A forward dynamics simulation of human lumbar spine flexion predicting the load sharing of intervertebral discs, ligaments, and muscles.

Determining the internal dynamics of the human spine's biological structure is one essential step that allows enhanced understanding of spinal degeneration processes. The unavailability of internal load figures in other methods highlights the importance of the forward dynamics approach as the most powerful approach to examine the internal degeneration of spinal structures. Consequently, a forward dynamics full-body model of the human body with a detailed lumbar spine is introduced. The aim was to determine the internal dynamics and the contribution of different spinal structures to loading. The multi-body model consists of the lower extremities, two feet, shanks and thighs, the pelvis, five lumbar vertebrae, and a lumped upper body including the head and both arms. All segments are modelled as rigid bodies. 202 muscles (legs, back, abdomen) are included as Hill-type elements. 58 nonlinear force elements are included to represent all spinal ligaments. The lumbar intervertebral discs were modelled nonlinearly. As results, internal kinematics, muscle forces, and internal loads for each biological structure are presented. A comparison between the nonlinear (new, enhanced modelling approach) and linear (standard modelling approach, bushing) modelling approaches of the intervertebral disc is presented. The model is available to all researchers as ready-to-use C/C++ code within our in-house multi-body simulation code demoa with all relevant binaries included.

Effects of osteoarthritis and pathological walking on contact stresses in femoral cartilage.

Osteoarthritis is a widespread abnormality in synovial joints leading to increasing pain and potential work disability in middle-aged and older populations. A primary cause of osteoarthritis is related to damages from high local stresses combined with insufficient self-healing of cartilage. In this framework, it is the goal of the present contribution to offer a thermodynamically consistent simulation of a highly anisotropic, heterogeneous, osmotic swelling and poroviscoelastic model of healthy and osteoarthritic articular cartilage based on the Theory of Porous Media. Physiological and pathological loading patterns are included by means of multi-body system calculations on patients. The contact stresses at the cartilage surface are represented by means of three-dimensional and simplified stereographic views of the femoral head. For normal walking, the stress peaks are higher in the degenerated case than in the healthy case. Interestingly, pathological walking combined with degenerated cartilage tissue minimises the occurrence of high local stresses.

The effect of bezafibrate on the fibrinolytic enzyme system and the drug interaction with racemic phenprocoumon.

The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.

Factors affecting therapeutic concentration of topical aminocaproic acid in traumatic hyphema.

Epsilon-aminocaproic acid (EACA) decreases rebleeding in traumatic hyphema through antifibrinolytic activity. Therapeutic levels were achieved in aqueous humor of rabbits after topical application. Aqueous humor EACA levels were significantly higher after pretreatment with 0.5% proparacaine. Use of EACA (60%) in a carboxypolymethylene (CPM) vehicle (0.5%, 1%, 2%, 3%, and 4%) was examined. Aqueous humors levels at 4 hours ranged from 6.18-20.42 micrograms/ml. The 2% and 3% formulas achieved the highest concentrations in aqueous. Use of EACA (15%, 30%, 40%, and 60%) in 4% CPM was also studied. At 2 and 4 hours after treatment, the 30% EACA solution most effectively achieved therapeutic levels. Velcro closure devices were attached to the rabbit's eyelids, and 200 microliters of 30% EACA in 2% CPM was administered. After 3 hours the patched eyes had a mean aqueous EACA level of 60.09 micrograms/ml compared with 8.97 micrograms/ml in unpatched eyes. When dose size was studied in patched eyes, 200-microliters doses achieved aqueous levels of 60.09 micrograms/ml, and 100-microliters doses resulted in levels of 10.40 micrograms/ml. Since epithelial toxicity was observed in eyes that had been patched, the optimum topical regimen appeared to be 200 microliters of 30% EACA in 2% CPM every 6 hours in unpatched eyes.

LOH analyses in the region of the putative tumour suppressor gene C13 on chromosome 13q13.

BACKGROUND: In previous studies we isolated a new cDNA fragment named C13 which is down-regulated in malignant prostate tissues. The corresponding gene is localized on chromosome 13q13 between the known tumour suppressor genes (TSG) BRCA-2 and RB-1. MATERIALS AND METHODS: Loss of heterozygosity (LOH) analyses were carried out in the region of C13 in order to investigate the importance of the new putative TSG for prostate cancer development. Using semiquantitative LOH analysis, we screened 21 prostate carcinoma patients of different tumour stages (pT2-pT4) for 14 microsatellite markers in the region of C13 (13q13) and in the flanking BRCA-2 and the RB-1 loci. RESULTS: For 18 (86%) patients LOH or allelic imbalances were found. We identified three to nine alterations in affected tumours per marker. An overall genetic alteration frequency per patient of 38% (86 of 225 informative cases) could be calculated. One important finding regarding the overall frequency of determined microsatellite instability is that the LOH/AI rate of 47% for the seven C13-associated markers was higher than for the four markers of the RB-1 locus (39%) and for the three BRCA-2 markers (25%). Surprisingly, defining LOH critical regions (LCR) for the investigated marker panel, eight of the ten affected LCR cases showed chromosomal imbalances simultaneously for the RB-1 and the C13 LOH markers. CONCLUSIONS: The high LOH rate for eight different microsatellite markers in and around the putative TSG locus C13 on chromosome 13q13 further supports an involvement of C13 in prostate tumourigenesis.

Inflammatory and papulosquamous disorders of the skin and eye.

We have discussed herein the dermatologic and ocular manifestations of several inflammatory diseases. Cooperation between ophthalmologists and dermatologists can significantly enhance patient care and comfort. It is hoped that this review will stimulate increased awareness of the prevalence of ocular findings in these diseases and encourage cooperation between these specialties for the benefit of our patients.

Peripheral corneal infiltrates associated with contact lens wear.

PURPOSE: A retrospective study was performed to review the clinical characteristics of peripheral corneal infiltrates in contact lens wearers. METHODS: The charts of all contact lens patients with peripheral corneal infiltrates 1.5 mm or less in size who presented to the office from 1987 to 1994 were reviewed. RESULTS: The epidemiological and clinical characteristics of peripheral corneal infiltrates associated with contact lens wear were reviewed in 52 patients (64 infiltrates). Forty-four patients presented with a single infiltrate, while the remaining 8 patients had multiple infiltrates. While there was no predilection for a specific quadrant of the cornea, when a subgroup of patients who wore extended wear lenses was analyzed, 19 of the 40 infiltrates were located in the superior quadrant. Forty percent of the patients were wearing disposable extended wear contact lenses, 21% were wearing conventional extended wear lenses, 33% were wearing conventional or frequent replacement/disposable daily wear contact lenses and 6% were wearing rigid gas permeable lenses. The majority of patients had minimal conjunctival inflammation, an anterior stromal cellular reaction and minimal anterior chamber activity. A subgroup of 16 patients had corneal cultures of their infiltrates. In this group, 8 of the 16 had positive cultures. All patients had a resolution of the infiltrates without complications and the majority were refitted to daily wear soft or rigid contact lenses. CONCLUSION: Peripheral corneal infiltrates in contact lens wearers appears to be more common in patients wearing extended wear soft contact lenses. While often considered "sterile" in the literature, a significant number have been shown to be culture-positive. The organisms that have been associated with peripheral infiltrates appear to be less "pathogenic" than those that have been reported to be associated with central corneal ulcer. However, it is probably advisable that patients with peripheral corneal ulcers secondary to contact lens wear should be initially treated with topical antibiotics.

Application of the polynomial chaos expansion to approximate the homogenised response of the intervertebral disc.

A possibility to simulate the mechanical behaviour of the human spine is given by modelling the stiffer structures, i.e. the vertebrae, as a discrete multi-body system (MBS), whereas the softer connecting tissue, i.e. the softer intervertebral discs (IVD), is represented in a continuum-mechanical sense using the finite-element method (FEM). From a modelling point of view, the mechanical behaviour of the IVD can be included into the MBS in two different ways. They can either be computed online in a so-called co-simulation of a MBS and a FEM or offline in a pre-computation step, where a representation of the discrete mechanical response of the IVD needs to be defined in terms of the applied degrees of freedom (DOF) of the MBS. For both methods, an appropriate homogenisation step needs to be applied to obtain the discrete mechanical response of the IVD, i.e. the resulting forces and moments. The goal of this paper was to present an efficient method to approximate the mechanical response of an IVD in an offline computation. In a previous paper (Karajan et al. in Biomech Model Mechanobiol 12(3):453-466, 2012), it was proven that a cubic polynomial for the homogenised forces and moments of the FE model is a suitable choice to approximate the purely elastic response as a coupled function of the DOF of the MBS. In this contribution, the polynomial chaos expansion (PCE) is applied to generate these high-dimensional polynomials. Following this, the main challenge is to determine suitable deformation states of the IVD for pre-computation, such that the polynomials can be constructed with high accuracy and low numerical cost. For the sake of a simple verification, the coupling method and the PCE are applied to the same simplified motion segment of the spine as was used in the previous paper, i.e. two cylindrical vertebrae and a cylindrical IVD in between. In a next step, the loading rates are included as variables in the polynomial response functions to account for a more realistic response of the overall viscoelastic intervertebral disc. Herein, an additive split into elastic and inelastic contributions to the homogenised forces and moments is applied.

Linking continuous and discrete intervertebral disc models through homogenisation.

At present, there are two main numerical approaches that are frequently used to simulate the mechanical behaviour of the human spine. Researchers with a continuum-mechanical background often utilise the finite-element method (FEM), where the involved biological soft and hard tissues are modelled on a macroscopic (continuum) level. In contrast, groups associated with the science of human movement usually apply discrete multi-body systems (MBS). Herein, the bones are modelled as rigid bodies, which are connected by Hill-type muscles and non-linear rheological spring-dashpot models to represent tendons and cartilaginous connective tissue like intervertebral discs (IVD). A possibility to benefit from both numerical methods is to couple them and use each approach, where it is most appropriate. Herein, the basic idea is to utilise MBS in simulations of the overall body and apply the FEM only to selected regions of interest. In turn, the FEM is used as homogenisation tool, which delivers more accurate non-linear relationships describing the behaviour of the IVD in the multi-body dynamics model. The goal of this contribution is to present an approach to couple both numerical methods without the necessity to apply a gluing algorithm in the context of a co-simulation. Instead, several pre-computations of the intervertebral disc are performed offline to generate an approximation of the homogenised finite-element (FE) result. In particular, the discrete degrees of freedom (DOF) of the MBS, that is, three displacements and three rotations, are applied to the FE model of the IVD, and the resulting homogenised forces and moments are recorded. Moreover, a polynomial function is presented with the discrete DOF of the MBS as variables and the discrete forces an moments as function values. For the sake of a simple verification, the coupling method is applied to a simplified motion segment of the spine. Herein, two stiff cylindrical vertebrae with an interjacent homogeneous cylindrical IVD are examined under the restriction of purely elastic deformations in the sagittal plane.

An extended biphasic model for charged hydrated tissues with application to the intervertebral disc.

Finite element models for hydrated soft biological tissue are numerous but often exhibit certain essential deficiencies concerning the reproduction of relevant mechanical and electro-chemical responses. As a matter of fact, singlephasic models can never predict the interstitial fluid flow or related effects like osmosis. Quite a few models have more than one constituent, but are often restricted to the small-strain domain, are not capable of capturing the intrinsic viscoelasticity of the solid skeleton, or do not account for a collagen fibre reinforcement. It is the goal of this contribution to overcome these drawbacks and to present a thermodynamically consistent model, which is formulated in a very general way in order to reproduce the behaviour of almost any charged hydrated tissue. Herein, the Theory of Porous Media (TPM) is applied in combination with polyconvex Ogden-type material laws describing the anisotropic and intrinsically viscoelastic behaviour of the solid matrix on the basis of a generalised Maxwell model. Moreover, other features like the deformation-dependent permeability, the possibility to include inhomogeneities like varying fibre alignment and behaviour, or osmotic effects based on the simplifying assumption of Lanir are also included. Finally, the human intervertebral disc is chosen as a representative for complex soft biological tissue behaviour. In this regard, two numerical examples will be presented with focus on the viscoelastic and osmotic capacity of the model.

[Objective diagnosis of pre-Oedipal disorders]. / Zur objektivierenden Diagnostik präödipaler Störungen.

According to the diagnosis of preoedipal disturbances it should be worked out, that the test-results are not inconceivable formality and uncomprehension. From the selfrating of 74 neurotic patients we determined on 8 scales of narcism clinical description of well-known personality-dimensions of preoedipal fixation. With a Q-factor-analysis 3 subgroups could be established, which are marked as borderline- and narcistical typus against a typus without narcistic disturbance. The validity of such classification can be estimated about the clinical diagnose of 28 patients of this sample. It proves to be much promising for the diagnostic of preoedipal disturbances.

Diagnosis of narcissistic self-esteem regulation in patients with factitious illness (Munchausen syndrome).

A quantitative taxonomy for the identification of patients with narcissistic pathology and with borderline personality disorders based on test results is presented. The quantitative identification of these subgroups was produced using a Q-factor analysis. Based on the correlation of the subjects by means of the 241 questions from the narcissistic inventory of Deneke and Müller [27], three subgroups could be defined. Two of these groups exhibited a pathology of the self-system which corresponded to the pathology described by Kernberg [24] for narcissistic and borderline personality disorders. The third group is characterized by reduced observable self-pathology traits from the narcissistic inventory. By means of the reclassification of these three taxonomical groups with the discriminant analysis, two discriminant functions could be calculated, using the weighting of the single test scales for a classification of new patients. These classification functions were used to examine 18 patients suffering from factitious disorders. The evaluation of test profiles with the reduced narcissistic inventory of Deneke and Müller [11] in order to identify the three taxonomical groups showed that 9 patients (50%) had a borderline personality disorder and 6 patients (33%) a narcissistic personality disorder, while 3 patients (17%) could be assigned to the subgroup without self-pathology. In summary, 83% of the examined patients with factitious disorders exhibited a disorder in self-regulation. The previous clinical observations of self-regulation for patients with factitious disorders could thus be confirmed. It becomes clear that different high levels of disorder in self-regulation (position in the sphere of the discriminant function) correspond to varying degrees of prognostic significance.

A linear viscoelastic biphasic model for soft tissues based on the Theory of Porous Media.

Based on the Theory of Porous Media (mixture theories extended by the concept of volume fractions), a model describing the mechanical behavior of hydrated soft tissues such as articular cartilage is presented. As usual, the tissue will be modeled as a materially incompressible binary medium of one linear viscoelastic porous solid skeleton saturated by a single viscous pore-fluid. The contribution of this paper is to combine a descriptive representation of the linear viscoelasticity law for the organic solid matrix with an efficient numerical treatment of the strongly coupled solid-fluid problem. Furthermore, deformation-dependent permeability effects are considered. Within the finite element method (FEM), the weak forms of the governing model equations are set up in a system of differential algebraic equations (DAE) in time. Thus, appropriate embedded error-controlled time integration methods can be applied that allow for a reliable and efficient numerical treatment of complex initial boundary-value problems. The applicability and the efficiency of the presented model are demonstrated within canonical, numerical examples, which reveal the influence of the intrinsic dissipation on the general behavior of hydrated soft tissues, exemplarily on articular cartilage.

[Effect of hypnosis and suggestion on the EEG-powerspectrum in the preparatory interval (author's transl)]. / Leistungsspektren des EEG bei Hypnose und Suggestion in der Vorreizperiode.

Fourier-analysis of the EEG (P4 02, P3 O1, CZ A1) in the stimulation period (1 sec) before acoustic stimulation showed significant differences between hypnosis and waking. Diminished power was found in the slower spectrum (0-3 and 4-7 c/sec) over the right hemisphere (P4O2) during hypnosis. Increased power was found in the alpha-spectrum (8-13 c/sec) over the Vertex (CZA1) during suggestion. We interpreted this effect as inhibition of exteroceptive perception during suggestion. Powerspectrum was averaged over 30 stimulation periods before acoustic stimulation with identic tones (sinus of 500 c/sec, 70 dB, duration 40 msec, stimulus interval 3--10 sec). The combination of experimental conditions (Hypnosis/Waking and Suggestions) were given in a balanced order to control seriel effects. We examined 12 persons in a repeated measurement design.

Taxonomic aspects of clinical character typology.

Whereas clinical character typology is based upon one typological idealized personality description of the same illness model, empirical character typology is concerned with the identification of the different personality structures for the same illness model. We have been able to prove that in a taxonomical analysis (Q-factor analysis) of patients and healthy persons subgroups can be identified whose mean-value profiles justify designation as depressive, compulsive, and hysterical personality. This classification was replicated from a second sample. Through this personality classification it becomes possible to determine the distribution of the three personality structures from a clinical group. The distribution of the personality structure in neurotic depression was 59% for the depressive, 19% for the compulsive, and 22% for the hysterical personality. We were able to prove that they can be characterized by various coping strategies which presumably require different psychotherapeutic interventions.

Allergic ocular disorders: a spectrum of diseases.

Allergic eye disease is commonly encountered in clinical practice. The external eye is exposed to a host of environmental, cosmetic, and pharmacologic antigens. Although individual responses show a wide range of variability, a number of distinctive syndromes have emerged to define the spectrum of allergic eye disease. They consist of seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and contact allergies involving the conjunctiva.

Operational diagnostic approaches in the assessment of defense mechanisms.

A model for the operationalization of empirical research of defense mechanisms is presented. Measures for operationalized defense diagnoses are discussed against the background of a cognitive model of different coding of information channels (linguistic and perceptual coding). Studies for the operationalized diagnoses in the clinical assessment of defense mechanism are discussed for the identification of the defense mechanism, reliability of rating procedures, and the prognostic aspects in psychotherapy and psychosomatics. The regulation of defense on different levels of a hierarchy of complex systems of variables is demonstrated with paradigmatic results.

[Changes in reaction potentials in neurotic depression]. / Anderungen der Reaktionspotentiale bei der neurotischen Depression.

An investigation, comparing the event related potential (ERP) of depressive patients and a control group is presented. The components N100, P200, N200 and P300 have been recorded during the Stroop colour-word-interference test. The task is to name the colour of a colour word presented in a different colour, to read the word of an achromatic colour word and to name the colour of colour strips. The reaction time to name the colour or the word resulted in a general retardation for the patients with neurotic depression in comparison to the control group. The components of the acoustic evoked potentials, recorded after a warning stimulus S1, 4 s before the single Stroop stimuli showed no differences in amplitude or latency. The visual evoked potentials, associated to the Stroop stimuli showed, in case of the neurotic depressive patients an increase of the P300-amplitude. This result is interpreted as an increased cognitive effort of the patients in case of the employed experimental approach.

A comparison of contact lens-related complications in various daily wear modalities.

PURPOSE: To determine the incidence of contact lens-related complications in various daily wear contact lens modalities. METHODS: The charts of 138 daily wear contact lens patients (35 daily disposable, 34 two week replacement, 34 frequent replacement, and 35 conventional daily wear lens users) were reviewed for subjective and objective contact lens problems. We also looked at two subgroups: first time lens wearers and patients with previous lens-related problems. The rate of lens related complications were calculated as events per person per year (E/P/Y) of lens wear for each year and for the total 3-year study. The percentage of patients in each group who experienced any complication was calculated. We also compared the complication rate for the groups in our current study to the rates calculated for disposable extended wear and conventional extended wear patients from our previous study. RESULTS: We found that the E/P/Y were significantly lower for daily disposable lens wearers, but no significant differences were noted for all other lens wear modalities. There was a trend in most groups toward decreased numbers of complications in the second and third years of lens wear. Of the 23 individual signs and symptoms that were analyzed, three occurred most frequently among daily disposable lens wearers, two were most common in the 2-week replacement group, four occurred most often in frequent replacement patients, and eight were most frequent in conventional daily lens wearers. (In three categories, there were two groups with ties for the highest rate of occurrence, and two categories with zero rates for all groups.) Most of the observed differences in complication rates for individual signs and symptoms did not reach the level of statistical significance. CONCLUSIONS: Daily disposable lens wearers had the lowest overall complication rate.