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Biomedical subjects

David M Mills

Publications and source records attributed to David M Mills.

17 recordsLinked to original sources
PubMed2006

Pediatric ophthalmic computed tomographic scanning and associated cancer risk.

PURPOSE: To review pediatric neuroimaging studies of the head and orbit and the radiation-induced cancer risk associated with computed tomography in light of recent attention to pediatric radioimaging by the US Food and Drug Administration, the National Cancer Institute, pediatricians, and radiologists. DESIGN: Perspective. METHODS: Literature review. SETTING: Institutional. PATIENT POPULATION: Pediatric ophthalmic patients requiring neuroimaging studies. INTERVENTION/PROCEDURE: Review of the current literature. MAIN OUTCOME MEASURES: After review of the current literature and discussion of the related issues, recommendations are made for pediatric neuroimaging studies of the head and orbit. RESULTS: Computed tomography (CT) of the head and orbit may be performed in children with the appropriate indications as long as the radiation exposure is minimized. CONCLUSIONS: Information obtained from CT scans of the head and orbit may determine or affect management in the pediatric ophthalmic population. Because of the concern of cancer induced by radiation exposure in children, neuroimaging modalities without radiation exposure, such as magnetic resonance imaging or ultrasound, may be considered. However, when CT is indicated, it is reasonable and acceptable to perform CT of the head and orbit while minimizing the radiation exposure, thereby adhering to the "ALARA" (as low as reasonably achievable) policy recommended by the US Food and Drug Administration. Further studies of the actual radiation dose delivered during pediatric CT of the head and orbit and the true incidence of radiation-induced cancers after scans are warranted.

Child↗
PubMed2006

Acquired nasolacrimal duct obstruction.

Acquired nasolacrimal duct obstruction is a common problem. Although tearing is the usual complaint, the clinical presentation can range from a patient having no symptoms to one with a life-threatening infection. Despite many studies providing useful clues, the exact pathophysiology of the obstructive process is incompletely understood. The clinician must be able to accurately make the diagnosis, which is often a clinical one, because many treatments with excellent success are available.

Humans↗
PubMed2006

Cost-benefit analysis in the selection of efficient multipollutant strategies.

Pollution control efforts are motivated by the desire to protect human health and the environment. Often, those efforts involve selecting among multiple options for attaining air quality objectives. For example, state and local decision-makers must choose the mix of control strategies for meeting the requirements of the National Ambient Air Quality Standards (NAAQS) and the Regional Haze Rule. We demonstrate that including assessments of the human health and environmental benefits when evaluating alternative strategies may help decision-makers to identify multipollutant attainment strategies that achieve greater net benefits than would accrue under strategies optimized for cost alone. This paper presents a conceptual framework that decision-makers could use to choose among alternative multipollutant control strategies, accounting for the benefits and the costs of different types and locations of emissions reductions.

Air Pollutants↗
PubMed2006

Determining the cause of hearing loss: differential diagnosis using a comparison of audiometric and otoacoustic emission responses.

OBJECTIVE: The purpose of this study was to further investigate the possibility of developing noninvasive methods of differential diagnosis of hearing disorders through the study of experimental animals with induced lesions. In particular, it was desired to compare distortion product otoacoustic emission (DPOAE) responses and auditory brain stem response (ABR) thresholds in Mongolian gerbils having either acoustic or strial damage, using as a reference the same responses measured in a control group of normal young adult gerbils. The goal was to evaluate the potential clinical application of this approach to determining the dominant contribution to sensorineural hearing loss in individual human subjects. DESIGN: DPOAE input-output functions and ABR thresholds were measured over a wide range of stimulus frequencies for three groups: (1) a reference group of normal young adult gerbils; (2) a group in which acoustic damage had been induced 2 wk earlier; (3) a group in which damage to the stria vascularis was induced by a series of furosemide injections. The responses in the experimental groups relative to the normal means were compared to determine which combinations of responses were effective in discriminating between animals with different lesions. Three measures were evaluated in detail: the ABR threshold, the emission threshold at a criterion emission amplitude, and the emission amplitude at a high stimulus level. RESULTS: Considering cases with significant hearing loss (ABR thresholds elevated by 20 dB or more), the best method for distinguishing between the two lesions involved a two-dimensional plot comparing emission and ABR thresholds at the same stimulus frequencies. Acoustic damage cases were found in a broad region where the emission and ABR thresholds were roughly equal, whereas strial damage cases were found in a narrower region where the emission threshold was about 0.4 times the ABR threshold (both in dB). These two cases were compared with a third case introduced by definition, that is, damage to inner hair cell or neural systems resulting in an increase in audiometric threshold but no change in emission responses (e.g., auditory neuropathy). The responses for these three cases were found to lie in different regions of the two-dimensional plot comparing emission and ABR thresholds, provided only that ABR thresholds were elevated 20 dB or more. This diagram also revealed cases of preclinical acoustic damage, in which the ABR threshold was shifted less than 20 dB but where the emission threshold was significantly elevated. CONCLUSIONS: The results clearly demonstrate the possibility of developing a clinical method of noninvasive differential diagnosis of hearing loss. The method demonstrated was to add to a standard audiometric evaluation the measurement of DPOAE growth functions over the range of frequencies where these emissions were relatively easy to measure and consistent. The DPOAE stimulus frequencies were chosen to match the audiometric frequencies, and the corresponding emission and audiometric thresholds were compared on a threshold-threshold plot for each individual at a number of stimulus frequencies. Responses in different regions in this plot were found to correspond to different types of sensorineural hearing loss.

Animals↗
PubMed2006

Climate change and human health impacts in the United States: an update on the results of the U.S. national assessment.

The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods) , air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure-response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.

Adolescent↗
PubMed2005

A fresh look at the benefits and costs of the US acid rain program.

The US Acid Rain Program (Title IV of the 1990 Clean Air Act Amendments) has achieved substantial reductions in emissions of sulfur dioxide (SO2) and nitrogen oxides (NOx) from power plants in the United States. We compare new estimates of the benefits and costs of Title IV to those made in 1990. Important changes in our understanding of and ability to quantify the benefits of Title IV have occurred. Benefits to human health now take a much higher profile because the contribution of SO2 and NOx emissions to the formation of fine particulate (PM2.5) is substantial, and evidence of the harmful human health effects of PM2.5 has emerged in the last 15 years. New estimates of the health benefits of PM2.5 reductions are the largest category of quantified health and environmental benefits and total over 100 billion US dollars annually for 2010 when the program is expected to be fully implemented. Although important uncertainties exist in any specific estimate of the benefits, even if the estimates were calculated using more limiting assumptions and interpretations of the literature they would still substantially exceed the costs. Estimates of annualized costs for 2010 are about 3 billion US dollars, which is less than half of what was estimated in 1990. Research since 1990 also suggests that environmental problems associated with acid deposition and nitrogen deposition are more challenging to resolve than originally thought and will require larger reductions in emissions to reverse. The greater than expected benefits to human health, the greater vulnerability of natural resources and ecosystems, and the lower than expected costs all point to the conclusion that further reductions in SO2 and NOx emissions from power plants beyond those currently required by Title IV are warranted.

Acid Rain↗
PubMed2004

Promotion of B cell immune responses via an alum-induced myeloid cell population.

Exposure of naïve B cells to the cytokine interleukin-4 (IL-4) and/or antigen leads to a state of "priming," in which subsequent aggregation of major histocompatibility complex class II molecules induces the mobilization of calcium ions and cell proliferation. However, it is not clear how critical this priming is for immune responses or how it is normally induced in vivo. Injection of mice with the commonly used adjuvant alum led to priming of splenic B cells and to the accumulation in the spleen of a previously unknown population of IL-4-producing, Gr1+ cells. These cells and IL-4 were both required for in vivo priming and expansion of antigen-specific B cells, as well as for optimal production of antibody. These studies reveal a key role for a previously unknown accessory myeloid cell population in the generation of humoral immune responses.

Adjuvants, Immunologic↗
PubMed2004

Cognate B cell signaling via MHC class II: differential regulation of B cell antigen receptor and MHC class II/Ig-alpha beta signaling by CD22.

Recent studies demonstrate that MHC class II molecules can signal via associated Ig-alphabeta dimers, signal transducers previously thought to function only in B cell Ag receptor (BCR) signaling. Surprisingly, the biologic outputs of MHC class II and BCR ligation (by thymus-dependent Ags) differ, e.g., MHC class II signaling leads to robust proliferation and extension of pseudopods. It seemed possible that these differences might be due, at least in part, to differential use of inhibitory coreceptors thought to modulate membrane Ig signals. In this study, we demonstrate that CD22, an inhibitory BCR coreceptor, neither associates with nor functions in MHC class II/Ig-alphabeta signaling. Interestingly, CD22 is actively excluded from cell surface MHC class II aggregates.

Animals↗
PubMed2004

Relationship of neural and otoacoustic emission thresholds during endocochlear potential development in the gerbil.

Distortion product otoacoustic emissions and auditory brainstem responses (ABRs) were measured in neonatal gerbils at three ages: at 15-16 days after birth (dab), near the onset of hearing when the endocochlear potential (EP) is known to be still immature; at 22 dab, when the EP first reaches mature levels; and at 30 dab. Comparing individual 15-16 dab animals to the 22 dab group, ABR threshold changes were typically larger than those for cubic distortion tone (CDT, 2f1-f2) emission thresholds which were, in turn, larger than those for the simple difference tone (DT, f2-f1). In contrast, from 22 to 30 dab there were no important changes in CDT or DT emission thresholds. Observed threshold-change relationships were very similar to those found in differential diagnosis investigations, where the EP was experimentally decreased using a chronic furosemide application. Therefore, most of the change in cochlear function over the two week period studied could be attributed to the maturation of EP during the first week. Model calculations further show that relative changes in CDT and DT emission thresholds are compatible with a movement of the operating point of the cochlear amplifier toward its symmetrical "central" point as the EP reaches mature levels.

Animals↗
PubMed2003

Metabolic presbycusis: differential changes in auditory brainstem and otoacoustic emission responses with chronic furosemide application in the gerbil.

Auditory characteristics of metabolic or strial presbycusis were investigated using an animal model in which young adult Mongolian gerbils ( Meriones unguiculates) were implanted with an osmotic pump supplying furosemide continuously to the round window. This model causes chronic lowering of the endocochlear potential (EP) and results in auditory responses very similar to those seen in quiet-aged gerbils (Schmiedt et al., J. Neurosci. 22:9643-9650, 2002). Auditory function was examined up to one week post-implant by measurement of auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). Emission "threshold" was defined as the stimulus level required to reach a criterion emission amplitude. Comparing all responses on a "threshold-shift diagram," where emission threshold increases were plotted versus ABR threshold increases, the following results were obtained: (1) On average, the increase of the emission threshold was about 55% of the increase in ABR threshold, with comparatively little scatter. (2) The main dysfunction in metabolic presbycusis appears to be a decrease in the gain of the cochlear amplifier, combined with an additional, smaller increase in neural threshold, both effects caused by a chronically low EP. (3) For ABR threshold increases over 20 dB, the points for the chronic low-EP condition were largely separate from those previously found for permanent acoustic damage. The threshold-shift diagram therefore provides a method for noninvasive differential diagnosis of two common hearing dysfunctions.

Animals↗
PubMed2003

B lymphocyte activation during cognate interactions with CD4+ T lymphocytes: molecular dynamics and immunologic consequences.

Productive interaction between T and B lymphocytes is required for humoral immune responses to many foreign protein antigens and production of pathogenic antibodies characteristic of several autoimmune conditions. Thus, much attention has been given in recent years to understand the dynamic molecular interactions and signal transduction required for productive T-B interaction. In this review we highlight current knowledge of signaling and biologic responses that occur in B cells during cognate interactions with helper T cells, focusing on the dynamic function of B cell-surface molecules in T-B synapses.

B-Lymphocytes↗
PubMed2003

Differential responses to acoustic damage and furosemide in auditory brainstem and otoacoustic emission measures.

Characteristics of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) were measured in Mongolian gerbil before and after the introduction of two different auditory dysfunctions: (1) acoustic damage with a high-intensity tone, or (2) furosemide intoxication. The goal was to find emission parameters and measures that best differentiated between the two dysfunctions, e.g., at a given ABR threshold elevation. Emission input-output or "growth" functions were used (frequencies f1 and f2, f2/f1 = 1.21) with equal levels, L1 = L2, and unequal levels, with L1 = L2 + 20 dB. The best parametric choice was found to be unequal stimulus levels, and the best measure was found to be the change in the emission threshold level, delta x. The emission threshold was defined as the stimulus level required to reach a criterion emission amplitude, in this case -10 dB SPL. (The next best measure was the change in emission amplitude at high stimulus levels, specifically that measured at L1 x L2 = 90 x 70 dB SPL.) For an ABR threshold shift of 20 dB or more, there was essentially no overlap in the emission threshold measures for the two conditions, sound damage or furosemide. The dividing line between the two distributions increased slowly with the change in ABR threshold, delta ABR, and was given by delta x(t) = 0.6 delta ABR + 8 dB. For a given delta ABR, if the shift in emission threshold was more than the calculated dividing line value, delta x(t), the auditory dysfunction was due to acoustic damage, if less, it was due to furosemide.

Animals↗
PubMed2002

Multi-layered PZT/polymer composites to increase signal-to-noise ratio and resolution for medical ultrasound transducers part II: thick film technology.

Increasing transducer bandwidth and signal-to-noise ratio (SNR) is fundamental to improving the quality of medical ultrasound images. In previous work, we have proposed the use of multi-layer 1-3 PZT/polymer composites to increase both, but have encountered significant fabrication challenges [19]. These difficulties include making the bond thickness between the layers small relative to the ultrasound wavelength and aligning the posts of the composite to increase coupling coefficient. Thus, we have developed a multi-layer composite hybrid array that will not require post alignment. Starting from a 2-MHz, three-layer PZT-5H, thick film transducer designed for 1.5-D arrays, cuts are made only through the top layer and back-filled with epoxy, forming a composite layer on top of two ceramic layers. Finite element (PZFlex) simulations show that for a 2-MHz phased-array element with a single matching layer, the three-layer hybrid structure increases the pulse echo SNR by 11 dB versus a single layer PZT element and improves -6 dB pulse echo fractional bandwidth by a factor of 1.4. Composite hybrid arrays fabricated in our laboratory showed an improvement in SNR of 6 to 11 dB over a PZT control and an increase in -6 dB bandwidth by a factor of 1.1. Images from a phased-array scanner confirmed these improvements.

Ceramics↗
PubMed2002

Finite element comparison of single crystal vs. multi-layer composite arrays for medical ultrasound.

Finite element (PZFlex; Weidlinger Assoc., New York, NY and Los Altos, CA) simulations predict that for a 2-MHz phased array element with a single matching layer, the three-layer hybrid structure [1] increases the pulse echo signal-to-noise ratio (SNR) by 16 dB over that from a single layer PZT element and -6 dB pulse echo fractional bandwidth from 58% for the PZT element to 75% for the hybrid element. Analogous finite element method (FEM) simulations of single crystal material [lead zinc niobate (PZN)-8% lead titanate (PT)] showed increased SNR by only 3.1 dB, but a -6 dB bandwidth of 108%.

Ceramics↗
PubMed2002

Interpretation of standard distortion product otoacoustic emission measurements in light of the complete parametric response.

Emission characteristics (at 2f1-f2) are measured in Mongolian gerbil as a function of the independent variation of all four stimulus parameters, the frequencies (f1 and f2) and the intensities (L1 and L2) of the two stimulus tones. The main five-dimensional display chosen is a logarithmic grid of frequencies, where for each frequency pair there is a contour map of the emission amplitude as a function of the two stimulus levels. The feature which leads to the greatest complexity in the proper interpretation of emission responses is the widespread presence of "notches" in these contour maps. Notches are lines of relative minima in the emission amplitude, and are found at either: (1) constant L1, but only in regions where L1 > L2; or (2) at constant L2, only where L2 > or = L1. Notches are not found at any other orientations, and are associated with emission phase shifts of about 180 degrees as the notch line is traversed. These notch characteristics are explained by phase cancellation in a simple cochlear amplifier model in which there is a change, as a function of the stimulus level alone, of relevant characteristics of the cochlear response to a single tone. Only one mechanism of emission generation is required to explain the observed patterns, i.e., there is no need to invoke different "active" and "passive" mechanisms. Unless properly accounted for, the presence of notches adversely affects all of the standard emission measurements, i.e., all methods which cover a restricted parameter set such as DPgrams, input-output or "growth" functions, and frequency ratio functions. Conversely, because the notch location appears approximately invariant in the cochlea, notches potentially make it possible to use certain emission growth functions to estimate forward and reverse middle-ear transfer functions.

Acoustics↗
PubMedDate not supplied

Optic neuritis is nothing to sneeze at.

A 36-year-old man developed acute visual loss, mimicking an optic neuritis in the left eye. Cranial magnetic resonance imaging revealed a sphenoid sinus mucocele with extension into the anterior clinoid process abutting the left optic nerve. Endoscopic marsupialization of the mucocele led to marked improvement of vision. Sphenoid sinus mucocele is discussed, as is the differential diagnosis of optic neuritis.

Adult↗