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.

Thalamocortical relations in taste aversion learning: I. Involvement of gustatory thalamocortical projections in taste aversion learning.

The anterior insular gustatory neocortex (AIGN) has been implicated as a functional substrate of conditioned taste aversion (CTA) learning. Results of previous neuroanatomical and neurobehavioral experiments indicate that projections from gustatory-responsive neurons in the posterior ventromedial thalamic nuclei (parvicellular division; VPMpc) may provide relevant input to the AIGN during CTA learning. In rat, gustatory thalamocortical projections from VPMpc thalamus traverse the ventrolateral neostriatum (VLS) enroute to the AIGN. In these experiments, various neuroanatomical and neurobehavioral manipulations in the VLS were used to examine the contribution of presumed gustatory thalamocortical projections to CTA learning. These experiments demonstrate that projections from VPMpc thalamus to the AIGN are essential for normal CTA learning. Because both VPMpc thalamus and the AIGN each have been implicated as functional substrates of CTA learning, the present results suggest that the gustatory thalamocortical relay per se is necessary for normal taste-illness learning.

Extensive intracranial xanthoma associated with type II hyperlipidemia.

Xanthomas are associated with a spectrum of medical conditions, most commonly disorders of lipid storage and lipid metabolism. They occur primarily in the subcutaneous tissues, especially along the Achilles tendon and the extensor tendons of the hands. Intracranial xanthomas are extremely rare. We present a case of an extensive xanthoma of the temporal bone in a patient with hyperlipidemia.

Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study.

Neuropathological studies of 10 confirmed cases of Alzheimer's disease (AD) revealed increased numbers of neurofibrillary tangles and neuritic plaques in olfactory cortex compared to other brain regions. This was most evident when AD tissues were compared to tissues from seven gender- and age-matched controls. In the AD cases, examination of other brain regions which receive olfactory projections also revealed high concentrations of neuritic plaques and neurofibrillary tangles. These data also confirm previous observations that neurofibrillary tangle formation is more prevalent than neuritic plaque formation in AD. This is the first quantitative neuropathological study that demonstrates significant damage to various components of the central olfactory apparatus in AD. Our data suggest that damage to these areas may be related to the behavioral, emotional, and cognitive abnormalities commonly observed in affected patients. The use of antemortem evaluation of the olfactory system as a diagnostic tool for AD is discussed.

Partial recovery of gustatory function after neural tissue transplantation to the lesioned gustatory neocortex.

The ability of homotypic cortical tissue grafts to induce recovery of function after a gustatory neocortex (GN) lesion was studied using the conditioned taste aversion (CTA) paradigm. On acquisition day, 26 GN-lesioned and 8 sham-lesioned rats were presented with a saccharin solution, followed by an injection of the illness-inducing agent lithium chloride (LiCl). On the test day, 2 days later, saccharin was presented again. The GN-lesioned rats showed significantly less aversion to saccharin on the test day, indicating that the lesion impaired their ability to form taste-illness association. Nine of the lesioned rats were then bilaterally transplanted with fetal GN tissue. Nine weeks after the transplantation, the rats were presented with a LiCl solution, which served as both a tastant and an illness-inducing agent. An NaCl solution, which tasted very similar to the LiCl solution, was used to test the CTA to salt 3 days later. The nontransplanted rats consumed significantly more LiCl than the transplanted and sham-operated rats on the acquisition day, but both transplanted and nontransplanted rats consumed more NaCl than sham-operated rats on the test day. Nissl and Golgi stainings showed numerous somata and extensive arborization of neurons within the grafts. The results indicate that fetal GN grafts can restore the ability to integrate gustatory and visceral inputs but not to form long-lasting taste-illness associations.

Sham feeding, flavor associations and diet self-selection as indicators of feeding satiety or aversive effects of peptide hormones.

We have attempted to develop a constellation of behaviors which show differential effects following the administration of putative satiety hormones (CCK-8, BBS, insulin) as opposed to effects seen following a toxin, such as LiCl. In the initial behavior assessed, sham feeding of differently paired, flavored milks (flavor paired with insulin, BBS or saline) was carried out. Male adult Sprague-Dawley rats which sham fed milk flavors paired with 16 micrograms/kg BBS showed a significant aversion of that flavor in a two-bottle taste test (compared to saline-paired flavors, p less than 0.001) but a significant preference for flavored milk paired with 0.4 and 0.75 U insulin/rat. Lower dosages of BBS (4 and 8 micrograms/kg) and insulin (0.1 U/rat) showed no significant aversion or preference when compared to saline. The second behavioral paradigm evaluated the effects of the hormones CCK-8 and BBS and the toxin, LiCl, upon self-selection of pure macronutrients. While CCK-8 reduced intake of calories by significantly lowering ingestion/selection of fats (55%, p less than 0.01 compared to saline, control injections) and carbohydrates (50%, p less than 0.01), LiCl and BBS reduced calories by decreasing selection of primarily proteins (LiCl--49%, p less than 0.03; BBS--63% at 4 micrograms/kg and 80% at 8 micrograms/kg, both p less than 0.025). In both paradigms then, BBS at doses sufficient to significantly reduce sham intake or suppress caloric ingestion in a self-selection paradigm produced behavioral effects most similar to those observed following the injection of a toxin. LiCl, rather than effects seen following other various putative satiety signals.

Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning.

When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness.

Taste discriminations in rats lacking anterior insular gustatory neocortex.

Previous neurobehavioral investigations have demonstrated that the anterior insular gustatory neocortex (AIGN) mediates taste-illness learning. The present experiment evaluated taste discriminations in rats lacking AIGN. Two groups of rats received distinct surgical treatments. One-half of the animals received bilateral electrolytic lesion placements in the AIGN: Remaining animals received anesthesia and scalp incisions only. Following postoperative recovery animals received standard two-bottle preference tests with various concentrations of sucrose to evaluate gustatory reactivity. Animals thereafter received two-bottle discrimination tests with selected sucrose concentrations. At the conclusion of preference tests and discrimination tests with sucrose, preference tests and discrimination tests were conducted with sodium chloride. Following those tests animals received taste aversion conditioning to determine whether or not AIGN lesions impaired taste-illness learning. Results of two-bottle taste tests indicated that AIGN lesions do not obviously alter taste reactivity nor taste discriminations to preferred concentrations of sucrose and NaCl. Anterior insular lesions did, however, impair normal taste aversion learning. These results, in combination with those of previous investigators, provide further evidence that the AIGN preferentially contributes to taste learning functions.

Hungry, but not thirsty, rats prefer flavors paired with ethanol.

The present experiments examined the reinforcing effects of an ethanol (EtOH) unconditioned stimulus (UCS) on conditioned flavor preferences in food-deprived rats and in water-deprived rats. In Experiment 1A food and water deprived animals received distinct conditioning treatments. One half of the animals were intragastrically intubated with EtOH (0.5 g/kg), and thereafter allowed 20 min free access to similar flavored drinking solutions. Remaining animals were intubated with distilled water. All animals received 15 presentations of an EtOH-paired flavor. A two-bottle preference test was subsequently used to evaluate preferences or aversions to flavors paired with EtOH in food-deprived and water-deprived animals. Results of Experiment 1A showed that food-deprived animals preferred the flavor associated with EtOH. Conversely, preferences for EtOH-paired flavors were not established in water-deprived animals. In Experiment 1B deprivational states of animals used in Experiment 1A were reversed without further drug training. Following a two week habituation period to deprivation state animals again received a two-bottle preference test to re-evaluate preferences or aversions to the EtOH-paired flavors. Results of those manipulations indicated that an ethanol aversion was established in the water-deprived animals. Those results indicated that water-deprived animals of Experiment 1B reversed their EtOH-paired flavor preference when the caloric need associated with food deprivation conditions was eliminated. Since deprivational state determined the development of EtOH preferences, the present results indicate that caloric need may play an initial role in establishing conditioned preferences for EtOH.

Preservation of the stapedius tendon in laser stapes surgery.

OBJECTIVES/HYPOTHESIS: The stapedius tendon is routinely transected during stapes surgery. The objective of this study was to evaluate the technique of stapedial tendon preservation during stapes surgery and to compare results of these cases with cases where the stapedial tendon was not preserved. STUDY DESIGN: Retrospective study. METHODS: Four groups of patients were evaluated. Two groups had undergone stapes surgery with preservation of the stapedial tendon. One of these groups underwent a laser stapedotomy minus prosthesis (laser STAMP) procedure, while the other group had a prosthesis inserted. The other two groups had undergone laser stapedotomy with one of two different prostheses being used. Audiometric data were obtained and reviewed both preoperatively and at approximately 6 weeks postoperatively. RESULTS: All groups had overall successful results demonstrating that stapedial tendon preservation is technically possible and does not compromise outcomes. CONCLUSIONS: Based on the results, it is recommended that the stapedius tendon be preserved whenever possible during laser stapes surgery. Reasons justifying its preservation are discussed.

The effect of human olfactory biopsy on olfaction: a preliminary report.

Normal human olfactory function is subject to a wide variety of factors. Although biopsy of human olfactory neuroepithelium has been reported by several researchers, there are no studies which have evaluated the effect of this procedure on olfactory function. In this retrospective study, we sought to determine if tissue removal from the olfactory cleft has an adverse influence on the sense of smell. Nineteen subjects underwent bilateral olfactory testing and subsequent endoscopic olfactory mucosal biopsy. All subjects were retested 6 weeks to 1 year after olfactory neuroepithelial biopsy. No statistical difference was found between olfactory tests performed before or after biopsy. These data suggest that biopsy of human olfactory neuroepithelium has no discernible adverse effect on the ability to smell.

Spontaneous resolution of dysgeusia.

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.

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.

Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center.

Smell and taste disorders are common in the general population, yet little is known about their nature or cause. This article describes a study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia. Major findings suggest that: chemosensory dysfunction influences quality of life; complaints of taste loss usually reflect loss of smell function; upper respiratory infection, head trauma, and chronic nasal and paranasal sinus disease are the most common causes of the diminution of the sense of smell, with head trauma having the greatest loss; depression frequently accompanies chemosensory distortion; low body weight accompanies burning mouth syndrome; estrogens protect against loss of the sense of smell in postmenopausal women; zinc therapy may provide no benefit to patients with chemosensory dysfunction; and thyroid hormone function is associated with oral sensory distortion. The findings are discussed in relation to management of patients with chemosensory disturbances.

Complications of ethmoidectomy: a survey of fellows of the American Academy of Otolaryngology-Head and Neck Surgery.

A survey regarding complications of sinus surgery was mailed to 6969 otolaryngologists; 3933 responses (56.44%) were obtained, and 3043 of these physicians (77.37%) reported that they performed ethmoidectomy. Completed questionnaires were available for review from 42.21% of all Academy fellows (2942 physicians). Responses were tabulated and summarized question by question. Physicians generally did not rate their residency training in ethmoidectomy highly. The survey confirmed that there has been a marked rise in the frequency of ethmoidectomy and in the amount of training in ethmoidectomy since 1985. Empirical complication rates were calculated for different procedures and time periods. Poisson regression models were then constructed to describe the rate of complications under varying conditions such as the type of surgery performed, time period, experience and training of the surgeon, and type of complication encountered. The models permitted determination of the statistical significance of variables in relation to incidence or complications. The study did not demonstrate a clear and consistent statistical relationship between the incidence of complications, the type of surgery performed, and the quality of training. Moreover, physicians who provided data from record review tended to report higher rates than those who estimated responses. The majority of physicians discussed specific potential complications with their patients before surgery and routinely performed preoperative computed tomography. The study demonstrated that physicians who experienced complications at higher rates were more likely to discuss these complications with patients before surgery.

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.

Relationship between liver biochemical tests and dietary intake in patients with liver disease.

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.