Validation of the optimal site in the neck region for detecting swallowing sounds.

Recently, the swallowing sound has been used to detect swallowing events non-invasively. A previous study, using an accelerometer, showed that the site over the lateral border of the trachea immediately inferior to the cricoid cartilage was the optimal site for detecting swallowing sounds. However, the optimal site for detection of the swallowing sound using a microphone remains undetermined. To validate the optimal site in the neck region for detecting swallowing sounds. Fourteen healthy subjects (mean age, 27·6 ± 2·2 years; seven male and seven female) participated in this study. Twenty condenser microphones were attached to 20 sites on the left neck surface to detect swallowing sounds. Participants were instructed to swallow five different stimuli three times as follows: Resting saliva, 1 and 5 mL of Japanese tea, and 1 and 5 mL of yoghurt. Mean relative peak intensity was used to indicate the magnitude of the swallowing sound. Sound spectrograms were used to illustrate differences in the properties of swallowing sounds. Mean relative peak intensity number was highest in sites at the inferior border of the mandible just above the sternocleidomastoid muscle (site 11) and sites over the lateral border of the trachea immediately inferior to the cricoid cartilage (site 8). Comparison of spectrograms showed a greater density distribution of higher frequency components at site 11 compared with site 8. These results indicate that the inferior border of the mandible just above the sternocleidomastoid muscle is the optimal site for the detection of swallowing sounds.

New method of neck surface electromyography for the evaluation of tongue-lifting activity.

Elevation of the posterior part of the tongue is important for normal deglutition and speech. The purpose of this study was to develop a new surface electromyography (EMG) method to non-invasively and objectively evaluate activity in the muscles that control lifting movement in the posterior tongue. Neck surface EMG (N-EMG) was recorded using differential surface electrodes placed on the neck, 1 cm posterior to the posterior border of the mylohyoid muscle on a line orthogonal to the lower border of the mandible. Experiment 1: Three healthy volunteers (three men, mean age 37·7 years) participated in an evaluation of detection method of the posterior tongue lifting up movement. EMG recordings from the masseter, temporalis and submental muscles and N-EMG revealed that i) N-EMG was not affected by masseter muscle EMG and ii) N-EMG activity was not observed during simple jaw opening and tongue protrusion, revealing the functional difference between submental surface EMG and N-EMG. Experiment 2: Seven healthy volunteers (six men and one woman, mean age 27·9 years) participated in a quantitative evaluation of muscle activity. Tongue-lifting tasks were perfor-med, exerting a prescribed force of 20, 50, 100 and 150 gf with visual feedback. For all subjects, a significant linear relationship was observed bet-ween the tongue-lifting force and N-EMG activity (P < 0·01). These findings indicate that N-EMG can be used to quantify the force of posterior tongue lifting and could be useful to evaluate the effect of tongue rehabilitation in future studies.

Effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients.

Articulation is driven by various combinations of movements of the lip, tongue, soft palate, pharynx and larynx, where the tongue plays an especially important role. In patients with cerebrovascular disorder, lingual motor function is often affected, causing dysarthria. We aimed to evaluate the effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients with cerebrovascular disorder. Fifteen dysarthria patients (10 men and 5 women; mean age, 70.7 ± 10.3 years) agreed to participate in this study. A device for measuring the movement of the posterior part of the tongue was used for the visual biofeedback. Subjects were instructed to produce repetitive articulation of [ka] as fast and steadily as possible between a lungful with/without visual biofeedback. For both the unaffected and affected sides, the range of ascending and descending movement of the posterior tongue with visual biofeedback was significantly larger than that without visual biofeedback. The coefficient of variation for these movements with visual biofeedback was significantly smaller than that without visual biofeedback. With visual biofeedback, the range of ascent exhibited a significant and strong correlation with that of descent for both the unaffected and affected sides. The results of this study revealed that the use of visual biofeedback leads to prompt and preferable change in the movement of the posterior part of the tongue. From the standpoint of pursuing necessary rehabilitation for patients with attention and memory disorders, visualization of tongue movement would be of marked clinical benefit.

Effect of nasal speaking valve on speech intelligibility under velopharyngeal incompetence: a questionnaire survey.

Velopharyngeal incompetence is known as a contributing factor to speech disorders. Suwaki et al. reported that nasal speaking valve (NSV) could improve dysarthria by regulating nasal emission utilising one-way valve. However, disease or condition which would be susceptible to treatment by NSV has not been clarified yet. This study aimed to evaluate the effect of NSV by questionnaire survey using ready-made NSV. Subjects were recruited through the internet bulletin, and NSV survey set was sent to the applicant. Sixty-six participants, who agreed to participate in this study, used NSV and mailed back the questionnaire which included self-evaluation and third-party evaluation of speech intelligibility. Statistical analysis revealed that the use of NSV resulted in significant speech intelligibility improvement in both self-evaluation and third-party evaluation (P < 0·01). Regarding the type of underlying disease of dysarthria, significant effect of NSV on self-evaluation of speech intelligibility could be observed in cerebrovascular disease and neurodegenerative disease (P < 0·01) and that on third-party evaluation in neurodegenerative disease (P < 0·01). Eighty-six percent of subjects showed improvement of speech intelligibility by shutting up nostrils by fingers, and the significant effect of NSV on both self-evaluation and third-party evaluation of speech intelligibility was observed (P < 0·001). From the results of this study, it was suggested that NSV would be effective in cerebrovascular disease and neurodegenerative disease, as well as in subjects whose speech intelligibility was improved by closing nostrils.

A novel automated detection system for swallowing sounds during eating and speech under everyday conditions.

The wave analysis of swallowing sounds has been receiving attention because the recording process is easy and non-invasive. However, up until now, an expert has been needed to visually examine the entire recorded wave to distinguish swallowing from other sounds. The purpose of this study was to establish a methodology to automatically distinguish the sound of swallowing from sound data recorded during a meal in the presence of everyday ambient sound. Seven healthy participants (mean age: 26·7 ± 1·3 years) participated in this study. A laryngeal microphone and a condenser microphone attached to the nostril were used for simultaneous recording. Recoding took place while participants were taking a meal and talking with a conversational partner. Participants were instructed to step on a foot pedal trigger switch when they swallowed, representing self-enumeration of swallowing, and also to achieve six additional noise-making tasks during the meal in a randomised manner. The automated analysis system correctly detected 342 out of the 352 self-enumerated swallowing events (sensitivity: 97·2%) and 479 out of the 503 semblable wave periods of swallowing (specificity: 95·2%). In this study, the automated detection system for swallowing sounds using a nostril microphone was able to detect the swallowing event with high sensitivity and specificity even under the conditions of daily life, thus showing potential utility in the diagnosis or screening of dysphagic patients in future studies.

A new quantitative screening method for removable prosthesis using pressure-indicating paste.

Aim of this study was to quantitatively evaluate the adaptation of the denture base to the mucosa using a non-setting pressure-indicating paste and to examine the relationship between quality of fit and the need for denture relining. A total of 123 dentures from 70 partially edentulous patients were studied. Examination paste extruded from the tip of the 18-G needle was applied to those denture surfaces contacting the alveolar crest. The denture was manually positioned with all clasps engaged on abutment teeth, and adaptation was assessed through paste distribution. Multiple logistic regression was used to analyse variables associated with diagnosing the need for a denture reline, producing odds ratios and 95% confidence intervals. The spread width was inversely proportional to the gap between the denture and mucosa. Regression analysis revealed statistically significant associations between the need for a denture reline and both the paste spread width and the duration of denture use. According to ROC curve analysis of the 'reline' and 'non-reline' groups, the need for a denture reline was indicated at a paste spread width of 2·0 mm or less. At this 2·0-mm threshold, the sensitivity was 85·1% and the specificity was 75·0%. The fit of removable denture bases was quantitatively evaluated by measuring the spread width of non-setting pressure-indicating paste extruded onto denture fit surfaces. The results suggest that the paste spread width is a useful parameter for discriminating the need for a denture reline.

Effect of occlusal rehabilitation on spatial memory and hippocampal neurons after long-term loss of molars in rats.

Experimental loss of occlusal support caused by the extraction or grinding of molar teeth has been reported to foment the impairment of learning and memory in laboratory animals. The purpose of this study was to examine the effect of occlusal reconstruction after long-term loss of molars on spatial memory by using 8-arm radial maze and by assessing histopathological changes of neuron density in the hippocampus. Experimental dentures were inserted into the oral cavities of molarless rats to recover the occlusal support. Age-matched groups of control, molarless and denture-wearing rats were trained to perform the maze tasks. The difference of the error incidence in the maze task was evaluated between three groups. The difference of neuron density between three groups was also evaluated at the end of the maze task. Serum corticosterone levels were also measured to estimate the chronic stress, which could be caused by extraction, insertion of the experimental denture or any experimental procedure. The error incidence in the denture-wearing group was significantly higher than that of the control group, but significantly lower than that of the molarless group. Significant differences of neuron density were observed between three groups in each of the hippocampal CA1, CA3 and DG subfields. No significant difference of the serum corticosterone levels between three groups could be observed. From the results of this study, it was suggested that the recovery of occlusal support would bring amelioration of cognitive impairment concomitant with long period loss of molars in rats.

Masticatory efficiency in complete denture wearers with reduced dental arches--a randomised cross-over study.

One obstacle to placing artificial posterior teeth in manufacturing complete dentures is a reduction of the space between the maxilla and the mandible. Occasionally, second molar placement is not performed, as it does not affect aesthetics, phonetics or comfort. The aim of this study was to compare the masticatory efficiency between patients wearing maxillary and mandibular complete dentures with reduced dental arches (without second molars) (WSM) and with full dental arches (FDA). Twenty subjects were divided into two groups and randomly received new complete dentures. Patients in Group 1 were given dentures WSM, and those in Group 2 were given dentures with FDA. After the post-placement visits, an initial masticatory efficiency test was performed with Optocal, an artificial test food. Fifteen days later, second molars were placed in Group 1 and removed from Group 2, and a new test was performed. Comminuted material was treated and sieved under vibration. The mean and standard deviation of masticatory efficiency with FDA were 10.4 and 8.1, respectively. In the tests WSM, the mean and standard deviation were 8.4 and 3.3, respectively. After removing the second molars in Group 2 and adding them in Group 1, the mean and standard deviation were 15.7 and 14.7 for Group 1 and 12.5 and 10.4 for Group 2, respectively. Within the limitations of this study, placing artificial teeth up to the first molars can be performed when needed without compromising masticatory efficiency.

Development of a speech-discriminating electromyogram system for routine ambulatory recordings for the low-level masseter muscle activity.

Previous work suggests a relationship between sustained low-level tooth clenching and the aetiology of myogenous temporomandibular disorder (TMD) pain. This study aimed to establish a reliable system with which to evaluate low-level electromyographic (EMG) activity related to low-level tooth clenching while discriminating speech activity, which is one of the most common facial muscle activities to be discriminated from low-level clenching. This device should facilitate the clinical evaluation of awake muscle activity in TMD patients. Eight female and eight male subjects (38.9 ± 11.3 years) participated in the study to evaluate the validity of estimation of speech duration. Actual speech duration was defined by one examiner by pointing out the timing of beginning and end point of each speech on wave-editing software. Speech duration, as detected by a voice sensor system, which was activated by a voice loudness of 54.71 ± 5.00 dB, was significantly correlated with the above actual speech duration (P < 0.01, R(2) = 0.9935). An actual recording with the system was carried out in one TMD patient and one healthy volunteer and revealed that the duration of diurnal EMG activity higher than 5% MVC was 1649.16 s and 95.99 s, respectively. As the voice sensor system adopted in this study could define the exact onset and offset of each segment of speech, EMG activity during speech could be precisely discriminated. The results of this study demonstrate that the EMG system with voice sensor system would be an effective tool for the evaluation of low-level masticatory muscle activity.

Image analysis of food particles can discriminate deficient mastication of mixed foodstuffs simulating daily meal.

Because food texture is regarded as an important factor for smooth deglutition, identification of objective parameters that could provide a basis for food texture selection for elderly or dysphagic patients is of great importance. We aimed to develop an objective evaluation method of mastication using a mixed test food comprising foodstuffs, simulating daily dietary life. The particle size distribution (>2 mm in diameter) in a bolus was analysed using a digital image under dark-field illumination. Ten female participants (mean age ± s.d., 27·6 ± 2·6 years) masticated a mixed test food comprising prescribed amounts of rice, sausage, hard omelette, raw cabbage and raw cucumber with 100%, 75%, 50% and 25% of the number of their masticatory strokes. A single set of coefficient thresholds of 0·10 for the homogeneity index and 1·62 for the particle size index showed excellent discrimination of deficient masticatory conditions with high sensitivity (0·90) and specificity (0·77). Based on the results of this study, normal mastication was discriminated from deficient masticatory conditions using a large particle analysis of mixed foodstuffs, thus showing the possibility of future application of this method for objective decision-making regarding the properties of meals served to dysphagic patients.

New theoretical model to measure pressure produced during impression procedure for complete dentures-Visual inspection of impression material flow.

OBJECTIVE: A theoretical model, based on fluid dynamics, was developed to measure impression pressure. The purpose of this study was to evaluate the validity of this theoretical model by comparing its theoretical analysis against actual pressure measurements conducted using an impression tray and edentulous oral mucosa analog embedded with pressure sensors. METHODS: In the theoretical model, a hollow tube was mounted onto an impression tray by penetrating through the tray. When force was applied to the tray, pressure was produced which then caused the impression material to flow into the hollow tube. Length of impression material which flowed into tube was denoted as l. In the calculation formula for theoretical model, pressure impulse I was expressed as a function of impression flow length l. For actual pressure measurements, four electric pressure sensors were embedded in an experimental edentulous arch. To visually observe and measure length of impression material flow, four transparent silicon tubes were mounted vertically at different positions on tray. During tray seating, impression material flowed into tubes and pressure which caused material flow movement was measured by the embedded sensor at each tube's position. RESULTS: Based on actual pressure measurements under one experimental condition, regression analysis of pressure data acquired from electric sensors yielded the formula, Y=0.056X²+0.124X. Based on theoretical analysis using a particular viscosity value, the numerical formula yielded was Y=0.057X², which resembled that of the regression formula. SIGNIFICANCE: Theoretical model presented in this paper augured well for clinical application as an easy and economical means to examine magnitude and distribution of impression pressure by measuring lengths of impression material flow in tubes fixed to impression tray.

HEMA inhibits interfacial nano-layering of the functional monomer MDP.

Previous research showed that the functional monomer 10-methacryloxydecyl dihydrogen phosphate (MDP) ionically bonds to hydroxyapatite (HAp) and forms a nano-layered structure at the interface with HAp-based substrates. Such hydrophobic nano-layering is considered to contribute to the long-term durability of the bond to tooth tissue. However, dental adhesives are complex mixtures usually containing different monomers. This study investigated the effect of the monomer 2-hydroxyethylmethacrylate (HEMA) on the chemical interaction of MDP with HAp by x-ray diffraction (XRD), nuclear magnetic resonance (NMR), and quartz crystal microbalance (QCM). We examined the chemical interaction of 5 experimental MDP solutions with increasing concentrations of HEMA. XRD revealed that addition of HEMA inhibits nano-layering at the interface, while NMR confirmed that MDP remained adsorbed onto the HAp surface. QCM confirmed this adsorption of MDP to HAp, as well as revealed that the demineralization rate of HAp by MDP was reduced by HEMA. It was concluded that even though the adsorption of MDP to HAp was not hindered, addition of HEMA inhibited interfacial nano-layering. Potential consequences with regard to bond durability necessitate further research.

New image analysis of large food particles can discriminate experimentally suppressed mastication.

Objective parameters that could provide a basis for food texture selection for elderly or dysphagic patients have not been established. We, therefore, aimed to develop a precise method of measuring large particles (>2 mm in diameter) in a bolus and an analytical method to provide a scientific rationale for food selection under masticatory dysfunction conditions. We developed a new illumination system to evaluate the ability of twenty female participants (mean age, 23·4 ± 4·3 years) to masticate carrots, peanuts and beef with full, half and one quarter of the number of masticatory strokes. We also evaluated mastication under suppressed force, regulated by 20% electromyographic of the masseter muscle. The intercept and inclination of the regression line for the distribution of large particles were adopted as coefficients for the discrimination of masticatory efficiency. Single set of coefficient thresholds of 0·10 for the intercept and 1·62 for the inclination showed excellent discrimination of masticatory conditions for all three test foods with high specificity and sensitivity. These results suggested that our method of analysing the distribution of particles >2 mm in diameter might provide the basis for the appropriate selection of food texture for masticatory dysfunction patients from the standpoint of comminution.

Dynamics of posterior tongue during pronunciation and voluntary tongue lift movement in young adults.

The lifting-up movement of the posterior part of the tongue to touch the palate, which is a requirement for performing physiological functions such as deglutition and speech, is an important phenomenon that is difficult to objectively evaluate. The purpose of this study was to develop a new modality to evaluate the tongue-lifting function, especially in the posterior part of the tongue, and to elucidate the dynamic properties of the tongue in normal subjects. Twenty-three healthy volunteers (9 men and 14 women; mean age, 27·6years) participated in this study. A new device was developed that could evaluate the up-down movement of the posterior part of the tongue in a non-invasive manner. The experimental tasks were as follows: (i) /a/ pronunciation for 1s followed by /ka/ pronunciation (a-ka task), (ii) /a/ pronunciation for 1s followed by /ga/ pronunciation (a-ga task) and (iii) /a/ pronunciation for 1s followed by a voluntary push-up movement of the posterior part of the tongue (a-lift task). Maximum upward velocity in the a-ga task was larger than that in the a-ka task (P<0·05). The a-lift task showed the highest tongue lift range among the three tasks, and the a-ga task showed a higher range than that of the a-ka task (P<0·05). This study revealed that precise quantification of the motility of the posterior part of the tongue, which would be useful in rehabilitation of articulation and/or swallowing, could be achieved using this new device in a non-invasive manner.

Self-etch monomer-calcium salt deposition on dentin.

Previous research, in which the bonding effectiveness of the 3 self-etch monomers HAEPA, EAEPA, and MAEPA was determined, showed that MAEPA was most effective. In this study, the molecular interactions of these monomers with hydroxyapatite and dentin were investigated by combining x-ray diffraction, infrared spectroscopy, and scanning electron microscopy. We tested the null hypothesis that the bonding performance of these monomers does not correlate to the formation of monomer-calcium salts and to hydrolytic stability of these monomer-calcium complexes. Monomer/ethanol/water solutions were prepared and applied to synthetic hydroxyapatite and dentin. While HAEPA and EAEPA dissolved dentin considerably and deposited unstable calcium-phosphate salts (DCPD), MAEPA formed hydrolysis-resistant monomer-calcium salts that remained attached to the dentin surface even after being washed. The chemical stability of the monomer-Ca salts was thought to contribute in particular to the bond durability, but this study shows that the formation of stable monomer-calcium salts also enhances the 'immediate' bonding performance of self-etch adhesives.

Manifestation of preferred chewing side for hard food on TMJ disc displacement side.

The purpose of this study was to reveal the relationship between chewing-side preference and anterior disc displacement (ADD) of the TMJ. Thirty-two healthy subjects with ages ranging from 26 to 34 years were selected from volunteer students at the Okayama University Dental School. Subjects were asked to chew freely with two kinds of test foods, beef jerky (hard food) and chiffon cake (soft food), thus expecting different amounts of mechanical loading on the TMJ. One, 4, and 7 s after starting the mastication, subjects were asked to open their mouth momentarily to have a digital image of their mouth taken. The bolus placement area was measured by processing the digital images, calculated as the number of pixel of bolus area. Area asymmetry index was used for the determination of preferred chewing side (PCS). Oblique sagittal MRI scanning in the closed mouth position was taken to evaluate the articular disc position. In asymptomatic subjects with ADD, a significant predominance of the PCS on the ipsilateral side of ADD was observed during the mastication of hard food. On the contrary, no correlation was found between unilateral ADD and PCS for the soft food. From the results of this study, it is suggested that ADD is the associating factor of PCS for hard food. Therefore, it would be necessary to break down the concept of PCS into at least two categories, one for hard food and one for soft food, considering the mechanical loading on the TMJ.

The effect of nasal speaking valve on the speech under experimental velopharyngeal incompetence condition.

Velopharyngeal incompetence (VPI) is a contributing factor to speech disorders, frequently accompanying disorders, such as cleft palate, congenital paralysis of the soft palate, and cerebrovascular disease. For the treatment of these types of dysarthria, a Nasal Speaking Valve (NSV), which regulates nasal emission utilizing one-way valve, has been reported to be effective. As the unpleasantness while wearing the NSV was less than that with the conventional Palatal Lift Prosthesis, the NSV could be worn for a longer period of time. As NSV is inserted into the nostrils, this device could easily be provided for edentulous patients. This study aimed to evaluate the effect of NSV on experimentally induced VPI condition. Intelligibility of monosyllabic speech, intelligibility of conversational speech, nasalance score and acoustic analysis were used to evaluate the effect of NSV. Local infiltration anaesthesia was achieved to the area of levator veli palatini muscle and tensor veli palatine muscle of seven adult male subjects. In all subjects, remarkable suppression of the soft palate movement could be observed after the local infiltration anesthesia. Although the utterance supported by NSV under the experimentally induced VPI condition was less natural than the normal utterance, the intelligibility was markedly improved by the device. From the results of this study, the acoustic properties of NSV on the pure VPI condition, which was enabled by the newly established experimental induction, were revealed. This experimental model was also proved to provide a basis for the improvement in the treatment modalities for VPI.

Nasal speaking valve: a device for managing velopharyngeal incompetence.

Velopharyngeal incompetence is a contributing factor for speech disorders, and other frequently accompanying disorders, such as cleft palate, congenital paralysis of the soft palate and cerebrovascular disease. A palatal lift prosthesis (PLP) has been fabricated for managing velopharyngeal incompetence to improve speech. Because of discomfort, such as difficulty in swallowing or vomiting reflex, while wearing the PLP, rigorous adjustment is required. Patients may have difficulty becoming accustomed to using the prosthesis. This article reports on a newly developed device, the nasal speaking valve, for improving hypernasal speech caused by velopharyngeal incompetence.

Enhanced vertical alveolar bone augmentation by recombinant human bone morphogenetic protein-2 with a carrier in rats.

This study aimed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on vertical bone regeneration of edentulous ridge. Bilateral upper first and second molars of 8-week-old Wistar rats were extracted and the ridges were allowed to heal for 3 weeks. Compressed poly(lactic-co-glycolic acid) copolymer/gelatin sponge (PGS) was used as a carrier of rhBMP-2. PGS alone (control group) or PGS with 5 mug rhBMP-2 (test group) was implanted at the top part of alveolar ridge. The sham group received no implantation. The rats were killed at 1, 2, 4, 8 and 12 weeks after implantation and examined histologically and histomorphometrically. In the test group, significant bone augmentation was evident on the alveolar ridge throughout the experimental period. Histomorphometric analysis revealed greater tissue volume and height of alveolar bone in the test group compared with the control and sham groups (P < 0.05) from 4 weeks onward and the augmented tissues (5 mm3 in tissue volume and 1.5 mm in bone height) were maintained until 12 weeks. Osteoblast surface increased at 2 and 4 weeks and osteoid thickness reached a peak (25 microm) at 2 weeks. Dynamic variables, which represented calcification, were higher in the test group than the control and sham groups at 4 and 8 weeks (P < 0.05). These results suggest that use of rhBMP-2/PGS may achieve vertical bone augmentation, and stabilizes denture prosthesis or makes up for inadequate bone mass for implant prosthesis.

Is the posterior belly of the digastric muscle palpable? A qualitative systematic review of the literature.

Palpation of the posterior belly of the digastric muscle in the postmandibular region is included in many study protocols and examination schemes of the masticatory system. The aim of the present investigation was to systematically search the dental/medical literature to find evidence for the palpability of this muscle. In August 2004, a systematic search was carried out using different electronic databases (PubMed, Cochrane Library, Web of Science, Japana Centra Revuo Medicina, MedPilot, Latin American and Caribbean Health Sciences, and three on-line databases of dental journals not listed currently in Medline), supplemented by manual search in the Austrian journal Stomatologie. Additional manual searches were carried out in the Journal of Orofacial Pain and Journal of Dental Research to identify pertinent abstracts of scientific congresses. One relevant hit was found in the Japanese database. The manual search showed one pertinent congress abstract. In both publications, the authors concluded that due to anatomical reasons the posterior belly of the digastric muscle was not palpable. Hence, evidence is lacking that the posterior digastric muscle is accessible to palpation. Because the postmandibular region is usually tender upon palpation, a high incidence of positive findings can be expected even among healthy subjects. This may lead to wrong clinical judgments, possibly provoking unnecessary diagnostic and therapeutic measures.