Biomedical subjects

B M Johnstone

Publications and source records attributed to B M Johnstone.

At least 19 recordsLinked to original sources

PubMed1996

Determinants of life-course variation in the frequency of alcohol consumption: meta-analysis of studies from the collaborative alcohol-related longitudinal project.

OBJECTIVE: This report evaluates the relative contribution of predictors of change in the frequency of alcohol consumption among drinkers, based on the quantitative synthesis of data from 27 longitudinal studies of the general population. The analysis has two objectives: (1) to evaluate the impact of selected demographic characteristics on the magnitude and trajectory of change in drinking across multiple samples, and (2) to assess the influence of methodological characteristics on the consistency of results across studies. METHOD: Raw data from studies including two serial measures of the frequency of alcohol consumption are analyzed. Fixed, random and mixed effects models for meta-analysis are used to pool measures across observations and model the influence of predictors on variability between results. RESULTS: Gender-based variation in the patterning of change is present across all observations, but concentrated in early periods of the life course. Age displays significant predictive effects across all observations, but statistically uniform results are obtained for subjects aged 30 and over. The national origin of study predicts larger amounts of variation than do other demographic predictors in the models. Significant effects are observed for several methodological characteristics of studies. Variation among effect estimates is associated with differences between samples in the interval between first and final measurements, the date of first measurement (a proxy for the historical context of the sample), the percentage retention of subjects between measurements and the time frame of the original alcohol measure. CONCLUSIONS: Based on the synthesis of data from multiple longitudinal samples, this study (1) characterizes normative developmental patterning in the frequency of alcohol consumption and demonstrates the varying effects of demographic factors across the life-course: (2) indicates the key influence of cultural and historical context on the establishment of drinking patterns; and (3) confirms the impact of methodological differences on variation in the results of studies.

Adolescent↗

PubMed1995

Meta-analysis of the effects of soy protein intake on serum lipids.

BACKGROUND: In laboratory animals, the consumption of soy protein, rather than animal protein, decreases serum cholesterol concentrations, but studies in humans have been inconclusive. In this meta-analysis of 38 controlled clinical trials, we examined the relation between soy protein consumption and serum lipid concentrations in humans. METHODS: We used a random-effects model to quantify the average effects of soy protein intake on serum lipids in the studies we examined and used hierarchical mixed-effects regression models to predict variation as a function of the characteristics of the studies. RESULTS: In most of the studies, the intake of energy, fat, saturated fat, and cholesterol was similar when the subjects ingested control and soy-containing diets; soy protein intake averaged 47 g per day. Ingestion of soy protein was associated with the following net changes in serum lipid concentrations from the concentrations reached with the control diet: total cholesterol, a decrease of 23.2 mg per deciliter (0.60 mmol per liter); 95 percent confidence interval, 13.5 to 32.9 mg per deciliter [0.35 to 0.85 mmol per liter]), or 9.3 percent; low-density lipoprotein (LDL) cholesterol, a decrease of 21.7 mg per deciliter (0.56 mmol per liter); 95 percent confidence interval, 11.2 to 31.7 mg per deciliter [0.30 to 0.82 mmol per liter]), or 12.9 percent; and triglycerides, a decrease of 13.3 mg per deciliter (0.15 mmol per liter; 95 percent confidence interval, 0.3 to 25.7 mg per deciliter [0.003 to 0.29 mmol per liter]), or 10.5 percent. The changes in serum cholesterol and LDL cholesterol concentrations were directly related to the initial serum cholesterol concentration (P < 0.001). The ingestion of soy protein was associated with a nonsignificant 2.4 percent increase in serum concentrations of high-density lipoprotein (HDL) cholesterol. CONCLUSIONS: In this meta-analysis we found that the consumption of soy protein rather than animal protein significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.

Cholesterol↗

PubMed1993

Modulation of f2-f1: evidence for a GABA-ergic efferent system in apical cochlea of the guinea pig.

f2-f1, but not 2f1-f2, was reduced in amplitude during continuous stimulation of the test ear with the primary tones, and with single tones near the primary frequencies. Stimulation of the contralateral ear, either with broad band noise or with single tones near the primary frequencies, also reduced f2-f1. Ipsilateral and contralateral effects were additive and were restricted to the frequency range between about 2 kHz and 7 kHz. Contralateral, but not ipsilateral suppression, was blocked after systemic administration of strychnine. Ipsilateral suppression was eliminated by perfusion of the cochlea with tetrodotoxin. Both contralateral and ipsilateral suppression were abolished after perfusion of the cochlea with bicuculline. The results are evidence for a role for a GABA-ergic efferent system in the modulation of outer hair cell mechanics in the apical cochlea.

Acoustic Stimulation↗

PubMed1993

Effects of intra-cochlear perfusion of salicylates on cochlear microphonic and other auditory responses in the guinea pig.

The ototoxic action of salicylate was investigated in the guinea pig by perfusion of both salicylate and bromosalicylate through scala tympani. The results qualitatively confirmed experiments using intravenous administration in cats (Stypulkowski, 1990), showing dose-dependent elevations in compound action potential (CAP) thresholds, increases in cochlear microphonics (CM) and level-dependent reductions in 2f1-f2 acoustic distortion products. The endocochlear potential was not significantly affected and iontophoretic injection of salicylate into scala media had no measurable effect on CAP thresholds, consistent with an action on the basolateral walls of the hair cells. Perfusion with indomethacin produced effects similar to those of the salicylates, but at non-physiological doses. Together with the great effectiveness of 5-bromosalicylate, this suggests that salicylate does not act by inhibiting prostaglandin synthesis. The results are qualitatively consistent with the proposition that salicylates act on the basolateral walls of the outer hair cells. However, the magnitude of the CM increases, particularly at high drug concentrations, and the fact that salicylate reduced, but did not eliminate the effects of olivocochlear efferent stimulation on CM amplitude indicate that a simple explanation for salicylate effects based solely on a conductance increase in the outer hair cell membranes may be inadequate.

Acoustic Stimulation↗

PubMed1993

A cross-study contextual analysis of effects from individual-level drinking and group-level drinking factors: a meta-analysis of multiple longitudinal studies from the collaborative alcohol-related longitudinal project.

In contextual (cross-level) analysis within multiple longitudinal general population studies, individual-level drinking behaviors (quantity per typical occasion, frequency of drinking per month and total volume of drinks per month) at final measurement are assessed by three models that simultaneously enter individual- and group-level measures. Two age groups (15-20 and 21-30) are independently assessed. In each model, the Time 1 individual-level drinking behavior and one of three group-level factors are entered. The group-level factors are (1) the percentage of abstainers at Time 1 for each age/sex cohort, (2) the Time 1 group mean for the drinking measure for the age/sex cohort and (3) the mean difference of the age/sex cohort's change in the drinking measure over time. All variables in the model are controlled by variations to exposure in per capita consumption of alcohol during the age/sex cohort's formative years and at Time 2. Meta-analysis assesses the homogeneity of the findings across studies. Models were proposed with the rationale that (1) understanding of individual drinking behavior can be advanced if individual-level data and group-level data are considered in the same models, and (2) integration of these two levels of analyses are, to date, rare. The rationale for using meta-analysis is that findings from the models can be assessed across social contexts with respect to their generalizability. The mean difference model, controlling for individual drinking at Time 1, is the most influential of the group-level models for the younger age group: the degree to which the group changes its drinking pattern is positively related to individual-level drinking behavior at final measurement, over and above the individual's drinking behavior at Time 1, for individual-level frequency of drinking among males (homogeneous among drinkers only). Younger females show more significant relationships for the mean difference females show more significant relationships for the mean difference model. Findings are significant for all relationships examined for the mean difference of the drinking of the group and the individual drinking among the older males and females. Measures of individual-level drinking for all measures at Time 1, controlling for the group-level effects, are significantly related to individual-level drinking at final measurement. The results are homogeneous for quantity (drinkers only) and volume among the young. Findings indicate that characterizations of the drinking for both the individual and the group to which the individual belongs predict measures of drinking practices on the individual level over time.

Adolescent↗

PubMed1992

Mechanical preprocessing in the mammalian cochlea.

The mammalian cochlea responds with exquisite sensitivity to the small fluctuations in air pressure that make up the stimulus of sound. Moreover, it responds to pressure fluctuations that occur extremely rapidly and that vary over a wide range of intensities--in both cases, to an extent outside the capabilities of unaided nerve fibres. Research performed during the past decade has shown that these properties are dependent on a physiological source of mechanical energy that operates probably within the outer hair cells of the organ of Corti. These cells, which are anatomically and functionally similar to the primary receptor cells, the inner hair cells, are believed to function as a source of mechanical power to assist the mechanical sensitivity of the cochlea, by mechanisms that currently are not understood. Several possible mechanisms have been proposed, but each has limitations that may make it an unsuitable candidate. Recent work has also demonstrated the likely role of mechanoelectrical transduction in outer hair cells in controlling the power source and thereby influencing the sensitivity and amplitude range of the cochlea.

Animals↗

PubMed1991

Preliminary results from a meta-analysis of drinking behavior in multiple longitudinal studies.

This paper introduces the scope and rationale of The Collaborative Alcohol-Related Longitudinal Project and describes the individual longitudinal studies which contribute to this large collaborative project, representing studies from 15 countries. It also serves as an introduction to four reports of the preliminary findings from the project. The project is distinguished by (1) its interdisciplinary research approach which has assembled a multidisciplinary group of scholars to direct and interpret analyses, (2) its use of primary data from multiple longitudinal studies, (3) the parallel analyses of primary data from multiple studies, using comparable measures across studies recorded to a standard format and common analytic model, and (4) its use of meta-analysis to combine results across studies. Its research objectives include determining the cross-study consistency of findings of (1) the incidence and chronicity of drinking patterns and problems, (2) exogeneous factors which initiate and alter drinking careers, (3) socio-behavioral factors measured in childhood and adolescence which predict adult drinking problems, (4) inter-generational biological and social factors which predict adult drinking problems, and (5) aggregate-level factors which account for study differences. The method of sampling of studies from the world's alcohol-related general population longitudinal research is described.

Alcohol Drinking↗

PubMed1991

An integrated approach to meta-analysis in alcohol studies.

The research design and methods utilized by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta-analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sizes, and random effects models.

Alcohol Drinking↗

PubMed1991

A meta-analysis of life course variation in drinking.

Meta-analysis combines results from multiple longitudinal studies to describe life course variation by age and sex for quantity of drinking per typical occasion (20 studies) and frequency of drinking during one month (27 studies). There is cross-study heterogeneity for the Time 1 means of the drinking variables blocking for age and sex. Age distributions for the Time 1 means are similar by gender within nations; in the aggregate, males exceed females in the magnitude of drinking. Dramatic shifts in the standardized mean difference (M2-M1) occur among the young; greater homogeneity and moderate change (declines) occur later in life. Implicated in improving cross-study homogeneity for M2-M1 among the young are interval between measurements, nation, Time 1 per capita consumption (PCC), difference in PCC and the Time 1 mean. Lower unstandardized regression coefficients are found for quantity among youth, but are not consistently homogeneous within nations; the association for frequency becomes increasingly stable with increasing age. Nation and interval are implicated in improving homogeneity. Decline in quantity occurs among the old. M2-M1 produces homogeneously higher regressions for groups of the young who increase quantity v. those who do not. Linkage of the group-level and individual-level findings is discussed.

Adolescent↗

PubMed1990

The ototoxic mechanism of cisplatin.

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.

Aminooxyacetic Acid↗

PubMed1990

Absence of tonic activity of the crossed olivocochlear bundle in determining compound action potential thresholds, amplitudes and masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities.

In Nembutal- or Urethane-anaesthetised guinea pigs N1 audiograms and N1 input-output functions were measured as were compound action potential (CAP) tuning curves under forward masking and simultaneous masking conditions. Then the crossed olivocochlear bundle was lesioned at the floor of the fourth ventricle and the cochlear responses were re-measured. There were never any changes in the N1 audiograms, input-output functions, or the CAP tuning curves. Thus, the crossed efferent pathways do not appear to play any tonic role in determining cochlear threshold sensitivities, selectivities or masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities.

Action Potentials↗

PubMed1990

Saturation of outer hair cell receptor currents causes two-tone suppression.

Zwicker [Biol. Cybern. 35, 243-250, (1979); J. Acoust. Soc. Am. 80, 163-176 (1986)] has previously proposed that many nonlinear phenomena in the mammalian cochlea can be explained by saturation of a positive feedback process which enhances mechanical sensitivity, although the site of the nonlinearity producing this saturation has so far remained obscure. In this paper we present evidence suggesting that the nonlinearity of mechano-electrical transduction in the outer hair cells is the dominant nonlinearity producing two-tone suppression in the mammalian cochlea. In particular, we show that: (i) suppression of the extracellular summating potential (SP), recorded from a particular place within the organ of Corti, has characteristics similar to the suppression of activity in the auditory-nerve; (ii) that SP suppression occurs at approximately constant basilar membrane displacement, inferred from the SP iso-response contours; and that (iii) the onset of SP suppression with suppressor tones on the tail of the frequency tuning curve closely parallels the onset of nonlinearity in the local cochlear microphonic. Since previous studies (Patuzzi et al., 1989) have demonstrated that the vibration of the basilar membrane at its characteristic frequency is very sensitive to changes in outer hair cell receptor current, we consider that interference in outer hair cell currents caused by nonlinearity in mechano-electrical transduction is an adequate explanation of two-tone suppression. This requires that outer hair cell receptor currents deviate from linearity at a suppressor tone level below that required to produce a significant DC receptor potential within the inner hair cells, and that the active process within the cochlea is distributed along a local region of the cochlea, basal of the vibration peak.

Acoustic Stimulation↗

PubMed1990

Effects of L-glutamate on auditory afferent activity in view of its proposed excitatory transmitter role in the mammalian cochlea.

This report describes the effects of L-glutamate (Glu) introduced into the perilymph of scala tympani on the spontaneous and tone-evoked activity of guinea pig single primary auditory afferents. Concentrations below 2 mmol/l were in general ineffective, while a concentration of 5 mmol/l caused a marked decrease of the neural activity. At 2 mmol/l, roughly 60% of the Glu-perfusions were effective and produced a variety of changes. The most prominent effect was a reduction of the tone-evoked activity without a change in spontaneous rate. Indeed, in some cells, the tone-evoked activity could be almost totally abolished without affecting the spontaneous activity. More rarely observed was a moderate, generally transient increase of the spontaneous activity which was occasionally followed by a decrease in both tone-evoked and spontaneous firing rate. The increase in firing rate was always small relative to the maximum discharge rate evoked by tone stimuli. Desensitization of the Glu-evoked response without an obvious change in the spontaneous activity was also found. In a few cells Glu caused a reduction of the discharge rate below the spontaneous firing rate during loud tone presentation. Higher Glu doses generally caused a reduction of spontaneous and tone-evoked activity without any sign of a preceding increase. Thus, the effects of Glu in the mammalian cochlea appear to be complex and on balance seem inconsistent with the effects predicted for an excitatory transmitter. The findings argue against the hypothesis that Glu is the afferent transmitter released by inner hair-cells. However, the results do not exclude an involvement of Glu as a neuromodulator or co-transmitter.

Acoustic Stimulation↗

PubMed1989

Contralateral cochlear destruction mediates protection from monoaural loud sound exposures through the crossed olivocochlear bundle.

Destruction of the cochlea contralateral to one subsequently exposed to a high intensity acoustic exposure has been shown to reduce the threshold losses caused by the exposure (Rajan and Johnstone, 1983a). The present study tested this manipulation on a wide variety of exposures of varying intensity and duration and found that the amount by which ipsilateral threshold losses were reduced was related to the amount of threshold losses that would have occurred in the absence of the contralateral manipulation. This loss-related protection is also found when the COCB is electrically stimulated during loud sound exposures (Rajan, 1988b; Rajan and Johnstone, 1988b). When the COCB was lesioned at the floor of the fourth ventricle contralateral cochlea destruction no longer protected the test cochlea, confirming that the crossed cochlear protection was exercised through the COCB. The contralateral manipulation did not appear to directly activate the COCB but may have acted in a facilitatory manner on the COCB, allowing activation only when a sufficiently high level exposure was subsequently presented ipsilaterally: a variety of responses at the ipsilateral cochlea and at the brainstem, remeasured after contralateral cochlear destruction and prior to an ipsilateral loud sound exposure, were found to be unaltered, although the TTS to the subsequent exposure was significantly reduced.

Animals↗

PubMed1989

The origin of the low-frequency microphonic in the first cochlear turn of guinea-pig.

Low-frequency microphonic potentials (100 Hz to 2000 Hz) have been measured in the first turn of the guinea pig cochlea before and after a variety of manipulations of the cochlea. These included ablation of the apical turns, iontophoresis of streptomycin, dc current injection into the first turn, acoustic trauma and two-tone interference with pure tones. These manipulations indicate that the low-frequency microphonic measured in the first turn and at the round window is generated predominantly by the hair cells of this region. It is a convenient and relatively uncomplicated indicator of the integrity of the mechano-electrical transduction process of these cells.

Acoustic Stimulation↗

PubMed1989

Changes in cochlear microphonic and neural sensitivity produced by acoustic trauma.

The low-frequency (200 Hz) microphonic potentials at the round window and in the organ of Corti of the first turn of the guinea pig cochlea have been measured before and after acoustic overstimulation. Reductions in the amplitude of this microphonic after loud sound are highly correlated with neural threshold elevation in this region. The fall in the microphonic amplitude appears due to an inactivation of mechano-electrical transduction channels at the apex of the outer hair cells into a closed state. These results are consistent with the idea that the current through the outer hair cells controls the mechanical sensitivity of the organ of Corti, and that the temporary loss of mechanical and neural sensitivity following loud sound is due to a simple inactivation of the mechano-electrical transduction channels.

Action Potentials↗

PubMed1989

Outer hair cell receptor current and sensorineural hearing loss.

It is argued in this paper that many nonlinear phenomena in audition and many types of sensorineural hearing loss can be explained by a disruption of the mechano-electrical transduction process at the apex of the outer hair cells. This is done using experimental data and a simple model of the active role of outer hair cells in cochlear mechanics based on our previous experiments with acoustic trauma. The causes of sensorineural loss addressed include acoustic trauma, aminoglycoside ototoxicity, intoxication with loop diuretics, hypoxia and Meniere's disease. The nonlinear phenomena discussed include loudness compression, two-tone suppression and modulation of cochlear sensitivity by very low-frequency tones. In every case considered the reduction in neural sensitivity was related to the reduction in outer hair cell receptor current in a quantitatively similar way. We conclude that the link is causal.

Animals↗

PubMed1989

Stimulus-related potassium changes in the organ of Corti of guinea-pig.

1. Potassium concentration was measured with double-barrelled K+-selective microelectrodes within the organ of Corti in the first turn of the guinea-pig cochlea. 2. Penetration of the electrode from scala tympani through the basilar membrane was accompanied by an increase in K+ resting level from 3.0 mmol/l in perilymph to 3.4 mmol/l in cortilymph (n = 8). K+ resting level was not significantly different in various extracellular regions of the organ of Corti. On penetration of the cuticular plate, the K+ level reached 140 mmol/l simultaneously with the occurrence of a +80 mV endocochlear potential. Impalement of hair cells and supporting cells was accompanied by an increase in K+ level, but intracellular K+ level was not systematically measured. 3. Stimulation with pure tones over the frequency range 500 Hz to 25 kHz produced changes in the K+ level in the organ of Corti. The magnitude of these changes was dependent on stimulus frequency and intensity. At high sound intensities the K+ level in the tunnel of Corti could increase by typically 1 mmol/l, while a maximum increase of 3 mmol/l with respect to the resting level was observed immediately adjacent to inner hair cells. 4. During brief exposures to moderate intensity, pure tone acoustic stimulation (10 s, less than 80 dB SPL (sound pressure level] of frequency 4 kHz or greater the K+ level in the extracellular fluid of the organ of Corti rose monotonically to a steady peak level. On cessation of the stimulus the K+ level fell monotonically with a time constant of about 2 s to a level close to the pre-stimulus level. In some cases this level was slightly above the pre-stimulus level. 5. For brief exposures to moderate intensity sound (10 s, less than 80 dB SPL) the extracellular potential in the organ of Corti became more positive. The amplitude of this sound-evoked change adapted during stimulation to a level approximately one-fifth of its initial value. Upon cessation of the stimulus the potential fell transiently below its pre-stimulus level, before recovering to that level. The time constant of these changes was between 2 and 3 s. 6. Iso-response tuning curves for the sound-evoked elevation in K+ level in the organ of Corti in animals in good condition were similar to iso-rate tuning curves for primary afferent fibres reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗