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Improving drug delivery from medical nebulizers: the effects of increased nebulizer flow rates and reservoirs.

Drug delivery from jet nebulizers can be considered in terms of the dose inhaled and the respirability of that dose. It is proposed that dose respirability and dose per breath can be controlled through specification of the driving gas flowrate, and that the dose inhaled per breath can also be increased through the use of nebulizer reservoirs. When a Hudson Micromist nebulizer was used and assessments of respirability were made utilizing phase Doppler interferometry, it was noted that the portion of the spray mass in droplet sizes of <or=5 microm (general respirability) and in droplet sizes of <or=3 microm (deep lung respirability) increased linearly with gas flowrate for both tank air and helium-oxygen (70/30). Drug mass in the 2-6 microm range (tracheobronchial respirability) peaked at air flowrates of 8-10 LPM and decreased slightly for higher flowrates. Two portable compressors provided respirabilities similar to tank air at the same flowrates. Changing the nebulizer flowrate did not affect the ratio of the inhaled dose to the dose expelled by exhalation when a typical breathing pattern was simulated. A version of the Micromist with an attached reservoir (the Hudson AeroTee) provided a higher dose per breath to the patient and a higher total dose for the same treatment time by conserving the aerosol generated during exhalation. The inhaled dose increased approximately 28% when compared to a standard Micromist, despite significant deposition in the reservoir bag. Nebulizer reservoirs could be used to attain higher doses or to more efficiently utilize expensive medications.

Administration, Inhalation↗

Astrobiologically interesting stars within 10 parsecs of the sun.

The existence of life based on carbon chemistry and water oceans relies upon planetary properties, chiefly climate stability, and stellar properties, such as mass, age, metallicity, and galactic orbits. The latter can be well constrained with present knowledge. We present a detailed, up-to-date compilation of the atmospheric parameters, chemical composition, multiplicity, and degree of chromospheric activity for the astrobiologically interesting solar-type stars within 10 parsecs of the Sun. We determined their state of evolution, masses, ages, and space velocities, and produced an optimized list of candidates that merit serious scientific consideration by the future space-based interferometry probes aimed at directly detecting Earthsized extrasolar planets and seeking spectroscopic infrared biomarkers as evidence of photosynthetic life. The initially selected stars number 33 solar-type within the total population (excluding some incompleteness for late M-dwarfs) of 182 stars closer than 10 parsecs. A comprehensive and detailed data compilation for these objects is still lacking; a considerable amount of recent data has so far gone unexplored in this context. We present 13 objects as the nearest "biostars," after eliminating multiple stars, young, chromospherically active, hard x-ray- emitting stars, and low metallicity objects. Three of these "biostars"-- Zeta Tucanae, Beta Canum Venaticorum, and 61 Virginis -- closely reproduce most of the solar properties and are considered as premier targets. We show that approximately 7% of the nearby stars are optimally interesting targets for exobiology.

Evolution, Planetary↗

A stress analysis of the periodontal ligament under various orthodontic loadings.

The accurate modelling of teeth under orthodontic load in the laboratory has many shortcomings in that it has not been possible to integrate methods, such as three-dimensional models, photo-elastic stress analysis, laser holographic interferometry, and animal studies, to give comprehensive and repeatable results. In this study, using a three-dimensional finite element model of a human maxillary canine tooth, the maximum principal stresses in the periodontal ligament produced by various orthodontic forces were determined. 1 Newton tipping forces produced stresses at the cervical margin of the periodontal ligament as high as 0.196 N/mm2 and apical stresses up to -0.034 N/mm2, while rotatory forces of two equal, but opposing forces of 0.5 Newton at the cervical margin of the crown produced cervical margin stresses ranging between -0.035 and 0.051 N/mm2, and apical stresses of between 0.0018 and 0.0027 N/mm2. These stresses are examined and discussed in relation to previous clinical, laboratory, and histological studies.

Computer Simulation↗

The importance of humidity in the in vitro study of the cranium with regard to initial bone displacement after force application.

The aim of this pilot study was to find a suitable model for simulating in vivo initial displacements of the maxilla after force application. Force was exerted on the maxillae of four dogs by means of a dental splint. To register the bone displacement, speckle interferometry was used as the measurement technique. The initial orthopaedic effect as a result of force application in vivo was registered by the construction of rotation centres around which the maxilla rotated. The orthopaedic effect after force application in vivo was compared with different in vitro situations of the laboratory animal. After the animal had been killed and its maxilla macerated, the cranium was placed in a sealed conditioned box. Only three skulls were found to be suitable for this experiment. The environment thus created can be influenced by changes in relative humidity. Various forces were applied in various directions on the maxilla of three Alsatians. By changing the relative humidity, an attempt was made to create a situation in which the initial bone displacements after force application were comparable to the in vivo situation. None of the laboratory animals used showed a comparable condition for the in vivo situation through manipulation of relative humidity. As only three dogs were experimented on, these findings are tentative. This experiment will be extended to three more dogs from the same litter.

Animals↗

Amplitude-division three-electron-wave interference for observing pure phase objects having low spatial frequency.

A new interferometry is presented for direct visualization of pure phase objects having low spatial frequency, such as electromagnetic microfields. A thin crystal of silicon prepared using argon ion milling is installed at the standard specimen position. This silicon crystal works as an electron beam splitter and forms diffraction spots in the back focal plane. Using the objective aperture, [000], [111] and [111] spots are selected as coherent electron sources to illuminate the specimen located at the area-selecting aperture position. The lattice image of silicon is formed below the area-selecting aperture position by decreasing the electric current of the objective lens. Three defocused images of the specimen are observed in the fluorescent screen by overexciting the first intermediate lens. We have successfully visualized equipotential lines around a latex particle charged by electron beam irradiation. The computer-simulated image was consistent with the experimental image.

Journal Article↗

Proton (fat/water) chemical shift imaging in medical magnetic resonance imaging. Current status.

Fat/water CSI has recently been transformed from an experimental method to a routine clinical MRI approach, particularly for evaluating paramagnetic contrast enhancement in fat-rich regions and as a piggyback method for decreasing MRI artifacts, such as in MR angiographic and echo-planar imaging. The full and appropriate use of CSI in medical MRI requires consideration of the factors and strategies outlined in this review. As the commercial implementation of fat/water CSI continues, we can expect further applications in clinical and experimental studies. For example, in imaging areas where MRI has been of limited efficacy, such as pancreas imaging, skin microimaging and vascular imaging, there are indications that these CSI methods may have practical importance. It seems reasonable to project that for high chemically specific detail, medical fat/water CSI will ultimately be supplanted by SI methods, and certainly by localized spectroscopy. The power of the fat/water CSI method remains its extremely high anatomic resolution, which cannot be achieved by current spectroscopy or SI methods. The fat/water CSI methods provide a means for clinically relevant MRI with more accurate and chemically specific information. Expansion of these methods into three-dimensional and fast imaging formats is already taking place at or near the commercial level. For example, the feasibility of combining echo-planar imaging and CSI methods has already been demonstrated. Methods based on the phase-contrast techniques, such as susceptibility mapping and interferometry, are additional implementations that can provide detailed and more specific information in a high anatomic detail format.

Adipose Tissue↗

Stapes prosthesis attachment: the effect of crimping on sound transfer in otosclerosis surgery.

OBJECTIVES/HYPOTHESIS: Although in stapes surgery successful hearing improvement may be achieved in the majority of patients, unsatisfactory closure of the air-bone gap can be recorded. One of many reasons for unexpected failures of stapes surgery may be the insufficient crimping of a stapes prosthesis onto the incus. The objectives of the study were to assess the amount of sound transmission loss in response to the quality of prosthesis crimping and to identify a required loop attachment pattern to obtain good sound transmission results. STUDY DESIGN: Experimental. METHODS: A temporal bone model was developed to measure the sound transmission properties between incus and prosthesis on 17 fresh human temporal bones. The attachment of a titanium stapes piston was assessed without crimping, followed by loose crimping and tight fixation to the incus, using scanning laser Doppler interferometry, endoscopic photography, micro grinding technique, and scanning electron microscopy. An algorithm had to be developed to simulate acoustical stimulation using electromechanical stimulation. RESULTS: Optimal tight crimping of the stapes piston revealed consistent good sound transfer function ranging from 0 to 7 dB loss, and loss remained, on average, at 2 dB. The mean transmission losses for conditions of loose crimping and no crimping were surprisingly small (within 10 dB). However, these unusual crimping conditions allowed a wide range of losses up to 28 dB. A close coupling at least at two opposite points was obligatory to obtain consistently good results. CONCLUSIONS: Perfect hearing reconstruction necessitates ideal crimping of a prosthesis to obtain consistently good results. However, the final functional gain depends on many different intraoperative and postoperative factors.

Acoustic Stimulation↗

A review of methods for measuring corneal topography.

A review of some methods and their optical principles for measuring the corneal topography are presented in this paper. The concepts of principal curvatures and the ambiguity concerning the axial curvature of surfaces without symmetry of revolution are analyzed. These methods are divided into three groups according to the following optical principles: (1) specular reflection, which includes the Placido disk system, interferometry, and moiré deflectometry; (2) diffuse reflection, which includes moiré fringes, rasterstereography, and Fourier Transform Profilometry; and (3) scattered light, which includes the slitlamp system. We avoided describing the details of commercial instruments, only their working principles.

Cornea↗

Corneal topography.

In the review period, limitations of individual Placido disk-based topography systems have been studied and new principles, such as raster photogrammetry, pancorneal slit topography, laser holographic interferometry, and confocal laser scanning topography, have been introduced for laboratory or clinical work. Both Fourier analysis and Zernike decomposition of topographic height data seem to be powerful new tools for cross-sectional analysis of complex topographic corneal images, such as after cataract surgery, penetrating keratoplasty, and refractive surgery, as well as for longitudinal studies of corneal changes, such as in schoolchildren. Subdividing into rational optical components may improve consistency and standardization of topography data from different systems. Topography-based flying-spot-mode excimer laser photoablation after Zernike decomposition of topography height data has been proposed for correction of irregular corneal astigmatism. Topography-based central power measurements are of increasing value for intraocular lens power calculation before cataract surgery in eyes with irregular corneal surfaces, such as in keratoconus or after refractive surgery procedures. Quantitative and qualitative classification of corneal topography maps after corneal transplantation following conventional mechanical and nonmechanical trephination or after refractive surgery may lead to a better understanding of impaired visual acuity despite a clear graft or despite significantly reduced ametropia or corneal astigmatism.

Cornea↗

Treating astigmatism at the time of cataract surgery.

An increasingly important goal of modern cataract and implant surgery is to obtain the most desirable refractive outcome for our patients, and in so doing, decrease their dependence upon spectacle correction. Refined spherical outcomes are now achieved by directing close attention to biometry technique, through the use of third generation intraocular lens (IOL) power formulae, and refinements in technology such as partial coherence interferometry. Similarly, improvements in astigmatic outcomes are now possible by focusing upon and obtaining more accurate preoperative cylinder measurements, careful surgical planning particularly in regard to incision(s) design, use of toric IOLs, and employing advanced postoperative enhancement techniques. Because of these refinements in technique and technology, the field of cataract and implant surgery has emerged as a true and recognized form of refractive surgery.

Astigmatism↗

Pars flaccida displacement pattern in purulent otitis media in the gerbil.

HYPOTHESIS: Our hypothesis is that purulent otitis media and otitis media with effusion cause stiffness loss of the tympanic membrane. This loss of stiffness may be persistent and precede the development of retraction pockets and cholesteatoma. BACKGROUND: Postinflammatory changes such as retraction pockets and cholesteatoma develop in the pars flaccida and in the pars tensa of the tympanic membrane. In our previous experimental studies, stiffness changes were shown to develop early in the pars tensa in response to purulent otitis media and otitis media with effusion. These changes are suggested to be precursors to a later development of retraction pockets and cholesteatoma. In the clinical situation, retraction pockets are often found in the pars flaccida only. The aim of the current study was thus to investigate whether stiffness changes appear also in the pars flaccida during purulent otitis media. METHODS: Streptococcus pneumoniae type 3 was injected into the middle ear to induce purulent otitis media. As a measure of pars flaccida stiffness, peak displacement versus middle ear pressure was used. The peak displacement measurements were obtained from full-field moiré; interferometry, which is a noncontacting optical technique for deformation measurements. RESULTS: Ears with purulent otitis media showed increased peak displacement of the pars flaccida at a middle ear pressure of 200 daPa, compared with normal controls. CONCLUSION: There was a decreased mechanical stiffness of the pars flaccida in acute purulent otitis media. This decreased stiffness may predispose for future retraction pocket formation and cholesteatoma development.

Animals↗

The brilliant beauty of the eye: light reflex from the cornea and tear film.

PURPOSE: Light reflex from the cornea and tear film as contributors to beautiful eyes ("eye sparkling") are reviewed. METHODS: A systematic literature review was conducted using "Purkinje-Sanson image," "corneal light reflex," "corneal topography," "corneal wavefront aberration," and "tear interference image" as search terms. RESULTS: Articles on corneal surface regularity and stability and tear interferometry of the precorneal tear lipid layer were reviewed. PS-1 image, that is light reflex from the cornea and tear film, is widely used in practical ophthalmic examination. CONCLUSION: To achieve a brilliant beauty of the eye ("eye sparkling"), it is important that the tear film (aqueous layer) surface is smooth and stable with adequate tear volume and that the tear lipid layer is present in adequate thickness.

Beauty↗

Post-laser in-situ keratomileusis ectasia: current understanding and future directions.

PURPOSE OF REVIEW: The aim of this article is to review the causes, risk factors, management, and future research directions for corneal ectasia after laser in situ keratomileusis. RECENT FINDINGS: Complex corneal biomechanical processes influence the integrity of the normal and postoperative cornea, and developing an understanding of these processes facilitates recognition of risk factors for ectasia after laser in-situ keratomileusis. Currently identified risk factors include keratoconus, high myopia, low residual stromal bed thickness from excessive ablation or thick flap creation, and defined topographic abnormalities such as forme fruste keratoconus and pellucid marginal corneal degeneration. Ectasia can also rarely occur in patients without currently identifiable risk factors, and future identification of at-risk patients may be facilitated by corneal interferometry and corneal hysteresis measurements. Utilization of intraoperative pachymetry measurements at the time of surgery and confocal microscopy prior to enhancement to measure residual stromal bed thickness should avoid unanticipated low residual stromal bed thickness. Management options for ectasia after laser in situ keratomileusis include intraocular pressure reduction, rigid gas permeable contact lenses, and intracorneal ring segments, in addition to corneal transplantation. In the future, collagen cross-linking may reduce corneal steepening and improve refractive error. SUMMARY: When ectasia develops, early recognition and proper management are essential to prevent progression, to promote visual rehabilitation, and to reduce the need for corneal transplantation for these patients.

Cornea↗

Tear film and ocular surface abnormalities after eyelid tattooing.

A 45-year-old woman who underwent eyelid tattooing 20 years earlier presented with decreased left vision and eye discomfort. Her ocular history revealed an uneventful LASIK procedure 4 years previously with epithelial problems of the flap followed by S. aureus keratitis. Resultant corneal opacity necessitated a deep lamellar keratoplasty performed 9 months prior to admission followed by frequent epithelial problems. At the time of admission, her left eye had a corneal epithelial defect and both lower eyelid margins revealed subepidermal pigmentation and keratinization. Her initial examination revealed tear instability with increased ocular surface staining scores and advanced tear film lipid layer abnormality in both eyes. Meibography showed bilateral total meibomian gland dropout. Treatment with autologous serum eye drops resulted in full epithelialization. Meibomian gland disease-specific therapy did not result in any change in breakup time, vital staining scores, tear film lipid layer interferometry grades, or glandular dropout state.

Eyelid Diseases↗

Pars flaccida displacement pattern in otitis media with effusion in the gerbil.

HYPOTHESIS: Our hypothesis is that otitis media with effusion causes stiffness loss in the pars flaccida of the tympanic membrane. This loss of stiffness may be persistent and may trigger the development of retraction pockets and cholesteatoma. BACKGROUND: Otitis media with effusion is a very common disease in childhood. It can cause minor to moderate hearing loss and delayed speech development. Otitis media with effusion is a risk factor for retraction pocket formation. METHODS: Otitis media with effusion was induced unilaterally in 15 gerbils by obstructing the eustachian tube with glue. The contralateral ears served as normal controls. As a measure of mechanical stiffness, pars flaccida peak displacement versus pressure was used. The displacement measurements were made with moire interferometry. This is a noncontacting optical technique with which the displacement of an object can be measured in real time. RESULTS: The mean peak displacement of the pars flaccida in the group with otitis media with effusion was increased threefold as compared with normal controls. This difference was statistically significant. CONCLUSION: There was a loss of mechanical stiffness in the pars flaccida caused by otitis media with effusion. This loss of stiffness may be persistent and may predispose for retraction pocket formation and cholesteatoma development.

Animals↗

A new implantable middle ear hearing device for mixed hearing loss: A feasibility study in human temporal bones.

HYPOTHESIS: To assess the feasibility of a new, active middle ear device in temporal bones (TB). BACKGROUND: This device is designed for patients with mixed hearing loss subsequent to chronic middle ear infection, surgery, or trauma. This Bell-Vibroplasty is built from a VIBRANT MED-EL Vibrant Soundbridge and a Kurz Bell titanium partial ossicular replacement prosthesis. METHODS: In three fresh TBs, healthy and reconstructed middle ears were analyzed by means of laser Doppler interferometry. The sound transmission properties of a partial ossicular replacement prosthesis and a passive and an active Bell-Vibroplasty were compared with healthy middle ear function. RESULTS: The measurements provided reliable results with small standard deviations and good signal-to-noise ratios. The performance levels of the partial ossicular replacement prosthesis and of the passive Bell-Vibroplasty were comparable with that of healthy middle ear function. The activated Bell-Vibroplasty provided linear function and a flat frequency response within the measured frequency range (500 Hz-8 kHz), with peak deviations of less than 10 dB. The maximum output of the Bell-Vibroplasty was equivalent to 125-dB sound pressure level. CONCLUSION: Bell-Vibroplasty is feasible in TBs. Bell-Vibroplasty performance in TBs is sufficient to allow for a clinical trial as a next step.

Acoustic Stimulation↗

In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients.

OBJECTIVES: Optical coherence tomography (OCT) is an emerging imaging modality that combines low-coherence light with interferometry to produce cross-sectional images of tissue with resolution about 10 mum. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo. STUDY DESIGN: Prospective clinical trial. MATERIALS AND METHODS: OCT imaging of the larynx was performed in 82 of 115 patients who underwent surgical endoscopy for various head and neck pathologies. The OCT device employs a 1.3 microm broadband light source (FWHM, 80 nm). The frame rate is 1 Hz. Imaging was performed using a handheld probe placed in near contact with the target site. The maximum axial and lateral dimensions for the region of interest imaged were 2.5 mm x 6 mm, with resolutions of 10 microm. Simultaneously, conventional endoscopic images were obtained to provide anatomic correlation with OCT images and histology. Optical micrometry was performed to measure the epithelium thickness. RESULTS: Systematic OCT imaging of laryngeal structures and subsites provided information on the thickness of the epithelium, integrity of the basement membrane, and structure of the lamina propria. Microstructural features identified included glands, ducts, blood vessels, fluid collection/edema, and the transitions between pseudostratified columnar and stratified squamous epithelium. The mean epithelial thickness of laryngeal subsites was calculated: true vocal cord (129 microm), false vocal cords (124 microm), aryepiglottic fold (177 microm), subglottis (98 microm), and epiglottis (185 microm). True vocal cord pathology imaged included Reinke's edema, papillomatosis, polyps, mucous cysts, and granulation tissue. Subglottic imaging identified boundaries between epithelium, lamina propria, and cartilage. The OCT images compared favorably with conventional histopathology. CONCLUSION: OCT has the unique ability to image laryngeal tissue microstructure and can detail microanatomic changes in benign, premalignant, and malignant laryngeal pathologies. OCT holds the potential to guide surgical biopsies, direct therapy, and monitor disease, particularly when office-based systems are developed. This is a promising imaging modality to study the larynx.

Biopsy↗

The Study of Progression of Adult Nearsightedness (SPAN): design and baseline characteristics.

PURPOSE: The Study of Progression of Adult Nearsightedness (SPAN) is a 5-year observational study to determine the risk factors associated with adult myopia progression. Candidate risk factors include: a high proportion of time spent performing near tasks, performing near tasks at a close distance, high accommodative convergence/accommodation (AC/A) ratio, and high accommodative lag. METHODS: Subjects between 25 and 35 years of age, with at least -0.50 D spherical equivalent of myopia (cycloplegic autorefraction), were recruited from the faculty and staff of The Ohio State University. Progression is defined as an increase in myopia of at least -0.75 D spherical equivalent as determined by cycloplegic autorefraction. Annual testing includes visual acuity, noncycloplegic autorefraction and autokeratometry, phoria, accommodative lag, response AC/A ratio, cycloplegic autorefraction, videophakometry, ultrasound, and partial coherence interferometry (IOLMaster). Participants' near activities were assessed using the experience sampling method (ESM). Subjects carried a pager for two 1-week periods and were paged randomly throughout the day. Each time they were paged, they dialed into an automated telephone survey and reported their visual activity at that time. From these responses, the proportion of time spent performing near work was estimated. RESULTS: Three-hundred ninety-six subjects were enrolled in SPAN. The mean (+/- standard deviation) age at baseline was 30.7 +/- 3.5 years, 66% were female, 80% were white, 11% were black, and 8% were Asian/Pacific Islander. The mean level of myopia (spherical equivalent) was -3.54 +/- 1.77 D, the mean axial length by IOLMaster was 24.6 +/- 1.1 mm, and subjects were 1.7 +/- 4.0 Delta exophoric. Refractive error was associated with the number of myopic parents (F = 3.83, p = 0.023), and the number of myopic parents was associated with the age of myopia onset (chi2 = 13.78, p = 0.001). In a multivariate analysis, onset of myopia (early vs. late) still had a significant effect on degree of myopia (F = 115.1, p < 0.001), but the number of myopic parents was no longer significant (F = 0.65, p = 0.52). For the ESM, the most frequently reported visual task was computer use (mean, 18.9%; range, 0-60.0%) and, overall, subjects reported near work activity 34.1% of the time (range, 0-67.3%). CONCLUSIONS: The design of SPAN and the baseline characteristics of the cohort have been described. Parental history of myopia is related to the degree of myopia at baseline, but this effect is mediated by the age of onset of myopia.

Accommodation, Ocular↗