Olfactory processing: detection of rapid changes.

Changes in the olfactory environment have a rather poor chance of being detected. Aim of the present study was to determine, whether the same (cued) or different (uncued) odors can generally be detected at short inter stimulus intervals (ISI) below 2.5 s. Furthermore we investigated, whether inhibition of return, an attentional phenomenon facilitating the detection of new stimuli at longer ISI, is present in the domain of olfaction. Thirteen normosmic people (3 men, 10 women; age range 19-27 years; mean age 23 years) participated. Stimulation was performed using air-dilution olfactometry with 2 odors: phenylethylalcohol and hydrogen disulfide. Reaction time to target stimuli was assessed in cued and uncued conditions at ISIs of 1, 1.5, 2, and 2.5 s. There was a significant main effect of ISI, indicating that odors presented only 1 s apart are missed frequently. Uncued presentation facilitated detection at short ISIs, implying that changes of the olfactory environment are detected better than presentation of the same odor again. Effects in relation to "olfactory inhibition of return," on the other hand, are not supported by our results. This suggests that attention works different for the olfactory system compared with the visual and auditory systems.

Impact of chemotherapy for childhood leukemia on brain morphology and function.

OBJECTIVE: Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. METHODS: We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15-22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB's integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. RESULTS: Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. INTERPRETATION: Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.

Intrinsic chemosensory signal recorded from the human nasal mucosa in patients with smell loss.

Physiological investigation of olfactory receptor function in hyposmic or anosmic patients is rare. Pioneers examined the electro-olfactogram in patients with olfactory disturbance. Although the electro-olfactogram is an established method to record olfactory responses from human olfactory epithelium, the response is only measured at specific sites of the olfactory mucosa. In contrast to that the response of the olfactory epithelium to chemosensory stimuli can be studied in a specific nasal area by means of intrinsic optical signal recording. Five functionally anosmic patients were included in the present study. In all patients, responses could be obtained following trigeminal stimulation with CO2. In some patients, responses could be obtained after olfactory stimulation with H2S and PEA. The present data show that in the studied patients trigeminal function seems to be preserved, while it appears that in some patients olfactory function is preserved to a certain degree.

Novel humanized and highly efficient bispecific antibodies mediate killing of prostate stem cell antigen-expressing tumor cells by CD8+ and CD4+ T cells.

Prostate cancer is the most common noncutaneous malignancy in men. The prostate stem cell Ag (PSCA) is a promising target for immunotherapy of advanced disease. Based on a novel mAb directed to PSCA, we established and compared a series of murine and humanized anti-CD3-anti-PSCA single-chain bispecific Abs. Their capability to redirect T cells for killing of tumor cells was analyzed. During these studies, we identified a novel bispecific humanized Ab that efficiently retargets T cells to tumor cells in a strictly Ag-dependent manner and at femtomolar concentrations. T cell activation, cytokine release, and lysis of target cells depend on a cross-linkage of redirected T cells with tumor cells, whereas binding of the anti-CD3 domain alone does not lead to an activation or cytokine release. Interestingly, both CD8+ and CD4+ T cells are activated in parallel and can efficiently mediate the lysis of tumor cells. However, the onset of killing via CD4+ T cells is delayed. Furthermore, redirecting T cells via the novel humanized bispecific Abs results in a delay of tumor growth in xenografted nude mice.

Patient adjustment to reduced olfactory function.

OBJECTIVE: To compare the importance of olfaction in daily life between patients with olfactory disorders and healthy normosmic individuals. DESIGN: Quasiexperimental. PARTICIPANTS: A total of 470 individuals (235 anosmic or hyposmic patients and 235 normosmic control individuals). MAIN OUTCOME MEASURES: The Individual Importance of Olfaction Questionnaire (IO) and olfactory testing using the "Sniffin' Sticks" test kit. RESULTS: The IO scores were lower in people with smell disorders compared with normosmic subjects (P < .001) and lower in patients with anosmia compared with hyposmic patients (P < .001). CONCLUSIONS: These scores suggest adjustment processes in the daily use of the sense of smell by patients. Patients attach less importance to their current sense of smell in daily life than do normosmic individuals. This adjustment might be an example of regaining psychological health despite acquired and long-lasting impairments.

Topographical differences in the sensitivity of the human nasal mucosa to olfactory and trigeminal stimuli.

The olfactory and trigeminal systems play a role in the sensation of odors. The intrinsic optical signal (IOS) imaging method allows visualization of the neuronal activity. The IOS was measured after the nasal epithelium had been exposed to olfactory (H(2)S) and trigeminal (CO(2)) stimuli. The IOS was measured in the area of the middle turbinate. The response patterns of H(2)S and CO(2) on the middle turbinate were different, and some overlap between regions of activation was also observed. The response to CO(2) (20%) on the medial side of the middle turbinate was significantly higher than the response on the lateral side. In contrast, the response to H(2)S (5.6 ppm) was greater on the lateral side than on the medial side. There were no significant differences in response between the medial and lateral sides of the middle turbinate to stimuli of lower concentration (H(2)S 2.8 ppm, CO(2) 5% and 10%). These data suggest that the middle turbinate has regions which are sensitive to both olfactory and trigeminal stimuli.

A study about the frequency of taste disorders.

Although 5% of the general population exhibit a functional anosmia, little is known about the frequency of gustatory disorders. Whenever taste function has been tested within large sociodemographic studies, so far only short test versions were applied making the interpretation difficult. Using two psychophysical taste tests, the validated "taste strips" and suprathreshold taste solutions of the four basic tastes sweet, sour, salty and bitter we investigated 761 healthy subjects within the age range of 5-89 years. Prior to testing, all subjects rated their taste function. According to testing with the taste strips, 5.3% scored below the result considered as hypogeusia. All four taste sprays were correctly identified by 82.3% of all subjects. Results of the two taste tests correlated positively (r = 0.33, p < 0.001), and there was a significant negative correlation between age and test results. However, we never observed complete ageusia. Misinterpretations of tastes were surprisingly common. In summary, hypogeusia was present in 5% while complete ageusia seems to be very rare, in contrast to misinterpretations of tastes.

Comparison between odor thresholds for phenyl ethyl alcohol and butanol.

UNLABELLED: Aim of the study was to compare results of odor threshold test using different numbers of dilution steps, separately for butanol and phenyl ethyl alcohol (PEA). METHODS: A total of 116 subjects participated (29 patients with olfactory dysfunction and 87 normosmic subjects). The olfactory threshold for butanol and PEA was examined with 8 (wide step method) and 16 (narrow step method) dilutions. With a delay of about 1 week, all 4 tests were repeated. RESULTS: Test time was shortened by approximately 2 min (25%) for patients when using the wide step method. Butanol and PEA thresholds were not significantly different; in addition, a significant correlation was found between thresholds for the 2 odors (r = 0.60, P < 0.001). Threshold test with both odorants as well as with wide or narrow step method provided satisfying reproducibility (test-retest reliability: r = 0.80-0.84, P < 0.001). Patients with olfactory dysfunction could be clearly separated from normosmic subjects using all 4 different tests. DISCUSSION: The results indicate that threshold testing with PEA is an alternative to butanol. The wide step method provided similar results as the narrow step method but required less time.

The influence of olfactory loss on dietary behaviors.

OBJECTIVES: To assess dietary behavior and possible changes in food selection in patients with smell loss. PATIENTS AND METHODS: A total of 176 patients (114 women and 62 men) age 17 to 86 years were classified into three diagnostic groups (normosmia, n = 12; hyposmia, n = 75; functional anosmia, n = 89) according to their olfactory test scores obtained with "Sniffin' Sticks." Group differences in food intake and dietary behaviors were investigated with a specifically designed questionnaire providing a dietary alterations score (DAS). RESULTS: Numerous dietary changes were reported, e.g., 29% of all patients reported that they eat less since the onset of olfactory dysfunction, 39% use more spices with their food, 47% go out to eat at restaurants less frequently, 37% eat less sweets, and 48% drink less sweet beverages. Subjects with weight gain or weight loss scored higher on the DAS scale than subjects who did not report changes in weight. Similarly, DAS scale changes were more pronounced in subjects with a gradual onset of olfactory loss compared to subjects with a sudden loss of olfaction. Finally, a change of taste preferences toward savory and salty foods was observed across all patients enrolled in the present study. CONCLUSIONS: Patients with olfactory loss report alterations of dietary behaviors. Numerous factors appear to impact the results of olfactory loss in terms of changes in diet.

Optical recordings from the human nasal mucosa in response to olfactory stimulation.

Using the intrinsic optical signal the present study aimed to investigate changes in blood flow at the nasal epithelium in response to specific olfactory stimulation. Recording equipment included an endoscope, a CCD camera, and a light source of 617 nm. Two concentrations of the specific olfactory stimulant H(2)S (2.8 and 5.6 ppm), generated by a computer-controlled olfactometer, were used for olfactory stimulation. Eight healthy normosmic volunteers participated. Using 5.6 ppm H(2)S stimuli, responses were typically recorded from the olfactory cleft, middle turbinate, and middle meatus while responses were less pronounced for 2.8 ppm H(2)S stimuli. Response areas were significantly larger for the 5.6 ppm H(2)S stimuli. While further experiments are needed, recordings of the intrinsic optical signal may be used to obtain responses from the nasal cavity to specific olfactory stimuli.

Androstadienone odor thresholds in adolescents.

A sex-related difference in olfactory sensitivity to androstenone has been reported to occur during adolescence. More males than females exhibited anosmia to androstenone, or an increase in androstenone threshold with age. The current study addressed the question whether similar, sexually dimorphic effects of aging over puberty can also be found for androstadienone. A total of 102 subjects participated (36 females, 66 males). Similar to previous investigations, subjects were divided into a group of 47 individuals with a mean age of 13.3 years, defined as pre/peri-pubertal, and a group of 55 subjects with a mean age of 17.1 years, defined as post-pubertal. All subjects underwent tests for verbal abilities, general olfactory function, and measurements of androstadienone thresholds. The study provided the following major results: (1) Male subjects exhibited higher androstadienone sensitivity in the pre/peri-pubertal group as compared to the post-pubertal group. This difference was not observed in female subjects. Correspondingly, a negative correlation between age and androstadienone sensitivity was found for male subjects, but not for female subjects. (2) In contrast to this sex-specific change of the androstadienone odor threshold, verbal skills and odor identification abilities increased with age in all subjects regardless of their sex. In conclusion, the present observations confirm previous research on sex-differentiated effects of aging during puberty on sensitivity towards odorous steroids. While the underlying causes are unknown, it may be hypothesized that the decreased sensitivity could result from the increased endogenous levels of androstadienone in male subjects. Future studies should include both steroid and non-steroid odorants to further explore these age-related changes.