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T Hummel

Publications and source records attributed to T Hummel.

At least 127 records · Page 7Linked to original sources

Chronobiology of nasal chemosensitivity: do odor or trigeminal pain thresholds follow a circadian rhythm?

Odor and trigeminal pain thresholds were studied four times each at 24:00, 04:00, 08:00, 12:00, 16:00 and 20:00 h in randomized order on different days in five healthy male volunteers. No circadian rhythm of olfactory or trigeminal thresholds were observed. However, the variability of odor, but not pain thresholds, increased from 04:00 h (thresholds between 0.4 and 1.2 p.p.m.) to 16:00 h (thresholds between 0.1 and 2 p.p.m.). It is hypothesized that environmental influences contribute to this increase in variance.

Adult↗

Antinociceptive effects of the kappa-opioid receptor agonist RP 60180 compared with pentazocine in an experimental human pain model.

Agonists at kappa-opioid receptors may preserve the analgesic properties of mu-opioidergic agonists while avoiding their major adverse effects. The present study was aimed to investigate the antinociceptive effects of the new kappa-opioid receptor agonist RP 60180. An experimental pain model was used based on specific pain stimuli and event-related potentials. Effects of RP 60180 were compared to placebo and to pentazocine that served as positive control. Twenty healthy male volunteers participated in a placebo-controlled, randomized, double-blind, five-way cross-over study. Single peroral doses of RP 60180 (0.1, 0.5, and 1.0 mg), pentazocine (50 mg), and placebo were administered. Pain was induced by means of short pulses of gaseous CO2 applied to the nasal mucosa. In response to these stimuli, chemo-somatosensory event-related potentials (CSSERP) and pain ratings were recorded. Maximum antinociceptive effects were observed 2 h after the administration of 1.0 mg of RP 60180 and 50 mg of pentazocine. This was shortly after RP 60180 had reached the maximum plasma concentration and when highest plasma concentrations of pentazocine were measured. Both RP 60180 and pentazocine reduced pain-related CSSERP amplitudes by approximately 40% at this time. Pentazocine tended to produce more side effects. These results indicate the potential therapeutic value of kappa-agonist analgesics.

Adult↗

Responses of T2-4 spinal cord neurons to irritation of the lower airways in the rat.

The aim of the study was to investigate the information processing in the thoracic spinal cord (T2-4) after chemical irritation of the lower airways. Experiments were performed in pentobarbital sodium-anesthetized and pancuronium-paralyzed male Sprague-Dawley rats. Balloon distension of the esophagus was used as the search stimulus. Ammonia and smoke were applied by means of a tracheal cannula; they produced excitatory, inhibitory, and biphasic responses in a concentration-related manner (ammonia 39/39; smoke 23/ 39). Inhaled irritant-responsive neurons exhibited a number of similarities that have been described for neurons responding to stimulation of other thoracic viscera. These similarities relate to the distribution of neurons in the deeper laminae of the thoracic spinal cord, the relatively small number of neurons receiving input from the lower airways, the extensive convergent input from the skin and other thoracic viscera, and the pattern of responses. In addition, both stimulus-induced responses and spontaneous activity are subject to modulation from supraspinal sites. On the basis of responses to inhaled irritants after either spinal cord or vagus nerve block/transection, these T2-4 spinal neurons are likely to receive spinal afferent input that is modulated by vagal-brain stem input.

Ammonia↗

Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson's disease.

Decrease of olfactory function in patients with Parkinson's disease (PD) has been reported by several authors. The current study investigated olfaction in PD patients using olfactory event-related potentials (OERPs) as an electrophysiologic correlate of olfactory function in combination with psychophysical testing. A specific focus was the influence of antiparkinsonian drugs. We investigated PD patients treated with antiparkinsonian drugs (n = 13) and PD patients who received no pharmacologic treatment (n = 18). They were compared to age- and sex-matched control subjects (n = 38). To obtain OERPs, stimulants were chosen to stimulate specifically the olfactory nerve (2.1 ppm vanillin, 0.8 ppm H2S). In addition, chemosomatosensory event-related potentials were recorded after trigeminal stimulation with 52% v/v CO2. Moreover, the subjects' ability to identify and to discriminate odorants was tested by means of a "squeeze bottle" technique. The study yielded the following major results: (1) Odor identification was impaired in PD patients. It was not influenced by treatment with antiparkinsonian drugs. (2) The OERP latencies were prolonged in both PD patients taking and not taking antiparkinsonian drugs; however, this effect was more pronounced in PD patients taking antiparkinsonian drugs. (3) The intranasal chemosensory trigeminal system seemingly was neither affected by the neuronal degeneration seen in PD nor by treatment with antiparkinsonian drugs.

Adult↗

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes.

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.

Animals↗

CNS midline development in Drosophila.

The first cells specified during CNS development of vertebrates and invertebrates are the cells located at the midline of the neuroepithelium. In Drosophila the development of these cells requires inductive signals from the mesoderm. Later in CNS development, the midline cells are in turn influencing the flanking neuroectoderm, contributing to the establishment of dorsoventral positional information. During axonal pattern formation the midline cells are required in guiding commissural growth cones towards and across the midline. The midline consists of only few, easily identifiable neuronal and glial cells per segment. The development of midline glial cells is relatively well understood. Their differentiation appears to be controlled by the concomitant expression of two different sets of transcription factors. Activation of glial differentiation mediated by the ETS transcription factor encoded by pointed (whose activity depends on EGF-receptor signalling) occurs in concert with repression of neuronal differentiation mediated by the Zn-finger transcription factor encoded by tramtrack.

Animals↗

A test for the screening of taste function.

The overall aim of the present study was to investigate a new method for the screening of taste function in a clinical context. Instead of dripping liquids onto the tongue, thin edible wavers were used. One-hundred healthy subjects participated in the study (41 male, 59 female; mean age: 52 years; age range: 20-89 years). Supra-threshold taste stimuli were presented as flavoured wavers made from flour and water. Sequential testing was performed regionally on the anterior one-third of the tongue and as whole mouth testing. When comparing ratings for the 5 different wavers separately for regional and whole mouth testing, differences between qualities only emerged for regional testing. Women were found to have less difficulty in taste identification which was most pronounced for regional testing. No effects of the subjects' age were observed. In conclusion, the wavers were found to be easy to use; they have a shelf-life of 2 to 3 years and can be carried in the pocket. The results indicate that the wavers may be suited for the screening of gustatory function, especially in a clinical setting.

Adult↗

[Surgical interventions in extracorporeal membrane oxygenation (ECMO)].

Extracorporeal membrane oxygenation is a suitable technique for short-term treatment of resistant respiratory failure with a comparably low mortality rate of 32%. However, pulmonary complications are quite often encountered during ECMO therapy making thoracic interventions necessary. The most frequent of these complications is hemorrhage followed by lung fistula, which remain resistant to conventional therapy. The indication for operative lung resection during ECMO treatment must remain restricted to selected cases, since these procedures have a high morbidity.

Adult↗

Peripheral electrophysiological responses decrease in response to repetitive painful stimulation of the human nasal mucosa.

The study aimed to investigate the relation of both negative mucosal potentials (NMP) obtained from respiratory epithelium, and pain ratings to repetitive stimulation with CO2 (21 subjects). Trains of four stimuli of identical intensity (70% v/v) were applied at a constant interseries interval (approximately 60 s) but different interstimulus intervals (ISI) of 2 s or 6 s. At an ISI of 6 s, ratings decreased while they increased at an interval of 2 s (P < 0.01). This change was accompanied by the buildup of burning pain probably relating to the 'wind-up' of spinal neurons. In contrast, the decrease of NMP amplitudes was stronger the shorter the ISI (P < 0.01). These findings are in line with the view that the NMP reflects activation of epithelial nociceptors (C-fibers and/or A delta-fibers).

Adult↗

Peripherally obtained electrophysiological responses to olfactory stimulation in man: electro-olfactograms exhibit a smaller degree of desensitization compared with subjective intensity estimates.

After chemical stimulation of the human olfactory epithelium it is possible to record a negative response (electro-olfactogram, EOG) which is interpreted as the summated receptor potentials of the olfactory nerve. The aim of the present investigation was to test the EOG's changes in relation to pairs of stimuli. Stimulation was performed with vanillin (0.8 ppm) regarded to exclusively excite fibers of the olfactory nerve. Ten healthy volunteers participated in the experiments. Pairs of stimuli were applied at different interstimulus intervals ISIs (2-8 s). EOG could be recorded in 6 out of 10 subjects. After olfactory stimulation the responses' peak amplitude was found to range from 0.15 to 1.8 mV. When pairs of olfactory stimuli were applied responses obtained at an ISI of 8 s were clearly separated whereas at an ISI of 2 s responses were superimposed on each other. As with an ISI of 8 s, the amplitude produced by the second stimulus was nearly as great as the first responses' amplitude (decrease by approximately 20%). In contrast, intensity estimates obtained in an additional experiment (n = 10) decreased by 40-60%. Based on the present data peripheral encoding in the olfactory system appears to be less subject to desensitization compared to the decrease of intensity estimates.

Adult↗

Development and function of embryonic central nervous system glial cells in Drosophila.

Each abdominal neuromere of a Drosophila embryo contains about 60 glial cells [Klämbt C, Goodman CS (1991): Glia 4:205-213; Ito et al. (1995): Roux's Arch Dev Biol, 204:284-307]. Among these, the midline and longitudinal glia are described to some detail. The midline glia are located dorsally in the nerve cord ensheathing the two segmental commissures. They are required for the proper establishment of commissures. The longitudinal glia, the A and B glia, and the segment boundary cells (SBC) are covering the longitudinal connectives. The longitudinal glia prefigure longitudinal axon paths and appear capable of regulating the expression of neuronal antigens. In the following we summarize the knowledge on the function of these glial cells.

Animals↗

Intranasal chemoreception in patients with multiple chemical sensitivities: a double-blind investigation.

Multiple chemical sensitivities (MCS) has become an increasingly frequent diagnosis assigned to patients with symptoms associated with exposures to environmental chemicals. Since the characteristic symptoms of MCS are triggered by very low concentrations of chemicals, in the range of olfactory thresholds, it is widely believed that the intranasal chemoreceptive senses are involved in the pathophysiology of MCS. Thus, the present study addressed both the olfactory and trigeminal systems: using a double-blind approach we investigated whether MCS patients show differences in responses after exposure to either room air or low concentrations of a widely used chemical agent (2-propanol). A total of 23 patients participated in the experiments (mean age 47 years; 13 female, 10 male). MCS was diagnosed according to Cullen's criteria Performance of the nasal chemical senses was established by means of chemosensory event-related potentials (CSERP) and subjective measures of olfactory function (odor discrimination, phenylethyl alcohol odor thresholds). CSERP were recorded in response to olfactory (H2S), and trigeminal (CO2) stimuli. The study provided three major results: (1) Approximately 20% of patients diagnosed with MCS presented symptoms regardless of the type of challenge, suggesting the susceptibility of MCS patients to unspecific experimental manipulations. (2) Changes in CSERP latencies indicated a change in the processing of both olfactory and trigeminal stimuli. (3) While odor threshold remained unchanged, the patients' ability to discriminate odors decreased after exposure to room air. In contrast, this decrease was less pronounced after exposure to 2-prop. Summarily, MCS patients respond to challenge with 2-prop with changes of chemosensory perception which might increase their susceptibility to environmentally volatile chemicals. Changes in the pattern of event-related potentials are interpreted as the possible change of the orientation of cortical generators, i.e., neuronal populations that were involved in the processing of chemosensory information. However, investigations in healthy controls are needed in order to draw further conclusions.

1-Propanol↗

Analgesic effects of propyphenazone in comparison to its combination with caffeine.

OBJECTIVE: The aim of the study was to investigate whether the analgesic effect of propyphenazone (PROP) was increased when it was administered in combination with caffeine (CAFF). METHODS: For assessment of analgesia a model was chosen based on chemo-somatosensory event-related potentials (CSSERP) elicited by stimulation of the nasal mucosa. Twenty healthy volunteers participated in the experiments. The study followed a placebo-controlled, randomised, double-blind, 5-fold cross-over design. Each of the 5 medications (400 mg PROP, 600 mg PROP, 400 mg PROP + 100 mg CAFF, 600 mg PROP + 150 mg CAFF, placebo) was orally administered. Experiments were separated by at least 5 days. In addition to assessment of CSSERP, subjects estimated the intensity of the stimulus. Drug effects unrelated to nociception were monitored, and in addition, the plasma levels of PROP were also analysed. RESULTS: While 400 mg PROP did not significantly reduce the amplitude of CSSERP in comparison to placebo, all other medications produced a significant decrease in amplitudes. For both dosages of PROP, there was a significant amplification of the antinociceptive effect of PROP by CAFF, as indicated by the decrease in CSSERP amplitude. A significant effect of the factor "drug" was also found in the spontaneous EEG, indicating an arousal reaction after CAFF. No significant differences between plasma levels of PROP were found when applied either alone or in combination with CAFF. CONCLUSION: The significant increase in the antinociceptive effect of PROP when administered together with caffeine appears to be related either to amplification of PROP's antinociceptive actions by CAFF or an atinociceptive effect of CAFF itself.

Administration, Oral↗

[Venovenous extracorporeal membrane oxygenation (ECMO) with a heparin-lock bypass system. An effective addition in the treatment of acute respiratory failure (ARDS)].

Mortality of severe acute respiratory distress syndrome (ARDS) in Germany is about 60%. Respiratory therapy can make the lung injury worse by high positive airway pressures, high tidal volumes and high inspiratory oxygen concentrations. Extracorporeal membrane oxygenation (ECMO) was employed to reduce aggressive mechanical ventilation, but it has not been proved to be superior to conventional ventilation. However, encouraged by recently developed improvements in the technique and concept of ECMO, we introduced this therapy into our program for the treatment of ARDS. PATIENTS AND METHODS. All patients with severe ARDS (lung injury score > 2.5) admitted to our multidisciplinary intensive care unit from March 1992 to March 1995 were evaluated prospectively. After admission, the patients first underwent a conventional therapeutic approach, including pressure-controlled inverse-ratio ventilation, permissive hypercapnia, changes in body position (in particular, the prone position), negative fluid balance, anti-biotics, and low-dose hydrocortisone infusion. ECMO via a covalently heparin-coated, venovenous bypass-system with a vortex pump and two membrane lungs was performed if ARDS did not improve after 24-96 h of conventional therapy and if two of three of the slow-entry criteria for ECMO were fulfilled: (1) PaO2/FiO2 < 150 mmHg at PEEP > 5 mbar; (2) semistatic compliance < 30 ml/mbar; (3) right-left shunt > 30%. Only in cases of life-threatening hypoxemia (PaO2 < 50 mmHg at FiO2 1.0 and PEEP > 5 mbar for > 2 h (fast-entry criteria) was ECMO instituted immediately. RESULTS. Sixty patients fulfilled the entry criteria for our study. Thirty-nine patients were treated with a conventional protocol, 37 after improvement of ARDS and 2 who had not improved but in whom there were contraindications to the use of ECMO. ECMO was performed in 10 patients who had not improved, but who fulfilled the slow-entry criteria and in 11 primarily hypoxemic patients who fulfilled the fast-entry criteria. The survival rate was 30/39 (77%) for the conventional therapy group, 6/10 (60%) for the slow-entry group, and 11/11 (100%) for the fast-entry group. The onset of ECMO allowed a significant decrease in peak and mean airway pressures, tidal volume, ventilatory rate, minute volume and inspiratory oxygen concentration. Sufficient gas exchange was provided, and pulmonary artery pressures significantly decreased on bypass. The most frequent complications on bypass were pneumothorax (15/21 patients) and bleeding (7/21 patients). CONCLUSION. In comparison with the historical results at our own institution, the present study demonstrates an improvement in the survival rate from 56% to 78% since ECMO has become available. We conclude that venovenous ECMO with a heparin-bonded bypass circuit is an effective additional option for the treatment of patients with severe ARDS.

Adolescent↗

Assessment of analgesia in man: tramadol controlled release formula vs. tramadol standard formulation.

OBJECTIVE: The present study tested analgesia produced by a new controlled release formulation of tramadol. The investigation employed an experimental pain model based on chemo-somatosensory event-related potentials (CSSERP) in response to painful chemical stimuli applied to the nasal mucosa. STUDY: Twenty healthy volunteers participated in the experiments, which followed a controlled, randomised, double-blind, 3-way cross-over design. Each of the three medications (tramadol 100 mg [T100], tramadol controlled release 100 mg [TCR100] and tramadol controlled release 150 mg [TCR150]) was administered orally to fasting subjects. There was at least a 6 day washout period between tests. Each experiment was divided into five sessions, which took place before and 2, 4, 6, and 12 h after drug administration. In addition to the assessment of CSSERP, subjects rated the intensity of both the tonic and phasic painful stimuli. Nonspecific drug effects were also monitored by means of frequency analysis of the spontaneous EEG, ratings of adverse effects, and the subjects' performance in a tracking task. RESULTS: The significant reduction of amplitude N1 at central recording positions indicated that TCR 150 was the most effective analgesic 12 h after administration. Both 6 and 12 h after administration TCR 100 was more effective in terms of analgesia compared to T100. In addition, TCR100 appeared to produce fewer adverse effects than the standard formulation of tramadol. CONCLUSIONS: The controlled release formulation can be expected to become a valuable tool in peroral therapeutic regimens for chronic pain.

Adult↗

Loss of olfactory function leads to a decrease of trigeminal sensitivity.

Healthy controls were compared to patients with decreased olfactory sensitivity (n = 32) to investigate interactions between the olfactory and trigeminal systems. Amplitudes of chemo-somatosensory event-related potentials in response to suprathreshold trigeminal stimuli (CO2) were found to be smaller in patients (P < 0.05) indicating a decrease of trigeminally mediated sensations.

Action Potentials↗

"Sniffin' sticks": screening of olfactory performance.

"Sniffin' Sticks" is a new test of nasal chemosensory performance based on pen-like odour-dispensing devices. This portable test is suited for repetitive, inexpensive screening of odour identification. The test includes a forced odour-identification task for seven odours performed by means of a list of four items (multiple-choice). In 146 subjects the basic screening test was compared to a down-scaled version of the UPSIT (CC-SIT). Sniffin' Sticks exhibited a relatively higher coefficient of correlation with the subjects' age; they also demonstrated the women's superior olfactory sensitivity more pronounced when compared to men. In addition, the coefficient of correlation between age and olfactory performance was slightly higher when the sticks were used. Preliminary investigations in nine patients with impaired olfactory function (i.e., anosmic or hyposmic patients) revealed significantly lower scores in patients compared to healthy controls matched for age and sex (p < 0.001). It is concluded that Sniffin' Sticks may be useful in the routine clinical assessment of olfactory performance where both time and costs matter.

Adult↗