Biomedical subjects

T Hummel

Publications and source records attributed to T Hummel.

At least 19 recordsLinked to original sources

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↗

PubMed1998

Factors affecting pain intensity in a pain model based upon tonic intranasal stimulation in humans.

OBJECTIVE: The present publication describes an inflammatory pain model based on an air-stream introduced in the nasal cavity. The aim of the present study was to investigate the influence of flow, humidity and temperature of the air-stream on the intensity of the evoked pain sensations. METHODS: Six healthy volunteers participated in the study. Pain was produced by a stream of air introduced to the nasal cavity at different flow rates (5, 6 and 81/min), humidity (20 and 80% relative humidity) and temperature (16, 24, and 32 degrees C). The evoked pain was quantified by means of visual analogue scales. RESULTS: The air-stream induced a dull and burning painful sensation. The intensity of pain was found to be related to the air-stream's humidity and temperature. Specifically, a dry air-stream (20% relative humidity) evoked significantly stronger pain than a humidified air-stream (80% relative humidity). Pain was significantly greater at a temperature of 32 degrees C than at 24 degrees and 16 degrees C, while the temperatures of 16 and 24 degrees C did not differ with respect to pain intensity. In contrast, a tendency towards stronger pain produced by a flow of 81 compared to that with 51 could not be statistically justified within the present study. CONCLUSIONS: The non-invasive pain stimulus was found to be easily applicable and the evoked pain sensation could be modified by variation of humidity and temperature of the air-stream.

Adult↗

PubMed1998

[Health-related quality of life. Long-term survival in patients with ARDS following extracorporeal membrane oxygenation (ECMO)].

UNLABELLED: Treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) can be lifesaving but requires maximal use of intensive care resources over prolonged periods of time, resulting in high costs. Little is known about the health-related quality of life (HRQL) in long-term survivors. This case-controlled retrospective study was designed to assess the health-related quality of life in long-term survivors of ARDS and ECMO-therapy. METHODS: 14 long-term survivors of ARDS (APACHE II score = 24, Lung Injury Score = 3.25, median values) treated using ECMO between 1992 and 1995 (median time interval between data collection and discharge from the ICU 16 months) and 14 ARDS-patients conventionally treated during the same period (group I) were identified and completed the SF-36 Health Status Questionnaire (Medical Outcome Trust, Boston, USA). 14 healthy subjects (group II) were drawn at random from a large data base generated to provide normal values for the SF-36 in a German population. All three groups were comparable with respect to sex and age. RESULTS: Long-term survivors of ECMO-therapy reported significant reductions in physical functioning when compared with patients treated by mechanical ventilation alone (group I, -12.5%, p < 0.05) and with healthy controls (group II, -50%, p < 0.05) and showed a higher incidence of chronic physical pain (+5% and +24%, respectively, p < 0.05). There were no differences with regard to the mental health dimensions of the SF-36 (e.g. vitality, mental health index or social functioning) between ECMO-patients and all controls. Nine patients (64.3%) from the ECMO group versus all patients treated conventionally (group I) had full-time employment (p = 0.46, Chi2 test). CONCLUSIONS: The majority of long-term survivors of ECMO-treatment show good physical and social functioning, including a high rate of employment. The more aggressive approach of ECMO-therapy and a possibly more severe underlying disease process may explain impairments in health-related quality of life outcomes after ECMO-treatment. Despite these limitations, long-term survivors of ECMO-therapy are able to reach a highly satisfactory health-related quality of life.

APACHE↗

PubMed1998

Effects of the nasal decongestant oxymetazoline on human olfactory and intranasal trigeminal function in acute rhinitis.

OBJECTIVE: The placebo-controlled, randomized, double-blind study was performed to investigate dose-related effects of oxymetazoline on olfactory function during the course of the spontaneously occurring cold. METHODS: Drug effects were assessed using olfactory/ trigeminal event-related potentials (ERPs) and psychophysical measures (intensity ratings, odor discrimination, butanol threshold); nasal volume was monitored by means of acoustic rhinometry. The investigation was performed in 36 subjects (mean age 24.6 years). The subjects were assigned to treatment groups A, B or C (three groups with 12 subjects each; six women and six men per group). All the subjects received placebo on the left side; on the right side, group A subjects received placebo and group B and C subjects received 0.25 mg x ml(-1) and 0.5 mg x ml(-1) oxymetazoline, respectively. After onset of the rhinitis (day 0) measurements were performed on days 2, 4, 6 and 35. RESULTS: Oxymetazoline clearly produced an increase in nasal volume. However, during the 2-h observation period, effects produced by the two dosages were not significantly different. Despite the increase in nasal volume, oxymetazoline produced only an increase of the overall intensity of H2S stimuli; it had no systematic effect on other measures of olfactory or trigeminal function. In addition, after all the subjects had recovered from the cold, oxymetazoline had no significant main effect on olfactory/trigeminally mediated sensations. CONCLUSIONS: Oxymetazoline appeared to have neither negative nor major positive effects on intranasal chemosensory function. It is hypothesized that oxymetazoline needs to be applied locally to the area of the olfactory cleft in order to significantly improve olfaction during the course of the common cold.

Acute Disease↗

PubMed1998

Chemosensory event-related potentials change with age.

The study examined age-related changes in the perception of olfactory and trigeminal chemical stimuli using chemosensory event-related potentials (CSERP). Three groups of healthy volunteers, each comprised of 8 men and 8 women, were tested (age ranges 15-34, 35-54, and 55-74 years). Subjects underwent extensive psychological testing focusing on impairments of memory and attention. In addition, odor identification and discrimination ability was evaluated, as well as detection threshold sensitivity for two odorants. Odor discrimination scores exhibited a significant age-related decrease. Significant age-related changes were also observed for CSERP N1P2 and P2 amplitudes, and for the N1 peak latency. The age-related decrease of CSERP amplitudes appeared to follow a different time course for responses to trigeminal and olfactory stimulants.

Adolescent↗

PubMed1998

Relation of olfactory event-related potentials to changes in stimulus concentration.

OBJECTIVE: The aim of this study was to investigate the influence of odorant concentration on the olfactory event-related potential (OERP). METHODS: OERP were evaluated in 8 men and 8 women (17-34 years of age) in response to 4 concentrations of vanillin (7, 28, 56 and 84% v/v). Sixteen presentations of each concentration (stimulus duration 200 ms, interval 40 s, flow 81/min) were applied in a randomized order. EEG recordings were made at 3 midline sites (pos. Fz, Cz, Pz). Amplitudes and latencies of four peaks were measured (latencies in ms at Pz after stimulation with 84% v/v vanillin): P1 (277), N1 (348), P2 (412) and P3 (496). Statistical analysis was performed with MANOVAs ('concentration', 'recording site' = within-subject-factors; 'age' as covariate). RESULTS: With increasing stimulus concentration amplitudes became significantly larger; this was most pronounced for P3 (P1N1: F = 2.90, P < 0.05; N1P2: F = 5.15, P < 0.01; N1P3: F = 35.7, P < 0.001; P3: F = 38.6; P < 0.001). Correspondingly, latencies shortened with increasing concentrations (P1: F = 25.2; N1: 17.51; P2: 14.8; P3: 13.4; all P < 0.001). While there was no correlation between OERP amplitudes and butanol odor detection thresholds, latencies were the shorter the lower the subjects' thresholds (coefficients of correlations for peak latencies at Cz for 84% v/v: P1 rl5 = -0.59; N1 rl5 = 0.58; P2 r15 = -0.55; P3 r15 = -0.45). CONCLUSIONS: The results indicated that both OERP amplitudes and latencies are related to the concentration of olfactory stimuli. They also suggested that latencies exhibit a stronger relation to changes in stimulus intensity compared to OERP amplitudes.

Adolescent↗

PubMed1998

Handedness is a determining factor in lateralized olfactory discrimination.

The study aimed to re-investigate differences in olfactory thresholds and odor discrimination between the left and right sides in relation to the handedness of healthy subjects. Twenty left- and 20 right-handers participated; all were in excellent health with no indication of any major nasal or health problems, and all were non-smokers. The two groups were comparable in terms of sex and age (left-handers: 11 women, 9 men, median age 25 years; right-handers: 9 women, 11 men, median age 26 years). Odor thresholds did not differ in relation to handedness. However, in the odor discrimination task the left-handers performed significantly better at the left side compared with the right nostril; this pattern was reversed in the right-handers. The data indicate that, similar to other sensory systems, higher olfactory functions exhibit a certain degree of lateralization.

Adult↗

PubMed1998

Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome.

OBJECTIVES: Despite considerable progress in intensive care management of the acute respiratory distress syndrome (ARDS), little is known about health-related quality of life in long-term survivors. In addition, intensive care treatment can be extremely stressful, and many survivors of ARDS report adverse experiences such as respiratory distress, anxiety, or pain during intensive care unit (ICU) treatment. This study was performed to assess health-related quality of life in survivors of ARDS and to test the hypothesis that adverse experiences during ICU treatment result in posttraumatic stress disorder (PTSD) and negative effects on health-related quality of life. DESIGN: Retrospective, cohort, case-controlled analyses. SETTING: A 12-bed multidisciplinary ICU of a tertiary care university hospital, capable of providing extracorporeal life support for adults with severe ARDS. PATIENTS: We studied 80 patients who were admitted to our hospital from 1985 to 1995 and who survived an episode of ARDS. ARDS was defined according to the criteria of the American-European Consensus Conference on ARDS. INTERVENTIONS: Health-related quality of life was measured using the Health Status Questionnaire of the self-administered Medical Outcomes Study Short Form Survey that consists of 36 questions (SF-36) and the German version of the Post Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10), a self-report scale for the diagnosis of posttraumatic stress disorder based on the Diagnostic and Statistical Manual (Third Edition) criteria (American Psychiatric Association). The number of adverse experiences (anxiety, respiratory distress, pain, and nightmares) during intensive care was evaluated by means of a structured questionnaire. For each patient with ARDS, three age- and gender-comparable controls were randomly selected from databases providing normal values for the SF-36 and PTSS-10 scores in populations at risk for posttraumatic stress disorder. MEASUREMENTS AND MAIN RESULTS: Survivors of ARDS showed statistically significant impairments in all eight health dimensions of the SF-36 when compared with normal controls (median reduction 21.3%, p < .006) with maximal impairments in physical function (median reduction 28.9%, p = .000) and a 38% higher frequency of chronic pain (p = .0001). Three of 34 patients reporting none, or one, adverse experience had evidence of posttraumatic stress disorder vs. 19 of 46 patients remembering multiple traumatic episodes (p = .007). Patients reporting multiple adverse experiences described the lowest health-related quality of life, with maximal impairments in psychosocial functioning (p < .005) and only small limitations in physical function. CONCLUSIONS: Long-term survivors of ARDS describe a good overall health-related quality of life. Major impairments in mental health domains of health-related quality of life are associated with the development of posttraumatic stress disorder and are a possible result of traumatic experiences during ICU therapy.

Adolescent↗

PubMed1998

Lateralized and bilateral olfactory function in patients with chronic sinusitis compared with healthy control subjects.

Results of this study demonstrated that a new olfactory test, the "Sniffin' Sticks," can be used to distinguish hyposmic patients with chronic sinusitis (n = 63) from control subjects. Dirhinic testing yielded improved olfactory sensitivity compared with monorhinic testing. However, dirhinic results were not significantly different from results obtained for the best nostril.

Adolescent↗

PubMed1998

Olfactory and intranasal trigeminal event-related potentials in anosmic patients.

The aim of this study was to investigate the usefulness of chemosensory event-related potentials (CSERPs) in response to both olfactory and intranasal trigeminal stimulation in the diagnosis of anosmia. Forty-four patients participated. Gaseous CO2 was used for trigeminal stimulation, vanillin and H2S were used as olfactory stimulants. Event-related potentials to olfactory stimuli could not be obtained in any of the anosmic patients, indicating the complete loss of the sense of smell. However, all patients responded to stimulation of the trigeminal nerve with CO2. These data clearly demonstrate the clinical significance of CSERPs in the assessment of anosmia.

Adolescent↗

PubMed1998

Scratch density differentiates microsmic from normosmic and anosmic subjects on the University of Pennsylvania Smell Identification Test.

During assessment of smell function using the University of Pennsylvania Smell Identification Test, we observed that some persons with diminished smell perception seemed to perserverate in their attempts to release the odorant from the microencapsulated odorant strips. In this study we quantified the marked area of 1680 such strips from tests administered to 42 anosmics, normosmics, and microsmics. The density of pixels on the microencapsulated labels from the microsmic patients was greater than that from the other two groups, which did not differ significantly from one another. These data suggest (i) that persons with diminished olfactory ability attempt to increase the perceived intensity of the stimulus by marking the test's scent strips more vigorously and (ii) that the density of such marking may prove useful in detecting malingerers attempting to feign microsmia.

Aged↗

PubMed1998

Asthma management: the challenge of equivalence.

Increasing prevalence and severity of asthma worldwide encourage the development of new antiasthmatic drugs, alternative treatment regimens and improved formulations of established drugs. Whereas the efficacy of new chemical entities (NCEs) is usually demonstrated by superiority over placebo or a subtherapeutic dose of the active drug, equivalence concepts have to be used in the following situations: the need to replace chlorofluorocarbon (CFC) propellants for inhalative asthma medications by suitable alternatives, and the need to demonstrate that an alternative treatment regimen is not clinically inferior to an established reference treatment. To cover both situations, the recent ICH guidance on biostatistics clearly distinguishes between two-sided equivalence trials and one-sided non-inferiority trials. In this context, non-inferiority always means "not inferior by a clinically relevant amount". After having confirmed non-inferiority, superiority of the alternative test treatment over the reference treatment can additionally be tested without the need to adjust the significance level. The definition of equivalence acceptance limits becomes crucial, particularly in studies conducted in the flat range of the dose-response curve of inhaled steroids. In order to assess the non-inferiority of steroid sparing add-on treatments we propose a one-sided test based on post-/pre-ratios which have substantially reduced coefficients of variation compared to the post-treatment values themselves. The non-inferiority acceptance limit of 0.90 - as opposed to 0.80 in bioequivalence assessment - reflects clinically irrelevant changes of lung function variables. The proposed methodology is illustrated by 2 examples from randomized, double-blind, parallel-group studies comparing inhaled steroid plus theophylline versus doubling the steroid dose in asthmatics who are symptomatic on low-dose inhaled steroid.

Administration, Inhalation↗

PubMed1997

[ARDS and Wegener granulomatosis].

UNLABELLED: Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. This disease can present as a clinical picture which resembles sepsis and adult respiratory distress syndrome (ARDS). Wegener's disease requires immunosuppression which can have detrimental consequences when used in sepsis. The following case report illustrates the diagnostic difficulties encountered by intensive care physicians treating severe pulmonary failure and multiple organ dysfunction in Wegener's granulomatosis appearing as ARDS with sepsis. CASE REPORT: A 19-year-old female patient had developed acute respiratory and renal failure after a prolonged period (many months) of antibiotic resistant otitis, sinusitis and mastoiditis. The patient had required intubation at another hospital and there was a history of tension pneumothorax and cardiopulmonary resuscitation during mechanical ventilation. Emergency extracorporeal membrane oxygenation (ECMO) for acute hypercapnic and hypoxic respiratory failure was instituted and the patient was transported to our institution while on ECMO. The patient was treated empirically for suspected pulmonary and systemic infection and received hydrocortisone (0.18 mg/kg/h) as part of a protocol-driven treatment of septic shock in addition to antibiotic and antimycotic regime. The use of ECMO was required for 10 and mechanical ventilation for another 50 days after admission. After successful extubation, central nervous system dysfunction became evident with a somnolent and generally unresponsive patient. When the hydrocortisone dose was gradually tapered, the clinical status of the patient further deteriorated, pulmonary gas exchange worsened and she developed renal failure with proteinura and hematuria. A renal biopsy was performed demonstrating vasculitis and focal segmental glomerulonephritis, a systemic granulomatous vasculitis was suspected; the serum was tested for anti-proteinase 3 antibodies (PR3-ANCA) and turned out to be positive (17.5 U/ml; normal range < 7 U/ml). The morphologic findings from renal biopsy, the positive test for antiproteinase 3 antibodies and the pulmonary-renal involvement with evidence of multisystem disease established the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and prednisolone was instituted resulting in rapid improvement with recovery of pulmonary, renal and central nervous system function within two weeks. The use of ECMO in this patient served as a life-saving immediate measure usefull to "buy time" until a definite diagnosis could be established. ARDS represents an uniform pulmonary reaction to a large number of different noxious stimuli and disease entities. This case demonstrates that intensive care physicians caring for critically ill patients with ARDS should include even rare causes of pulmonary injury into their differential diagnosis.

Acute Kidney Injury↗

PubMed1997

Comparison of the antinociception produced by two oral formulations of ibuprofen: ibuprofen effervescent vs ibuprofen tablets.

OBJECTIVE: The aim of this study was to compare the dose-related effects of both ibuprofen tablets and ibuprofen effervescent [placebo, 400 and 800 mg ibuprofen (Aktren)] on phasic pain. PATIENTS: Twenty volunteers participated in this randomized, double-dummy, fivefold crossover study. METHODS: Measurements were obtained before and 15, 60 and 240 min after drug administration. Pain was produced by CO2 pulses applied to the left nostril. Subjects rated the intensity of the painful stimuli by means of a visual analogue scale. In addition, chemosomatosensory event-related potentials were recorded. RESULTS: In line with previous work, ibuprofen produced a dose-related decrease in pain-related potential amplitudes P1N1, indicating its antinociceptive effects. Higher plasma concentrations of ibuprofen were reached 15-40 min after administration of the effervescent while ibuprofen tablets had a tmax 60-90 min after administration. In addition, 60 min after intake of the effervescent a prolongation of the latencies of the potentials was observed, possibly reflecting superior antinociceptive properties when compared to ibuprofen tablets. In addition, the effervescent appeared to have more consistent effects on intensity estimates compared to ibuprofen tablets.

Administration, Oral↗

PubMed1997

The negative mucosal potential: separating central and peripheral effects of NSAIDs in man.

OBJECTIVE: We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. METHODS: According to a double-blind, randomised, controlled, threefold cross-over design, 18 healthy subjects (11 males, 7 females; mean age 26 years) received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration 500 ms, interval approximately 60 s), and tonic pain was induced in the nasal cavity by means of dry air of controlled temperature, humidity and flow rate (22 degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as peripheral correlates of pain were obtained in response to the CO2 stimuli. Additionally, the subjects rated the intensity of both phasic and tonic pain by means of visual analogue scales. RESULTS: As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans.

Adult↗

PubMed1997

'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold.

'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.

Adult↗

PubMed1997

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↗

PubMed1997

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↗