New methodology for mechanical characterization of human superficial facial tissue anisotropic behaviour in vivo.

Mechanical characterization of human superficial facial tissue has important applications in biomedical science, computer assisted forensics, graphics, and consumer goods development. Specifically, the latter may include facial hair removal devices. Predictive accuracy of numerical models and their ability to elucidate biomechanically relevant questions depends on the acquisition of experimental data and mechanical tissue behavior representation. Anisotropic viscoelastic behavioral characterization of human facial tissue, deformed in vivo with finite strain, however, is sparse. Employing an experimental-numerical approach, a procedure is presented to evaluate multidirectional tensile properties of superficial tissue layers of the face in vivo. Specifically, in addition to stress relaxation, displacement-controlled multi-step ramp-and-hold protocols were performed to separate elastic from inelastic properties. For numerical representation, an anisotropic hyperelastic material model in conjunction with a time domain linear viscoelasticity formulation with Prony series was employed. Model parameters were inversely derived, employing finite element models, using multi-criteria optimization. The methodology provides insight into mechanical superficial facial tissue properties. Experimental data shows pronounced anisotropy, especially with large strain. The stress relaxation rate does not depend on the loading direction, but is strain-dependent. Preconditioning eliminates equilibrium hysteresis effects and leads to stress-strain repeatability. In the preconditioned state tissue stiffness and hysteresis insensitivity to strain rate in the applied range is evident. The employed material model fits the nonlinear anisotropic elastic results and the viscoelasticity model reasonably reproduces time-dependent results. Inversely deduced maximum anisotropic long-term shear modulus of linear elasticity is G∞,maxaniso=2.43kPa and instantaneous initial shear modulus at an applied rate of ramp loading is G0,maxaniso=15.38kPa. Derived mechanical model parameters constitute a basis for complex skin interaction simulation.

Dynamic material characterization of the human heel pad based on in vivo experimental tests and numerical analysis.

A numerical-experimental, proof-of-concept approach is described to characterize the mechanical material behavior of the human heel pad under impact conditions similar to a heel strike while running. A 3D finite-element model of the right foot of a healthy female subject was generated using magnetic resonance imaging. Based on quasi-static experimental testing of the subject's heel pad, force-displacement data was obtained. Using this experimental data as well as a numerical optimization algorithm, an inverse finite-element analysis and the 3D model, heel pad hyperelastic (long-term) material parameters were determined. Applying the same methodology, based on the dynamic experimental data from the impact test and obtained long-term parameters, linear viscoelastic parameters were established with a Prony series. Model validation was performed employing quasi-static and dynamic force-displacement data. Coefficients of determination when comparing model to experimental data during quasi-static and dynamic (initial velocity: 1480mm/s) procedure were R(2) = 0.999 and R(2) = 0.990, respectively. Knowledge of these heel pad material parameters enables realistic numerical analysis to evaluate internal stress and strain in the heel pad during different quasi-static or dynamic load conditions.

Method for characterizing viscoelasticity of human gluteal tissue.

Characterizing compressive transient large deformation properties of biological tissue is becoming increasingly important in impact biomechanics and rehabilitation engineering, which includes devices interfacing with the human body and virtual surgical guidance simulation. Individual mechanical in vivo behaviour, specifically of human gluteal adipose and passive skeletal muscle tissue compressed with finite strain, has, however, been sparsely characterised. Employing a combined experimental and numerical approach, a method is presented to investigate the time-dependent properties of in vivo gluteal adipose and passive skeletal muscle tissue. Specifically, displacement-controlled ramp-and-hold indentation relaxation tests were performed and documented with magnetic resonance imaging. A time domain quasi-linear viscoelasticity (QLV) formulation with Prony series valid for finite strains was used in conjunction with a hyperelastic model formulation for soft tissue constitutive model parameter identification and calibration of the relaxation test data. A finite element model of the indentation region was employed. Strong non-linear elastic but linear viscoelastic tissue material behaviour at finite strains was apparent for both adipose and passive skeletal muscle mechanical properties with orthogonal skin and transversal muscle fibre loading. Using a force-equilibrium assumption, the employed material model was well suited to fit the experimental data and derive viscoelastic model parameters by inverse finite element parameter estimation. An individual characterisation of in vivo gluteal adipose and muscle tissue could thus be established. Initial shear moduli were calculated from the long-term parameters for human gluteal skin/fat: G(∞,S/F)=1850 Pa and for cross-fibre gluteal muscle tissue: G(∞,M)=881 Pa. Instantaneous shear moduli were found at the employed ramp speed: G(0,S/F)=1920 Pa and G(0,M)=1032 Pa.

Mechanical gluteal soft tissue material parameter validation under complex tissue loading.

BACKGROUND: Finite element (FE) simulations of mechanical tissue loading help provide insight into internal tissue stress and strain distribution. Thus, better understanding of pressure sore aetiology and pressure sore prophylaxis can be acquired. Indispensable in the simulation process is adequate mechanical description of interacting soft tissue and body support materials. Sufficient verification of employed material parameters is required. METHOD OF APPROACH: Gluteal soft tissue material parameters, previously derived from experimental tissue indentation of a geometrically limited buttock sub-domain are shown to be suitable in simulating complex deformation of the entire buttocks. In the context of parameter verification, defined tissue loading via a soft foam material specimen was performed. Making use of magnetic resonance imaging (MRI), the scenario was scanned to gain tissue displacement information. Anatomical surface data was reconstructed and an FE-model of the experimental situation was generated and simulated. MR-image information was compared with simulation results. RESULTS: Deformation of gluteal skin/fat and passive muscle tissue and support material under loading was in good agreement with the corresponding MR-image data. Visual accordance was found for deformed skin boundary as well as for internal fat-muscle tissue boundaries by superimposing experimental and numerical output. In addition, section surface boundaries of the MR-images and the FE-model of skin/fat and muscle at the deformed state were discretized and sufficient sample points were provided. A correlation factor of R2= 0.998 for skin/fat deformation was derived, comparing simulation with MRI output. CONCLUSION: Reliability of employed tissue material parameters for use in realistic loading scenarios at finite strains including complex tissue and bone anatomy, non-linear tissue support material, multiple tissue types and contact interactions is shown.

Analysis of mechanical interaction between human gluteal soft tissue and body supports.

Pressure sores are the most common complication associated with patient immobilization. They develop through sustained localized tissue strain and stress, primarily caused by body supports. Modifying support design can reduce the risk and extent of pressure sore development with computational simulations helping to provide insight into tissue stress-strain distribution. Appropriate material parameters for human soft tissue and support material, as well as precise anatomical modelling, are indispensable in this process. A finite element (FE) model of the human gluteal region based on magnetic resonance imaging (MRI) data has been developed. In vivo human gluteal skin/fat and muscle long-term material parameters as well as open-cell polyurethane foam support long-term material parameters have been characterised. The Ogden form for slightly compressible materials was employed to describe human gluteal soft tissue behaviour. Altering support geometries and support materials, effects on human gluteal soft tissue could be quantified. FE-analysis indicated maximal tissue stress at the muscle-bone interface, not at the skin. Shear strain maxima were found in the muscle layer near the fat-muscle interface. Maximum compressive stress magnitude at the sacral bone depended strongly on the behaviour of the pelvic diaphragm musculature. We hypothesize that the compliance of the muscles forming the pelvic diaphragm govern the relative motion of the buttock tissue to the adjacent bone structure under compression, thus influencing tissue stress magnitudes.

A method for a mechanical characterisation of human gluteal tissue.

The most common complication associated with immobilization is pressure sores caused by sustained localized tissue strain and stress. Computational simulations have provided insight into tissue stress-strain distribution, subject to loading conditions. In the simulation process, adequate soft tissue material parameters are indispensable. An in vivo procedure to characterise material parameters of human gluteal skin/fat and muscle tissue has been developed. It employs a magnetic resonance imaging (MRI) device together with an MRI compatible loading device. Using the derived data as constraints in an iterative optimization process the inverse finite element (FE) method was applied. FE-models were built and the material constants describing skin/fat and muscle tissue were parameterized and optimized. Separate parameter sets for human gluteal skin/fat and muscle were established. The long-term shear modulus for human gluteal skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa. The Ogden form for slightly compressible materials was chosen to define passive human gluteal soft tissue material behaviour. To verify the approach, the human skin/fat-muscle tissue compound was simulated using the derived material parameter sets and the simulation result was compared to empirical values. A correlation factor of R;{2} = 0.997 was achieved.

A review of the causes of upper gastrointestinal tract bleeding in children.

Bleeding may occur anywhere along the gastrointestinal tract, which covers a large surface area and is highly vascularized. While gastrointestinal bleeding is an alarming symptom for patients of any age, it can cause panic for children and their care givers. Early diagnosis and treatment of gastrointestinal bleeding may be essential. The differential diagnosis of bleeding from the upper gastrointestinal tract in infants and children includes numerous possibilities ranging from benign disorders which require little or no treatment at all, to serious diseases which require immediate intervention. This article reviews a variety of disorders which may cause upper gastrointestinal bleeding in infants and children. This is part one, of a two part series, on gastrointestinal bleeding in children. Part two will discuss bleeding from the lower gastrointestinal tract.

A review of the causes of lower gastrointestinal tract bleeding in children.

Bleeding may occur anywhere along the gastrointestinal (GI) tract, which covers a large surface area and is highly vascularized. Seeing blood in the child's stools, the caregiver and child may become extremely anxious, fearing a devastating diagnosis. The differential diagnosis of lower GI bleeding in infants and children, however, includes numerous possibilities ranging from benign disorders, which require little or no treatment at all, to serious diseases that require immediate intervention. This article reviews a variety of disorders that may produce lower GI bleeding in infants and children. This is Part 2 of a two-part series on GI bleeding in children. Part 1 discussed bleeding from the upper GI tract.

A cluster of microvillous inclusion disease in the Navajo population.

We report 4 unrelated patients with characteristic microscopic findings of microvillous inclusion disease (MID) with early-onset phenotype. All 4 patients came from the Navajo reservation in northern Arizona. A literature search revealed a fifth unrelated Navajo child with MID. The unusually high incidence in this population indicates that a founder effect might be responsible for an increased frequency of this rare genetic disorder in the Navajo. It is recommended that all Navajo infants presenting with severe diarrhea during early infancy undergo investigation for MID.

Sedation in children: adequacy of two-hour fasting.

OBJECTIVES: (1) To investigate the relationship between the duration of time that children fasted before a procedure and their gastric volume and pH at the time of the procedure. (2) To compare the variables of gastric pH and volume with historical standards. METHODS: We performed 285 gastroscopies for children aged 0.1 to 18.6 years (mean, 7.5 +/- 5.3) between October 1991 and January 1995. Duration of fasting was 0.5 to 24 hours (mean, 6.7 +/- 5.3) after ingestion of clear liquids. Immediately after intravenously administered sedation, the gastric contents were removed endoscopically with suction and direct visualization to ensure complete evacuation. The volume and pH of the gastric contents were measured and analyzed in comparison with the duration of fasting. The values obtained were also compared with historical standards thought to minimize the risk of aspiration pneumonia: gastric volume 0.4 ml or less per kilogram of body weight and pH of 2.5 or greater. RESULTS: There was no significant correlation between duration of fasting and either gastric volume divided by body weight (mean, 0.68 +/- 1.31 ml/kg; range, 0 to 15.23 ml/kg) or pH (mean, 2.03 +/- 1.40; range, 1 to 8). There was less no significant difference in the percentage of children with gastric volume of 0.4 ml/kg or less or with pH of 2.5 or greater between the groups with the following fasting times: 30 minutes to 3 hours, more than 3 hours to 8 hours, and more than 8 hours. CONCLUSIONS: On the basis of the data in this study and a review of the literature, we concluded that (1) fasting longer than 2 hours after ingesting clear liquids does not significantly change gastric volume or pH, (2) there is no advantage in requiring children to fast for longer than 2 hours after clear liquid ingestion before sedation or anesthesia for any procedure, and (3) fewer than half of pediatric patients actually achieve the "desirable" values of a gastric volume of 0.4 ml/kg or less and a pH value of 2.5 pH units or more, regardless of fast duration, even though these values are presented in the literature as a goal to minimize the risk of aspiration pneumonia.

Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children.

STUDY OBJECTIVE: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease. DESIGN: Prospective measurement of interleukin-6 in children with signs of sepsis. (Controls, retrospective from serum bank.) SETTING: Emergency department of an urban children's hospital. PARTICIPANTS: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures. RESULTS: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae. Ten of these 11 had detectable interleukin-6. The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died. One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did. The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease. CONCLUSION: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid.

Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis.

In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1-year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults.

Lower gastrointestinal bleeding.

The differential diagnosis of lower gastrointestinal bleeding in children can be reduced markedly simply by taking into account the age of the child. The clinical condition of the patient can further help narrow the diagnostic possibilities. Newborns and infants who are clinically unstable are more likely to have diseases such as necrotizing enterocolitis, volvulus, Hirschprung disease, intussusception, or Meckel diverticulum. A baby who appears healthy should be examined for swallowed blood, allergic colitis, anal fissures, or lymphonodular hyperplasia. An older child of healthy appearance with bleeding is likely to have a juvenile polyp or infectious colitis, but a child who appears sick may have hemolytic uremic syndrome, Henoch-Schoenlein purpura, or inflammatory bowel disease. This information, along with that gleaned from the physical examination, can lead the pediatrician to determine the need for specific tests, such as abdominal radiographs, stool cultures, and an endoscopic evaluation. We have come a long way in our ability to diagnose the causes of lower gastrointestinal bleeding. With the availability of newer radiographic and nuclear medicine modalities and the ability to visualize the colon endoscopically, the need for exploratory laparotomy for diagnosis is rarer. While surgery may still be the therapy of choice, new diagnostic modalities give the surgeon much more preoperative information.

Attenuation of allergen sensitivity early in the course of ragweed immunotherapy.

During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.

Human lactation. II: Endogenous fatty acid synthesis by the mammary gland.

We studied the effects of a diet that was low in fat, high in carbohydrate (CHO) on milk lipid composition and de novo endogenous fatty acid synthesis by the mammary gland in five lactating women. The women consumed either a low fat (LF) (5% fat, 80% CHO) diet or a high fat (HF) (40% fat, 45% CHO) diet. Fat synthesis was determined after an oral dose of 500 mg/kg D2O by measuring the incorporation of deuterium into C10:0 to C18:0 saturated fatty acids of milk fat and plasma triglycerides by gas chromatography-mass spectrometry. Synthesis of plasma C16:0 and C18:0 triglycerides was barely detectable while women consumed the HF diet, but was increased 6-fold during the LF diet. Medium chain fatty acids secreted by the mammary gland increased from 12.8% (HF diet) to 16.3% (LF diet) in milk fat from four of five subjects (p = 0.027). Medium chain fatty acid secretion, however, increased from 13.9% (HF diet) to 29.9% (LF diet) in one subject. The primary fatty acids synthesized during lactation were C10:0, C12:0, and C14:0 in the majority of women studied. The LF diet significantly increased the apparent synthesis of C14:0 (p = 0.05), whereas no changes were observed in C12:0, C16:0, or C18:0. One subject had highly enriched C16:0 and C18:0 fatty acids in her milk on the LF diet, which could have been the result of mammary synthesis or of transport and secretion of hepatically synthesized lipids.

Manipulation of maternal diet to alter fatty acid composition of human milk intended for premature infants.

Ten lactating mothers (five of preterm and five of term infants) 9-17 d postpartum consumed a 5% fat, 15% protein, and 80% carbohydrate diet for 5 d. Their milk was analyzed for fatty acid composition by gas chromatography. Significant increases in the sum of the absolute and relative concentrations of C10:0, C12:0, and C14:0 fatty acids and significant decreases in the absolute and relative concentrations of C18:0, C18:1, and C18:2 fatty acids were detected on day 4 in both groups (p less than 0.01). Women who delivered prematurely or at term responded similarly in early lactation to a low-fat, high-carbohydrate diet with an increase in the concentration of fatty acids less than 16 carbons in length. The magnitude of this response is highly variable and may be controlled by total energy balance as well as by individual endocrine responses.

In vivo release of inflammatory mediators by hyperosmolar solutions.

Hyperosmolar environments induce histamine release from mast cells and basophils in vitro. To assess whether the same stimulus induces mediator release in vivo, 15 healthy human volunteers underwent nasal challenges with instilled solutions of differing osmolalities: lactated Ringer's solution (257 +/- 3 mOsm/kg), isosmolar mannitol (277 +/- 6 mOsm/kg), and hyperosmolar mannitol (869 +/- 8 mOsm/kg). The effect of these challenges on the volume, osmolality, and inflammatory mediator content of subsequent 5-ml isosmolar lavages was determined. The volumes of lavages returned after hyperosmolar challenges were significantly greater than those after isosmolar challenges (5.5 +/- 0.2 ml versus 4.2 +/- 0.1 ml; p less than 0.01) and these lavage solutions had higher osmolalities. Even when corrected for increased volumes, the lavages after hyperosmolar challenges contained significantly higher quantities of inflammatory mediators such as histamine (29.0 versus 10.1 ng; p less than 0.01), TAME-esterase activity (32.7 versus 11.1 cpm x 10(-3); p less than 0.01), and immunoreactive leukotrienes (9.9 versus 3.4 ng; p less than 0.01). The changes in mediators were dose dependent in that incremental increase in challenge osmolality were associated with incremental increases in histamine release. Therefore, when exposed to hyperosmolar stimuli in vivo, the nasal respiratory airway releases inflammatory mediators and fluid rapidly shifts into the airway lumen. It has been suggested that the mediator release observed on breathing cold and dry air is due to increased osmolality of airway secretions; the present data confirm that osmotic variations at the airway surface can provide an adequate stimulus for cell activation.

Reconstitution of T- and B-cell function after T-lymphocyte-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency due to adenosine deaminase deficiency.

A 4-month-old male received a T-lymphocyte-depleted haploidentical bone marrow transplant (BMT) for correction of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency. Although previous haploidentical bone marrow transplants have been attempted in ADA-deficient SCID, complete reconstitution of both B-lymphocyte and T-lymphocyte function has not been obtained after a single transplant. In this patient, however, rapid, complete, and persistent engraftment occurred. Potential reasons for this successful reconstitution include the use of ablation by chemotherapy (busulfan, cyclophosphamide, and cytosine arabinoside), the in vitro technique of using monoclonal antibody (CT-2) and complement to deplete the donor cells of T lymphocytes, and the relative good health of the patient prior to the transplant. Further trials using this method of haploidentical BMT may prove it to be a successful method of immunologic reconstitution in ADA-deficient SCID patients for whom an HLA-identical marrow is not available.

Sclerosing cholangitis and ulcerative colitis in a mother and her son.

We present two cases, a 32-year-old mother and her 10-year-old son, both of whom had ulcerative colitis and sclerosing cholangitis. The mother had radiologic as well as pathologic evidence of both diseases, while the child's disease was demonstrated pathologically. A review of the literature indicates the rarity of sclerosing cholangitis in childhood, with no reported instances of a parent-child affliction. The hypothesis that there is a genetic component to the development of sclerosing cholangitis may be supported by this family.