Biomedical subjects
Publications and source records attributed to R L Doty.
Odor identification was assessed in 20 Huntington's disease (HD) patients, 20 normal adults with the genetic mutation that causes HD, and 20 mutation-negative adults. The University of Pennsylvania Smell Identification Test (UPSIT) revealed substantial odor identification deficits only in HD patients.
The discovery of variably decreased olfactory ability in Type Ia pseudohypoparathyroidism (PHP), a syndrome in which generalized hormone resistance is associated with deficiency of the alpha chain of the stimulatory guanine nucleotide-binding protein (Gs alpha) of adenylyl cyclase, has been used to support the hypothesis that Gs alpha plays a major role in human olfactory transduction. However, only a limited number of olfactory tests have been administered to such patients, and these patients have other problems that might cause or contribute to their olfactory dysfunction, including an unusual constellation of skeletal and developmental deficits termed Albright hereditary osteodystrophy (AHO). In this study, we administered tests of odor detection, identification, and memory to (i) 13 patients with Type Ia PHP; (ii) 8 patients with Type Ib PHP; (iii) 7 patients with pseudopseudohypoparathyroidism (PPHP); and (iv) 3 sets of normal controls matched to these groups on the basis of age, gender, and smoking history. Although we confirm that PHP Type Ia patients evidence olfactory dysfunction, we also demonstrate that (i) patients with Type Ib PHP, who have no AHO, no generalized hormone resistance, and normal Gs alpha activity, also evidence olfactory dysfunction relative to matched controls; and (ii) patients with PPHP, who have AHO, no generalized hormone resistance, and deficient Gs alpha protein activity, have relatively normal olfactory function. These observations do not support the hypothesis that the olfactory dysfunction associated with PHP is the result of generalized Gs alpha protein deficiency and imply that other mechanisms (e.g. ones associated with PTH or PTHrP resistance) are responsible for the olfactory deficits of this disorder.
In Exp. 1, the "protheticity" of the pleasantness of a diverse set of relatively isointensive odorants was estimated using exponents from power functions fitted by an interative least squares procedure between scale values established by (a) magnitude estimation and (b) category rating and rank ordering. In Exp. 2, this procedure was applied to intensity data derived from quarter-log-step volume dilution series of two hedonically disparate odorants, furfural and methyl salicylate. The goodness of fit of the power functions was somewhat better for the intensity than for the pleasantness data. The pleasantness dimension of the diverse stimuli was slightly prothetic (respective category scaling and rank order/magnitude estimation exponents = 0.60 and 0.63). The intensity dimension of furfural was considerably more prothetic than that of methyl salicylate (respective category/magnitude estimation exponents = 0.20 and 0.68; respective rank order/magnitude exponents = 0.21 and 0.69). These data suggest that the degree of olfactory protheticity depends upon the stimuli as well as the attributes chosen for investigation and support the view that Stevens' metathetic/prothetic dichotomy has little utility in classifying the scaling attributes of odors. Whether the degree of protheticity reflects the nature or distribution of olfactory system receptive elements within the main olfactory pathway remains an empirical question which awaits a more specific understanding of the nature of olfactory coding at the level of the neuroepithelium.
Odor identification ability and detection threshold sensitivity were measured in 25 probands with Huntington's disease, 12 at-risk offspring, and 37 unrelated controls. Relative to controls and at-risk offspring, HD patients exhibited significant impairment on both measures of olfactory function. By contrast, at-risk offspring did not evidence any olfactory impairment relative to controls. Thus, impaired olfactory function does not aggregate in the family members of HD patients, and does not serve as an indicator of genetic vulnerability to the disorder.
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BACKGROUND: Dysgeusia, distortion of taste perception, is a debilitating disorder that affects thousands of Americans. Presently, most forms of dysgeusia are considered to be untreatable, and no data are available for counseling patients on the probability of recovery. OBJECTIVE: To examine the probability of resolution of symptoms among patients with dysgeusia who were evaluated at the University of Pennsylvania Smell and Taste Center, Philadelphia, from January 1989 to December 1994. DESIGN: In this retrospective study, 117 patients with primary complaints of dysgeusia were initially identified from a population of 429 patients with smell and taste disorders who were seen during this period. PARTICIPANTS: Forty-eight patients agreed to participate. Each patient completed a telephone interview and a questionnaire that contained a dysgeusia severity rating scale, medical health questions, and the Beck Depression Inventory. RESULTS: Two thirds of the patients experienced spontaneous resolution of the dysgeusia, with the average duration being 10 months. A distinct relationship between the resolution of dysgeusia and depression was identified. CONCLUSION: These findings, along with the evidence that some dysgeusias are treatable, bode well for a disorder that was heretofore considered by many physicians as unrelenting.
The influence of hypothyroidism on the odor detection ability of male Long-Evans rats was determined using high-precision olfactometry and a go/no-go operant task. Nonparametric signal detection measures of sensitivity and responsitivity, as well as measures of S+ response latency, the number of aborted trials, and session time were obtained in daily 200-trial test sessions prior to, during, and after 50 days of maintenance on 0.1% propylthiouracil (PTU). Similar determinations were made in control animals. Neither odor detection nor associated nonsensory performance measures were influenced by hypothyroidism. These results suggest that PTU-induced hypothyroidism does not affect the odor detection performance of rats.
The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT), is described. In developing this test, the authors initially selected UPSIT items that are familiar to most persons from North American, European, South American, and Asian cultures. The CC-SIT was then administered to 198 people ranging in age from 5 to 96 years, and the the test scores were compared to analogous items from UPSITs administered to 198 age-, sex-, race-, and smoking-habit-matched control subjects. Since the pattern of test scores did not differ for the two groups, the authors developed normative data for the 12-item test using equivalent UPSIT items sampled from a database containing UPSIT scores for 3760 subjects. Norms are provided for determining the percentile ranks of a given patient's score as a function of age and gender. The CC-SIT provides, for the first time, a self-administered means for reliably assessing olfactory function in less than 5 minutes.
Decreased ability to smell is present in adults with Down's syndrome, many of whom are known to have brain pathology analogous to that seen in Alzheimer's disease. Because olfactory loss is well documented in Alzheimer's disease, the question arises whether young adolescents with Down's syndrome, who have no clear Alzheimer's disease-like neuropathology, also exhibit olfactory dysfunction. To consider this issue, standardised tests of odour discrimination and identification were administered to 20 young adolescents with Down's syndrome (mean age (SD) 13.89 (1.98) years) and their test scores were compared with 20 mentally retarded and 20 non-mentally retarded control subjects matched to the patients with Down's syndrome on the basis of cognitive ability. No significant differences in olfactory function were found among the three study groups. These findings, along with those from studies of olfactory function in older patients with Down's syndrome, suggest that Down's syndrome related olfactory dysfunction occurs only at ages when Alzheimer's disease-like pathology is present.
OBJECTIVE: The purpose of this study was to evaluate patients with reduced or no sense of smell since birth for sites of abnormality by MR imaging. MATERIALS AND METHODS: Twenty-five patients who reported no olfactory function since birth were evaluated by olfactory testing, sinonasal endoscopy, and MR imaging. Surface coil and head coil images of the olfactory bulbs, olfactory tracts, subfrontal cortex, and temporal lobes in contiguous 3-mm sections were obtained. Two reviewers determined unilateral olfactory bulb and tract volumes and temporal lobe volumes in two separate sessions. Qualitative grading for olfactory bulb, olfactory tract, olfactory sulcus, subfrontal region, hippocampus, and temporal lobe damage also was performed. RESULTS: The absence of olfactory bulbs and tracts (68-84%) or the presence of hypoplasia (16-32%) was noted in all cases. Eight individuals had Kallmann's syndrome (hypogonadotropic hypogonadism with anosmia). Temporal and/or frontal lobe volume loss was noted in five individuals and was mild in all but one individual. CONCLUSION: Congenital anosmia or hyposmia appears to be an olfactory bulb-olfactory tract phenomenon rather than a cerebral process.
Although detection thresholds for odors are commonly measured in academic and medical settings, the influences of procedural factors on threshold values are poorly understood. The present study evaluated the influences of (i) trial sequence position and (ii) diluent type on the threshold value for the rose-like odorant phenyl ethyl alcohol. In Exp. 1, detection thresholds were measured in 24 subjects on two occasions in which different diluents were used in the concentration series, propylene glycol and light mineral oil. The thresholds were estimated using a 7-reversal initially ascending single-staircase procedure. Threshold values were significantly influenced by the type of diluent (lower for mineral oil) and trial sequence (lower for later threshold reversals). In Exp. 2, 24 subjects were administered a staircase threshold test which continued through 15 staircase reversals. Continued testing resulted in a significant lowering of the threshold measure. These findings demonstrate the importance of both diluent and test length on detection threshold values measured by a single staircase procedure and emphasize the need for standardization of procedures for threshold testing.
Fifty-five eating-disordered women and 16 normal controls participated in this study to determine whether olfactory function is altered in patients with food-restricting anorexia, anorexia with bulimic features, and bulimia nervosa. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test and by determining phenyl ethyl alcohol odor detection thresholds. Only the very low-weight anorexics showed impairments in their identification and detection of odors. This group's olfactory function did not improve from admission to discharge despite significant weight gain. Although, overall, smoking had only a minor influence on olfactory function, the very low-weight anorexic smokers had the lowest scores of all subjects. Since higher-weight anorexics did not show such impairments, the results suggest that the severe and prolonged starvation experienced by the very low-weight anorexics caused or contributed to intractable deficits in the olfactory system and that these deficits are compounded by smoking.
Since olfactory dysfunction is among the first signs of idiopathic Parkinson's disease (PD), olfactory testing may aid in the early of 'preclinical' diagnosis of this disorder. Indeed, the proportion of early-stage PD patients with olfactory dysfunction appears to be greater than the proportion of early-stage PD patients exhibiting some of the cardinal signs of PD. Because olfactory function varies in the general population and declines with age, empirically-based criteria are needed by the clinician to establish whether the degree of olfactory loss observed in a given patient is concordant with the presence of PD. In this study, we present cutoff criteria for the optimal assessment of olfactory dysfunction in the evaluation of PD. Specifically, we present scores for the University of Pennsylvania Smell Identification Test (UPSIT) that best discriminate between PD patients and age-matched controls. Receiver operating characteristic (ROC) curves, based upon sensitivity and specificity estimates, were computed for three age groups (< or = 60 yrs, 61-70 yrs, and > or = 71 yrs) and scores with highest sensitivity and specificity were determined. Sex- and age-related differences in the test scores were observed, with lower scores occurring for men and for the older patient groups.
Two odor memory tests were administered unilaterally (left and right) and bilaterally to the same set of 24 men and 24 women on two test occasions. These tests were (i) a "multiple-target" test (MTT) in which three target stimuli were selected, after 10-, 30-, and 60-sec retention intervals, from stimulus sets containing both target and distracter stimuli, and (ii) a 9-item "single-target" three-choice test (STT), in which single stimuli were selected from stimuli sets containing two distracters. Overall, odor memory scores were higher under bilateral than unilateral testing, and higher on the second than on the first test session. Unilateral testing resulted in a monotonic delay-related forgetting function. No differences were observed in the odor memory test scores of the left and right sides of the nose, and no significant correlations were present between these scores and scores on a battery non-olfactory memory tests. On the STT, the female, but not the male, subjects demonstrated better performance on the second, than on the first, test session. The results of this study imply that odor memory is facilitated centrally by bilateral activation, and that a memory system may exist for odors which is distinct from other memory systems.
Using a signal detection procedure and a microprocessor-controlled gustometer, sensitivity to three concentrations of NaCl (0.01, 0.1 and 1.0 M) was measured on the tongue tip, and on a region 3.0 cm posterior to the tongue tip in 12 young (20-29 years of age) and 12 elderly (70-79 years of age) subjects. Stimulus duration was 2 s; the sizes of the tongue areas stimulated were 12.5, 25 and 50 mm2. On average, the young subjects were more sensitive to NaCl on the tongue tip than on the more posterior stimulation site and exhibited, at both tongue loci, an increase in detection performance as stimulus concentration increased. The elderly subjects, on the other hand, performed at chance level at both tongue loci for all three stimulus sizes and concentrations tested. No sex differences were observed. In the young subjects, the mean R-index increased monotonically as a function of stimulus size for the two highest NaCl concentrations at both tongue loci. A hyperbolic function provided the best fit to these data at the tongue tip, and an exponential function at the more posterior tongue region, implying a different pattern of spatial summation at these two sites. Overall, this study demonstrates that marked age-related changes in regional taste sensitivity to NaCl are present in elderly persons.
Ten tests of olfactory function (including tests of odor identification, detection, discrimination, memory, and suprathreshold odor intensity and pleasantness perception) were administered on two test occasions to 57 subjects ranging in age from 18 to 83 years. The stability of the average test scores was determined across the two test sessions for 14 measures derived from these 10 tests and for subcomponents of the Japanese T&T olfactometer threshold test. In addition, the test-retest reliability (Pearson r) of each test measure was established. With the exception of a response bias measure, the average test scores did not differ significantly across the two test sessions. Statistically, the reliability coefficients of the primary test measures fell into three general classes bound by the following r values: 0.43-0.53; 0.67-0.71; 0.76-0.90. Detection threshold values were more reliable than recognition threshold values; those based upon a single ascending presentation series were much less reliable than those based upon a staircase procedure. The relationship between test length and reliability was examined for several of the tests and mathematically modeled. For example, within the staircase series incorporating the odorant phenyl ethyl alcohol, reliability was related (R2 = 0.984) to the number of reversals included in the threshold estimate by a function derived from the Spearman-Brown formula; namely, reliability = 0.455* # reversals/[1 + 0.455 (# reversals - 1)]. Reversal location, per se, had little influence on reliability. Overall, this study suggests that (i) considerable variation is present in the reliability of olfactory tests, (ii) reliability is a function of test length, and (iii) caution is warranted in comparing results from nominally different olfactory tests in applied settings since the findings may, in some instances, simply reflect the differential reliability of the tests.
Olfactory auras accompany some cases of epilepsy. Several aspects of olfactory function, including sensitivity, also may be altered. We reviewed the literature on these topics, as well as studies evaluating the influences of temporal lobe resection and other seizure management procedures on olfactory function. We concluded that: (a) despite several studies, the prevalence of olfactory auras in epilepsy is unknown, with estimates ranging from < 1% to > 30%; (b) epilepsy appears to cause a generalized decrease in olfactory functioning, although increased sensitivity may occur in some epileptic patients at some time in the preictal period; (c) other sensory modalities are also affected by the epileptic process which, in some cases, involve limbic-related temporal lobe structures; (d) many of the olfactory deficits previously attributed to temporal lobe resection actually exist preoperatively; (e) a taste/flavor confusion exists in the reporting of taste auras; (f) unpleasant auras are associated with hyperresponsiveness of neurons, which may explain why most epilepsy-related olfactory auras are described as "bad"; and (g) interesting parallels exist between the effects of the neuroendocrine system on seizure activity and olfactory function.
17 beta-Estradiol (E2) can serve as a potent unconditioned stimulus in producing a conditioned taste aversion to saccharin in rats, with the effect being greater in males than in females. To determine whether the female's lower susceptibility to such conditioning is due, in part, to early experience with estrogen, we performed the following experiment. First, we pretreated groups of prepubertally ovariectomized female rats with either sesame oil (control group) or low doses of E2 (0.3, 0.75, or 1.50 microgram). Second, in subsequent conditioning sessions, we presented a 0.2% saccharin solution to the rats prior to the injection of 100 micrograms of E2 (the unconditioned stimulus). Third, we tested the magnitude of the conditioned aversion to the saccharin solution and its tendency to extinguish during the following week. The E2-pretreated animals evidenced significantly weaker taste aversions and extinguished them more rapidly than did the oil-pretreated controls, even at the lowest E2 pretreatment dose, suggesting that prior experience with low levels of estrogen can significantly mitigate, in female rats, the magnitude of a conditioned taste aversion produced by a high dose of estrogen.