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.

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.

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.

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.

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.

Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.

METHODS AND RESULTS: By differential display we isolated a new cDNA-fragment, named C13, that is downregulated in malignant prostate tissues. Northern hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs. Fluorescence in situ hybridization, Southern blotting and radiation hybrid mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes of the allelic status in 13 of 21 prostate cancers. A downregulation was detected at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino acids. The corresponding protein contains a putative nuclear localization signal, several glutamine clusters and an alpha-helix-rich domain. By in situ RNA hybridization we could demonstrate the mainly epithelial expression of the C13 mRNA in prostatic tissue. CONCLUSIONS: The localization of C13 between the tumor suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the downregulation of its mRNA in some prostatic cancer tissues, the epithelial expression and the described protein structure suggest that this gene encodes a protein that may have tumor or metastasis suppressing function in prostate tissue.

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.

The effects of therapeutic contact lenses on intraocular pressure measurement.

PURPOSE: To evaluate the accuracy of intraocular pressure (IOP) measurements taken through three commonly used therapeutic contact lenses, using both the Tono-Pen and pneumatonometer. METHODS: We measured the IOP of ten normal eyes and ten eyes with abnormal anterior segments using Tono-Pen, pneumatonometry, and Goldman application tonometry. Three different soft contact lenses (Acuvue, 04, and Permalens) were sequentially placed on the eyes and repeat measurements were taken. The readings obtained for each contact lens were compared to the baseline readings taken without a lens in place in order to assess the effect that each contact lens had on the accuracy of IOP measurements. RESULTS: All three contact lenses permitted accurate IOP measurements in eyes with both normal and abnormal anterior segments. Variations in water content and central thickness did not affect the accuracy of IOP measurements. CONCLUSIONS: Both Tono-Pen and pneumatonometry proved to be equally reliable in recording accurate IOP measurements through therapeutic contact lenses.

Peripheral corneal infiltrates associated with contact lens wear.

PURPOSE: We describe the epidemiological and clinical characteristics of peripheral corneal infiltrates associated with contact lens wear. METHODS: We conducted a retrospective study of 52 patients with contact lens associated peripheral corneal infiltrates. Demographic data, clinical characteristics of the infiltrates, contact lens parameters, treatment modality, and the time to resolution for the infiltrates were analyzed. RESULTS: Forty-four of the 52 patients in this study presented with a single infiltrate, while the remaining 8 patients had multiple infiltrates. Types of contact lenses worn were as follows: 40% of the patients wore disposable extended wear contact lenses; 21% wore conventional extended wear lenses; 19% wore conventional daily wear lenses; 12% used frequent replacement daily wear lenses; 6% wore rigid gas permeable (RGP) contact lenses; and 2% used disposable lenses as daily wear. Although there was no predilection for a specific quadrant of the cornea, when a subgroup of extended wear contact lens patients was analyzed, 19 of their 40 infiltrates were located in the superior quadrant. The epithelium was intact in 42% of the infiltrates, while 58% of the infiltrates had epithelial involvement, either punctate staining or frank defect. Eight of the 16 patients who had corneal cultures performed had positive cultures. All patients who had positive cultures used extended wear contact lenses. Smoking did not appear to have an effect on the associated inflammatory reaction, positive cultures, or time to resolution. Seventy-five percent of patients were treated with topical antibiotics. Antibiotic steroids were prescribed for 23% of patients, and 2% of patients were treated with topical steroids. The mean time to resolution for all infiltrates was 1.74 weeks. CONCLUSIONS: Focal peripheral infiltrates with or without epithelial disturbance represent a distinct clinical complication associated with contact lens wear. All patients in this study had resolution of their infiltrates without complications. We recommend that after resolution of corneal infiltrates, patients should be refit with daily wear soft or RGP contact lenses.

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.

[Structure and structural disorder]. / Struktur und strukturelle Störung.

One of the central tasks of psychodynamic diagnosis, next to determining intrapsychic conflicts, central relational patterns, and subjective forms of experiencing is assessing the psychic structure or the structural disorder. This article develops the structure term from object relationship theoretical, ego-psychological, and self-psychological concepts of psychoanalysis. This "Structure of the self in the relationship to others" thus obtained is described with six structural criteria (self-perception, self-control, defence, object perception, communication, attachment). In order to be able to distinguish the extent and the quality of structural disorders four structure levels of integration based on psychoanalytic experience in the out-patient and the in-patient setting are differentiated. A basis for an operationalization is then made; it is made in the system OPD (Operationalized Psychodynamic Diagnostics). First studies regarding practicalibility and reliability are promising.

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.

Changes in refraction and keratometry after surgery for acquired ptosis.

A retrospective study involving 47 lids in 26 patients was conducted to determine changes in refraction and keratometry after surgery for acquired ptosis. Refractive and keratometric data were obtained prior to and 6 months after levator surgery. Data were analyzed for changes in refractive sphere, cylinder, and cylindrical axis, as well as keratometry, toricity, and axis of toricity. Although patients noted subjective change in vision postoperatively and demonstrated changes in their refractive error, the changes were statistically insignificant. Consistency was noted; the cylindrical axis and the axis of toricity remained relatively stable after surgery.

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.

The induction of anterior chamber inflammation by factors released from hydrogen peroxide-injured corneas: effect of dexamethasone and indomethacin.

Studies from our laboratory have demonstrated the release of high levels of neutrophil chemotactic factors (NCF) from isolated rabbit corneas injured by hydrogen peroxide (H2O2). The purpose of the present study was to determine the biological activity of these factors and to test the hypothesis that the intracameral injection of these factors can induce inflammation of the anterior segment. Under sterile conditions, the epithelial surfaces of isolated rabbit corneas were incubated with a 300 ul mixture of glucose (G) (1mg/ml) and glucose oxidase (GO) (20 U/ml) at 37 degrees C for 6 hours. This supernatant solution was collected and a 100 ul sample containing NCF, but not H2O2, was injected into the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associated with a fibrinous anterior chamber reaction, was evident 2 and 4 hours after injection. Aqueous humor analysis revealed the presence of fibrin and a large number of neutrophils (32 +/- 5 x 10(4) cells/ml). Control eyes, on the other hand, showed normal morphology and low levels of neutrophils after the injection of 100 ul minimum essential medium (MEM) (n = 8) (1.2 +/- 0.14 x 10(4) cells/ml), G/GO mixture (n = 8) (5 +/- 0.86 x 10(4) cells/ml), or supernatant solutions collected from MEM-treated corneas (n = 8) (15 +/- 2 x 10(4) cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidonic acid (AA) metabolites, we pretreated rabbit eyes with a sterile solution of 0.1% dexamethasone (n = 8 eyes) or with a sterile solution of 3.4% indomethacin (n = 8 eyes) three times a day, for one day, prior to the injection of NCF supernatant solution. Examination 2 hours and 4 hours after injection revealed inflammation characterized by mild-to-moderate corneal edema associated with a fibrinous anterior chamber reaction was observed with or without prior treatment with AA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H2O2-injured corneas can directly induce inflammation of the anterior segment, and that metabolites of AA are not mediating the observed in vivo response.

A comparison of conventional and disposable extended wear contact lenses.

The charts of 126 extended wear contact lens patients (65 disposable and 61 conventional extended wear lens users) were reviewed for subjective and objective contact lens problems. We found that the number of complication events per person per year of lens wear was higher for conventional extended lens wearers than for disposable extended wear patients. There was a trend in both groups toward decreased numbers of complications in the second and third years of lens wear. Within each group, we also examined first time lens wearers and patients with a history of contact lens related complications. Both of these subgroups also fared better with disposable lenses, with fewer complication events per year and fewer complications overall. Of the 20 individual signs and symptoms that were analyzed, 13 occurred more frequently among conventional extended wear lens users; this difference was statistically significant for itching, burning and dryness, poor vision, foreign body sensation, torn and lost lenses, giant papillary conjunctivitis, mucus, and superficial punctate keratopathy. Five signs were more frequent among the disposable extended wear lens users, but the difference was not statistically significant. There were no cases of ulcerative keratitis in either group. The average wearing time was 11.2 +/- 5.9 days for conventional extended wear patients and 6.7 +/- 2.3 days in the disposable group. The difference in wearing time between the two groups may have been a factor in the higher complication rate among conventional extended wear lens patients.

Causative factors in unilateral giant papillary conjunctivitis.

Giant papillary conjunctivitis (GPC) is usually a bilateral disease. However, in a small number of cases, GPC can be manifested as a unilateral, or a markedly asymmetrical disease in patients wearing bilateral contact lenses. We reviewed the clinical records of 148 patients with GPC to determine the incidence of unilateral GPC and its causative factors. Specifically, charts were reviewed for data on refractive error, keratometry, lens fit, lens care, lens replacement, and the presence or absence of associated ocular abnormalities (dry eyes, blepharitis, previous injury, or surgery). Fourteen patients with unilateral or markedly asymmetrical disease were identified. Overall, no statistically significant difference was found in lens care, refractive error, or keratometric measurements in the affected and unaffected eyes. While not statistically significant, infrequent lens replacement appears to be an important factor in the development of unilateral GPC. Three patients had a history of wearing an older lens in the GPC eye. Two patients were found with unilateral meibomian gland dysfunction involving the affected eye, and one patient had undergone surgery on the affected eye. No causative factor was identified in eight cases.

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.