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Biomedical subjects

Richard L Doty

Publications and source records attributed to Richard L Doty.

At least 19 recordsLinked to original sources

Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders.

BACKGROUND: Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. METHODS: Confined space welding in construction of a new span of the San Francisco-Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose-effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. RESULTS: The mean time weighted average of Mn-air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose-effect relationships with CEI and/or MnB were found for IQ (p<or=0.05), executive function (p<or=0.03), sustaining concentration and sequencing (p<or=0.04), verbal learning (p<or=0.01), working (p<or=0.04) and immediate memory (p<or=0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose-effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant. CONCLUSIONS: Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.

Adult↗

Olfactory dysfunction and its measurement in the clinic and workplace.

OBJECTIVES: To provide an overview of practical means for quantitatively assessing the sense of smell in both the clinic and workplace. To address basic measurement issues, including those of test sensitivity, specificity, and reliability. To describe and discuss factors that influence olfactory function, including airborne toxins commonly found in industrial settings. METHODS: Selective review and discussion. RESULTS: A number of well-validated practical threshold and suprathreshold tests are available for assessing smell function. The reliability, sensitivity, and specificity of such techniques vary, being influenced by such factors as test length and type. Numerous subject factors, including age, sex, health, medications, and exposure to environmental toxins, particularly heavy metals, influence the ability to smell. CONCLUSIONS: Modern advances in technology, in conjunction with better occupational medicine practices, now make it possible to reliably monitor and limit occupational exposures to hazardous chemicals and their potential adverse influences on the sense of smell. Quantitative olfactory testing is critical to establish the presence or absence of such adverse influences, as well as to (a) detect malingering, (b) establish disability compensation, and (c) monitor function over time.

Air Pollutants, Occupational↗

Olfactory functioning in schizophrenia: relationship to clinical, neuropsychological, and volumetric MRI measures.

Deficits in odor identification and detection threshold sensitivity have been observed in schizophrenia but their relationship to clinical, cognitive, and biologic measures have not been clearly established. Our objectives were to examine the relationship between measures of odor identification and detection threshold sensitivity and clinical, neuropsychological, and anatomic brain measures. Twenty-one patients with schizophrenia and 20 healthy controls were administered psychophysical tests of odor identification and detection threshold sensitivity to phenyl ethyl alcohol. In addition, clinical symptom ratings, neuropsychological measures of frontal and temporal lobe function and whole brain MRIs were concurrently obtained. Patients exhibited significant deficits in odor identification but normal detection threshold sensitivity. Poorer odor identification scores were associated with longer duration of illness, increased negative and disorganized symptoms, and the deficit syndrome, as well as impairments in verbal and nonverbal memory. Better odor detection thresholds were specifically associated with first-rank or productive symptoms. Larger left temporal lobe volumes with MRI were associated with better odor identification in controls but not in patients. Given the relevance of the neural substrate, and the evidence of performance deficits, psychophysical probes of the integrity of the olfactory system hold special promise for illuminating aspects of the neurobiology underlying schizophrenia.

Adult↗

Olfactory dysfunction in leprosy.

Leprosy (Hansen's disease) is associated with a high incidence of nasal pathology. Despite this fact, the influence of this disorder on the sense of smell is poorly understood. In this study, we administered a standardized 12-item odor identification test to 77 patients with three types of leprosy: tuberculoid (n = 9), borderline (n = 42), and lepromatous (n = 26). All three types exhibited significantly lower test scores than their respective age-, sex-, and smoking-habit-matched controls. Patients with lepromatous leprosy exhibited significantly lower test scores than those with the other two types. Only patients with lepromatous leprosy exhibited meaningful improvement in smell function after treatment. No association between disease duration, per se, and the severity of the olfactory deficit was present. Overall, 100% of the patients exhibited olfactory dysfunction, suggesting that earlier prevalence estimates based on nonstandardized olfactory testing have underestimated the prevalence of this problem.

Adult↗

Antifreeze ingestion by dogs and rats: influence of stimulus concentration.

Ingestive responses of 50 rats and 4 gastric-cannulated dogs to ethylene glycol-based antifreeze (AF) were found to be inversely related to concentration. The antifreeze was never preferred to water. Do thirsty animals that encounter weak AF solutions drink them solely for their water content, water-related oral tactile sensations, or both, being inadvertently poisoned in the process?

Animals↗

Episodic odor memory: influences of handedness, sex, and side of nose.

It is not known whether, or to what degree, odor memory is influenced by lateralized brain processes. In this study, we administered a 12-item match-to-sample odor memory test separately to the left and right sides of the nose of 30 left- and 30 right-handed subjects of equivalent age, sex distribution, and overall general smell ability. For each test item, one of three delay intervals (10-, 30-, and 60-s) was interspersed between smelling the target stimulus and smelling the first of four response alternatives. Women, but not men, performed significantly better on the left than on the right side of the nose, conceivably reflecting greater reliance upon left-hemisphere semantic processes. Subjects who received the first test on the right side of the nose outperformed those who received the first test on the left side of the nose. As in previous work, an age-related decrement in odor memory test scores was present. These data contribute to the debate on the role of lateralized brain processes in episodic odor memory, and suggest that performance on a standardized match-to-sample odor memory task is influenced by a number of interacting factors.

Adult↗

A 10-item smell identification scale related to risk for Alzheimer's disease.

University of Pennsylvania Smell Identification Test data from control subjects (n = 63), patients with mild cognitive impairment (n = 147), and patients with Alzheimer's disease (n = 100) were analyzed to derive an optimal subset of items related to risk for Alzheimer's disease (ie, healthy through mild cognitive impairment to early and moderate disease stages). The derived 10-item scale performed comparably with the University of Pennsylvania Smell Identification Test in classifying subjects, and it strongly predicted conversion to Alzheimer's disease on follow-up evaluation in patients with mild cognitive impairment. Independent replication is needed to validate these findings.

Aged↗

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably reduced or absent CNS sedative effects. Therefore, the CNS effects are entirely avoidable, and the first-generation H 1 -antihistamines should no longer be used in the management of allergic rhinitis. The considerably rarer but potentially very serious cardiac arrhythmogenic effects of H 1 -antihistamines are appreciated to be molecule-specific rather than class-specific. The in vitro screening of new compounds to eliminate the further development of those with cardiotoxicity ideally will lead to this adverse effect being historic. The incorporation of electrocardiogram recording in clinical trials provides direct information relating to prolongation of QT interval corrected for heart rate. Although administered at low doses, intranasal steroids still have the potential for systemic absorption and adverse consequences. However, it is appreciated that meaningful differences exist in the bioavailability of different steroid molecules, and although a small but statistically significant effect on growth in children has been identified with the long-term use of intranasal beclomethasone when administered twice daily for 1 year, this is not evident with all intranasal steroids. In addition, twice-daily intranasal steroid administration may have more effect--from the endocrinologic perspective--than once-daily administration in the morning, which coincides better with the natural diurnal variation in cortisol. Thus, once-daily intranasal steroid administration is preferable, and when used in studies in children, measurement of height change during the study period is an important outcome variable together with other indices of systemic steroid bioavailability (eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations have even greater relevance if children are concurrently also receiving inhaled steroids for asthma, because the total steroid load will be greater.

Anti-Allergic Agents↗

Electrical taste thresholds established on the medial tongue using two sizes of electrodes.

OBJECTIVES/HYPOTHESIS: The present study determined whether a 125 mm electrode would produce lower and more reliable electrical taste thresholds than a 25 mm electrode when measurement occurred in a medial tongue region relatively sparse in taste bud numbers. We hypothesized this would be the case and that the obtained threshold values would be higher than those previously reported for anterior and lateral tongue regions. STUDY DESIGN AND METHODS: Sixteen college-age subjects were tested twice, once using the 25 mm electrode and once using the 125 mm electrode on each of two sessions separated by 2 to 16 days. The order of presentation of the sessions was counterbalanced across subjects. Measurement was confined to the medial tongue, 0.7 cm lateral to the median furrow. RESULTS: As hypothesized, the larger electrode resulted in lower and more reliable threshold values than the smaller electrode (respective median threshold values = 20.06 microA & 33.59 microA, P = .001; respective test-retest rs = 0.78 [P < .001] and 0.46 [P < .05]). Also as hypothesized, the threshold values were higher (i.e., sensitivity lower) than previously reported for anterior and lateral tongue regions. CONCLUSIONS: The magnitude and reliability of electrical taste thresholds depends on the tongue region examined and the size of the electrodes used. These results suggest that relatively large electrodes should be considered for electrogustometric threshold testing, particularly when lingual regions not highly populated with taste buds are evaluated.

Adult↗

Objective assessment of terbinafine-induced taste loss.

OBJECTIVES: Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so-called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole-mouth testing of a single subject, found no terbinafine-related deficit. In this study, we quantitatively assessed, using well-validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age-, race-, and sex-matched normal controls. METHODS: Taste function was measured using a 96-trial regional test that assesses sweet, sour, bitter, and salty taste perception within the anterior (cranial nerve [CN] VII) and posterior (CN IX) lingual taste bud fields. Smell function was bilaterally evaluated using the 40-item University of Pennsylvania Smell Identification Test. RESULTS: Taste function for sweet-, sour-, and bitter-tasting stimuli was significantly depressed in both the anterior and posterior lingual regions. For sodium chloride, the decrements were confined to the posterior region. Olfactory function was within normal limits. CONCLUSION: These findings 1) support anecdotal case reports of taste loss after terbinafine use, 2) demonstrate that all four major taste qualities are affected, and 3) suggest that olfactory dysfunction is not involved. Because self-report markedly underestimates chemosensory deficits, more extensive quantitative testing of patients receiving terbinafine will likely reveal a much higher prevalence of terbinafine-induced taste loss than currently reported. Since being older than 65 years of age and having a low body mass index are reportedly risk factors for terbinafine-induced taste loss, physicians should be particularly on the alert for elderly persons taking this medication who may become depressed or alter their food intake in response to decreased taste sensation.

Adult↗

Utility of a three-item smell identification test in detecting olfactory dysfunction.

OBJECTIVE: Physicians rarely assess smell function, largely because of time considerations. Therefore, there is clinical need for very brief cranial nerve I screening tests. Although a few such tests exist, none have been adequately validated. The goal of this study was to empirically assess the utility of a three-item microencapsulated odor identification test in detecting olfactory dysfunction. SETTING: Smell and taste center at a university medical center. METHODS: The test was administered to 224 consecutive patients (98 men and 126 women ranging in age from 15-88 years). As part of their overall assessment, the well-validated 40-item University of Pennsylvania Smell Identification Test (UPSIT) was also administered. Sensitivity, specificity, and both negative and positive predictive values of the three-item test were established relative to UPSIT dysfunction categories. Test-retest reliability was determined in a subset of 39 patients. RESULTS: The three-item test was abnormal in 99% (67/68) of patients with anosmia, 85% (35/41) of those with severe microsmia, 76% (31/41) of those with moderate microsmia, and 50% (17/34) of those with mild microsmia. Of the 40 normosmic patients, 62.5% (25/40) correctly identified all odors, 25% (10/40) two odors, and 12.5% (5/40) one odor. None of the normosmic patients missed all three items. Using a cut-off score of 2, the test's sensitivity and specificity were 99% and 40%, respectively, for detecting total anosmia. The corresponding negative and positive predictive values were 98% and 43%. For detecting anosmia and severe microsmia, these values were 93%, 45%, 88%, and 63%. For detecting any olfactory pathology, they were 82%, 63%, 42%, and 91%. The test-retest reliability was 0.87. CONCLUSION: The brief three-item test used in this study was found to be highly sensitive in identifying olfactory loss in patients with chemosensory complaints, particularly those with severe dysfunction. Although only moderately specific, its high reliability and negative predictive value suggests it may be an appropriate screening test for olfactory loss.

Adolescent↗

A ChemoSensory questionnaire for patients treated for cancer of the head and neck.

OBJECTIVES: To investigate primary chemosensory issues experienced by patients who undergo treatment for cancer of the head and neck and to develop and assess a ChemoSensory Questionnaire (CSQ). DESIGN: Cross sectional survey for questionnaire development and testing. METHODS: Literature, expert opinion, and focus group methodology were used to identify aspects of smell and taste affecting patients before, during, and after therapy for cancer of the head and neck. A draft instrument was compiled, reviewed, and revised. The revised instrument was administered along with a demographic and clinical form, the SF-12, the Performance Status Survey, and the University of Michigan Head and Neck Quality of Life Questionnaire (HRQOL) to a sample of patients. After item and scale analyses and reductions, a final instrument was assembled. Construct validity and test-retest reliability were assessed. RESULTS: Two hundred six patients were included in the study. The final survey instrument consisted of eight items, four on smell and four on taste. Cronbach's alpha was 0.89 for the smell scale and 0.78 for the taste scale. Correlations with other HRQOL scales ranged from 0.20 to 0.64 for the taste scale and from 0.10 to 0.33 for the smell scale. Good construct validity of the CSQ scores was demonstrated. CONCLUSIONS: Treatment for head and neck cancer negatively impacts smell and taste. A survey instrument was developed to evaluate chemosensory function that is simple to administer and is brief. This instrument will be of value in identifying factors that contribute to chemosensory disturbance and may serve as a guide for planning treatment regimens that minimize such disturbance.

Aged↗

Odors and the perception of hygiene.

Although certain odors, such as lemon, are commonly associated with cleanliness and positive hygiene, empirical assessment of such associations for other odors and attributes is generally lacking. Moreover, differences between men and women in such associations have not been established. In this study of lemon, onion, pine, and smoke odors, ratings were obtained from 142 men and 336 women (M age= 30.1 yr., SD = 12.3) for odor intensity, gender association (masculine/feminine), and the success, sociability, intelligence, cleanliness, and attractiveness of a hypothetical person whose clothes smell like the odor in question. Ratings of the pleasantness or unpleasantness one would attribute to each odor in various rooms of the home were obtained, as well as a specification of whether such ratings are influenced by laundry habits, e.g., whether laundry is smelled before or after washing. Numerous associations were found. For example, a hypothetical person whose clothes smell of pine was rated as relatively more successful, intelligent, sociable, sanitary, and attractive than one whose clothes smelled of lemon, onion, or smoke. Sex differences, as well as differences between people who reported smelling their own laundry, were also found.

Adult↗

Olfactory dysfunction occurs in transgenic mice overexpressing human tau protein.

Disorders of olfaction are among the first clinical signs of neurodegenerative diseases such as Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD). In this study, we employed an odor habituation paradigm to evaluate the olfactory function of T alpha 1-3RT transgenic mice that overexpress tau, a key pathogenic protein in AD, and compared such function to that of wild-type controls who do not overexpress this protein. The T alpha 1-3RT mice, but not the controls, exhibited responses indicative of decreased olfactory function. These data lend support to the notion that tau may be involved in the pathogenesis of the olfactory dysfunction of some neurodegenerative diseases. Future studies need to similarly assess other pathogenic markers, as well as their distribution within various sectors of the brain, to determine the specificity of this phenomenon.

Animals↗

Effects of drugs on olfaction and taste.

The fact that so many varied medications reportedly affect taste and smell is a testament to the complexity of the gustatory and olfactory systems. The reception, transduction, propagation, and perception of a chemical tastant or odorant requires the effective operation of numerous mechanisms--all of which may be susceptible in one way or another to a prescribed medication. Just as a diuretic may block the apical ion channels on a taste bud, or an antifungal can inhibit cytochrome p450-dependent enzymes at the level of the receptors, a chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a steroid can lead to candidal overgrowth on the tongue surface. Medications not only have a perceivable taste themselves at times, but they can alter the mechanisms responsible for the ultimate perception of tastes and smells--either by direct or secondary means. It should be emphasized, as noted earlier in this article, that while many medications are to blame for the impairment or distortion of the gustatory or olfactory systems, it is not uncommon that the underlying medical problem for which they are prescribed is actually the culprit. Examples include epilepsy, migraines, hypothyroidism, schizophrenia, infections, and cancer. In fact, simple partial seizures emanating from regions of the brain such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can lead to the chemosensory sensations that are most commonly considered unpleasant, such as "rotten apples," "cigarette," "peculiar," or "vomitus". While removing or changing an offending medication can reverse the effects on smell or taste perception, it is important to remember that lasting impairment may occur. This is vital for a physician to recognize prior to prescribing a medication. It is also necessary to report this to patients who may be devastated by chemosensory alterations after starting a new medication (eg, pastry chef, perfumist, wine specialist, plumber). Among the "risks" in a risks/benefits discussion with a patient regarding the use of a new medication, alterations in olfaction and taste appear to play an increasingly recognized role.

Drug-Related Side Effects and Adverse Reactions↗

Effects of stimulation duration on electrogustometric thresholds.

The ability to detect low electrical currents presented to the lingual surface is widely used to assess taste function in humans. Despite this fact, the influence of stimulus duration on electrical taste thresholds is not well established. In this study, we evaluated the effects of current duration (0.5, 1.0, and 1.5 s) on electrogustometric detection thresholds for two regions of the anterior tongue in 24 college students. Anodal stimulation was produced using a stainless steel 12.5-mm(2) electrode, and thresholds were determined using a single-staircase procedure. A non-monotonic function for the threshold values was observed for both tongue regions across the stimulus durations, with the 1.0-s duration stimulus resulting in a lower threshold value (i.e., higher sensitivity) than either the 0.5- or 1.5-s durations, which did not differ in magnitude from one another. These data suggest that stimulus-duration-related enhancement of lingual detection threshold sensitivity to electric currents disappears at some point after 1 s.

Adolescent↗