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Biomedical subjects

R L Doty

Publications and source records attributed to R L Doty.

At least 91 records · Page 5Linked to original sources

Human odor intensity perception: correlation with frog epithelial adenylate cyclase activity and transepithelial voltage response.

Although a number of odorants are hypothesized to depolarize frog olfactory receptor cells by binding to ciliary glycoproteins which activate membrane-bound G-proteins to induce adenylate cyclase-mediated increases in intracellular cAMP (cyclic adenosine 3',5'-monophosphate), it is not known whether these odorants influence human odor perception via similar mechanisms. In this paper we present evidence derived from odor attribute ranking and multidimensional scaling procedures that the perceived intensity of such odorants to humans is correlated with (a) the amount of adenylate cyclase activity they induce in an in vitro frog olfactory cilia preparation and (b) the magnitude of their influence on the frog transepithelial voltage response or electro-olfactogram (EOG). These observations are in accord with the hypothesis that the perception of the intensity of some odors by humans is associated with cAMP-related epithelial processes and imply that remarkable homologies exist between the intensity-related olfactory receptor mechanisms of frog and man.

Adenylyl Cyclases↗

Dose-related effects of cigarette smoking on olfactory function.

Little is known about the influence of cigarette smoking on the ability to smell; previous studies on this topic have led to contradictory findings and have failed to take into account smoking dose and duration. In the present study, the 40-odorant University of Pennsylvania Smell Identification Test was administered to 638 subjects for whom detailed smoking histories were available. Smoking was found to be adversely associated with odor identification ability in a dose-related manner in both current and previous cigarette smokers. Among previous smokers, improvement in olfactory function was related to the time elapsed since the cessation of smoking. Logistic regression analysis found current smokers to be nearly twice as likely to evidence an olfactory deficit than persons who have never smoked. Overall, the data suggest that (1) smoking causes long-term but reversible adverse effects on the ability to smell and (2) the failure of some studies to demonstrate smoking effects may be caused by the inclusion of persons with a history of smoking in the nonsmoking groups.

Adolescent↗

Fluprazine hydrochloride: no influence on the odor detection performance of male rats.

Fluprazine hydrochloride (DU 27716) decreases copulatory and offensive attack behaviors of male rats and increases their latency to locate buried food in an open field. Since such behaviors are mediated to some degree by the olfactory system, several investigators have hypothesized that this drug may produce an overall impairment in olfactory sensitivity. To test this hypothesis, the influences of five doses of fluprazine hydrochloride (1.0, 2.5, 5.0, 7.5 and 10.0 mg/kg IP) on the odor detection performance of 12 adult male Long Evans rats was assessed, relative to saline, using high precision olfactometry and a go/no-go operant odor detection task. Treatments were administered every 3rd day in counterbalanced order, with the drug or saline injections occurring 30 minutes before the 260-trial test sessions. No significant influence of fluprazine was observed on odor detection performance, as measured by the nonparametric signal detection sensitivity index SI and the percentage of correct trials. These results indicate that fluprazine does not induce generalized olfactory impairment.

Animals↗

A comparison of response characteristics of airflow and pressure transducers commonly used in rhinomanometry.

Although the ranges in which pneumotachographs evidence linear output to static flows are documented in the literature, measures of output reliability or the stability of calibration functions resulting from the input of dynamic nonsinusoidal flows (such as those which occur during nasal breathing) have not been investigated. Furthermore, it is not known whether the type of requisite pressure transducer used in conjunction with the pneumotachograph influences the pneumotachograph's linearity, output reliability, or dynamic response. To provide information on these points, we determined the dynamic and static responsiveness of three pneumotachographs commonly used in rhinomanometry, in combination with three requisite pressure transducers. In general, a) output reliability depended on the pneumotachograph/pressure transducer combination and was not readily predictable from the reliabilities of the individual components, b) heating increased pneumotachograph reliability, and c) differences in accuracy existed among transducer combinations at high, but not low, flow frequencies. In addition, results from the calibration syringe study (in which the pneumotachograph is calibrated with dynamic non-sinusoidal flows) suggested that: a) a single calibration factor, as supplied by most pneumotachograph manufacturers, is inadequate for accurately measuring the full range of flows produced in sniffing and breathing tasks; b) the measurement of complex waveforms, even when the dominate frequencies of such waveforms are low, requires pneumotachographs that accurately respond to relatively high frequencies; and c) the use of dynamic nonsinusoidal flows (as opposed to static flows) to calibrate pneumotachographs results in a calibration function with higher reliability.

Calibration↗

The olfactory and cognitive deficits of Parkinson's disease: evidence for independence.

In the present study we sought to determine whether the olfactory deficits of parkinsonism are related to the cognitive and perceptual-motor manifestations of the disease. Pearson correlation coefficients were computed among a number of olfactory, neurological, and neuropsychological measures obtained from 58 Parkinson's disease patients, including the University of Pennsylvania Smell Identification Test, a modified Randt memory test, a reaction time test, a finger-tapping test, ratings of motor and neurological function, and selected verbal and performance subtests of the Wechsler Adult Intelligence Scale--Revised. Data from 38 patients with Parkinson's disease who received odor detection threshold testing were also evaluated. The intercorrelation matrix was subjected to a principal components factor analysis which yielded six clear-cut factors: cognitive/memory, gross motor, oral motor, fine motor, olfactory, and tremor. The olfactory factor received strong and nearly exclusive loadings from the olfactory measures (which did not evidence meaningful loadings on any of the other factors). A ten-trial jackknife procedure revealed the factor structure to be stable. Further support of the independence of the olfactory variables from the other measures was provided by multiple regression and canonical correlation analyses. Overall, these findings lend support to the hypothesis that the olfactory disorder of parkinsonism is independent of the cognitive, perceptual-motor, and memory manifestations of the disease.

Aged↗

Influence of the D-2 dopamine receptor agonist quinpirole on the odor detection performance of rats before and after spiperone administration.

The influence of five doses of the D-2 receptor agonist quinpirole (0.025, 0.05, 0.075, 0.10, and 0.20 mg/kg IP) on the odor detection performance of 21 adult male Long Evans rats was assessed using high precision olfactometry and a go/no-go operant task. Additionally, ten rats were pre-treated with the D-2 receptor antagonist spiperone (0.62 mg/kg IP) and their performance monitored following quinpirole administration. Treatments were administered every third day in a counterbalanced order, with the quinpirole injections occurring 15 min before, and the spiperone injections 35 min before, the 260-trial test sessions. Quinpirole injection resulted in a dose-dependent decrease in odor detection performance, as measured by the percentage of correct trials and by the non-parametric signal detection sensitivity index SI. Prior treatment with spiperone eliminated these effects. Dose-related influences of quinpirole on (a) the average latency to initiate a detection response (i.e., the S + response latency), (b) the total session duration, and (c) the number of aborted trials were also eliminated or greatly attenuated by prior spiperone injection. These results suggest that D-2 receptors may be involved in the modulation of odor detection performance and related behaviors.

Acetates↗

No influence of adrenalectomy on measures of taste sensitivity in the rat.

The influence of adrenalectomy on the taste sensitivity and responsivity of Long-Evans rats to sodium chloride and sucrose tastants presented separately and in mixtures was examined using high precision gustometry, computer-controlled go/no-go operant procedures, and nonparametric signal detection measures. Relative to baseline levels, adrenalectomized rats' plasma corticosterone levels decreased by 328% while sodium chloride and water consumption increased by 548% and 165%, respectively. The same measures remained unchanged in sham-operated animals. Taste sensitivity and responsivity to sodium chloride and sucrose did not differ between adrenalectomized and sham-operated animals and discrimination performance remained the same between the groups as well. The present results support and extend previous findings that adrenalectomy and the resultant corticosteroid deficiency does not influence taste sensitivity or responsivity in the rat.

Adrenal Cortex↗

Influence of adult castration on the olfactory sensitivity of the male rat: a signal detection analysis.

The effect of adult castration on the male rat's ability to detect ethyl acetate odor was measured with high-precision olfactometry and a go-no-go signal detection task. Castration was found to significantly mitigate the tendency observed in sham castrates to improve detection performance across an 18-week postoperative test period. No significant castration-related alterations on the responsivity or S+ response latency measures were observed. These findings indicate that castration influences the male rat's ability to improve odor detection performance over time, although it is not known whether this effect is attributable to sensory or to memory mechanisms.

Animals↗

Influence of age and age-related diseases on olfactory function.

It is clear from this review that olfactory function is markedly altered in old age and in a number of age-related diseases. The deficits appear to be rather general and detectable by several types of olfactory tests. Considerable interindividual variability exists, however, and the physiologic bases of these changes are not clear. In many healthy elderly persons, smell loss appears to occur as a result of one or more causes, including viral insult, cumulated exposure to toxic fumes, head trauma, and calcification of the cribriform plate. Several reviews have appeared suggesting that the olfactory system may be a center of primary involvement in AD. Of particular interest is the hypothesis that environmental agents (related etiologically to the disease process) pass into the central nervous system via the highly active transport mechanisms of the olfactory receptors. This latter notion, although attractive, must be viewed conservatively, as it is possible that the olfactory pathways are simply selectively vulnerable to destruction by various disease processes. This may explain why Huntington's chorea and multiinfarct dementia, in addition to AD and PD, are associated with alterations in smell function. Although it is tempting to assume, as have authors such as Koss et al., that alterations in threshold function reflect peripheral olfactory dysfunction and that alterations in odor identification and other more demanding tasks reflect central olfactory dysfunction, there is little empirical support for such a simple dichotomy. Despite the fact that a peripheral/central distinction is useful in clinical audiology (where threshold loss is commonly associated with CN VIII pathology), an evaluation of the utility of this distinction in olfaction requires further research. The limited data suggest that both identification and detection deficits commonly arise from damage to the olfactory epithelium, even though identification deficits unassociated with detection deficits may occur in some central brain disorders. It is apparent from the studies reviewed in this chapter that considerable progress has been made during the last decade in elucidating the nature and prevalence of olfactory disturbances in elderly patients, as well as in patients with dementia-related diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

The shelf life of the University of Pennsylvania Smell Identification Test (UPSIT).

The shelf life of the University of Pennsylvania Smell Identification Test was studied by comparing, using a within-subjects design, scores for tests manufactured within 2 months of the time of testing, 2 1/2 years before the time of testing, and 4 years before testing. A three-way analysis of variance (test age by gender by booklet presentation order) revealed no significant effects of test age, presentation order, or any of the interactions on the average test scores. However, a significant gender main effect was observed (the women outperformed the men). The number of persons who correctly identified each test item was examined using the Cochran Q test. A significant difference was found among the three groups for only one of the 40 items (lemon). The percentage of persons who correctly identified lemon was lowest with the 4-year-old tests (respective percentages of correct values for the recent, 2 1/2-year, and 4-year tests were 100%, 97%, and 67%). It is not clear, however, whether this variation is the result of test age, per se, or vagaries in the manufacturing process. Overall, the data indicate that tests stored in a dry place at room temperature have a long shelf life and can be validly used for assessing patient smell function.

Adult↗

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible.

Acrylates↗

Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test.

The internal consistency reliability (ICR) of the 40-item University of Pennsylvania Smell Identification Test (UPSIT) and its 10-, 20-, and 30-item fractions was explored, as well as the relationships between the fractions and the entire 40-item test. Pearson correlation coefficients (rs) were computed among all independent combinations and permutations of the four 10-item UPSIT booklets using data from 774 subjects. The median r values of the 10- and 20-item combinations were used to establish the ICRs of the 10- and 20-item tests. The ICRs of the 30- and 40-item tests were estimated using the Spearman-Brown formula and the median rs of the 20-item combinations. Additional ICR estimates of the 40-item UPSIT were obtained from nonsymmetrical fractions using the Horst formula. The ICRs for the UPSIT and its 10-, 20-, and 30-item fractions were 0.922, 0.752, 0.855 and 0.898, respectively. No major sex differences emerged. Estimates of correlations between (1) single booklets and two-booklet combinations and (2) the 40-item UPSIT using Guilford's (1953) correction for nonindependence ranged from 0.812 to 0.871. Overall, these results indicate that (1) the UPSIT and its 10-, 20-, and 30-item fragments have very high ICRs and (2) individual UPSIT booklets or their combinations can be used to assess smell function in a reliable manner where extreme time constraints are present (e.g., in surveys and in brief neuropsychological test batteries).

Adult↗

Influence of nasal obstruction on smell function.

This article has reviewed studies that document a relationship between loss of smell function and disturbances in nasal airflow function. In some cases (for example, hypertrophied adenoids and nasal sinus disease), medical or surgical intervention appears to be useful in restoring some, if not all, of the smell loss associated with the disorder. In other cases (for example, septoplasty), empirical evidence of such efficacy is wanting. Given the current research interest on these topics, however, a clear understanding of both the positive and negative influences of surgical and medical interventions in most cases of obstructive nasal disease or malformities will be forthcoming.

Adenoidectomy↗

Effects of intrabulbar injections of 6-hydroxydopamine on ethyl acetate odor detection in castrate and non-castrate male rats.

The function of norepinephrine-containing neurons which project to the olfactory bulb is poorly understood. Although there has been suggestion that norepinephrine (NE) may modulate general olfactory sensitivity by attenuating the inhibitory feedback of granule cells upon mitral and tufted cells, behavioral indices of olfactory sensitivity have not been measured in animals with depletions of bulbar NE. The present experiment used computerized olfactometry and signal detection methodology to assess the odor detection performance of castrate and non-castrate male rats to a range of perithreshold concentrations of ethyl acetate following 6-hydroxydopamine (6-OHDA) depletion of bulbar NE. Such depletion had no significant influence on odor detection performance at any of the odorant concentrations examined in either castrate or non-castrate animals, as indexed by the non-parametric sensitivity measure SI. This observation implies that general olfactory sensitivity is unaltered by major depletion of intrabulbar NE, but does not preclude the possibility that NE modulates sensitivity to select odorants or odorant mixtures, or alters detection ability under atypical states of arousal.

Acetates↗

Olfactory sensitivity, nasal resistance, and autonomic function in patients with multiple chemical sensitivities.

A frequent, if not predominant, complaint of persons reporting symptoms of multiple chemical sensitivities (MCS) is that of heightened sensitivity to smells. In this study odor detection thresholds for phenyl ethyl alcohol (a major component of rose oil) and methyl ethyl ketone (a common solvent) were measured in 18 persons exhibiting symptoms of MCS and in 18 matched normal controls. In addition, nasal resistance, blood pressure, heart rate, and respiration rate were determined before and after the olfactory tests. Scores on the Beck Depression Inventory were obtained prior to testing. Although olfactory thresholds were equivalent in the two study groups, the MCS group evidenced significantly higher nasal resistances, respiration rates and Beck Depression Inventory scores. Decreases in systolic blood pressure and pulse were noted in both groups across the test sessions. These results do not support the hypothesis that MCS is associated with greater olfactory threshold sensitivity (at least to the two target chemicals), but do suggest that MCS is associated with depression, increased respiration rate, and decreased nasal airway patency.

Adult↗

Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration.

To explore the nature of the olfactory dysfunction associated with Parkinson's disease (PD), 81 PD patients who scored well on a cognitive screening test were administered the 40-odorant University of Pennsylvania Smell Identification Test; 38 were additionally given a forced-choice phenylethyl alcohol odor detection threshold test. Clinical ratings of 11 neurologic symptoms (three bilateral) were obtained at the time of testing, and odor identification was retested in 24 patients at intervals ranging from 5 to 39 months. Relative to matched controls, the PD patients exhibited consistent and marked decrements on both types of olfactory tests (ps less than 0.0001). The odor identification deficit was not restricted to any subset of odorants and did not evidence longitudinal change. A factor analysis of the intercorrelations among the variables yielded six easily interpretable factors: general motor, oral motor, olfactory function, cognitive function, tremor, and gender. Olfactory test scores were independent of all other measures, including disease stage and duration. Seventy-two percent of the PD patients were unaware of a smell disorder before testing; those who were aware had significantly lower test scores. A statistical comparison of PD patients' olfactory test scores to those obtained from Alzheimer's disease patients found the olfactory disorders of these diseases to be indistinguishable. The data support the hypothesis that the olfactory deficit of PD is a general and stable one which likely occurs early in the disease process.

Aged↗

Influence of body tilt within the sagittal plane on odor identification performance.

Odor identification performance, nasal airflow resistance, blood pressure, and heart rate were assessed in 8 men and 8 women in the following body tilt positions within the sagittal plane: 0 degree (upright), 90 degrees (supine), 135 degrees, and 180 degrees (upside down). The order of testing across the tilt conditions was systematically counterbalanced using a Latin square procedure. Average odor identification performance decreased monotonically as a function of increased body tilt. Significant decreases in heart rate and blood pressure were observed as the body was tilted from the upright condition, although blood pressure was equivalent in the upright and upside down conditions. Nasal resistance was highly variable and was not systematically altered as a function of body tilt. These data support the hypothesis that olfactory function, like visual, auditory, and vestibular function, is significantly influenced by body position within a gravitational field.

Adult↗