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Biomedical subjects

I J Russell

Publications and source records attributed to I J Russell.

At least 37 records · Page 2Linked to original sources

A possible role for saliva as a diagnostic fluid in patients with chronic pain.

OBJECTIVES: The focus of this review was on proteins and peptides found in saliva. Of greatest interest were those neuropeptides relevant to nociception and to the pathogenesis of chronic pain syndromes. An additional goal was to develop a standardized protocol to collect saliva for laboratory assessment. METHODS: Data were obtained through discussion with experts at the medical schools in San Antonio and Heidelberg and a Medline literature search involving all relevant studies from 1966 to 1997. The literature search was based on the following key terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF). RESULTS: The mean concentration of SP in the saliva of healthy normal controls ranged from 9.6 to 220 pg/mL. Generally, the concentration of SP was approximately three times higher in saliva than in plasma. In a number of painful conditions, particularly tension headache, substantial elevations of salivary SP were found. Mean values for salivary CGRP in healthy controls were approximately 22 pmol/L and were significantly elevated in patients with migraine attacks or cluster headache. There were no data to indicate prior quantitative determination of NGF in human saliva. CONCLUSIONS: After sampling and processing techniques have been standardized, measurement of neuropeptides in human saliva could provide a valuable tool for study of patients with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and even fibromyalgia syndrome.

Animals↗

Advances in fibromyalgia: possible role for central neurochemicals.

The neurophysiologic term allodynia has been applied to fibromyalgia because people with that disorder experience pain from pressure stimuli which are not normally painful. The nociceptive neurotransmitters of animal studies are now relevant to this human model of chronic, widespread pain. Evidence is presented to implicate several chemical pain mediators (including serotonin, substance P, nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This perception is hopeful because it offers many new options for the development of innovative therapy.

Analgesia↗

A descriptive model of the receptor potential nonlinearities generated by the hair cell mechanoelectrical transducer.

This paper describes a model for generating the hair cell receptor potential based on a second-order Boltzmann function. The model includes only the resistive elements of the hair cell membranes with batteries across them and the series resistance of the external return path of the transducer current through the tissue of the cochlea. The model provides a qualitative description of signal processing by the hair cell transducer and shows that the nonlinearity of the hair cell transducer can give rise to nonlinear phenomena, such as intermodulation distortion products and two-tone suppression with patterns similar to those which have been recorded from the peripheral auditory system. Particular outcomes of the model are the demonstration that two-tone suppression depends not on the saturation of the receptor current, but on the behaviour of the hair cell transducer function close to the operating point. The model also shows that there is non-monotonic growth and phase change for any spectral component, but not for the fundamental of the receptor potential.

Basilar Membrane↗

The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I.

OBJECTIVE: To assess the effects of delta wave sleep interruption (DWSI) on pain thresholds and fibromyalgia-like symptoms. To examine the potential correlations between DWSI and serum insulin-like growth factor 1 (IGF-1). METHODS: Thirteen healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain thresholds were measured by dolorimetry and symptoms by visual analog scale. Six subjects not undergoing DWSI served as dolorimetry and symptom controls (Group 2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and after DWSI. RESULTS: No significant differences in pain thresholds as a function of condition (baseline, DWSI, recovery) or overnight change were detected between or within groups (p>0.05). Morning mean dolorimeter scores were lower than evening scores in both groups during all 3 conditions, and were lower in Group 1 than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum levels of IGF-1 from Group 1 subjects showed no significant change after DWSI (p>0.05). CONCLUSION: In our study subjects, 3 nights of DWSI caused no significant lowering of pain thresholds compared with a control group. Subjects appeared to have lower pain thresholds in the mornings, and DWSI appeared to augment this effect. Symptoms were more apparent during DWSI, but were primarily related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather than acute DWSI, or may be dependent on factors other than disturbances of delta wave sleep.

Adolescent↗

The location of the cochlear amplifier: spatial representation of a single tone on the guinea pig basilar membrane.

Acoustic stimulation vibrates the cochlear basilar membrane, initiating a wave of displacement that travels toward the apex and reaches a peak over a restricted region according to the stimulus frequency. In this characteristic frequency region, a tone at the characteristic frequency maximally excites the sensory hair cells of the organ of Corti, which transduce it into electrical signals to produce maximum activity in the auditory nerve. Saturating, nonlinear, feedback from the motile outer hair cells is thought to provide electromechanical amplification of the travelling wave. However, neither the location nor the extent of the source of amplification, in relation to the characteristic frequency, are known. We have used a laser-diode interferometer to measure in vivo the distribution along the basilar membrane of nonlinear, saturating vibrations to 15 kHz tones. We estimate that the site of amplification for the 15 kHz region is restricted to a 1.25 mm length of basilar membrane centered on the 15 kHz place.

Acoustic Stimulation↗

A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia.

OBJECTIVE: To study, for the first time, service utilization and costs in fibromyalgia, a prevalent syndrome associated with high levels of pain, functional disability, and emotional distress. METHODS: Five hundred thirty-eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7-year prospective study of fibromyalgia outcome. Patients were assessed every 6 months with validated, mailed questionnaires which included questions regarding fibromyalgia symptoms and severity, utilization of services, and work disability. RESULTS: Fibromyalgia patients averaged almost 10 outpatient medical visits per year, and when nontraditional treatments were considered, this number increased to approximately 1 visit per month. Patients were hospitalized at a rate of 1 hospitalization every 3 years. In each 6-month study period, patients used a mean of 2.7 fibromyalgia-related drugs. Costs increased over the course of the study. The mean yearly per-patient cost in 1996 dollars was $2,274. However, results were skewed by high utilizers, and many patients used few services and had limited costs. Total costs and utilization were independently associated with the number of self-reported comorbid or associated conditions, functional disability, and global disease severity. Compared with patients with other rheumatic disorders, those with fibromyalgia were more likely to have lifetime surgical interventions, including back or neck surgery, appendectomy, carpal tunnel surgery, gynecologic surgery, abdominal surgery, and tonsillectomy, and were more likely than other rheumatic disease patients to report comorbid or associated conditions. Almost 50% of hospitalizations occurring during the study were related to fibromyalgia-associated symptoms. CONCLUSION: The average yearly cost for service utilization among fibromyalgia patients is $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions, and symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.

Adult↗

Health status and disease severity in fibromyalgia: results of a six-center longitudinal study.

OBJECTIVE: To determine the intermediate and long-term outcomes of fibromyalgia in patients seen in rheumatology centers in which there is special interest in the syndrome. METHODS: We conducted a longitudinal outcome study by mailed comprehensive Health Assessment Questionnaire administered every 6 months to 538 patients, from 6 rheumatology centers, whose median duration of disease at first assessment was 7.8 years. The final assessment took place after 7 years. In addition, there was study followup on 85 patients who had attended the Wichita center for > 10 years. RESULTS: Although functional disability worsened slightly and health satisfaction improved slightly, measures of pain, global severity, fatigue, sleep disturbance, anxiety, depression, and health status were markedly abnormal at study initiation and were essentially unchanged over the study period. Correlations between first and last assessment values were as high as r = 0.82. For some variables, abnormalities were 3 times greater at one center compared with another. CONCLUSION: Patients with established fibromyalgia, seen in rheumatology centers in which there a special interest in the disease and followed up for as long as 7 years, have markedly abnormal scores for pain, functional disability, fatigue, sleep disturbance, and psychological status, and these values do not change substantially over time. Half the patients are dissatisfied with their health, and 59% rate their health as fair or poor. There are marked differences in disease severity among the various centers, but < 14% of the variance in outcomes can be explained by demographic or center factors. Values at the first assessment are predictive of final values.

Cohort Studies↗

The voltage dependence of the mechanoelectrical transducer modifies low frequency outer hair cell electromotility in vitro.

The fast outer hair cell (OHC) electromotility is voltage dependent and is driven by changes in the OHC transmembrane potential. Those changes include the receptor potential generated by the variable conductance of the mechanoelectrical transducer (Evans and Dallos, 1993). In the experiments described here, we show that the voltage dependence of the mechanoelectrical transducer influences the low frequency motile responses of OHCs to an external electrical field. OHCs were fully inserted into a glass suction pipette, the microchamber, so that only the cuticular plate and hair bundle were exposed to the bath solution. With this technique, a rectification of the mechanical response, equivalent to an excitatory displacement of the hair bundle, was observed when the command voltage inside the microchamber depolarized the apical membrane. The shape of the response persisted when the OHC voltage-gated conductances were blocked. Following treatment of the hair bundle with BAPTA or dihydrostreptomycin, which are known to impair transduction function (Assad et al., 1991; Kroese et al., 1989), rectification of the motile response disappeared.

Animals↗

Medial efferent inhibition suppresses basilar membrane responses to near characteristic frequency tones of moderate to high intensities.

Efferent inhibition of low and medium spontaneous-rate fiber activity in response to characteristic frequency (CF) tones is greater at levels between 50 and 75 dB SPL than at lower levels, and even occurs at levels of 100 dB SPL [Guinan and Stankovic, J. Acoust. Soc. Am. 100, 1680-1690 (1996)]. The self-mixing effect of a laser diode was used to measure tone-evoked, basilar membrane (BM) displacements in the basal turn of the guinea pig cochlea during electrical stimulation of the medial efferent system. Efferent stimulation suppresses BM displacement and, for frequencies close to the CF of the measurement site and above, attenuation of tone-evoked displacements appears to be greatest for levels between 50 and 75 dB SPL, and efferent attenuation could exceed 10 dB SPL for tones at 90 dB SPL. By comparison, the attenuation of the BM vibrations caused by tones at frequencies below CF was found to be greatest for low sound pressure levels. The findings of Guinan and Stankovic therefore have their origin in events present in the vibrations of the BM.

Acoustic Stimulation↗

Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population.

OBJECTIVE: To investigate the association of serum serotonin with fibromyalgia (FM), and to study the relationship of serotonin to clinical variables associated with FM. METHODS: Serum samples (n = 292) were obtained on subjects without pain, with regional pain, and with widespread pain during a population survey. The tender point examination was made according to American College of Rheumatology examination criteria by an examiner blind to the subjects' complaints. Serotonin was determined by high performance liquid chromatography coupled to an electrochemical detector. RESULTS: No associations between clinical variables and serotonin levels were found in the group as a whole. Subjects with FM had lower serotonin levels unadjusted (p = 0.019) and adjusted for age and sex (p = 0.059) than those without FM. Within the FM group, associations between serotonin and tender point count (r = 0.563) and depression (r = 0.549) were noted, but the direction of association was opposite to previous reports and expectations. CONCLUSION: Serum serotonin levels are significantly lower in persons with FM compared to those without FM, but the range of values is wide. Difficult to explain correlations with reversed directions are noted for tender point count, dolorimetry, depression, and anxiety among those with FM. Serotonin is not correlated with any clinical variables in the general population, and separate pain groups cannot be distinguished.

Analysis of Variance↗

Work and disability status of persons with fibromyalgia.

OBJECTIVE: To determine the prevalence and determinants of self-reported work disability in persons with fibromyalgia (FM). METHODS: A longitudinal, multicenter survey of 1604 patients with FM from 6 centers with diverse socioeconomic characteristics was begun in 1988. Assessments were by self-report questionnaire and telephone contact, and included work and disability events that occurred before and after 1988. Comparative analyses were performed on the entire data set and, separately, on the Wichita data set. RESULTS: More than 16% of patients reported receiving US Social Security disability (SSD) payments (highest center rate 35.7%; lowest center rate 6.3%) compared to 2.2% of the US population (US Social Security Administration data) and 28.9% of patients with rheumatoid arthritis seen at the Wichita outpatient rheumatology clinic. Overall, 26.5% reported receiving at least one form of disability payment when SSD and other sources of disability payments were considered. In Wichita, less than 25% of SSD awards were made specifically for FM, but after 1988 that figure increased to 46.4%. Work disability was greatest at the San Antonio and Los Angeles centers. Multivariate predictors (correlates) included pain, Health Assessment Questionnaire disability, and unmarried status. In addition, more than 70% of patients reporting being disabled did receive disability payments. On the other hand, 64% reported being able to work all or most days, and more than 70% were employed or were homemakers. CONCLUSION: Although most patients (64%) report being able to work, we found high rates of self-reported work disability awards among persons with FM followed in 6 rheumatology centers. But we also found great variability among centers as to awards and as to self-reported work ability. Center differences in work disability might reflect clinic referral patterns, physician beliefs, or socioeconomic status.

Aged↗

The effect of efferent stimulation on basilar membrane displacement in the basal turn of the guinea pig cochlea.

Tone-evoked basilar membrane (BM) displacements were measured with a laser diode interferometer from the basal turn of the guinea pig cochlea. The olivocochlear bundle (OCB) was electrically stimulated for 60--80 msec periods at rates of < 200 sec-1 via electrodes placed at the point at which the OCB crosses the floor of the fourth ventricle. For tones close to the best or characteristic frequency (CF), OCB stimulation tended to linearize the highly compressive displacement-level functions and to displace the steep, low-level region toward higher intensities along the intensity axis by < 27 dB sound pressure levels. This shift resulted in a desensitization of the tip of the BM displacement tuning curve that was associated sometimes with downward shifts in the tuning curve CF of < 500 Hz. OCB-induced suppression of the BM response was not associated with a consistent broadening of the tuning curve or with major changes in the phase of the BM response. At frequencies in the low-frequency tail of the tuning curve, OCB stimulation had no observable effect on the motion of the BM. The effect of OCB stimulation on the BM response was blocked by perfusing the scala tympani with 1 microM strychnine. Thus, the effect of OCB stimulation on the frequency tuning of the BM is very similar to the effect of OCB stimulation on the sensitivity and frequency tuning of afferent fibers and inner hair cells. The results indicate that the postsynaptic action of the OCB may cause a change in gain of the voltage-dependent outer hair cell motility without observable changes in the stiffness of the cochlear partition or the position of the BM.

Animals↗

Basilar membrane resonance in the cochlea of the mustached bat.

The mustached bat (Pteronotus parnellii) detects the wing beats of prey insects by resolving small frequency modulations in the return echoes to the constant frequency component of its echolocation call at about 61 kHz. The fine frequency discrimination required for this task is due largely to the mechanical properties of the cochlea, as indicated indirectly by the presence of large otoacoustic emissions at 61 kHz. A laser diode interferometer was used to measure basilar membrane displacements in the basal turn of the cochlea at a location that is 4-6 mm basal to the 61-kHz place on the basilar membrane. The region of the basilar membrane from which the measurements were made was tuned not only to those characteristic of this location (88-98 kHz) but also very sharply tuned to 61 kHz. The 61-kHz tuning was labile and could be modeled as a simple resonance. The resonance is not restricted to the 61-kHz place but involves more basal regions. We also provide direct evidence to show that otoacoustic emissions from the ear propagate along the basilar membrane.

Acoustic Stimulation↗

The prevalence and characteristics of fibromyalgia in the general population.

OBJECTIVE: To determine the prevalence and characteristics of fibromyalgia in the general population. METHODS: A random sample of 3,006 persons in Wichita, KS, were characterized according to the presence of no pain, non-widespread pain, and widespread pain. A subsample of 391 persons, including 193 with widespread pain, were examined and interviewed in detail. RESULTS: The prevalence of fibromyalgia was 2.0% (95% confidence interval [95% CI] 1.4, 2.7) for both sexes, 3.4% (95% CI 2.3, 4.6) for women, and 0.5% (95% CI 0.0, 1.0) for men. The prevalence of the syndrome increased with age, with highest values attained between 60 and 79 years (> 7.0% in women). Demographic, psychological, dolorimetry, and symptom factors were associated with fibromyalgia. CONCLUSION: Fibromyalgia is common in the population, and occurs often in older persons. Characteristic features of fibromyalgia--pain threshold and symptoms--are similar in community and clinic populations, but overall severity, pain, and functional disability are more severe in the clinic population.

Adult↗

Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms.

OBJECTIVE: To investigate relationships between sex, pain threshold and fibromyalgia (FM) symptoms in the general population. METHODS: Data were obtained from a randomized populations survey of 3,006 persons in Wichita, KS and a subsample of 391 who completed a detailed interview and had an examination. Tender point counts, dolorimetry scores, clinical and psychological variables were measured. RESULTS: Dolorimetry scores were 2.04 kg/cm (1.42-2.66) lower in women than men, and women were almost 10 times more likely to have 11 tender points [OR 9.6 (2.00-46.3)] than men. Women are also more likely to have FM symptoms than men: "Pain all over," [OR 3.94 (1.34-11.38)], sleep disturbance [OR 3.06 (1.45-6.46)], fatigue [OR 4.52 (2.03-10.09)], and irritable bowel syndrome [OR 5.23 (1.83-14.96)]. Tender point counts are more correlated with FM symptoms than dolorimetry scores. CONCLUSION: Symptoms of FM are correlated with pain threshold in the general population, but tender point counts correlate better than dolorimetry. These 2 measures of pain threshold assay different but overlapping factors. Pain threshold is lower in women; and women have more FM symptoms. Decreased pain threshold correlates with all of the symptoms of FM, even in those who do not meet criteria for the syndrome. This suggests that decreased pain threshold, as measured by the tender point counts, is an intrinsically important aspect of patient distress, regardless of the extent and kind of concomitant disease; and that much can be learned about patients by employing this examination.

Disability Evaluation↗

Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study.

OBJECTIVE: To study the efficacy and safety of Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg), in treatment of primary fibromyalgia syndrome (FM). METHODS: Twenty-four sequential patients with primary FM were randomized to a fixed dose (3 tablets bid), placebo controlled, 4-week/course, pilot trial followed by a 6-month, open label, dose escalation (up to 6 tablets bid) trial. A 2-week, medication free, washout period was required before receiving treatment, between blinded courses, and again before starting open label treatment. The 3 primary outcome variables were measures of pain and tenderness but functional and psychological measures were also assessed. RESULTS: No clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial. With dose escalation and a longer duration of treatment in the open label trial, significant reductions in the severity of all 3 primary pain/tenderness measures were obtained without limiting risks. CONCLUSIONS: These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.

Cross-Over Studies↗

Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.

OBJECTIVE: To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients. METHODS: CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radioimmunoassay. Clinical measures included tender point examination and standardized questionnaires. RESULTS: CSF SP levels were 3-fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination. CONCLUSION: SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.

Adult↗