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M Knecht

Publications and source records attributed to M Knecht.

At least 19 recordsLinked to original sources
PubMed2004

Recording of the human electro-olfactogram.

Electro-olfactograms (EOG) are electrical potentials of the olfactory epithelium that occur in response to olfactory stimulation. The EOG represents the sum of generator potentials of olfactory receptor neurons. While this response has been used extensively in animal research, there are only a handful of papers describing the properties of the human EOG. In addition to a discussion of methodological issues related to the EOG, this review summarizes the characteristics and uses of these recordings. Among other results, EOGs have been used to provide evidence for the dominant role of the central nervous system in olfactory desensitization, for the functional characterization of the olfactory epithelium, the specific topographical distribution of olfactory receptors, or the expression of olfactory receptor neurons in response to exposure to odorants, and the characterization of certain odorants as olfactory receptor antagonists. In conclusion, in combination with nasal endoscopy and air-dilution olfactometry, the EOG is a unique part of a large array of techniques used to provide a complete picture of the processing of olfactory information in humans.

Animals↗
PubMed2003

[The human vomeronasal organ].

Odors influence human behavior. The perception of so-called pheromones is frequently mentioned in the context of a functional vomeronasal organ. Vomeronasal ducts can be detected in approximately half of the population. Its functionality, still a matter of debate, seems to be unlikely, at least after birth. It is easily conceivable that pheromone-induced changes in behavior are mediated through receptors in the human olfactory epithelium.

Adult↗
PubMed2002

On the chemosensory nature of the vomeronasal epithelium in adult humans.

In contrast to many lower vertebrates, the vomeronasal epithelium (VNE) in humans has long been regarded as absent or functionally irrelevant. For example, the neural connection between the VNE and the accessory olfactory bulb has been reported to degenerate during the second half of pregnancy and its presence has not been demonstrated in adults. Further, reports on the organ's occurrence in adult humans have been contradictory. The aims of this study were to collect immunohistochemical data on the neurogenic or epithelial character of the VNE [for example, with antibodies against protein gene product 9.5 (PGP 9.5), olfactory marker protein (OMP), beta-tubulin, and cytokeratin], determine its proliferative capacity (for example, proliferating cell nuclear antigen), as well as to examine the differentiation activity of VNE cells and their interactions with extracellular matrix components (for example, hyaluronan receptor CD44, galectins, and caveolin). To this end, we studied the vomeronasal organs (VNOs) of 22 human cadavers, three adult biopsies, one embryo (week 8) and one fetus (week 13) by means of immunohistochemistry. The histology of the VNE appeared extremely heterogeneous. There were sections of stratified, respiratory, and typical "pseudostratified" vomeronasal epithelia consisting of slender bipolar cells. Mostly negative immunohistochemical results for OMP indicated that the human VNE does not function like the mature olfactory epithelium. In addition, the investigations did not support the hypothesis that neural connections between the VNE and central brain structures might be present. On the other hand, the presence of some bipolar cells positive for both PGP 9.5 and soybean lectin (SBA) pointed to a neuron-like activity of a small subset of VNE cells. Proliferation antigens located in the nuclei of basally located cells of the VNE were not regularly expressed. However, positive reactions for CD44 demonstrated a high activity of VNE cells in terms of differentiation and migration. Some bipolar cells showed immunoreactivity for caveolin indicating its possible role in signal transduction and differentiation. In summary, the reaction patterns of most antibodies in the adult human VNE are different from those obtained in the olfactory epithelium and the VNO of the rat. However, the VNE shows a specific pattern of activity unique to the mucosa of the nasal cavity. Considering the histologically well differentiated epithelium and its steady maintenance, the VNE of the adult human appears to be a highly differentiated structure the function of which remains unclear.

Adult↗
PubMed2002

Hadronic light-by-light scattering contribution to the muon g - 2: an effective field theory approach.

The hadronic light-by-light contribution to a(mu), the anomalous magnetic moment of the muon, is discussed from the point of view of an effective low-energy theory. As an application, the coefficient of the leading logarithm arising from the two-loop graphs involving two anomalous vertices is computed, and found to be positive. This corresponds to a positive sign for the pion-pole contribution to the hadronic light-by-light correction to a(mu), and to a sizable reduction of the discrepancy between the present experimental value of a(mu) and its theoretical counterpart in the standard model.

Journal Article↗
PubMed2001

Imaging of the human vomeronasal duct.

The human vomeronasal duct (VND) is described as a tubular or pouch-like mucosal invagination of the anterior nasal septum. This study investigated shape, size and orientation of the VND using magnetic resonance imaging (MRI). Fifteen subjects participated (eight women, seven men; mean age 39 years, age range 18-66 years); they had been pre-selected with regard to the presence of a VND opening of 1 mm. MRI was performed before and after application of diluted gadolinium-diethylene-triamino-penta-acetic actetate (Gd-DTPA) into the left or right VND. A tubular structure was found in 12 subjects with a median length of 7 mm (range 3-22 mm; one VND with a length 47 mm). In three subjects a nearly circular, pouch-like structure was observed. Seven of the tubular VNDs were slightly bent upwards, the other five VNDs ran parallel to the floor of the nasal cavity. There was no significant gender-related difference in the length of VNDs. These data indicate considerable variability of shape, size and orientation of the human VND.

Adolescent↗
PubMed2001

Frequency and localization of the putative vomeronasal organ in humans in relation to age and gender.

OBJECTIVES/HYPOTHESES: In many species the vomeronasal organ (VNO) serves as a chemosensory organ in addition to the olfactory system. The present investigation was undertaken to study 1) the frequency of monolateral or bilateral detection of the putative VNO (pVNO) in humans, 2) its localization in humans, and 3) whether detectability of the pVNO varies with age or gender. STUDY DESIGN: Prospective. METHODS: A total of 173 subjects participated in this study (88 women and 85 men; age range, 2-91 y). Inspection of the nose was performed with a speculum and a 30 degrees endoscope. The exact localization of the VNO was measured with custom-built rulers. RESULTS: The study revealed the following major results: 1) A pVNO is detectable in approximately two-thirds of the population and bilateral pVNOs are present in approximately 40% of investigated subjects, 2) its localization on the left and right nasal septum is almost symmetrical, and 3) and detectability of the pVNO is not related to age or gender. CONCLUSIONS: The present data indicated that the pVNO is present in approximately two-thirds of the population. This value may be biased by methodological or biological factors; nevertheless, it indicates that the pVNO is not observed in all humans regardless of age and gender. Thus, considering its variability in shape and immunohistochemical characteristics and the missing nerval connections between the peripheral "organ" and the central nervous system, the present results are not suited to argue for a functional significance of the pVNO in humans.

Adolescent↗
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↗
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

Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure.

BACKGROUND: Impaired endothelium-dependent, nitric oxide (NO)-mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is unknown. METHODS AND RESULTS: To specifically assess the synthetic activity of the L-arginine-NO metabolic pathway, urinary excretion of [15N]nitrates and [15N]urea was determined after a primed continuous intravenous infusion of L-[15N]arginine (40 micromol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise. After infusion of L-[15N]arginine, 24-hour urinary excretion of [15N]nitrates was decreased in patients with congestive heart failure at rest (2.2+/-0.5 versus 8.0+/-2.3 micromol/24 h) and during submaximal exercise (2.4+/-1.2 versus 11. 4+/-4.0 micromol/24 h) compared with control subjects (both P<0.01). After infusion of L-[15N]arginine, 24-hour urinary excretions of [15N]urea at rest in patients with congestive heart failure and control subjects were not different (1.1+/-0.3 versus 1.2+/-0.2 mmol/24 h, P>0.20). CONCLUSIONS: A specific decrease in synthetic activity of the L-arginine-NO metabolic pathway contributes to decreased endothelium-dependent vasodilation in patients with congestive heart failure.

Adult↗
PubMed1999

Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure.

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes of aortocaval shunt. Left and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unchanged in compensated heart failure. In overt heart failure, however, the AM-mRNA expression was significantly increased in the left ventricle (145+/-20 vs. 100+/-3% of control, p<0.05). The right ventricular AM-mRNA expression was significantly increased only in a subgroup of animals with pulmonary congestion (lung weight >2.0 g, 141+/-16 vs. 100+/-11% of control, p<0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496+/-95 vs. 143+/-7 pmol/l, p<0.01). These data indicate that ventricular AM-mRNA expression and AM concentrations were upregulated only in advanced stages of heart failure. However, the exact contribution of cardiac AM synthesis to the increased AM plasma levels remains to be established.

Adrenomedullin↗
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↗
PubMed1997

Physical training alters the pathogenesis of pacing-induced heart failure through endothelium-mediated mechanisms in awake dogs.

BACKGROUND: Beneficial effects of exercise training on cardiovascular function in chronic heart failure (CHF) have been suggested previously, but the underlying mechanisms are unknown. We tested whether daily exercise training improves systemic hemodynamics and preserves endothelium-mediated vasodilator function during development of heart failure. METHODS AND RESULTS: Fifteen dogs were surgically instrumented for hemodynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another group underwent pacing plus daily exercise training (4.4+/-0.3 km/h, 2 h/d). Pacing-alone dogs developed CHF characterized by typical hemodynamic abnormalities, blunted endothelium-mediated vasodilator function in coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to GAPDH expression; normal, 1.15+/-0.31 versus CHF, 0.29+/-0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-mediated vasodilator function, and gene expression of ECNOS (0.72+/-0.16 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventricular end-diastolic pressure (7.7+/-0.3 to 19+/-3.4 mm Hg, P<.05), suggesting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF state. CONCLUSIONS: Long-term exercise training altered the natural history of heart failure due to rapid cardiac pacing. One of the underlying mechanisms is through the preservation of endothelial vasodilator function.

Animals↗
PubMed1997

Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs.

Endothelial dysfunction in coronary circulation is well documented in heart failure (HF). However, whether this dysfunction is a consequence of heart failure or precedes the development of HF remains unknown. To determine endothelium-dependent regulation in the remote coronary vasculature in a canine coronary microembolization-induced HF model, seven dogs were chronically instrumented for measurement of systemic hemodynamics, for selective coronary microembolization via an implanted coronary catheter and for measurement of coronary blood flow in the non-embolized coronary artery. Microembolizations were performed daily until hemodynamic and echocardiographic measurements showed HF. The responses of coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 microg/kg), nitroglycerin (0.2, 0.8, 5, 25 microg/kg), adenosine (0.25, 0.5, 2, 5 micromol/kg) and brief coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF developed and the responses of coronary blood flow to nitroglycerin, adenosine and occlusions were not altered, the response to acetylcholine was selectively reduced after 1 week of embolization (275,000+/-55,000 microspheres). Resting coronary flow increased from 21.3+/-1.4 ml/min in control state to 27.7+3.5 ml/min (P<0.001). As HF developed, characterized by an elevated left ventricular end-diastolic pressure (6.4+/-1.6 v 16+/-1.6 mmHg, P<0.001), a decreased area ejection fraction (54+/-5 v 36+/-5%, P<0.05) and a reduced beta-adrenergic response to isoproterenol, the responses of coronary blood flow to acetylcholine, nitroglycerine, adenosine and occlusions were consistently depressed. Resting coronary blood flow was decreased to 15.4+/-2.7 ml/min (P<0.01). Our results indicate, that there is a selectively impaired endothelium-mediated dilator capacity of the resistance coronary vasculature before the development of HF and a reduction of the coronary flow reserve.

Acetylcholine↗
PubMed1997

Impact of exercise training on ventricular properties in a canine model of congestive heart failure.

Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHF(EX), 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2,540 +/- 440 vs. 1,720 +/- 300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 +/- 5 vs. 19 +/- 4 mmHg, P < 0.05) in CHF(EX) compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 +/- 0.47 in CHFs, 1.77 +/- 0.38 in CHF(EX), and 3.05 +/- 0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 +/- 3 in CHFs, 21 +/- 3 in CHF(EX), 20 +/- 4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties.

Analysis of Variance↗
PubMed1996

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↗
PubMed1996

Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide.

OBJECTIVES: This study was undertaken to investigate the role of endothelium-derived nitric oxide in the regulation of forearm blood flow during exercise in normal subjects and patients with congestive heart failure. BACKGROUND: Nitric oxide-mediated vasodilation in response to muscarinic stimulation is impaired in the peripheral circulation of patients with congestive heart failure. Whether nitric oxide-mediated vasodilation during exercise is also impaired in patients with congestive heart failure is unknown. METHODS: Forearm blood flows (ml/min per 100 ml) were determined during rhythmic hand grip exercise at 15%, 30% and 45% of maximal voluntary contraction by venous occlusion plethysmography before and after regional inhibition of nitric oxide synthesis with administration of L-NG-monomethylarginine (L-NMMA) in the brachial artery of 17 patients with congestive heart failure (mean age 49 years, mean left ventricular ejection fraction 0.22) and 10 age-matched normal subjects. RESULTS: Before administration of L-NMMA in the brachial artery, forearm blood flows in patients with congestive heart failure during rhythmic hand grip exercise at 15%, 30% and 45% of maximal voluntary contraction were slightly but not significantly lower than that of normal subjects ([mean +/- SE] 6.8 +/- 1.0, 8.5 +/- 1.0 and 12.9 +/- 1.7 ml/min per 100 ml, respectively, in patients with congestive heart failure vs. 6.6 +/- 1.2, 11.6 +/- 1.9 and 16.2 +/- 1.9 ml/min per 100 ml, respectively, in normal subjects, p = NS). After administration of L-NMMA in the brachial artery, forearm blood flows in normal subjects significantly decreased by 10% to 21% during hand grip exercise but did not change during exercise in patients with congestive heart failure. CONCLUSIONS: Regional inhibition of nitric oxide synthase with administration of L-NMMA in the brachial artery significantly decreased forearm blood flows during rhythmic hand grip exercise in normal subjects but not in patients with congestive heart failure. These findings suggest that nitric oxide-mediated vasodilation during submaximal exercise is impaired in the forearm circulation of patients with congestive heart failure.

Adult↗
PubMed1996

Effects of levosimendan on myocardial contractility and oxygen consumption.

Levosimendan is hypothesized to be primarily a calcium sensitizer in vitro. Therefore, its inotropic action may be similar in both the normal and the congestive heart failure (CHF) state, and it may be associated with a decreased energetic cost of inotropism in vivo. To test these hypotheses, we gave levosimendan to cross-circulated isolated hearts from normal (n = 11) and CHF (n = 7, 4-week rapid pacing) dogs. Peak isovolumic left ventricular pressure at an end-diastolic pressure of 5 mm Hg (Pmax,5) measured by an intraventricular balloon was 120 +/- 15 mm Hg in normal dogs, and it was increased by approximately 40% in response to approximately 0.63 microM levosimendan. In CHF dogs, base-line Pmax,5 was only 60 +/- 12 mm Hg (P < .01 compared to normals), and approximately 8.4 microM levosimendan (P < .05) was required to increase Pmax,5 by approximately 40%. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and falling hearts. The blunted inotropic response in CHF and the energetic cost of inotropism were also comparable to those obtained with isoproterenol. In other studies, there was no significant inotropic action of levosimendan in Langendorff-perfused rat hearts (n = 5), and intracellular calcium concentration, estimated by macroinjected aequorin, in ferret hearts (n = 2) increased dose-dependently. These findings suggest that inotropic actions of levosimendan in vivo may be mediated in part by factors other than calcium sensitization.

Animals↗