubation with MPA resulted in a shift in the metabolite profile towards the production of NDMP at the expense of the other products. 5. In summary, h2D6v2 cells, lysates and microsomes can form all metabolites of MPA and can be used in drug interaction studies.

Amphetamines↗

Hyper- and hypo-responsiveness to dietary fat and cholesterol among inbred mice: searching for level and variability genes.

A concept proposed by Berg (Berg, K. 1989. Arteriosclerosis. 9: I-50-I-58) is that a combination of level and variability genes determine an individual's overall plasma lipid levels and atherosclerotic risk. Our goal was to determine which inbred mouse strains could be used to identify candidate level and variability genes controlling lipid levels and atherosclerosis susceptibility. Nine common inbred mouse strains were examined for responsiveness with respect to plasma lipoprotein and tissue lipid levels upon feeding diets rich in cholesterol and fat. Marked quantitative variations were observed in plasma cholesterol and triglyceride levels among mice fed rodent chow and the high fat test diets. Mice of strains DBA/2 and AKR appeared to be hyporesponsive to diets containing high levels of fat and cholesterol as compared to rodent chow. In contrast, several strains were primarily hyperresponsive to either dietary fat or cholesterol, or both ingredients. Determination of cholesterol absorption for selected strains fed test diets suggested that decreased cholesterol absorption, in part, contributes to hyporesponsiveness as seen in DBA/2 mice. Levels of mRNA for cholesterol 7 alpha-hydroxylase were estimated and shown to vary markedly among strains. An inverse correlation was seen among strains between cholesterol 7 alpha-hydroxylase mRNA, and plasma and hepatic cholesterol levels for some diets. Thus, genes controlling cholesterol absorption and bile acid synthesis are candidates for further study as level and variability genes affecting plasma cholesterol levels. Overall, inbred mouse strains will prove useful for identifying genes controlling level and variability traits.

Absorption↗

Optimal data acquisition for volumetric intracoronary ultrasound.

Three-dimensional analysis using intracoronary ultrasound (ICUS) pull-back data provides the unique ability to quantitate lumen and atherosclerotic plaque volumes. Optimal data acquisition parameters for volumetric acquisition were established using simulations on computer phantoms of stenotic arteries. Eleven computer phantoms were generated using cross-sectional area data from quantitative angiography of stenotic coronary arteries. Three methods of data acquisition were simulated: conventional manual pull-back; motorized pull-back; and manual pull-back with measured displacement. Effects of pull-back velocity and cardiac gating on cross-sectional area profiles and volumes were studied. Cardiac gating eliminated errors introduced by vessel deformation within a cardiac cycle. With cardiac gating, pull-backs with mean velocities up to 1.2 mm/sec allowed reconstruction of cross-sectional area profiles within 5% RMS error. With faster pull-backs, cardiac gating resulted in sparse spatial sampling and significant errors in cross-sectional area profiles. The accuracy of both motorized and measured required equal displacements of the catheter proximal and distal ends. This assumption was validated with in vitro experiments where X-ray fluoroscopy was used to measure the displacement of the imaging tip. Excellent correlation was found between the two displacements (r = 0.99). Finally, slow pull-backs were performed by 3 operators, and pull-back velocities were measured. It was found that mean pull-back velocities as low as 0.8 mm/sec were achievable. From our simulations, we predict that accurate volumetric analysis requires cardiac gated, calibrated, slow (< 1.2 mm/sec) pull-backs.

Calibration↗

Volumetric intracoronary ultrasound: methods and validation.

Intracoronary ultrasound (ICUS) not only allows visualization of the vessel lumen, it gives a unique view of the transmural components of the artery wall. Analysis of lumen and plaque volume is necessary for studying atherosclerotic disease progression or regression and the mechanisms of therapeutic coronary interventions. A real-time, ICUS pull-back data acquisition scheme was developed to acquire calibrated, cardiac-gated volumetric image data sets. A semiautomated border detection scheme was implemented using dynamic programming. In phantoms, estimated area profiles were very reproducible as measured by the root-mean-square from the mean (3.8-5.9%). In phantom volume estimates, improved reproducibility (standard deviation = 1.2-3.6%) was obtained as positive and negative errors in area profiles were averaged out. Phantom volumes were also accurate when compared to true water displacement volume. The mean error ranged from -2.59 to -8.94%. When compared to quantitative single and biplane angiographic analysis, ICUS volumetric estimates tended to be superior to single plane analysis (error -5.06 +/- 2.48% vs -9.96 +/- 8.01%), but similar to optimal biplane analysis (error -5.06 +/- 2.48% vs -6.34 +/- 3.08%). In vivo reproducibility was assessed by performing multiple cardiac-gated pull-backs through experimentally induced stenosis. Over the length of the stenosis, excellent reproducibility of area profiles (+/- 5.9%) and volumes (+/- 1.9%) was obtained for cardiac-gated acquisitions. We conclude that volumetric ICUS provides accurate and reproducible estimates of lumen volume. Thus this technique may be of use in clinical trials where changes lumen volumes and vessel area profiles are of interest.

Animals↗

Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans.

1. A cDNA that encodes a Kex2-like prohormone convertase (PC) containing an active site similar to that of mammalian PC2 has been isolated from C. elegans. Total RNA was isolated from a mixed population of strain BA713 worms. After poly-(A)-selection and reverse transcription, degenerate/nested polymerase chain reactions (PCR) were performed using primers based on conserved regions within the active sites of the known vertebrate and invertebrate endoproteases. 2. Two distinct 300-bp PCR products that shared homologies with the active sites of known Kex2-like endoproteases were isolated. These two PCR products were used to screen a C. elegans cDNA library. 3. The complete cDNA for a Kex2-like endoprotease, designated CELPC2, was isolated and determined to be 2527 bp in length. This size was confirmed by northern analysis. The deduced amino acid sequence for the CELPC2 cDNA is very similar to the known Kex2-like endoproteases, especially at conserved regions within the active sites, but not identical to any one of them. The strongest structural homology was to vertebrate and invertebrate PC2 sequences. 4. In situ hybridization suggests that CELPC2 is synthesized primarily in cells associated with the circumpharyngeal nerve ring and the dorsorectal ganglion.

Amino Acid Sequence↗

The analysis of survival (mortality) data: fitting Gompertz, Weibull, and logistic functions.

Survival functions are fitted to survival data from several large populations. The Gompertz survival function corresponds to exponential mortality rate increases with time. The Weibull survival function corresponds to mortality rates that increase as a power function of time. A two-parameter, logistic survival function is introduced, and corresponds to mortality rates that increase, and then decrease, with time. A three-parameter logistic-mortality function also is examined. It reflects mortality rates that rise, and then plateau, with age. Data are from published studies of medflies, Drosophila, house flies, flour beetles, and humans. Some survival data are better fit by a logistic survival function than by the more traditionally used Gompertz or Weibull functions. Gompertz, Weibull, or logistic survival functions often fit the survival of 95+% of a population, and the 'tails' of the survival curves usually appear to fall between the values predicted by the three functions. For some populations, such 'tails' appear to be too complex to be fit well by any simple function. Survival data for males and females in some populations are best fit by different functions. Populations of 100 or more are needed to distinguish among the functions. When testing effects of environmental or genetic manipulations on survival, it has been common to determine the changes in parameter values for a given function, such as Gompertz. It may be equally important to determine whether the best-fit function has changed as well.

Animals↗

Perception of fluoroscopy last-image hold.

Last-image hold (LIH) is used in x-ray fluoroscopy systems as a convenience and dose savings feature. In the case of an image sequence, temporal filtering in the human visual system (HVS) reduces perceived noise. In the case of a constant, single image frame, this phenomenon is not present: the image looks noisier, and low-contrast objects disappear. Using low-contrast, stationary cylinder and disk phantoms in noise, perception of single frames are compared with that of conventional 30 acq/s continuous fluoroscopy (continuous). The dose of continuous is fixed at Q/acq, and the dose of single-frame presentations is varied in order to determine an "equivalent-perception dose" for a paired-comparison task. The equivalent-perception dose depends upon the shape and size of an object. As cylinder diameter increases from 1 to 21 pixels, the equivalent-perception dose decreases from 4.6 to 2.8 Q/acq. At equal equivalent-perception dose values, the relationship between cylinder and disk diameters are determined; a cylinder diameter of 10 pixels is roughly equivalent to a disk diameter of 20 pixels. For interventional angiography, an average equivalent-perception dose of approximately 3.5 Q/acq for a single-frame presentation is predicted. Thus processing by the HVS effectively reduces noise variance by a factor of 3.5, corresponding to an effective averaging time of 3.5 frames or 120 ms. Several variance reduction techniques are suggested to create an LIH frame having perception equal to the fluoroscopy sequence.

Biophysical Phenomena↗

Perceptual comparison of pulsed and continuous fluoroscopy.

Pulsed fluoroscopy (hereafter called pulsed) at reduced acquisition rates, typically 15 acq/s (pulsed-15), is proposed to reduce x-ray dose in interventional procedures. However, since the human visual system (HVS) acts as a temporal low-pass filter that interacts with such acquisitions, the proper dose for pulsed must be obtained in perception experiments. We determine the dose for low-frame-rate pulsed that gives visualization equivalent to that of conventional 30 acq/s fluoroscopy, hereafter called continuous. Computer-generated phantoms are used. They consist of stationary, low-contrast disks on a flat background containing Poisson noise that mimics quantum noise in fluoroscopy. Image sequences are displayed on the video tachistoscope, a device with considerable display flexibility. Three experimental paradigms are used. (1) In a paired-comparison study, pulsed and continuous are displayed side-by-side on the same monitor, and the visibility of a contrast detail phantom is compared. (2) Using this same display, subjects record the minimally detectable disk contrast (the min-contrast measurement). (3) In a four-alternative forced-choice experiment, a disk is placed in one of four positions, and the subject determines the position of the disk. The methods are complementary--the forced-choice experiment properly eliminates the subjectivity of the observer threshold while the paired-comparison study is much more time efficient. With regard to pulsed and continuous comparisons, remarkable similarity is found between the supra-threshold experiments (1 and 2) and the detectability experiment (3); i.e., the average absolute differences in the equivalent-perception dose as determined by the three measures is approximately 3%. No difference is found between interlaced and noninterlaced display. A relatively small dependence of dose savings on disk size is found with larger disks giving increased dose savings. Average dose savings of 22%, 38%, and 49% are found for pulsed-15, pulsed-10, and pulsed-7.5, respectively.

Fluoroscopy↗

The x-ray fovea, a device for reducing x-ray dose in fluoroscopy.

The x-ray fovea (U.S. patents pending) is a device for reducing x-ray dose to patients and operations during x-ray fluoroscopy. It consists of a semitransparent collimator with an open, circular, central hole. The fovea collimator is placed at the exit of the x-ray tube, and the attenuation of the peripheral x-ray beam reduces x-ray exposure to patients and operators. The shadow caused by the x-ray fovea can be compensated using real-time image processing hardware. Accurate compensation is demonstrated for both linearly and logarithmically acquired images using a model that accounts for beam hardening in the fovea collimator. The central fovea region has improved image quality due to reduced scatter and veiling glare from the periphery. From beam-stop measurements, a 40% reduction in scatter plus veiling glare is measured using the fovea. A contrast improvement ratio of 1.5 is measured throughout the central region. In the compensated periphery, noise is increased by a factor of 1.66 because fewer photons are detected, but a small amount of temporal filtering compensates this degradation. The Roentgen area product (RAP) exposure to patients is reduced by approximately 70%, while scattered exposure to operators is reduced by approximately 60%.

Equipment Safety↗

Model for perception of pulsed fluoroscopy image sequences.

Pulsed fluoroscopy at reduced frame rates can be used to lower x-ray dose with equivalent detection (hereafter called equivalent perception) of low-contrast, stationary objects. Experimentally average dose savings of 22%, 38%, and 49%, for pulsed fluoroscopy at 15, 10, and 7.5 acquisitions per second, respectively, are documented. Dose savings depend on object size, with fewer savings for smaller objects. To explain these data, we extend the framework of an ideal observer with three models for the spatiotemporal response of the human visual system (HVS). They are model 1, separable; model 2, nonseparable; and model 3, nonseparable with internal observer noise. With no free parameters, model 1 predicts the average dose savings within a 3% difference but does not describe the effect of object size. Models 2 and 3 explain the influence of size, and model 3, with a single free parameter, fits the measurements best. Perception of pulsed fluoroscopy is thus well described in terms of spatiotemporal processing by the HVS.

Fluoroscopy↗

A comparison of methods for estimating mortality parameters from survival data.

The Gompertz mortality function, Rm = R0e alpha t, is frequently used to describe changes in mortality rate (Rm) with time (t). In this paper, four methods for determining the best fit values of the two parameters, R0 and alpha, are compared. Three of the four methods use the Gompertz mortality function with mortality rate estimates derived from survival data to determine the best fit values for the two parameters. All three confront problems. The fourth method uses the Gompertz survival function, which can be derived from the Gompertz mortality function and which allows one to use survival data directly. It thereby avoids the problems and generally gives the best estimates for the two parameters. The use of the mortality function, with mortality rate estimates, confronts four distinct problems. One of these is caused by time intervals when zero organisms die. A second is caused by errors produced in estimating mortality rates from survival data. If too high a proportion of a population die in a given time interval, the mortality rate estimates are too low. A third problem is the sensitivity of the mortality-equation-based analyses to values at the end of the survival curve, where scatter in mortality values tends to be greater. A final problem occurs when time intervals greater than one time unit (day, week, year, etc.) are used in the analysis. Such problems with the use of mortality rates to estimate parameter values are revealed when the calculated parameters are used to produce a survival curve, or when known values of R0 and alpha are used to generate survival data. This paper introduces a non-linear regression analysis, using a Simplex algorithm to fit parameters R0 and alpha in the Gompertz Survival function and concludes that it gives more reliable and consistent results with a variety of data than do three methods that use the mortality function.

Animals↗