Christian A. Mueller

“Taste Strips” – A rapid, lateralized, gustatory bedside identification test based on impregnated filter papers

ObjectiveTo elaborate normative values for a clinical psychophysical taste test (“Taste Strips”).BackgroundThe “Taste Strips” are a psychophysical chemical taste test. So far, no definitive normative data had been published and only a fairly small sample size has been investigated. In light of this shortcoming for this easy, reliable and quick taste testing device, we attempted to provide normative values suitable for the clinical use.SettingNormative value acquisition study, multicenter study.MethodsThe investigation involved 537 participants reporting a normal sense of smell and taste (318 female, 219 male, mean age 44 years, age range 18–87 years). The taste test was based on spoonshaped filter paper strips (“Taste Strips”) impregnated with the four (sweet, sour, salty, and bitter) taste qualities in four different concentrations. The strips were placed on the left or right side of the anterior third of the extended tongue, resulting in a total of 32 trials. With their tongue still extended, patients had to identify the taste from a list of four descriptors, i. e., sweet, sour, salty, and bitter (multiple forcedchoice). To obtain an impression of overall gustatory function, the number of correctly identified tastes was summed up for a “taste score”.ResultsTaste function decreased significantly with age. Women exhibited significantly higher taste scores than men which was true for all age groups. The taste score at the 10th percentile was selected as a cut-off value to distinguish normogeusia from hypogeusia. Results from a small series of patients with ageusia confirmed the clinical usefulness of the proposed normative values.ConclusionThe present data provide normative values for the “Taste Strips” based on over 500 subjects tested.

A Novel Type of Influenza Vaccine: Safety and Immunogenicity of Replication-Deficient Influenza Virus Created by Deletion of the Interferon Antagonist NS1

BACKGROUND. The nonstructural protein NS1 of influenza virus counteracts the interferon-mediated immune response of the host. By deleting the open reading frame of NS1, we have generated a novel type of influenza vaccine. We studied the safety and immunogenicity of an influenza strain lacking the NS1 gene (DeltaNS1-H1N1) in healthy volunteers. METHODS. Healthy seronegative adult volunteers were randomized to receive either a single intranasal dose of the DeltaNS1-H1N1 A/New Caledonia vaccine at 1 of 5 dose levels (6.4, 6.7, 7.0, 7.4, and 7.7 log(10) median tissue culture infective dose) (n = 36 recipients) or placebo (n = 12 recipients). RESULTS. Intranasal vaccination with the replication-deficient DeltaNS1-H1N1 vaccine was well tolerated. Rhinitis-like symptoms and headache were the most common adverse events identified during the 28-day observation period. Adverse events were similarly distributed between the treatment and placebo groups. Vaccine-specific local and serum antibodies were induced in a dose-dependent manner. In the highest dose group, vaccine-specific antibodies were detected in 10 of 12 volunteers. Importantly, the vaccine also induced neutralizing antibodies against heterologous drift variants. CONCLUSIONS. We show that vaccination with an influenza virus strain lacking the viral interferon antagonist NS1 induces statistically significant levels of strain-specific and cross-neutralizing antibodies despite the highly attenuated replication-deficient phenotype. Further studies are warranted to determine whether these results translate into protection from influenza virus infection. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00724997 .

Clinical significance of smell and taste disorders in patients with diabetes mellitus

Chemosensory dysfunction has been reported in patients with diabetes mellitus (DM). However, the clinical significance in relation to the disease stage remains unclear. The aim of this investigation was to assess olfactory and gustatory function with valid clinical tests in patients with DM types 1 and 2 with and without accompanying diseases. Seventy-six patients with DM were divided into three groups according to disease stage. Taste function was tested by means of impregnated paper strips and smell function was screened using a five-item smell identification test. The results of the patients with uncomplicated DM were compared with the results from 29 healthy subjects. The results showed no significant differences in smell and taste function between patients with uncomplicated DM and healthy subjects. However, patients with additional diseases exhibited decreased smell acuity. Moreover, patients with DM type 2 showed impaired smell function compared with patients with DM type 1.

A new procedure for the short screening of olfactory function using five items from the Sniffin' Sticks identification test kit

Background The aim of this study was to create a new protocol based on the “Sniffin’ Sticks” test kit, which would be suitable for short screening of olfactory function. Methods One hundred forty-one subjects were included in the investigation. In a first session, 106 subjects were presented five odorants together with a list of 20 descriptors. Additional choices were “no odor” and “undefinable.” The established 16-item identification test was then performed to assess olfactory function. In another session, the new procedure was repeated on 21 subjects to check the test-retest reliability. The Brief Smell Identification Test was used together with the five-item test in an additional 35 subjects for additional validation. Results The correlation coefficients between the results of the new test and the established procedures were r106 = 0.61 and r35 = 0.77 (p < 0.01). The new test procedure revealed two groups of subjects (score of 0 and scores 4 or 5). These groups had no overlapping results in the established odor identification tests. Repeated measurements of the short test showed a correlation coefficient of r21 = 0.77 (p < 0.01). Conclusion The present data indicate the usefulness of the short screening test. Given a maximum of one error, the test is able to confirm the presence of normosmia or mild hyposmia. The kit can be carried in a pocket and the test takes only 3 minutes to perform.

Recovery of Olfactory Function Induces Neuroplasticity Effects in Patients with Smell Loss

The plasticity of brain function, especially reorganization after stroke or sensory loss, has been investigated extensively. Based upon its special characteristics, the olfactory system allows the investigation of functional networks in patients with smell loss, as it holds the unique ability to be activated by the sensorimotor act of sniffing, without the presentation of an odor. In the present study, subjects with chronic peripheral smell loss and healthy controls were investigated using functional magnetic resonance imaging (fMRI) to compare functional networks in one of the major olfactory areas before and after an olfactory training program. Data analysis revealed that olfactory training induced alterations in functional connectivity networks. Thus, olfactory training is capable of inducing neural reorganization processes. Furthermore, these findings provide evidence for the underlying neural mechanisms of olfactory training.

Abolished tilt suppression of the vestibulo-ocular reflex caused by a selective uvulo-nodular lesion

Article abstract Within the cerebellum several structures are considered to modulate the function of the vestibulo-ocular reflex (VOR). The nodulus and uvula have been implicated with the low-frequency components of the VOR, which are mediated by the velocity storage system. We report a patient with a selective lesion of the nodulus and ventral uvula. The findings suggest that nodulus and uvula normally exert an inhibitory effect on the velocity storage mechanism.

Early Prediction of Hepatitis C Virus (HCV) Infection Relapse in Nonresponders to Primary Interferon Therapy by means of HCV RNA Whole-Blood Analysis

BACKGROUND Routine analysis of serum and/or plasma specimens for hepatitis C virus (HCV) RNA does not always correctly reflect the response to antiviral therapy. Analysis of whole-blood specimens for detection of viral RNA should provide more-accurate prognostic information. METHODS Whole-blood, serum, and plasma specimens (268 sample sets) were obtained from 56 patients who did not respond to initial interferon (IFN)- alpha 2b monotherapy (5 MU every 2 days for 3 months). Specimens were analyzed for HCV RNA by 4 different types of reverse-transcriptase polymerase chain reaction (RT-PCR) (Cobas Amplicor HCV-2.0 [Roche], LightCycler real-time PCR [Roche], and 2 in-house RT-PCRs) to determine whether specimen type can predict the rate of virologic response to high-dose treatment with IFN (10 MU every 2 days) and ribavirin (1-1.2 g/day). RESULTS Of the 56 patients who provided specimens, serum and plasma obtained from 18 tested negative for HCV RNA at the end of treatment, indicating a complete virologic response. In contrast, analysis of whole-blood specimens obtained at the same time revealed the presence of viral RNA in 12 of these 18 patients. All 12 subjects had relapse of HCV in serum and plasma: 11 relapsed a median of 4 weeks after the end of treatment, and 1 relapsed 20 weeks after the end of treatment. None of these 12 patients--all of whom consistently had whole-blood specimens that tested positive and plasma and serum specimens that tested negative for HCV RNA up to 20 weeks before the end of treatment--showed a sustained virologic response (P=.0002). CONCLUSIONS Results of whole-blood tests for detection of HCV RNA were highly predictive of viral relapse (positive predictive value, 100%) and thus may be useful tools for monitoring and tailoring IFN/ribavirin therapy. Testing of only serum or plasma specimens underestimates the true circulating HCV load and leads to an overestimation of antiviral response rates.

Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat)

Objectives The aim of this review is to examine the causes, pathophysiology and experimental models of non-infectious pharyngitis (sore throat).IntroductionThe causes of sore throat can be infectious (viruses, bacteria, and fungi) or non-infectious, although the relative proportion of each is not well documented.MethodsA PubMed database search was performed for studies of non-infectious sore throat.Results and conclusionsNon-infectious causes of sore throat include: physico-chemical factors, such as smoking, snoring, shouting, tracheal intubation, medications, or concomitant illness; and environmental factors including indoor and outdoor air pollutants, temperature and humidity, and hazardous or occupational irritants. The pathophysiology underlying non-infectious sore throat is largely uncharacterised, although neurogenic inflammation looks to be a promising candidate. It is likely that there will be individual disposition factors or the coincidence of more than one irritant with possible—up to now unknown—interactions between them. Therefore, experimental models with defined conditions and objective endpoints are needed. A new model using cold dry air to directly induce pharyngeal irritation in humans, with pharyngeal lavage to measure biomarkers, may provide a useful tool for the study of mechanisms and treatment of non-infectious sore throat.

Thalamic astasia from isolated centromedian thalamic infarction

In thalamic astasia a unilateral thalamic lesion causes postural instability or retropulsion or lateropulsion.1 In previous reports, the responsible lesions have been localized in the posterolateral thalamic area. In contrast to patients with pontomesencephalic lesions, patients with thalamic astasia did not exhibit the clinical signs of ocular tilt reaction.2 Furthermore, the assessment of static graviceptive function by means of the subjective visual vertical (SVV) revealed ipsiversive as well as contraversive deviations of the SVV in these patients.2 We describe a patient with thalamic astasia due to a highly selective unilateral centromedian thalamic lesion. An 82-year-old man with acute onset of astasia with body lateropulsion to the right was admitted to our hospital. Neurologic examination was otherwise normal. MRI disclosed an acute selective ischemic lesion in the left centromedian thalamus (figure). No further brain lesions were detected. An experienced neuroradiologist localized the exact anatomic lesion site using sections from a stereotactic atlas of the human thalamus.3 Figure Cerebral MRI and schematic horizontal thalamic section Axial diffusion-weighted imaging sequence of cerebral MRI shows a small hyperintense lesion with 5-mm diameter in the centromedian part of the left thalamus (left). The correlating lesion site is labeled in …

Clinical Assessment of Gustatory Function before and after Middle Ear Surgery: A Prospective Study with a Two-Year Follow-up Period

Objectives: Middle ear surgery can affect gustatory function because of the course of the chorda tympani nerve (CTN) close to the tympanic membrane. The aim of the study was to evaluate the sense of taste before and after middle ear surgery with a test suitable for clinical routine. Moreover, subjective complaints were assessed over a relatively long period of time. Methods: Forty-seven patients (26 female, 21 male; mean age, 42 years) were investigated before and 4 days after surgery on both sides of the anterior part of the tongue. Self-assessment of taste function was performed by visual analog scales. Results: The mean (±SD) taste scores significantly decreased on the side ipsilateral to the operated ear in patients with major manipulation of the CTN (12.0 ± 4.5 before surgery and 6.9 ± 4.5 after surgery; p < 0.001), whereas no significant changes were measured in patients with minor manipulation of the CTN (12.5 ± 3.1 before surgery and 11.2 ± 3.9 after surgery; p = 0.14). Self-assessed ratings of taste function significantly decreased after surgery in all patients (p < 0.001). Reassessment of subjective taste function after 2 years indicated no persisting complaints. Conclusions: Depending on the amount of manipulation of the CTN, taste function is decreased after surgery. However, long-lasting changes of gustatory function seem to be rare.