Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits.

AIM: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. METHODS: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8-9 m/kg body weight) for an additional 3 h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNFα IL-6 and IL-8 in lung homogenates were evaluated. RESULTS: Both surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1 h, P/F ratio and PaO2 at 1.5 h compared to rSP-C33Leu surfactant. CONCLUSION: This study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

Psychophysical suppression effects for tonal and speech signals.

This experiment assessed the benefits of suppression and the impact of reduced or absent suppression on speech recognition in noise. Psychophysical suppression was measured in forward masking using tonal maskers and suppressors and band limited noise maskers and suppressors. Subjects were 10 younger and 10 older adults with normal hearing, and 10 older adults with cochlear hearing loss. For younger subjects with normal hearing, suppression measured with noise maskers increased with masker level and was larger at 2.0 kHz than at 0.8 kHz. Less suppression was observed for older than younger subjects with normal hearing. There was little evidence of suppression for older subjects with cochlear hearing loss. Suppression measured with noise maskers and suppressors was larger in magnitude and more prevalent than suppression measured with tonal maskers and suppressors. The benefit of suppression to speech recognition in noise was assessed by obtaining scores for filtered consonant-vowel syllables as a function of the bandwidth of a forward masker. Speech-recognition scores in forward maskers should be higher than those in simultaneous maskers given that forward maskers are less effective than simultaneous maskers. If suppression also mitigated the effects of the forward masker and resulted in an improved signal-to-noise ratio, scores should decrease less in forward masking as forward-masker bandwidth increased, and differences between scores in forward and simultaneous maskers should increase, as was observed for younger subjects with normal hearing. Less or no benefit of suppression to speech recognition in noise was observed for older subjects with normal hearing or hearing loss. In general, as suppression measured with tonal signals increased, the combined benefit of forward masking and suppression to speech recognition in noise also increased.

Forward- and simultaneous-masked thresholds in bandlimited maskers in subjects with normal hearing and cochlear hearing loss.

Forward- and simultaneous-masked thresholds were measured at 0.5 and 2.0 kHz in bandpass maskers as a function of masker bandwidth and in a broadband masker with the goal of estimating psychophysical suppression. Suppression was operationally defined in two ways: (1) as a change in forward-masked threshold as a function of masker bandwidth, and (2) as a change in effective masker level with increased masker bandwidth, taking into account the nonlinear growth of forward masking. Subjects were younger adults with normal hearing and older adults with cochlear hearing loss. Thresholds decreased as a function of masker bandwidth in forward masking, which was attributed to effects of suppression; thresholds remained constant or increased slightly with increasing masker bandwidth in simultaneous masking. For subjects with normal hearing, slightly larger estimates of suppression were obtained at 2.0 kHz rather than at 0.5 kHz. For hearing-impaired subjects, suppression was reduced in regions of hearing loss. The magnitude of suppression was strongly correlated with the absolute threshold at the signal frequency, but did not vary with thresholds at frequencies remote from the signal. The results suggest that measuring forward-masked thresholds in bandlimited and broadband maskers may be an efficient psychophysical method for estimating suppression.

Psychophysical suppression measured with bandlimited noise extended below and/or above the signal: effects of age and hearing loss.

The objectives of this study were to measure suppression with bandlimited noise extended below and above the signal, at lower and higher signal frequencies, between younger and older subjects, and between subjects with normal hearing and cochlear hearing loss. Psychophysical suppression was assessed by measuring forward-masked thresholds at 0.8 and 2.0 kHz in bandlimited maskers as a function of masker bandwidth. Bandpass-masker bandwidth was increased by introducing noise components below and above the signal frequency while keeping the noise centered on the signal frequency, and also by adding noise below the signal only, and above the signal only. Subjects were younger and older adults with normal hearing and older adults with cochlear hearing loss. For all subjects, suppression was larger when noise was added below the signal than when noise was added above the signal, consistent with some physiological evidence of stronger suppression below a fiber's characteristic frequency than above. For subjects with normal hearing, suppression was greater at higher than at lower frequencies. For older subjects with hearing loss, suppression was reduced to a greater extent above the signal than below and where thresholds were elevated. Suppression for older subjects with normal hearing was poorer than would be predicted from their absolute thresholds, suggesting that age may have contributed to reduced suppression or that suppression was sensitive to changes in cochlear function that did not result in significant threshold elevation.

Experience with a yes-no single-interval maximum-likelihood procedure.

The report in 1993 by Green [J. Acoust. Soc. Am. 93, 2096-2105 (1993)] describing the application of a new psychophysical method requiring few trials and little time to measure auditory thresholds has generated considerable interest among experimentalists. The procedure uses a single-interval stimulus presentation, requests a yes-no decision by subjects, and implements a maximum-likelihood calculation to determine the next trial stimulus level within an adaptive track, as well as the final threshold estimate. Data are presented here describing separate experiences with this procedure in two laboratories in both detection and discrimination tasks. Issues addressed include comparisons with more traditional psychophysical methods, variability in threshold estimates, experimental time required, and possible minor modifications to improve the basic procedure. Results using this procedure are comparable in terms of variability of estimates to those emerging from more lengthy procedures. However, because it may be difficult for some listeners to maintain a consistent criterion and because attentional lapses may be costly, experimenters must be willing to monitor performance closely and repeat some tracks in cases where excessively high variability is noted. Further, this procedure may not be suitable for tasks for which the form of the psychometric function is not well-established. Modifications allowing a variable slope parameter in the maximum-likelihood evaluations of psychometric functions may be of benefit.

Use of context by young and aged adults with normal hearing.

Word recognition in sentences with and without context was measured in young and aged subjects with normal but not identical audiograms. Benefit derived from context by older adults has been obscured, in part, by the confounding effect of even mildly elevated thresholds, especially as listening conditions vary in difficulty. This problem was addressed here by precisely controlling signal-to-noise ratio across conditions and by accounting for individual differences in signal-to-noise ratio. Pure-tone thresholds and word recognition were measured in quiet and threshold-shaped maskers that shifted quiet thresholds by 20 and 40 dB. Word recognition was measured at several speech levels in each condition. Threshold was defined as the speech level (or signal-to-noise ratio) corresponding to the 50 rau point on the psychometric function. As expected, thresholds and slopes of psychometric functions were different for sentences with context compared to those for sentences without context. These differences were equivalent for young and aged subjects. Individual differences in word recognition among all subjects, young and aged, were accounted for by individual differences in signal-to-noise ratio. With signal-to-noise ratio held constant, word recognition for all subjects remained constant or decreased only slightly as speech and noise levels increased. These results suggest that, given equivalent speech audibility, older and younger listeners derive equivalent benefit from context.

Nursing process redesign with the implementation of a computer based patient record in the ambulatory setting.

Increasingly, health care organizations are considering moving to Computer Based Patient Records (CPR), a trend driven by managed care and capitated payments. Central to the change is recognition of the need for community based and clinically relevant information systems that span the care continuum. Thus, Aurora Health Care chose to start their CPR effort in the ambulatory setting as the focus of health care delivery in the evolving paradigm. This paper describes computerization of the ambulatory record in a 45 physician clinic and associated workflow redesign. Months were spent in the processes of: current state documentation and analysis, future state design, detail system design, and workflow reengineering. There was substantial impact on nursing care delivery with computer system interaction at the point of care in the exam room. Access to clinically relevant longitudinal data was found key to the implementation and evaluation of Care Management strategies.

Estimating parameters for psychometric functions using the four-point sampling method.

Although a psychometric function describing a subject's responses to some physical stimuli is of considerable value, characterizing such functions is time consuming and, hence, is not carried out routinely in psychophysical experiments. A principal reason for the lack of efficiency in characterizing a psychometric function is the use of sampling methods that either converge on a single point on the psychometric function, such as the PEST method, or which distribute observations uniformly over a wide range, such as the constant stimuli method. As an alternative, a multimodal four-point sampling method has been proposed [C. F. Lam, J. H. Mills, and J. R. Dubno, J. Acoust. Soc. Am. 99, 3689-3693 (1996)]. A psychometric function is then fitted to the four points (each with several trials) to estimate the threshold and slope parameters of the psychometric function. Adaptive methods, such as the up-down methods [H. Levitt, J. Acoust. Soc. Am. 49, 467-477 (1971)], can be used to provide good initial estimates of the threshold and spread parameters of a psychometric function described by a logistic function. In ongoing studies of age-related changes in auditory masking and discrimination, this new four-point sampling method has been applied to determine psychometric functions for absolute thresholds as a function of duration, thresholds in simultaneous and forward masking, frequency discrimination, and intensity discrimination in both young and aged human subjects. Results indicate that a reduction in data collection time of about 50% with no increase in variance can be achieved. This increase in efficiency applies to simple detection tasks by normal hearing subjects as well as to complex discrimination tasks by older subjects with hearing loss.

Comparison of probe insertion methods on estimates of ear canal SPL.

Real-ear sound pressure levels (SPLs) were compared among three methods used for positioning a probe microphone in the ear canal. The probe insertion techniques included (1) an acoustic method that incorporates use of the quarter-wave anti-resonance property of the ear to determine acoustically the location of the probe tube relative to the eardrum; (2) a constant insertion depth method (25 mm from the intratragal notch); and (3) the earmold +5-mm method, which places the probe 5 mm beyond the tip of the earmold, thereby avoiding problems associated with the transition region where sound exits from the bore of the earmold into the larger ear canal. Measurements were obtained at 32 test frequencies in 24 adults with normal middle ear impedance. Results indicated that the SPLs measured by the acoustic method were modestly higher than those measured by the other two methods. This result was most evident in subjects with long ear canals (> 25 mm) and at high test frequencies (3.0 to 6.3 kHz).

Growth of low-pass masking of pure tones and speech for hearing-impaired and normal-hearing listeners.

Tonal thresholds and consonant recognition were measured in low-pass maskers as a function of masker bandwidth and spectrum level. Thresholds and consonant-recognition scores were obtained for normal-hearing subjects, and for pairs of normal-hearing subjects (who listened in threshold-equating background noise) and hearing-impaired subjects. Consonant-recognition scores were compared to scores predicted by a modified articulation index. Mean thresholds measured in low-pass maskers were higher for hearing-impaired than for normal-hearing subjects for signal frequencies above the masker. Slopes of functions relating thresholds for signals above the masker to masker spectrum level were not significantly different between hearing-impaired and normal-hearing subjects listening in spectrally shaped broadband noise (SSBB), but were shallower than slopes of masking functions for normal-hearing subjects listening without SSBB. Slopes of masking functions for signals within the masker were equivalent for all subjects. Slopes of functions relating consonant recognition to masker spectrum level were similar within subject pairs, whereas, in some cases, slopes of functions relating consonant recognition to speech level were shallower for hearing-impaired subjects than for their normal-hearing counterparts. Although greater improvement in consonant recognition with speech level was predicted for hearing-impaired than for normal-hearing subjects, on average, less improvement with speech level was observed. Shallower slopes of functions relating score to speech level observed for some hearing-impaired listeners may result from more shallow growth of speech sensation levels in spectral regions above the low-pass masker.

Masked thresholds and consonant recognition in low-pass maskers for hearing-impaired and normal-hearing listeners.

Thresholds and consonant recognition were measured in six low-pass maskers as a function of masker bandwidth for hearing-impaired subjects and for normal-hearing subjects listening in spectrally shaped broadband noise (SSBB). SSBB was adjusted such that thresholds in that masker for a normal-hearing listener were equal to a hearing-impaired listener's absolute thresholds. Thresholds measured in low-pass maskers were higher for hearing-impaired than for normal-hearing subjects for signal frequencies both within and outside masker passbands, although threshold differences were larger for signal frequencies outside masker passbands. Slopes of functions relating consonant recognition to speech level were not significantly different between groups, due to the presence of SSBB for the normal-hearing listeners. However, 25% of observed scores for hearing-impaired listeners, compared to only 5% of observed scores for normal-hearing listeners, were significantly poorer than predicted by the articulation index (AI), when AIs were computed using subjects' absolute thresholds. Better correspondence between observed and predicted scores in low-pass maskers was achieved when AIs were derived empirically from thresholds measured in each low-pass masker. Hence poorer-than-predicted consonant recognition scores in low-pass maskers were accounted for by higher-than-normal thresholds in those maskers.

Effects of probe insertion depth on real ear measurements.

The purpose of this article is to provide an overall summary of the role probe insertion depth has on real ear measurements, and to compare the real ear sound pressure level measured by a probe microphone system, using three methods for positioning the probe in an ear canal. The probe insertion techniques that were compared included: (1) an acoustic method that incorporates use of the quarter-wave antiresonance property of the ear to determine acoustically the location of the probe tube relative to the eardrum in an individual ear; (2) a constant insertion depth method (25 mm from the intratragal notch); and (3) the earmold +5 mm method, which places the probe 5 mm beyond the tip of the individual's earmold in the canal, thereby avoiding problems associated with the transition region, where sound exits from the bore of the earmold into the larger ear canal. Measurements were obtained for each method at 32 frequencies in the unoccluded ears of 17 subjects. Results indicated that the sound pressure levels measured by the acoustic method were significantly larger than those measured by the other two methods. This result was most evident in subjects with long ear canals (> 25 mm) and at high test frequencies (4.0 to 6.3 kHz). For subjects with short or average length ear canals, the three methods provided essentially equivalent results.

Preferred frequency response for two- and three-channel amplification systems.

The purpose of these investigations was to compare the preferred frequency-gain responses obtained from two- and three-channel amplification systems. The current experiments were limited to a linear system in which the crossover frequency dividing the channels was systematically varied. The subjects for the experiment were nine individuals with mild to moderately severe sensorineural hearing loss with various audiometric configurations. The subjects listened to continuous discourse, in noise, via a computer-controlled digital master hearing aid containing two real-time data acquisition processors. Initially, a modified simplex procedure was used to obtain preferred frequency-gain responses using several different crossover frequencies. A round-robin procedure was then conducted in which each preferred response from the simplex was compared with every other preferred response. The frequency-gain responses chosen most often for the two- and three-channel systems were compared. The results showed no significant differences between the preferred frequency-gain response for the two- versus the three-channel system. In addition, the preferred response chosen most often was not consistently observed at the same crossover frequency for all subjects, with the exception of those with steeply sloping hearing loss who chose 1,120 Hz as the first or second preference for the two-channel system. The round-robin results were rank-ordered according to the number of times each frequency-gain response was chosen. In general, subjects chose several frequency-gain responses at various crossover frequencies, which were not significantly different from each other statistically. The results of a final experiment suggested that physical similarities in the preferred responses chosen at the various crossover frequencies played a role in the rank-ordering of the preference judgments obtained in the original investigation.

The glycosyl phosphatidylinositol-linked Fc gamma RIIIPMN mediates transmembrane signaling events distinct from Fc gamma RII.

To investigate the ability of FcgammaRIII(PMN), the GPI-anchored isoform of FcgammaRIII (CD16) in polymorphonuclear leukocytes (PMN), to mediate transmembrane signaling events, we measured changes in membrane potential with DiOC(5) and in intracellular calcium with indo-1. FcgammaR were ligated by anti-FcgammaRIII mAb 3G8 (IgG and Fab), anti-FcgammaRII mAb IV.3 (IgG and Fab), and human IgG aggregates. Cell bound mAbs were also crosslinked by goat F(ab')(2) anti-mouse IgG. 3G8 IgG elicited a rapid change in [Ca(2+)](i), which was unaffected by EGTA, Vibrio cholerae toxin (CT), or Bordetella pertussis toxin (PT), and was abolished by BAPTA . Univalent receptor binding with 3G8 Fab gave no response but crosslinking with F(aV)2 GAM gave a rapid [Ca2,](i) response. Neither IV.3 Fab, IV.3 IgG, nor crosslinking of IV.3 Fab elicited a calcium signal. PI-PLC-treated PMN with the density of FcgammaRIII(PMN) reduced to that of FcgammaRII showed an unattenuated change in [Ca(2+)](i), with a 3G8 stimulus. The effects of IgG aggregates paralleled those of 3G8 mAb. These data indicate that multivalent ligation of FcgammaRIII(PMN) initiates an increase in [Ca(2+)];, derived from intracellular stores, that is distinct from both the FMLP- and FcgammaRII-induced responses. Ligand-dependent interaction with FcgammaRII is not required. Since FcgammaRIII(PMN) can internalize the FcgammaRIII-specific probe Con A-opsonized E and lyse anti-FcgammaRIII heteroantibody-opsonized chick E, this GPI-anchored molecule mediates both signal transduction and integrated cell responses.

Relation between reaction time and loudness.

The loudness of one-third octave bands of noise centered at either 1, 2, or kHz was measured in 10 normal-hearing young adults for sound levels of 50-90 dB SPL. Reaction times (RT) in response to these same stimuli were also measured in the same subjects. A moderate-to-strong correspondence was observed between the slopes for functions depicting the growth of loudness with sound level and comparable slopes for the reaction-time data. The correlation between slopes for the RT-intensity function and the loudness-growth function was comparable in magnitude to the test-retest correlation for the loudness-growth function except at 1 kHz.