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Biomedical subjects

I J Russell

Publications and source records attributed to I J Russell.

At least 19 recordsLinked to original sources
PubMed2003

Postnatal development of cochlear function in the mustached bat, Pteronotus parnellii.

Postnatal development of the mustached bat's cochlea was studied by measuring cochlear microphonic and compound action potentials. In adults, a cochlear resonance is involved in enhanced tuning to the second harmonic constant frequency component (CF2) of their echolocation calls at approximately 61 kHz This resonance is present immediately after birth in bats that do not yet echolocate. Its frequency is lower (46 kHz) and the corresponding threshold minimum of cochlear microphonic potentials is broader than in adults. Long-lasting ringing of the cochlear microphonic potential after tone stimulus offset that characterizes the adult auditory response close to CF2 is absent in newborns. In the course of the first 5 postnatal weeks, there is a concomitant upward shift of CF2 and the frequency of cochlear threshold minima. Up to the end of the third postnatal week, sensitivity of auditory threshold minima and the Q value of the cochlear resonance increase at a fast rate. Between 2 and 4 wk of age, two cochlear microphonic threshold minima are found consistently in the CF2 range that differ in their level-dependent dynamic growth behavior and are 1.5-5.7 kHz apart from each other. In older animals, there is a single minimum that approaches adult tuning in its sharpness. The data provide evidence to show that during maturation of the cochlea, the frequency and the sensitivity of the threshold minimum associated with CF2 increases and that these increases are associated with the fusion of two resonances that are partly dissociated in developing animals.

Acoustic Stimulation↗
PubMed2003

Development of echolocation calls in the mustached bat, Pteronotus parnellii.

Adult mustached bats employ Doppler-sensitive sonar to hunt fluttering prey insects in acoustically cluttered habitats. The echolocation call consists of 4-5 harmonics, each composed of a long constant frequency (CF) component flanked by brief frequency modulations (FM). The 2nd harmonic CF component (CF2) at 61 kHz is the most intense, and analyzed by an exceptionally sharply tuned auditory system. The maturation of echolocation calls and the development of Doppler-shift compensation was studied in Cuba where large maternity colonies are found in hot caves. In the 1st postnatal week, infant bats did not echolocate spontaneously but could be induced to vocalize CF-FM signals by passive body motion. The CF2 frequency emitted by the smallest specimens was at 48 kHz (i.e., 0.4 octaves lower than the adult signal). CF-FM signals were spontaneously produced in the 2nd postnatal week at a CF2 frequency of 52 kHz. The CF2 frequencies of induced and spontaneous calls shifted upward to reach a value of 60.5 kHz in the 5th postnatal week. Standard deviations of CF2 frequency were large (up to +/-1.5 kHz) in the youngest bats and dropped to values of +/-250 Hz at the end of the 3rd postnatal week. Some individuals in the 4th and 5th postnatal weeks emitted with adultlike frequency precision of about +/-100 Hz. In the youngest bats, the 1st harmonic CF component (CF1) was up to 22 dB stronger than CF2. Adultlike relative levels of CF1 (-28 dB relative to CF2) were reached in the 5th postnatal week. In spontaneously emitted CF-FM calls, the duration of the CF2 component gradually increased with age from 5 ms to maximum values of 18 ms. Durations of the CF2 component in induced calls averaged 7 +/- 2.6 ms in the 1st postnatal week and 8.2 +/- 1.5 ms in the 5th postnatal week. There were no age-related changes in duration of the terminal FM sweep (3 +/- 0.4 ms) in both induced and spontaneous calls. The magnitude of the terminal FM sweep in spontaneous calls was not correlated with age (mean 13.5 +/- 2 kHz). Values for induced calls slightly increased with age from 11 +/- 2 to 13 +/- 2 kHz. The emission rate of induced CF-FM signals increased with age from values of 2.5 +/- 2 to 17 +/- 5 pulses/s. Values for spontaneously emitted calls were 4.4 +/- 3 and 9 +/- 4.5 pulses/s, respectively. Doppler-shift compensation, as tested in the pendulum task, emerged during the 4th postnatal week in young bats that were capable of very brief active flights, but before the time of active foraging outside the cave.

Acoustic Stimulation↗
PubMed2001

Origin of the bell-like dependence of the DPOAE amplitude on primary frequency ratio.

For low and medium sound pressure levels (SPLs), the amplitude of the distortion product otoacoustic emission (DPOAE) recorded from guinea pigs at the 2f1-f2 frequency is maximal when f2/f1 approximately 1.23 and decreases for lower and higher f2/f1 ratios. The high-ratio slope of the DPOAE dependence on the ratio of the primary frequencies might be anticipated since the f1 amplitude at the f2 place is expected to decrease for higher f2/f1 ratios. The low-ratio slope of the dependence at low and medium SPLs of the primaries is actually one slope of a notch. The DPOAE amplitude recovers from the notch when the f2/f1 ratio is further reduced. In two-dimensional space formed by the f2/f1 ratio, and the levels of the primaries, the notch is continuous and has a level-dependent phase transition. The notch is identical to that seen in DPOAE growth functions. Similar notches and phase transitions were observed for high-order and high-frequency DPOAEs. Theoretical analysis reveals that a single saturating nonlinearity is capable of generating similar amplitude notch and phase transition when the f2/f1 ratio is decreased because of the increase in f1 amplitude at the DPOAE generation place (f2 place). The difference between the DPOAE recorded from guinea pigs and humans is discussed in terms of different position of the operating point of the DPOAE generating nonlinearity.

Animals↗
PubMed2000

The spatial and temporal representation of a tone on the guinea pig basilar membrane.

In the mammalian cochlea, the basilar membrane's (BM) mechanical responses are amplified, and frequency tuning is sharpened through active feedback from the electromotile outer hair cells (OHCs). To be effective, OHC feedback must be delivered to the correct region of the BM and introduced at the appropriate time in each cycle of BM displacement. To investigate when OHCs contribute to cochlear amplification, a laser-diode interferometer was used to measure tone-evoked BM displacements in the basal turn of the guinea pig cochlea. Measurements were made at multiple sites across the width of the BM, which are tuned to the same characteristic frequency (CF). In response to CF tones, the largest displacements occur in the OHC region and phase lead those measured beneath the outer pillar cells and adjacent to the spiral ligament by about 90 degrees. Postmortem, responses beneath the OHCs are reduced by up to 65 dB, and all regions across the width of the BM move in unison. We suggest that OHCs amplify BM responses to CF tones when the BM is moving at maximum velocity. In regions of the BM where OHCs contribute to its motion, the responses are compressive and nonlinear. We measured the distribution of nonlinear compressive vibrations along the length of the BM in response to a single frequency tone and estimated that OHC amplification is restricted to a 1.25- to 1.40-mm length of BM centered on the CF place.

Animals↗
PubMed2000

Is fibromyalgia a distinct clinical syndrome?

The validity of the fibromyalgia syndrome (FMS) as a distinct clinical entity has been challenged for several reasons. Many skeptics express concern about the subjective nature of chronic pain, the subjectivity of the tender point (TeP) examination, the lack of a gold standard laboratory test, and the absence of a clear pathogenic mechanism by which to define FMS. Another expressed concern has been the relative nature of the pain-distress relationship in the rheumatology clinic. The apparently continuous relationship between TePs and somatic distress across a variety of clinical disorders is said to argue against FMS as a separate clinical disorder. The most aggressive challenges of the FMS concept have been from legal defenses of insurance carriers motivated by economic concerns. Other forms of critique have presented as psychiatric dogma, uninformed posturing, suspicion of malingering, ignorance of nociceptive physiology, and occasionally have resulted from honest misunderstanding. It is not likely that a few paragraphs of data and logic will cause an unbeliever to change an ingrained opinion. Therefore, this review describes the clinical manifestations of FMS, responds to some of the theoretic arguments against it, and discusses some possible pathophysiologic mechanisms by which FMS may develop and persist as a unique syndrome.

Autonomic Nervous System↗
PubMed2000

Electrostatic interaction between stereocilia: I. Its role in supporting the structure of the hair bundle.

This paper provides theoretical estimates for the forces of electrostatic interaction between adjacent stereocilia in auditory and vestibular hair cells. Estimates are given for parameters within the measured physiological range using constraints appropriate for the known geometry of the hair bundle. Stereocilia are assumed to possess an extended, negatively charged surface coat, the glycocalyx. Different charge distribution profiles within the glycocalyx are analysed. It is shown that charged glycocalices on the apical surface of the hair cells can support spatial separation between adjacent stereocilia in the hair bundles through electrostatic repulsion between stereocilia. The charge density profile within the glycocalyx is a crucial parameter. In fact, attraction instead of repulsion between adjacent stereocilia will be observed if the charge of the glycocalyx is concentrated near the membrane of the stereocilia, thereby making this type of charge distribution unlikely. The forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena that have been recorded from the periphery of the auditory and vestibular systems.

Animals↗
PubMed2000

Electrostatic interaction between stereocilia: II. Influence on the mechanical properties of the hair bundle.

This paper is based on our model [Dolgobrodov et al., 2000. Hear. Res., submitted for publication] in which we examine the significance of the polyanionic surface layers of stereocilia for electrostatic interaction between them. We analyse how electrostatic forces modify the mechanical properties of the sensory hair bundle. Different charge distribution profiles within the glycocalyx are considered. When modelling a typical experiment on bundle stiffness measurements, applying an external force to the tallest row of stereocilia shows that the asymptotic stiffness of the hair bundle for negative displacements is always larger than the asymptotic stiffness for positive displacements. This increase in stiffness is monotonic for even charge distribution and shows local minima when the negative charge is concentrated in a thinner layer within the cell coat. The minima can also originate from the co-operative effect of electrostatic repulsion and inter-ciliary links with non-linear mechanical properties. Existing experimental observations are compared with the predictions of the model. We conclude that the forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena, which have been recorded from the auditory periphery.

Animals↗
PubMed2000

A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback.

alpha-tectorin is an extracellular matrix molecule of the inner ear. Mice homozygous for a targeted deletion in a-tectorin have tectorial membranes that are detached from the cochlear epithelium and lack all noncollagenous matrix, but the architecture of the organ of Corti is otherwise normal. The basilar membranes of wild-type and alpha-tectorin mutant mice are tuned, but the alpha-tectorin mutants are 35 dB less sensitive. Basilar membrane responses of wild-type mice exhibit a second resonance, indicating that the tectorial membrane provides an inertial mass against which outer hair cells can exert forces. Cochlear microphonics recorded in alpha-tectorin mutants differ in both phase and symmetry relative to those of wild-type mice. Thus, the tectorial membrane ensures that outer hair cells can effectively respond to basilar membrane motion and that feedback is delivered with the appropriate gain and timing required for amplification.

Acoustic Stimulation↗
PubMed2000

The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5 functional scales and the development of the FM Health Assessment Questionnaire.

OBJECTIVE: Functional assessment by self-report questionnaire plays an important role in most rheumatic conditions, but psychometric properties of questionnaires have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which allows for examining adequacy of the questionnaire scale. To assess currently used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel) completed the FIQ. The HAQ questionnaires were completed by 1438 patients participating in the US National Data Bank for Rheumatic Diseases. Seven hundred sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was applied separately to each of these data sets. RESULTS: The FIQ systematically underestimated functional impairment by its handling of activities not usually performed. All questionnaires had problems with non-unidimensionality and ambiguous items when applied to patients with FM. In addition, scales were found to be non-linear. Because of these findings we used the 20 item HAQ questionnaire as an item bank to develop a new questionnaire more suitable for use in FM, the fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available functional assessment questionnaire works well in FM. A new questionnaire, the FHAQ, was developed. It has appropriate metric properties and should function well in this condition. Since the FHAQ is a subset of the larger HAQ questionnaire, a new questionnaire is not required; only a different method of scoring is needed. Additional studies regarding sensitivity to change are required to fully validate the FHAQ.

Disability Evaluation↗
PubMed1999

Evolutionary adaptations of cochlear function in Jamaican mormoopid bats.

Mormoopid bat species have their echolocation system adapted to different hunting strategies. To study the corresponding mechanical properties of their inner ear, we measured distortion-product otoacoustic emissions to assess cochlear sensitivity and tuning. Mormoops blainvillii, Pteronotus macleayii and P. quadridens use frequency-modulated echolocation signals, sometimes preceded by a short narrowband signal component. Their distortion-product otoacoustic emission-threshold curves are most sensitive between 30 and 50 kHz and show no adaptation to the narrowband echolocation components. In contrast, the constant-frequency bat P. parnellii always uses long constant-frequency call components. Its inner ear is maximally sensitive at 62 kHz, the echo-frequency of the dominant constant-frequency component, and pronounced insensitivities at 61 and 93 kHz (CF2 and CF3 call frequency) are the major evolutionary change in comparison to its relatives. Furthermore, in P. parnellii, the optimum cochlear frequency separation is minimal at 62 and 93 kHz, associated with enhanced cochlear tuning, while for the other mormoopids there is no indication of enhanced tuning. The phylogeny of mormoopids, assessed by mitochondrial DNA analysis, shows a close relationship between the Pteronotus species. This suggests that major cochlear redesign, associated with the acquisition of echolocation-call specific cochlear processing in P. parnellii, has occurred within a relatively short evolutionary time scale.

Acoustic Stimulation↗
PubMed1999

Timing of cochlear feedback: spatial and temporal representation of a tone across the basilar membrane.

Electromotile outer hair cell (OHC) feedback provides the sensitivity and sharp frequency tuning of the cochlea. Basilar membrane displacements in response to characteristic frequency (CF) tones were measured with an interferometer at up to 15 locations across the basilar membrane width in the basal turn of the guinea pig cochlea. For CF tones, basilar membranes vibrations were largest beneath the OHCs; these phase-led vibrations beneath outer pillar cells and adjacent to the spiral ligament by approximately 90 degrees. Post mortem, responses measured beneath the OHCs were reduced by up to 65 dB, and the basilar membrane moved with similar phase across its entire width. We suggest OHCs amplify basilar membrane responses to CF tones when the basilar membrane moves at maximum velocity.

Acoustic Stimulation↗
PubMed1999

Is fibromyalgia a distinct clinical entity? The clinical investigator's evidence.

SUBJECTIVE: Chronic widespread pain with multiple tender points (fibromyalgia syndrome) is a common clinical presentation. Criteria for inclusion of fibromyalgia patients into research studies have led to a medical model which integrates symptoms, signs, epidemiology, pathogenesis, responses to treatment, and prognosis. Controversy regarding fibromyalgia relates mostly to issues of compensation. THEORETICAL: The diagnosis of fibromyalgia has been challenged as an inappropriate extraction from an epidemiological continuum of subjective discomfort. There are many conditions in which normally distributed measures exhibit distinctly unique outcomes at their extremes. OBJECTIVE: Since fibromyalgia patients exhibit lowered pain thresholds, the process of nociception was studied. Samples of fibromyalgia urine, blood, and spinal fluid disclosed abnormalities consistent with a biomedical model of failed neuroregulatory inhibition, altered nociception, central sensitization, and allodynia. All three views support fibromyalgia as a distinct clinical syndrome deserving of informed medical care and continued research to better understand chronic widespread pain.

Autonomic Nervous System↗
PubMed1999

Reduction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sublingually with low doses of human interferon-alpha.

One hundred and twelve fibromyalgia syndrome (FMS) patients were randomized into one of four demographically similar groups (n = 28/group). Sequential primary FMS patient volunteers were to receive daily sublingual placebo or interferon-alpha (IFN-alpha) at 15, 50, or 150 IU. After a screening evaluation, analgesic or sedative hypnotic medications were withdrawn. Two weeks later, daily IFN-alpha or placebo was initiated with follow-up evaluations at 2-week intervals ending with week 6. One primary, three secondary, and seven tertiary variables were assessed. Study outcome was based on improvement in the tender point index (TPI). The TPI did not improve with any IFN-alpha dose. However, significant improvement was seen in morning stiffness and in physical function with the 50 IU IFN-alpha (p < 0.01). None of the other outcome means changed significantly and no adverse events were attributable to IFN-alpha therapy.

Administration, Sublingual↗
PubMed1999

Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity. After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for 6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.

Administration, Sublingual↗
PubMed1999

Micromechanical responses to tones in the auditory fovea of the greater mustached bat's cochlea.

An extended region of the greater mustached bat's cochlea, the sparsely innervated (SI) zone, is located just basally to the frequency place of the dominant 61-kHz component of the echolocation signal (CF2). Anatomic adaptations in the SI zone are thought to provide the basis for cochlear resonance to the CF2 echoes and for the extremely sharp tuning throughout the auditory system that allows these bats to detect Doppler shifts in the echoes caused by insect wing beat. We measured basilar membrane (BM) displacements in the SI zone with a laser interferometer and recorded acoustic distortion products at the ear drum at frequencies represented in the SI zone. The basilar membrane in the SI region was tuned both to its characteristic frequency (62-72 kHz) and to the resonance frequency (61-62 kHz). With increasing stimulus levels, the displacement growth functions are compressive curves with initial slopes close to unity, and their properties are consistent with the mammalian cochlear amplifier working at high sound frequencies. The sharp basilar membrane resonance is associated with a phase lag of 180 degrees and with a shift of the peak resonance to lower frequencies for high stimulus levels. Within the range of the resonance, the distortion product otoacoustic emissions, which have been attributed to the resonance of the tectorial membrane in the SI region, are associated with an abrupt phase change of 360 degrees. It is proposed that a standing wave resonance of the tectorial membrane drives the BM in the SI region and that the outer hair cells enhance, fine tune, and control the resonance. In the SI region, cochlear micromechanics appear to be able to work in two different modes: a conventional traveling wave leads to shear displacement between basilar and tectorial membrane and to neuronal excitation for 62-70 kHz. In addition, the SI region responds to 61-62 kHz with a resonance based on standing waves and thus preprocesses signals which are represented more apically in the CF2 region of the cochlea.

Acoustic Stimulation↗
PubMed1999

Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia.

OBJECTIVE: To determine whether there is a difference in the concentration of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) from patients diagnosed with primary fibromyalgia syndrome (FM), fibromyalgia associated with other secondary conditions (SFM), patients with other painful conditions but lacking fibromyalgia (OTHER), and healthy controls. METHODS: The clinical measures of pain threshold included the tender point index, a measure of pain threshold intensity measured by digital pressure, and the average pain threshold measured by dolorimetry. Concentrations of NGF in the CSF were measured using a 2 site enzyme immunoassay. RESULTS: The mean (+/- SEM) concentration of NGF measured in patients with FM was significantly increased (41.8 +/- 12.7 pg/ml) compared to controls (9.1 +/- 4.1 pg/ml), but with large variability. Concentrations of NGF is SFM (8.9 +/- 4.4 pg/ml) and OTHER (16.2 +/- 8.4 pg/ml) were not elevated compared to controls. CONCLUSION: The findings of increased concentrations of NGF in patients with FM suggest a central mechanism, involving abnormalities in neuropeptides such as NGF, may be a factor in the pathogenesis of FM.

Adolescent↗
PubMed1998

Neurochemical pathogenesis of fibromyalgia.

In contrast with the situation just a few years ago, the most widely accepted model for the pathogenesis of FMS now invokes CNS mechanisms like nociception and allodynia rather than pathologically painful muscles. The levels of platelet serotonin and CSF substance P appear to be abnormal in directions that could logically amplify pain perception. The extent to which these mechanisms are unique to FMS will be critical in determining the direction that future research should take. Certainly, a better understanding of the cause of FMS could represent an important step toward the development of more effective therapy.

Animals↗