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Biomedical subjects

Hans Gregersen

Publications and source records attributed to Hans Gregersen.

At least 19 recordsLinked to original sources

In vivo areal modulus of elasticity estimation of the human tympanic membrane system: modelling of middle ear mechanical function in normal young and aged ears.

The quasi-static elastic properties of the tympanic membrane system can be described by the areal modulus of elasticity determined by a middle ear model. The response of the tympanic membrane to quasi-static pressure changes is determined by its elastic properties. Several clinical problems are related to these, but studies are few and mostly not comparable. The elastic properties of membranes can be described by the areal modulus, and these may also be susceptible to age-related changes reflected by changes in the areal modulus. The areal modulus is determined by the relationship between membrane tension and change of the surface area relative to the undeformed surface area. A middle ear model determined the tension-strain relationship in vivo based on data from experimental pressure-volume deformations of the human tympanic membrane system. The areal modulus was determined in both a younger (n = 10) and an older (n = 10) group of normal subjects. The areal modulus for lateral and medial displacement of the tympanic membrane system was smaller in the older group (mean = 0.686 and 0.828 kN m(-1), respectively) compared to the younger group (mean = 1.066 and 1.206 kN m(-1), respectively), though not significantly (2p = 0.10 and 0.11, respectively). Based on the model the areal modulus was established describing the summated elastic properties of the tympanic membrane system. Future model improvements include exact determination of the tympanic membrane area accounting for its shape via 3D finite element analyses. In vivo estimates of Young's modulus in this study were a factor 2-3 smaller than previously found in vitro. No significant age-related differences were found in the elastic properties as expressed by the areal modulus.

Adult↗

Biomechanical remodeling of the chronically obstructed Guinea pig small intestine.

Small intestinal obstruction is a frequently encountered clinical problem. To understand the mechanisms behind obstruction and the clinical consequences, data are needed on the relation between the morphologic and biomechanical remodeling that takes place in the intestinal wall during chronic obstruction. We sought to determine the effect of partial obstruction on mechanical and morphologic properties of the guinea pig small intestine. Partial obstruction was created surgically in 2 groups of animals living for 2 and 4 weeks. Controls were sham operated and lived for 4 weeks. A combined impedance planimetry-high-frequency ultrasound system was designed to measure the luminal cross-sectional area and wall thickness. These measures were used to compute the circumferential stress and strain of the excised intestinal segments. The incremental elastic modulus was obtained by using nonlinear fitting of the stress-strain curve. Histologic analysis and the measurements of total wall collagen were also performed. The luminal cross-sectional area, wall thickness, and elastic modulus in circumferential direction increased in a time-dependent manner proximal to the obstruction site (P < 0.01), whereas no differences in these parameters were found distal to the obstruction site (P > 0.25). The circumferential stress-strain curves of the proximal segments in 2- and 4-week groups shifted to the left, indicating the intestinal wall became stiffer. Histologic examination revealed a massive increase in the thickness of the muscle layer especially the circular smooth muscle layer (P < 0.05). The collagen content proximal to the obstruction site was significantly larger in the partially obstructed animals compared to controls (P < 0.05). No difference was found distal to the obstruction site. Strong correlation was found between the collagen content and the elastic modulus at stress levels of 70 kPa stress (P < 0.01) and 10 kPa (P < 0.05) proximal to the obstruction site suggesting that the alteration of collagen has great impact on the mechanical remodeling. The morphologic and biomechanical remodeling likely influence the function of the intestine affected by partial obstructed intestine.

Animals↗

Manual pressure distension of the human saphenous vein changes its biomechanical properties-implication for coronary artery bypass grafting.

Patency rates of saphenous vein grafts following coronary artery bypass grafting (CABG) depend on multiple factors. Information regarding the impact of biomechanical properties of vein grafts on patency rates is not available. The objective of the present study was to evaluate whether uncontrolled manual pressure distension during routine preparation of the saphenous vein in CABG-induced changes in the biomechanical properties of the vein. The morphometric and stress-strain properties were studied in isolated segments of the saphenous vein from 12 patients undergoing elective CABG. Six segments were manually distended without pressure control and six were not distended. The mechanical test was performed as a ramp inflation using syringe pump. The vein dimensions were obtained from digitised images at different pressures as well as at the no-load and zero-stress states. The circumferences, the wall and lumen area, the wall thickness, and the outer diameter as function of the applied pressure were largest in the segments with uncontrolled manual distension compared to those without distension (P<0.05). The opening angle and the absolute value of the residual strains were lower (P<0.01) and the circumferential stress-strain curve shifted to the left, indicating the wall became stiffer with uncontrolled manual distension compared to those without distension (P<0.05). In conclusion, manual pressure distension changed the morphometric and biomechanical properties of the saphenous vein. The perspective is that studies on biomechanical properties on the saphenous vein may guide surgeons how to handle graft material without causing major changes of the biomechanical properties during harvesting and preparation.

Aged↗

Effect of Kaiyu Qingwei Jianji on the morphometry and residual strain distribution of small intestine in experimental diabetic rats.

AIM: To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji (KYQWJJ) used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin (STZ) -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS: Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ-induced diabetic rats were subdivided into four groups (n = 8 in each group), i.e. diabetic control group (DM); high dose of KYQWJJ (T1, 36 g/kg per day); low dose of KYQWJJ (T2, 17 g/kg per day) and Gliclazide (T3, 50 mg/kg per day). Another ten rats were used as non-diabetic control (CON). The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zero-stress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS: The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment (16.89+/-1.11 vs 3.44+/-0.15 mmol/L, P < 0.001). The blood glucose level in the T1 (16.89+/-1.11 vs 11.08+/-2.67 mmol/L, P < 0.01) and T3 groups (16.89+/-1.11 vs 13.54+/-1.73 mmol/L, P < 0.05), but not in T2 group (P > 0.05) was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group (10.98+/-1.02, 12.52+/-1.42,13.54+/-1.56,10.96+/-0.96 vs 17.84+/-2.34 pmol/L respectively, P < 0.05), but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group (wet weight (g/cm): duodenum 0.209+/-0.012 vs 0.166+/-0.010, jejunum 0.149+/-0.008 vs 0.121+/-0.004, ileum 0.134+/-0.013 vs 0.112+/-0.007; Wall thickness (mm): duodenum 0.849+/-0.027 vs 0.710+/-0.026, jejunum 0.7259+/-0.034 vs 0.627+/-0.025, ileum 0.532+/-0.023 vs 0.470+/-0.010, all P < 0.05), T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment (188+/-11 degrees, -0.31+/-0.02 and 0.35+/-0.03 vs 259+/-15 degrees, -0.40+/-0.02 and 0.43+/-0.05) and larger in jejunal (215+/-20 degrees, -0.30+/-0.03 and 0.36+/-0.06 vs 172+/-19 degrees, -0.25+/-0.02 and 0.27+/-0.02) and ileal segments (183+/-20 degrees, -0.28+/-0.01 and 0.34+/-0.05 vs 153+/-14 degrees, -0.23+/-0.03 and 0.29+/-0.04) in DM group than in CON group (P < 0.01). T1 and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment (duodenum 243+/-14 degrees, -0.36+/-0.02 and 0.42+/-0.06, jejunum 180+/-15 degrees, -0.26+/-0.03 and 0.30+/-0.06 and ileum 163+/-17 degrees, -0.23+/-0.03 and 0.30+/-0.05, compared with DM, P < 0.05). The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION: KYQWJJ (high dose) treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.

Animals↗

The functional lumen imaging probe (FLIP) for evaluation of the esophagogastric junction.

There is a need for new methods to study the dynamics of the esophagogastric junction (EGJ). The aims were to verify the efficacy and usefulness of a "functional lumen imaging probe" (FLIP) for the evaluation of the EGJ. Eight healthy volunteers (6 men), median age 26 (21-35) yr, and two achalasia patients underwent the FLIP procedure. The EGJ was located by manometry. The FLIP measured eight cross-sectional areas (CSAs) 4 mm apart together with the pressure inside a saline-filled cylindrical bag. The data showed the geometric profile of the EGJ reconstructed in a video animation of its dynamic activity. A plot of curve-fitted data for the smallest CSA vs. pressure after balloon distension indicated that the pressure increased from 18 cmH2O at a CSA of 38 mm2 to a pressure of 37 cmH2O at a CSA of 230 mm2 for the healthy controls. In one achalasia patient (unsuccessfully treated with dilations), the CSA never rose above the minimal measurable value despite the pressure increasing to 50 cmH2O. In another achalasia patient (successfully treated with dilations), the pressure only reached 15 cmH2O despite opening to a CSA of 250 mm2. In conclusion, FLIP represents the first dynamic technique to profile the function and anatomy of the EGJ. The method can be used practically to evaluate difficult cases of EGJ dysfunction and may provide a role in evaluating patients before and after therapies for diseases affecting the EGJ such as achalasia and gastroesophageal reflux disease.

Adult↗

Ultrasound-determined geometric and biomechanical properties of the human duodenum.

Methods based on cross-sectional ultrasound imaging may be valuable for assessment of biomechanical parameters in the duodenum in health and disease. In 12 healthy volunteers a specially designed duodenal bag containing a high-frequency ultrasound probe was inflated until the perception of moderate pain. The ultrasound images and bag pressures were recorded before and after administration of butylscopolamine. The duodenum approached a circular shape as the load was increased (P = 0.01). The tension-strain relations were exponential and the curve fitting constant alpha (stiffness) was 1.72+/-0.81 before and 1.13+/-0.22 after administration of butylscopolamine (P=0.5). In three subjects construction of stress-strain diagrams was possible. The wall thickness decreased after administration of butylscopolamine (P < 0.001). The wall thickness was nonhomogeneously distributed along the duodenal circumference, being thickest at high curvatures. In the future this may be useful for assessing the geometry, stiffness, remodeling, and mechanosensory properties in the duodenum and small intestine in health and disease.

Adult↗

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension.

AIM: To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS: Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale (VAS). The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anti-cholinergic drug butylscopolamine. RESULTS: The stimulus-response (volume-VAS) curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION: The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.

Adult↗

Longitudinal residual strain and stress-strain relationship in rat small intestine.

BACKGROUND: To obtain a more detailed description of the stress-free state of the intestinal wall, longitudinal residual strain measurements are needed. Furthermore, data on longitudinal stress-strain relations in visceral organs are scarce. The present study aims to investigate the longitudinal residual strain and the longitudinal stress-strain relationship in the rat small intestine. METHODS: The longitudinal zero-stress state was obtained by cutting tissue strips parallel to the longitudinal axis of the intestine. The longitudinal residual stress was characterized by a bending angle (unit: degrees per unit length and positive when bending outwards). Residual strain was computed from the change in dimensions between the zero-stress state and the no-load state. Longitudinal stresses and strains were computed from stretch experiments in the distal ileum at luminal pressures ranging from 0-4 cmH2O. RESULTS: Large morphometric variations were found between the duodenum and ileum with the largest wall thickness and wall area in the duodenum and the largest inner circumference and luminal area in the distal ileum (p < 0.001). The bending angle did not differ between the duodenum and ileum (p > 0.5). The longitudinal residual strain was tensile at the serosal surface and compressive at the mucosal surface. Hence, the neutral axis was approximately in the mid-wall. The longitudinal residual strain and the bending angle was not uniform around the intestinal circumference and had the highest values on the mesenteric sides (p < 0.001). The stress-strain curves fitted well to the mono-exponential function with determination coefficients above 0.96. The alpha constant increased with the pressure, indicating the intestinal wall became stiffer in longitudinal direction when pressurized. CONCLUSION: Large longitudinal residual strains reside in the small intestine and showed circumferential variation. This indicates that the tissue is not uniform and cannot be treated as a homogenous material. The longitudinal stiffness of the intestinal wall increased with luminal pressure. Longitudinal residual strains must be taken into account in studies of gastrointestinal biomechanical properties.

Animals↗

Viscoelastic properties of isolated rat colon smooth muscle cells.

The measurement of the biomechanical properties of gastrointestinal smooth muscle cells is important for the basic understanding of digestive function and the interaction of muscle cells with the matrix. Externally applied forces will deform the cells depending upon their mechanical properties. Hence, the evoked response mediated through stretch-sensitive ion-channels in the smooth muscle cell membrane will depend upon membrane properties and the magnitude of the external force. The aim of this study was to test the hypothesis that gastrointestinal smooth muscle cells behave in a viscoelastic manner. Smooth muscle cells were dissociated from the muscle layers of the descending colon. The viscoelastic properties of the isolated cells were characterized by measuring the mechanical deflection response of the cell membrane to a negative pressure of 1cm H(2)O applied across the cell through a micropipette and fitting the response to a theoretical viscoelastic solid model. The viscoelastic mechanical constants of the isolated cells (N=9) were found to be as follows: k(1)=19.99+/-2.86 Pa, k(2)=7.19+/-1.21 Pa, mu=25.36+/-6.14 Pas and tau=4.84+/-0.95 s. This study represents, to the best of our knowledge, the first quantitative mechanical properties of isolated living smooth muscle cells from the gastrointestinal tract. The mechanical properties determined in this study will be of use in future analytical and numerical smooth muscle cell models to better predict the mechanism between the magnitude of mechanical stimuli, mechanosensitivity and the evoked afferent responses.

Animals↗

The geometric configuration and morphometry of the rabbit oesophagus during luminal pressure loading.

The aim of the present study was to determine the geometric configuration and morphometric dimensions in the rabbit oesophagus during luminal pressure loading. The geometric configuration is of fundamental importance because it is related to stress and strain and determines the resistance to flow. The oesophagus was excised from rabbits, transferred to an organ bath and stretched to the in vivo length. Cannulas were inserted into both ends and each oesophagus was subjected to a luminal pressure up to 0, 1, 2, 5 and 10 cm H(2)O. After equilibrium was reached, the oesophagus was snap-frozen in liquid nitrogen. Sections were cut from five locations in the oesophagus and videotaped in the frozen state. Geometric and morphometric data including perimeter, circularities, area, thickness, buckles and strains in different layers were obtained from the video images. These variables did not show axial variation in the oesophagus. All variables changed as a function of the pressure. The whole wall thickness decreased as an inverse function of the pressure. The thickness decrease was mainly due to thinning of the submucosa and muscle. The number of buckles decreased from 4.05 +/- 0.34 at 0 cm H(2)O pressure to 0.07 +/- 0.07 at 10 cm H(2)O. Circumferential Green strain-pressure curves for the various layers all showed an exponential pattern. The curve obtained at the submucosa-muscle layer interface was located to the right of the other curves, indicating that the muscle layer was softest. The data obtained in this study will be useful for further modelling of the mechanics of the oesophagus.

Animals↗

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain.

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

Central Nervous System↗

Functional oesophago-gastric junction imaging.

Despite its role in disease there is still no definitive method to assess oesophago-gastric junction competence (OGJ). Traditionally the OGJ has been assessed using manometry with lower oesophageal sphincter pressure as the indicator. More recently this has been shown not to be a very reliable marker of sphincter function and competence against reflux. Disorders such as gastro-oesophageal reflux disease and to a lesser extend achalasia still effects a significant number of patients. This review looks at using a new technique known as impedance planimetry to profile the geometry and pressure in the OGJ during distension of a bag. The data gathered can be reconstructed into a dynamic representation of OGJ action. This has been shown to provide a useful representation of the OGJ and to show changes to the competence of the OGJ in terms of compliance and distensibility as a result of endoluminal therapy.

Biomechanical Phenomena↗

Gastric accommodation assessed by ultrasonography.

Gastric accommodation is important for the understanding of the pathophysiology in functional dyspepsia and is also relevant for symptom generation in other disorders. The term gastric accommodation has at least three different meanings: The accommodation process, the accommodation reflex, and the accommodation response. The gastric accommodation process is a complex phenomenon that describes how the size of the gastric compartment changes in response to a meal. The electronic barostat is considered the gold standard in assessing gastric accommodation. Imaging methods, including MRI, SPECT, and ultrasonography may also be used, particularly in patients who are stress-responsive, e.g. functional dyspepsia patients, as a non-invasive and less stress-inducing method is favourable. Ultrasonography satisfies these criteria as it does not by itself distort the physiological response in stress-responsive individuals.

Dyspepsia↗

Morphology and motor function of the gastrointestinal tract examined with endosonography.

Endosonography is a useful tool for studying the morphology and motor function of the gastrointestinal tract. Intraluminal ultrasonography is the common denomination of ultrasound examinations using intracorporal transducers which are inserted into the GI tract. Thus, the visceral wall and adjacent structures can be imaged in detail. This review describes the usefulness of endosonography in gastroenterology, in particular with respect to studies of the biomechanical and motor function of the gastrointestinal tract. New techniques such as 3-D EUS, elastography and strain rate imaging are discussed.

Biomechanical Phenomena↗

New perspectives of studying gastrointestinal muscle function.

The motor function of the gastrointestinal tract has primarily been studied using manometry and radiography, though more indirect tests have also been applied. Manometry and radiography do not provide detailed information about the muscle properties as can be assessed from studies of muscle properties in muscle strips in vitro. In recent years a technique based on impedance planimetric measurement of pressure-cross-sectional area relations in a distending bag has proven to provide more detailed information about the muscle function in vivo. This review shows examples of new muscle function analysis such as length-tension diagrams, force-velocity curves and preload-afterload diagrams.

Biomechanical Phenomena↗

Three-dimensional surface model analysis in the gastrointestinal tract.

The biomechanical changes during functional loading and unloading of the human gastrointestinal (GI) tract are not fully understood. GI function is usually studied by introducing probes in the GI lumen. Computer modeling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. The tension and stress distributions in the GI tract are related to distensibility (tension-strain relationship) and smooth muscle tone. More knowledge on the tension and stress on the GI tract are needed to improve diagnosis of patients with gastrointestinal disorders. A modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system has recently been developed. The 3-D anatomical model was constructed from digital images using ultrasonography, computer tomography (CT) or magnetic resonance imaging (MRI). Different mathematical algorithms were developed for surface analysis based on thin-walled structure and the finite element method was applied for the mucosa-folded three layered esophageal model analysis. The tools may be useful for studying the geometry and biomechanical properties of these organs in health and disease. These studies will serve to test the structure-function hypothesis of geometrically complex organs.

Algorithms↗

Multimodal pain stimulation of the gastrointestinal tract.

Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation (e.g., electrical, mechanical, thermal and chemical stimulation) of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.

Abdominal Pain↗

Biomechanical properties of the layered oesophagus and its remodelling in experimental type-1 diabetes.

Passive biomechanical properties in term of the stress-strain relationship and the shear modulus were studied in separated muscle layer and mucosa-submucosa layer in the oesophagus of normal and STZ (streptozotocin)-induced diabetic rats. The mucosa-submucosa and muscle layers were separated using microsurgery and studied in vitro using a self-developed test machine. Stepwise elongation and inflation plus continuous twist were applied to the samples. A constitutive equation based on a strain energy function was used for the stress-strain analysis. Five material constants were obtained for both layers. The mucosa-submucosa layer was significantly stiffer than the muscle layer in longitudinal, circumferential and circumferential-longitudinal shear direction. The mechanical constants of the oesophagus show that the oesophageal wall was anisotropic, the stiffness in the longitudinal direction was higher than in the circumferential direction in the intact oesophagus (P < 0.001) and in the muscle layer (P < 0.05). Diabetes-induced pronounced increase in the outer perimeter, inner perimeter and lumen area in both the muscle and mucosa-submucosa layer. The growth of the mucosa-submucosa layer (P < 0.001) was more pronounced than the muscle layer (P < 0.05). Furthermore, the circumferential stiffness of the mucosa-submucosa layer increased 28 days after STZ treatment. In conclusion, the oesophagus is a non-homogeneous anisotropic tube. Thus, the mechanical properties differed between layers as well as in different directions. Morphological and biomechanical remodelling is prominent in the diabetic oesophagus.

Animals↗