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Biomedical subjects

D A Leopold

Publications and source records attributed to D A Leopold.

At least 19 recordsLinked to original sources
PubMed2004

Pathology of the olfactory epithelium: smoking and ethanol exposure.

OBJECTIVE: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis. STUDY DESIGN: A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke. METHODS: Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis. RESULTS: Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage. CONCLUSIONS: These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium.

Animals↗
PubMed2003

Clinical presentation of qualitative olfactory dysfunction.

Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called "troposmia") or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis.

Adult↗
PubMed2003

The relationship between agricultural environments and olfactory dysfunction.

OBJECTIVES: To examine the olfactory ability of farmers and identify exposures in agricultural environments associated with olfactory loss. STUDY DESIGN: Cross-sectional. METHODS: 405 individuals (214 males and 191 females) completed a questionnaire assessing agricultural exposures, health status, and olfactory history. Participants then completed a scratch-and-sniff 12-item odor identification test. Data analysis was conducted using the method of least squares to fit general linear models. Equality of outcome measures (the number of correctly identified odorants) between groups was evaluated using the Wilcoxon rank sum test. Differences were considered to be significant at the 0.05 level. RESULTS: Approximately 80% of participants reported active participation in farm work. Farmers correctly identified an average of 9.3 of 12 odorants, compared to 10.1 of 12 correctly identified by non-farmers, a difference that was not statistically significant (p = 0.2). Participants reporting sneezing after handling soybeans, wheat, or oats scored significantly lower than those without symptoms. There were suggestive associations between olfactory ability and exposure to anhydrous ammonia, history of wheezing and asthma, and a history of flu-like illness after farm work. CONCLUSIONS: Results indicate that, in general, farming is not associated with olfactory loss. However, we identified certain groups of farmers with inflammatory-type reactions who appeared to be susceptible to olfactory loss. The association between inflammatory reactions or conditions and olfactory loss is a novel finding.

Adolescent↗
PubMed2001

Prototype-referenced shape encoding revealed by high-level aftereffects.

We used high-level configural aftereffects induced by adaptation to realistic faces to investigate visual representations underlying complex pattern perception. We found that exposure to an individual face for a few seconds generated a significant and precise bias in the subsequent perception of face identity. In the context of a computationally derived 'face space,' adaptation specifically shifted perception along a trajectory passing through the adapting and average faces, selectively facilitating recognition of a test face lying on this trajectory and impairing recognition of other faces. The results suggest that the encoding of faces and other complex patterns draws upon contrastive neural mechanisms that reference the central tendency of the stimulus category.

Adaptation, Physiological↗
PubMed2001

Dynamic assessment of paranasal sinus ventilation using xenon-enhanced computed tomography.

Disease of the paranasal sinuses is a common and costly condition. Evaluation of the efficacy of either medical or surgical methods of treatment is limited by the lack of quantitative methods to characterize sinus ventilation, which may be an important determinant of the baseline physiological state of the sinuses. Xenon-enhanced computed tomography (Xe-CT) measurement of sinus ventilation provides a noninvasive method of quantifying maxillary sinus ventilation using the nonradioactive, radiodense gas Xe as a tracer. Study subjects breathed a mixture of Xe gas and oxygen through a close-fitting nasal mask during serial CT imaging of a single radiographic plane through the maxillary sinuses--a generally well-tolerated protocol. Analysis of the sinus density-time curves allowed calculation of first-order exponential time constants from which specific ventilation rates could be determined for individual sinuses. Previously developed data analysis techniques were used to assess the statistical significance of the data and determine confidence intervals, allowing examination of the effects of noise in the data, and to demonstrate areas for further study protocol refinement. We conclude that Xe-CT measurement of sinus ventilation is a potentially valuable noninvasive technique for the diagnostic imaging of the human maxillary sinus.

Humans↗
PubMed2001

Effect of nasal dilators on nasal structures, sniffing strategies, and olfactory ability.

This paper describes the effects that nasal dilators have on olfactory ability. Experimental results demonstrate that nasal dilators increase odorant identification, lower odorant threshold, and increase perceptual odorant intensity. In other experiments, magnetic resonance imaging (MRI) data demonstrates that the size of the nasal cavity especially around the region of the nasal valve is increased when nasal dilators are worn. Additionally, pneumotachograph data demonstrates that during a sniff, the peak flow, maximum flow rate, volume, and duration are all increased when nasal dilators are worn. Taken together, the increase in olfactory ability can most easily be explained by an increase in both the amount and the proportion of inspired odorant molecules that are directed to the olfactory mucosa and are, therefore, available for odorant perception.

Adult↗
PubMed2000

Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.

CONTEXT: Chronic rhinosinusitis (CRS) is a common condition in the US general population, yet little is known about its underlying molecular cause. Chronic rhinosinusitis is a consistent feature of the autosomal recessive disorder cystic fibrosis (CF). OBJECTIVE: To determine whether mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which is responsible for CF, predispose to CRS. DESIGN: Case-control study conducted from 1996 to 1999 in which the DNA of CRS patients and controls was typed for 16 mutations that account for 85% of CF alleles in the general population. Chronic rhinosinusitis patients with 1 CF mutation were evaluated for a CF diagnosis by sweat chloride testing, nasal potential difference measurement, and DNA analysis for additional mutations. SETTING: Otolaryngology-head and neck clinic of a US teaching hospital. PARTICIPANTS: One hundred forty-seven consecutive adult white patients who met stringent diagnostic criteria for CRS and 123 CRS-free white control volunteers of similar age range, geographic region, and socioeconomic status. MAIN OUTCOME MEASURES: Presence of CF mutations by DNA analysis among CRS patients vs controls. RESULTS: Eleven CRS patients were found to have a CF mutation (DeltaF508, n = 9; G542X, n = 1; and N1303K, n = 1). Diagnostic testing excluded CF in 10 of these patients and led to CF diagnosis in 1. Excluding this patient from the analyses, the proportion of CRS patients who were found to have a CF mutation (7%) was significantly higher than in the control group (n = 2 [2%]; P =.04, both having DeltaF508 mutations). Furthermore, 9 of the 10 CF carriers had the polymorphism M470V, and M470V homozygotes were overrepresented in the remaining 136 CRS patients (P =.03). CONCLUSION: These data indicate that mutations in the gene responsible for CF may be associated with the development of CRS in the general population. JAMA. 2000;284:1814-1819.

Adult↗
PubMed2000

Anterior distribution of human olfactory epithelium.

OBJECTIVES/HYPOTHESIS: To functionally investigate the distribution of the olfactory epithelium in humans by means of the electro-olfactogram (EOG) and anatomically located biopsy specimens. STUDY DESIGN: Prospective, nonrandomized, investigational. METHODS: Supra-threshold EOG recordings were made on 12 healthy, trained volunteers (6 women, 6 men; age range, 21-48 y). Vanillin was used as the stimulus, since it exclusively excites olfactory receptor neurons. The EOG was recorded with tubular electrodes that were placed using thin-fiber endoscopic guidance. Biopsy specimens were obtained of anterosuperior nasal cavity mucosa in the same regions as the positive EOGs in 15 smell-tested patients (7 women, 8 men; age range, 22-60 y) during routine nasal and sinus surgery. This biopsied tissue was histologically processed and stained for olfactory and neural proteins. RESULTS: Viable responses to EOG testing were obtained in 7 of 12 subjects. In these seven subjects it was possible to identify nine sites above or below the anterior middle turbinate insertion where EOGs were obtained. The biopsy results showed mature olfactory receptor neurons in this same area. CONCLUSIONS: Human olfactory epithelium appears to be distributed more anteriorly than previously assumed.

Adult↗
PubMed1999

Relationship between uninasal anatomy and uninasal olfactory ability.

OBJECTIVE: To examine the relationship between uninasal anatomy and olfactory ability. DESIGN: A stepwise analysis of variance was used to regress the logarithm of the percentage of correct responses on the Odorant Confusion Matrix (a measure of olfactory ability) against the logarithm of nasal volume measurements determined from computed tomographic scans. PARTICIPANTS: Nineteen patients with hyposmia whose olfactory losses were thought to be related to conductive disorders. RESULTS: After correcting for sex differences, a mathematical model was developed in which the volume of 6 regions of the nasal cavity, 6 first-order interactions, and 3 second-order interactions accounted for 97% of the variation in the measure of olfactory ability. CONCLUSIONS: Increases in the size of compartments of the nasal cavity around the olfactory cleft generally increase olfactory ability. Also, anatomical differences in the nasal cavities of men and women may account, in part, for sex differences in olfactory ability.

Adult↗
PubMed1999

Disorders of smell and taste.

As with almost any aspect of medical practice, a thorough history and physical examination coupled with a good understanding of the anatomy and physiology of an organ system are the key factors in reaching a diagnosis. The information in this article is provided to assist the internist with the diagnosis of chemosensory disorders and the differentiation of malingering or other disease process as well as providing insight into the workup, prognosis, and treatment of patients with taste and smell disorders.

Diagnosis, Differential↗
PubMed1999

Sinus mucosal IL-8 gene expression in chronic rhinosinusitis.

BACKGROUND: Epithelial hyperplasia and mucosal infiltration of leukocytes are common features of chronic rhinosinusitis. The epithelium can produce chemoattractant cytokines that may contribute to leukocyte infiltration in rhinosinusitis. OBJECTIVE: We sought to determine whether mucosal IL-8 gene expression is increased in chronic rhinosinusitis and to relate IL-8 gene expression to disease severity. METHODS: We used both a noncompetitive and a quantitative, competitive reverse transcription-polymerase chain reaction to examine IL-8 gene expression in samples of sinus mucosal tissue obtained during surgery from 22 patients with chronic rhinosinusitis and 9 normal control subjects. IL-8 gene expression was related to disease severity assessed by sinus computed tomography (CT) scores and to symptom scores assessed by means of a questionnaire. RESULTS: Sinus mucosal IL-8 gene expression was not detected in any of the control subjects but was present in 12 of 22 (55%) patients with rhinosinusitis. Sinus CT scores and symptom scores were both significantly higher in patients with positive mucosal IL-8 gene expression than in subjects with no detectable IL-8 gene expression. Positive IL-8 gene expression was not predicted by history of prior surgery nor by atopic or asthmatic status. In 9 subjects with positive IL-8 gene expression, levels of mRNA expression, assessed by competitive reverse transcription-polymerase chain reaction, correlated significantly (rho = 0.72, P <.05) with sinus CT scores. CONCLUSION: Sinus mucosal expression of the gene for IL-8 is increased in patients with chronic rhinosinusitis, and the level of IL-8 gene expression correlates with disease severity.

Adult↗
PubMed1998

Microsaccades differentially modulate neural activity in the striate and extrastriate visual cortex.

Saccadic eye movements in primates continually shift the location at which a given stimulus strikes the retina. Even during periods of steady fixation, microsaccades frequently jerk the center of gaze by small but resolvable distances, yet perception remains stable and continuous, uninterrupted by sudden jumps or shifts. The effect of such fixational eye movements on the activity of single neurons was examined in several regions of the visual cortex in macaque monkeys. We found that the firing of many neurons in striate and extrastriate cortex is profoundly influenced by saccades much smaller than the neurons' receptive fields. In striate cortex (V1) many cells showed a transient decrease in their firing shortly following a saccade. In sharp contrast, cells in the extrastriate areas V2 and V4 showed strong excitatory responses that closely coincided in time with the striate depression. No appreciable activity change was observed in the inferotemporal cortex (IT) following saccades. This activity pattern is consistent with the notion that topographic extrastriate areas receive extraretinal input associated with saccadic events. Such signals may be necessary for the stable perception of objects and scenes during eye movements, mediating the mapping between central object representations and the constantly changing retinotopic input.

Animals↗
PubMed1998

Relation between CT scan findings and human sense of smell.

Symptom questionnaires were obtained from 106 patients immediately before nasal and sinus computed tomography scans at the Johns Hopkins Outpatient Center. Their scans were analyzed by two otolaryngologists and three neuroradiologists by using a semiobjective rating system of the size and opacity of 36 anatomic areas. Patients estimated their own left and right sense of smell as excellent, diminished, or absent. Results of the data are as follows: (1) There is no correlation between smell ability and size of the nasal and sinus structures. This indicates that there is no gross effect of the bulging of sinuses into the nasal airway; (2) As a rule, opacity of only left-sided anatomic structures was correlated with both left and right sense of smell (p < 0.01). This suggests that our subjects were using their left smell receptors preferentially, to the exclusion of and in place of the right smell receptors; and (3) Total, not partial, opacity of the left olfactory cleft, frontal recess, or ethmoidal infundibulum was correlated with decreased sense of smell. This suggests that these anterior structures in the region of the olfactory cleft do affect airflow, but complete obstruction of these spaces is needed. Possible explanations for the effect of opacified sinuses on the sense of smell include (1) The presence of fluid or thickened mucosa in the sinuses may interfere with perceived olfactory ability by changing nasal airflow patterns or odorant access to receptors; (2) There may be olfactory receptors inside the sinuses; and (3) There may be a relation between the trigeminal receptors in the sinuses and the olfactory system.

Humans↗
PubMed1997

Upper respiratory tract surface areas and volumes of laboratory animals and humans: considerations for dosimetry models.

To facilitate the development of regional respiratory tract dosimetry comparisons between laboratory animal species and humans, published surface area (SA) and volume (VOL) data for the upper respiratory tract (URT) were reviewed. The review of the literature revealed that (1) different studies used different techniques to prepare specimens and make measurements, (2) different areas of the URT were measured, and (3) URT surface areas and volumes have been reported for a limited number of individual subjects within a species but for a relatively wide range of species. The published data are summarized in tables in this article. New measurements made in an F344 rat and in a female human subject are also presented. Despite the differences in experimental protocols, it was possible to fit allometric scaling equations to the data: In(SA, cm2) = -0.34 + 0.52 In(body weight, g) and In(VOL, cm3) = 1.70 + 0.78 In(body weight, g). Separate scaling equations were also fitted for rats alone. To illustrate the use of these scaling equations in quantitative human health risk assessment, two dose metrics (fractional absorption/cm2 URT SA and fractional absorption/g body weight) for predicted URT uptake in laboratory animals and humans were calculated for acrolein and epichlorohydrin. Expressed as an animal-to-human ratio, the 95% confidence interval for URT SA could change the predicted dose ratio by up to a factor of 2. Additional studies are needed to describe the entire URT (from the nares through the larynx) quantitatively and to decrease variability in scaling equation predictions as well as to develop additional species-specific scaling equations. Three-dimensional imaging techniques provide a noninvasive method to obtain URT surface areas and volumes in humans and the larger laboratory animals. Comparisons of magnetic resonance image (MRI) and computed tomography (CT) scans made as part of this study suggest that the greater clarity of the mucosal-air interface in the CT image provides better resolution for the study of anatomic features. Because there is no radiation exposure associated with MRI imaging, however, it is more safely used than CT scans in making repeated measurements in a subject to elucidate changes in URT geometry associated with normal nasal cycling or other physiological changes.

Acrolein↗
PubMed1997

Recent trends in utilization of procedures in otolaryngology-head and neck surgery.

The development of minimally invasive techniques and increasing performance of surgery in outpatient settings have had a major influence on otolaryngology-head and neck surgery (OLHNS), but little is known about the extent to which these forces have affected the overall distribution and total rate of performance of OLHNS procedures. The aims of this study were to determine whether there has been a change in the total number of people undergoing OLHNS procedures between 1989 and 1992 in Maryland and to identify those procedures for which there has been a significant change in utilization. Data were obtained on 171,579 patients undergoing OLHNS procedures between 1989 and 1992 in Maryland's nonfederal, acute care hospitals, hospital-based outpatient centers, and freestanding multispecialty surgical centers. Age-adjusted annual surgical rates were calculated by direct standardization using 1990 Maryland census data, and changes in rates over time were examined using linear regression. From 1989 to 1992, there was no significant change in the total age-adjusted annual rate of performance of the most commonly performed OLHNS procedures (P>0.05), yet there was a significant increase (P<0.05) in the rates of ethmoidectomy from 37/100,000 to 73/100,000, intranasal antrotomy from 25/100,000 to 44/100,000, and septoplasty from 70/100,000 to 89/100,000, and a significant decrease (P>0.05) in the rate of rhinoplasty from 44/100,000 to 36/100,000. The data show an annual average decrease in inpatient surgery of 5.2% (P=0.006), and a corresponding increase in outpatient surgery of 5.1% (P=0.005). Maryland surgery rates for commonly performed procedures in OLHNS remained stable overall, except for an increase in sinus surgery and septoplasty rates and a decrease in rhinoplasty rates.

Adolescent↗
PubMed1997

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior.

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.

Brain Mapping↗