Biomedical subjects

T Hummel

Publications and source records attributed to T Hummel.

At least 91 records · Page 5Linked to original sources

PubMed2000

Peripheral and central nervous changes in patients with rheumatoid arthritis in response to repetitive painful stimulation.

It has been observed that patients with rheumatoid arthritis (RA) respond differently to repetitive painful stimulation. The present study investigated whether this is related to the peripheral or central nervous nociceptive system. EEG-derived potentials and the negative mucosal potential (NMP) from the respiratory epithelium were recorded in response to painful intranasal stimulation with gaseous CO(2). Differences between groups (12 RA patients, 12 controls) were found when stimuli were presented at short intervals. While the NMP did not differ between groups, patients had larger cortical responses to the first stimuli of a series of painful stimuli. This may indicate that in RA central nervous changes of nociceptive processing are present.

Adult↗

PubMed2000

Assessment of intranasal trigeminal function.

Intranasal trigeminal function is more and more understood as an integral part of human chemosensory perception. Sensations like burning, stinging, warmth, coolness, or itching are produced by almost all odorants so that they can be perceived by anosmics. Electrophysiological responses to trigeminal stimuli allow the specific assessment of trigeminally mediated information at different levels of processing including the periphery or the cortex. Information regarding the localization of these processes can be derived from magnetoencephalographic recordings or functional imaging data. When using these techniques in combination with psychophysical measures, it seems to be possible to specifically describe how and where the processing of irritation takes place, how it may interact with olfactory mediated sensations, and how it is modulated, e.g. by environmental influences or analgesic drugs.

Disease-Free Survival↗

PubMed2000

Drosophila Futsch/22C10 is a MAP1B-like protein required for dendritic and axonal development.

Here we report the description of the Drosophila gene futsch, which encodes a protein recognized by the monoclonal antibody 22C10 that has been widely used to visualize neuronal morphology and axonal projections. The Futsch protein is 5327 amino acids in length. It localizes to the microtubule compartment of the cell and associates with microtubules in vitro. The N- and C-terminal domains of Futsch are homologous to the vertebrate MAP1B microtubule-associated protein. The central domain of the Futsch protein is highly repetitive and shows sequence similarity to neurofilament proteins of which no Drosophila homologs have been reported. Loss-of-function analyses demonstrate that during embryogenesis Futsch is necessary for dendritic and axonal growth. Gain-of-function analyses demonstrate a functional interaction of Futsch with other MAPs. In addition, we show that during development, futsch expression is negatively regulated in nonneuronal tissues.

Aging↗

PubMed2000

Drosophila Futsch regulates synaptic microtubule organization and is necessary for synaptic growth.

We present evidence that Futsch, a novel protein with MAP1B homology, controls synaptic growth at the Drosophila neuromuscularjunction through the regulation of the synaptic microtubule cytoskeleton. Futsch colocalizes with microtubules and identifies cytoskeletal loops that traverse the lateral margin of select synaptic boutons. An apparent rearrangement of microtubule loop architecture occurs during bouton division, and a genetic analysis indicates that Futsch is necessary for this process. futsch mutations disrupt synaptic microtubule organization, reduce bouton number, and increase bouton size. These deficits can be partially rescued by neuronal overexpression of a futsch MAP1B homology domain. Finally, genetic manipulations that increase nerve-terminal branching correlate with increased synaptic microtubule loop formation, and both processes require normal Futsch function. These data suggest a common microtubule-based growth mechanism at the synapse and growth cone.

Animals↗

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↗

PubMed2000

Assessment of gustatory function by means of tasting tablets.

OBJECTIVE: To develop a simple test for the screening of gustatory function in clinical settings. STUDY DESIGN: We tested 101 healthy volunteers (44 male and 57 female volunteers; mean age, 47 y) with the following gustatory test: the substances sucrose (sweet), citric acid (sour), sodium chloride (salty), and caffeine (bitter) were presented as tablets (diameter 4 mm) similar to common sweetener tablets. For quantitative assessment of whole-mouth gustatory function we used six different dosages with dilutions of each tastant in 50% steps. The highest dosage could be easily detected (sucrose, 30 mg; citric acid, 3 mg; sodium chloride, 2 mg; caffeine, 2 mg), and the lowest concentration was within threshold range. METHODS: Twenty-eight tablets (six different dosages of the four basic tastes plus four tasteless tablets) were tried in a randomized order. The entire test required 15 to 20 minutes. To evaluate the within-subject test-retest reliability, sessions were repeated after 1 week. Results were compared with those obtained by means of a conventional three-drop, forced-choice procedure using the method of ascending limits. RESULTS: Results of the new gustatory test were significantly correlated with those obtained using the three-drop, forced-choice procedure (correlation coefficient [r] = 0.66, P<.001). In general, women performed better than men. Furthermore, younger subjects exhibited a significantly higher gustatory sensitivity in both tests compared with older subjects. CONCLUSIONS: This quantitative test of whole-mouth gustatory function is easy to use, can be self-administered, requires little time, and has a long shelf-life. It appears to be suited for routine clinical assessment of gustatory function.

Adult↗

PubMed2000

Olfactory and trigeminal event-related potentials in migraine.

BACKGROUND: Trigeminal/neuronal hyperexcitability and spreading depression activating the trigemino-vascular system are discussed in migraine-pathophysiology. This study investigated trigeminal and olfactory event-related potentials in migraineurs. METHODS: Nasal chemosensitivity was assessed in 19 female migraineurs with or without aura > 72 h before or after an attack and in 19 healthy females employing event-related cortical potentials (ERPs) after specific trigeminal stimulation of nasal nociceptors with short pulses of CO2, and specific olfactory stimulation with H2S. Odour thresholds and odour identification performance were also tested. RESULTS: Migraineurs exhibited greater responses to trigeminal stimulation, indicated by significantly larger ERP amplitudes N1. In contrast, olfactory ERP amplitudes P1N1 were significantly smaller in migraineurs. A leave-one-out classification procedure on the basis of these two parameters assigned 76.3% cases correctly. The olfactory ERP amplitude discriminated better between groups than trigeminal ERPs (71.1 vs. 68.4% correct classification). CONCLUSIONS: Our data suggest trigeminal hyperexcitability in migraineurs. A general increase of nasal chemosensitivity is not supported because of smaller olfactory ERP amplitudes in migraineurs. Olfactory ERPs discriminate better than trigeminal ERPs between migraineurs and controls, emphasizing the significance of the olfactory system in migraine.

Adult↗

PubMed1999

[Smell and taste disorders].

Disorders of the chemical senses are frequent. They can severely affect our lives. Appropriate testing is needed to determine the nature of the patient's complaints. Because many chemosensory disorders are secondary to a wide variety of diseases, olfactory or gustatory complaints may help in establishing certain differential diagnoses, e.g. in Alzheimer's disease. In turn, treatment of the underlying diseases may restore chemosensory function in these patients. Future developments appear possible in light of the availability of standardised tools for the assessment of chemosensory dysfunction.

Alzheimer Disease↗

PubMed1999

Commissure formation in the embryonic CNS of Drosophila.

In the ventral nerve cord of Drosophila most axons are organized in a simple, ladder-like pattern. Two segmental commissures connect the hemisegments along the mediolateral and two longitudinal connectives connect individual neuromeres along the anterior-posterior axis. Cells located at the midline of the developing CNS first guide commissural growth cones toward and across the midline. In later stages, midline glial cells are required to separate anterior and posterior commissures into distinct axon bundles. To unravel the genes underlying the formation of axon pattern in the embryonic ventral nerve cord, we conducted a saturating ethylmethane sulfonate mutagenesis, screening for mutations which disrupt this process. Subsequent genetic and phenotypic analyses support a sequential model of axon pattern formation in the embryonic ventral nerve cord. Specification of midline cell lineages is brought about by the action of segment polarity genes. Five genes are necessary for the establishment of the commissures. In addition to commissureless, the netrin genes, and the netrin receptor encoded by the frazzled gene, two gene functions are required for the initial formation of commissural tracts. Over 20 genes appear to be required for correct development of the midline glial cells which are necessary for the formation of distinct segmental commissures.

Animals↗

PubMed1999

Gender effects on odor-stimulated functional magnetic resonance imaging.

On standardized tests of odor identification and odor detection, women tend to score better than men at nearly all age groups. We sought to determine if these findings would translate to differences between the sexes in the volume of activated brain when odors are presented to subjects as the stimulants for functional magnetic resonance imaging (FMRI) experiments. The activation maps of eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years) were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D. 6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T. Olfactory stimuli were delivered to the patients in a passive fashion using a Burghart OM4-B olfactometer with a nose piece inserted into the patients' nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol alternating with hydrogen sulfide) that were selective for olfactory nerve stimulation in the nose. The odorants were delivered to both nostrils for 1 s every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient received room air at the same flow rate. The women's group-averaged activation maps showed up to eight times more activated voxels than men for specific regions of the brain (frontal and perisylvian regions). The left and right inferior frontal regions showed a statistically significant increase in activation in women at p<0.01. In general, more women showed activation than men. The results suggest that (1) FMRI activation maps in subject groups can demonstrate correlates to psychophysical tests of olfaction, and (2) one must control for gender when performing odor-stimulated FMRI experiments.

Adolescent↗

PubMed1999

Topical ephedrine administration and nasal chemosensory function in healthy human subjects.

OBJECTIVE: To investigate dose-related effects of ephedrine on olfactory function in healthy subjects. DESIGN: Placebo-controlled, randomized, double-blind study. METHODS: Drug effects were assessed using olfactory and trigeminal psychophysical measures (intensity ratings, odor discrimination, butanol and formic acid thresholds); nasal patency was assessed by means of anterior rhinoresistometry. The investigation was performed in 24 healthy volunteers; subjects were assigned to treatments A, B, or C (3 groups with 8 subjects each; 4 women and 4 men per group). All subjects received either placebo or ephedrine in both nostrils; group A subjects received placebo, and group B and C subjects received ephedrine in dosages of 0.12 and 0.24 mg, respectively. RESULTS: Treatment with ephedrine produced a tendency toward an increase of nasal airflow. However, during the time of observation there was no significant difference between effects produced by the 2 dosages. Ephedrine had no systematic effect on measures of olfactory function. The only significant correlation to the nasal airflow was found for perceived intensity of the trigeminal stimuli, which increased with increasing flow. CONCLUSIONS: Ephedrine appeared to have neither negative nor major positive effects on intranasal chemosensory function in healthy subjects. This indicates that ephedrine may be used as a decongestant in studies on olfaction.

Administration, Intranasal↗

PubMed1999

Glia development in the embryonic CNS of Drosophila.

The major axon tracts in the embryonic CNS of Drosophila are organized in a simple, ladder like pattern. Each neuromere contains two commissures which connect the contra-lateral hemi-neuromeres and two longitudinal connectives which connect the different neuromeres along the anterior-posterior axis. The formation of these axon tracts occurs in close association with different glial cells. Loss of specific glial cells within the CNS leads to predictable defects in the organization of the CNS axon pattern. To unravel the genes underlying CNS glia development, we have conducted a saturating F2 EMS mutagenesis, screening for mutations, which disrupt axon pattern in the embryonic nervous system. We found a large number of mutations that lead to phenotypes indicative for glia defects. The analysis of the genes identified, show that glial cell differentiation requires the function of two independent regulatory pathways.

Animals↗

PubMed1999

Chemosensory event-related potentials to trigeminal stimuli change in relation to the interval between repetitive stimulation of the nasal mucosa.

Event-related potentials (ERPs) to olfactory and trigeminal stimuli have been used commonly to evaluate chemosensory dysfunction. The aim of the present study was to investigate how ERPs could be modified by repetitive stimulations of the intranasal trigeminal nerve using 52% v/v CO2 stimuli for 200 ms periods. Nine subjects were exposed to 6 sessions each during which trains of 16 stimuli were applied. The interval between stimuli was constant for each experiment, but varied between experiments (10, 20, 30, 40, 60, and 90 s). Trigeminal ERPs were obtained from three positions on the skull. Both intensity ratings and ERP amplitudes decreased as the interstimulus interval (ISI) shortened. Specifically, ratings and response amplitudes were most strongly reduced by approximately 30-50% at the shortest ISI used (10 s) and were largest at an ISI of 90 s. The decrease of amplitudes was strongest for the P46 amplitude. Our findings suggest that this may be the result of both habituation and stimulus predictability. We hypothesize that the ISI dependence of chemosensory ERPs may also be a function of an interaction between Adelta and C fibers.

Adult↗

PubMed1999

[Gustatory olfactory function test with the Güttich technique: an evaluation of the clinical value].

BACKGROUND: Testing of retronasal olfactory sensitivity is routinely performed in many ENT-departments in German speaking countries. One of the most popular tests relates to an anecdotal report by Güttich [1]. In this test, liquids are placed on the patient's tongue; the patient is then asked to describe the aroma. Assuming that anosmic patients should not use other descriptors than "sweet," "sour," "salty," and "bitter", this test design is frequently applied in disability compensation settings. Surprisingly though, so far there are no studies regarding the sensitivity or specificity of this test in terms of the differentiation between hyposmic and anosmic patients. METHODS: The present investigation was performed in 50 anosmics, 42 hyposmics, and 13 normosmics. The diagnosis "hyposmia" or "anosmia" was based on 1. the patients' history, 2. psychophysical tests using an established test of olfactory function, the "Sniffin' Sticks," and 3. the recording of olfactory evoked potentials. RESULTS: We obtained the following major results: 1. In comparison to hyposmis and normosmics, anosmic patients had greater difficulty identifying the aromas. However, correct identification was not always possible for normosmics. 2. Regarding the differentiation between anosmic and hyposmic patients, the test's sensitivity was 86% with a specificity of 62%. This clearly limits routine clinical application of this test. CONCLUSIONS: Retronasal testing appears to be an elegant and simple means in order to screen olfactory function. However, the presently investigated approach is limited with regard to the discrimination between anosmic and hyposmic patients.

Adult↗

PubMed1999

Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.

OBJECTIVE: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. DESIGN: Prospective, randomized, double-blind, single-center study. SETTING: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital. PATIENTS: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score. INTERVENTIONS: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. CONCLUSIONS: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.

Adult↗

PubMed1999

Commissure formation in the embryonic CNS of Drosophila.

Most of the neurons of the ventral nerve cord send out long projecting axons which cross the midline. In the Drosophila central nervous system (CNS) cells of the midline give rise to neuronal and glial lineages with different functions during the establishment of the commissural pattern. Here we present evidence that beside the previously known NETRIN/FRAZZLED (DCC) signalling system an additional attractive system(s) is operating in the developing embryonic nervous system of Drosophila. Attractive cues appear to be provided by the midline neurons. We show that the glial cells present repulsive signals to the previously described ROUNDABOUT receptor in addition to a permissive contact-dependent signal helping commissural growth cones across the midline. A novel repulsive component is encoded by the karussell gene. Furthermore the midline glial cells separate anterior and posterior commissures. By genetic criteria we demonstrate that some of the genes we have identified are acting in the midline glia whereas other genes are required in the midline neurons. The results lead to a detailed model relating different cellular functions to axonal patterning at the midline.

Animals↗

PubMed1999

The effect of age on odor-stimulated functional MR imaging.

BACKGROUND AND PURPOSE: The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. METHODS: Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. RESULTS: Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian regions, and cingulate gyri, with greater volume in the younger group than in the older group. The right inferior frontal, right perisylvian, and right and left cingulum had the largest number of voxels activated. The most common sites of activation on individual maps in both groups were the right inferior frontal regions and the right and left superior frontal and perisylvian zones. CONCLUSION: Given similar olfactory task paradigms, younger subjects showed a greater number of activated voxels than did older subjects. One must be cognizant of this effect when designing studies of odor-stimulated functional MR imaging.

Adolescent↗

PubMed1999

Experimentally induced nasal irritation.

The aim of this study was to develop a method that is suited for the induction of nasal irritation. For this purpose inflammatory responses were analysed after challenging the nasal mucosa with experimentally induced cold, dry air (8 l/min, 22 degrees C, 20 %RH). To assess inflammatory effects we determined inflammatory mediators (prostaglandin E2 [PGE2], thromboxane B2 TXB2[, peptide leukotrienes pLT: LTC4, LTD4, LTE4[) in nasal lavage fluid which was sampled before, immediately after suprathreshold stimulation, and one hour after termination of the stimulation. In addition, subjects estimated the intensity of pain during the stimulation. Cold, dry air produced strong painful sensations which increased throughout the stimulation period. A significant increase of the inflammatory mediator pLT was observed after stimulation; mean concentrations of PGE2 and TXB2 also showed a tendency to increase. One hour after termination of the stimulation the concentration of these inflammatory mediators returned to baseline which indicates the reversibility of the effects of nasal irritation. These data suggest, that this model may be a useful tool in investigations of mucosal irritation as, for example, induced by environmental agents.

Adult↗