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Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and polarized primary monocyte-derived macrophages. Using this coculture, we studied the contribution of macrophages to epithelial innate immunity, wound healing capacity, and epithelial exposure to whole cigarette smoke

Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV1 level. Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.

RU Radboud Universiteit Nijmegen, 14 april 2009, Promotor : Verdonschot, N.J.J. Co-promotores : Stolk, J., Mann, K.A., Contains fulltext : 74397.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 14 april 2009, Promotor : Verdonschot, N.J.J. Co-promotores : Stolk, J., Mann, K.A., Contains fulltext : 74397.pdf (publisher's version ) (Open Access)

De afgelopen jaren is zowel in de praktijk als door het onderzoek intensief gewerkt aan de ontwikkeling van geïntegreerde bestrijding van chrysant. Dit heeft geresulteerd in een flinke toename in chrysantenbedrijven waarbij een geïntegreerde bestrijdingsstrategie wordt toegepast en een afname in afhankelijkheid van chemische gewasbescherming. Het is vooral de geïntegreerde spintbestrijding die succesvol is; de tripsbestrijding bleek nog steeds een van de belangrijkste knelpunten voor de (geïntegreerde) chrysantenteelt te zijn. Voor de Subcommissie gewasbescherming van de Landelijke Commissie chrysant was dit aanleiding om WUR Glastuinbouw, van Iperen BV en Syngenta Bioline te vragen onderzoek uit te voeren dat duidelijkheid moest geven, 1) onder welke omstandigheden trips met de beschikbare natuurlijke vijanden en biologische middelen onder controle kan worden gehouden, en 2) of er betere alternatieven zijn voor de tripsbestrijding dan de gangbare roofmijten. Dit heeft in 2006 geleid tot praktijk- en demo-onderzoek in samenwerking met 6 chrysantenbedrijven door van Iperen en Syngenta Bioline (i.s.m. Alliance en SVO Consultants). WUR Glastuinbouw heeft in 2006 en 2007 detailonderzoek met roofmijten en biologische middelen in proefkassen uitgevoerd. Het volledige rapport is full-text te raadplegen via de Website van het Productschap Tuinbouw.

Item does not contain fulltext, We developed a finite element model to preclinically test cemented hip implants for damage accumulation, including cement crack formation, creep, and stem migration. Using this model, we simulated the mechanical failure processes of four cemented total hip arthroplasty implants (Lubinus SPII, Mueller Curved, Exeter and Charnley, all with known clinical results) during cyclic normal walking and stair-climbing loads. These four implants were selected to ascertain whether the simulation predicted greater damage development around clinically inferior stems, whether clinically inferior designs could be identified by an initial stress analysis without the prediction of cement damage, and whether the simulation could predict high implant subsidence rates in combination with minimal cement damage. Based on the predicted cement crack patterns and crack formation rates, the simulation correctly identified the clinically inferior implant designs. Based only on the initial stress analysis under a stair-climbing load, it was not possible to identify clinically inferior designs. High subsidence values and minimal cement damage were predicted for the Exeter implant, similar to clinical findings. Our findings suggest the simulation may be effective in differentiating between a range of implants and design features.

Item does not contain fulltext, We developed a finite element model to preclinically test cemented hip implants for damage accumulation, including cement crack formation, creep, and stem migration. Using this model, we simulated the mechanical failure processes of four cemented total hip arthroplasty implants (Lubinus SPII, Mueller Curved, Exeter and Charnley, all with known clinical results) during cyclic normal walking and stair-climbing loads. These four implants were selected to ascertain whether the simulation predicted greater damage development around clinically inferior stems, whether clinically inferior designs could be identified by an initial stress analysis without the prediction of cement damage, and whether the simulation could predict high implant subsidence rates in combination with minimal cement damage. Based on the predicted cement crack patterns and crack formation rates, the simulation correctly identified the clinically inferior implant designs. Based only on the initial stress analysis under a stair-climbing load, it was not possible to identify clinically inferior designs. High subsidence values and minimal cement damage were predicted for the Exeter implant, similar to clinical findings. Our findings suggest the simulation may be effective in differentiating between a range of implants and design features.

Item does not contain fulltext, We developed a finite element model to preclinically test cemented hip implants for damage accumulation, including cement crack formation, creep, and stem migration. Using this model, we simulated the mechanical failure processes of four cemented total hip arthroplasty implants (Lubinus SPII, Mueller Curved, Exeter and Charnley, all with known clinical results) during cyclic normal walking and stair-climbing loads. These four implants were selected to ascertain whether the simulation predicted greater damage development around clinically inferior stems, whether clinically inferior designs could be identified by an initial stress analysis without the prediction of cement damage, and whether the simulation could predict high implant subsidence rates in combination with minimal cement damage. Based on the predicted cement crack patterns and crack formation rates, the simulation correctly identified the clinically inferior implant designs. Based only on the initial stress analysis under a stair-climbing load, it was not possible to identify clinically inferior designs. High subsidence values and minimal cement damage were predicted for the Exeter implant, similar to clinical findings. Our findings suggest the simulation may be effective in differentiating between a range of implants and design features.

Item does not contain fulltext, Clinical studies have shown that adequate fixation of ceramic cups using bone cement is difficult to achieve. As the cement-ceramic bond strength is low, a satisfactory fixation strength requires a cup design that allows mechanical interlocking, although such a design will probably promote cement cracking and therefore cup loosening in the long term. An investigation has been carried out to establish whether a cemented ceramic cup can be designed in such a way that both a satisfactory initial fixation strength is obtained and cement cracking is reduced to levels found around PE cups functioning well in vivo. By means of finite element analysis, the fatigue loading of three geometrically different cemented acetabular cups, with ceramic and PE material properties, has been simulated, and the severity of the crack patterns produced in the cement has been analysed. Furthermore, the fixation strength has been analysed by simulating a pull-out test prior to and after fatigue testing. All ceramic cups produced much larger amounts of cement damage during fatigue testing than any PE cup, caused by stress concentrations in the cement that were attributable to the high stiffness of the ceramic. Even a completely smooth ceramic cup produced more damage than a sharp-grooved PE cup. Owing to the excessive cement cracking, the fixation strength of the ceramic cups dropped after fatigue loading. It is concluded that cemented ceramic cups have an increased risk of long-term mechanical failure by comparison with PE cups, and that a ceramic cup design that combines sufficient fixation strength with low cement failure may be difficult to achieve.

Contains fulltext : 49896.pdf (publisher's version ) (Closed access), Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] <75% of predicted value) and 18 without (FEV(1) >85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P

Contains fulltext : 49482.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Purpose. To examine the relevance of physical disabilities for self-worth and perceived competence in children with cerebral palsy (CP), and to examine associations between behaviour problems and self-worth and perceived competence. Methods. The Harter scales for self-worth and perceived competence and a new scale for perceived motor competence were used in a sample of 80 children with CP. Their motor functioning was assessed with the Gross Motor Functioning Measure (GMFM) and behaviour problems with the Child Behaviour Check List administered to parents. Results. Self-worth and perceived competence for children with CP were comparable to the Dutch norm sample, except for perceived athletic competence. Within the CP sample, the GMFM showed a domain-specific effect on perceived motor competence. In the multivariate analysis, internalizing problems were associated negatively with all perceived competence scales and self-worth, whereas aggression was positively associated with perceived motor competence, physical appearance, and self-worth. Conclusions. Children with CP appear resilient against challenges posed to their self-worth caused by their disabilities. The relevance of the physical disability appears to be domain specific. For internalizing problems and aggression, different theoretical models are needed to account for their associations with self-worth and perceived competence.

Item does not contain fulltext, Clinical studies have shown that adequate fixation of ceramic cups using bone cement is difficult to achieve. As the cement-ceramic bond strength is low, a satisfactory fixation strength requires a cup design that allows mechanical interlocking, although such a design will probably promote cement cracking and therefore cup loosening in the long term. An investigation has been carried out to establish whether a cemented ceramic cup can be designed in such a way that both a satisfactory initial fixation strength is obtained and cement cracking is reduced to levels found around PE cups functioning well in vivo. By means of finite element analysis, the fatigue loading of three geometrically different cemented acetabular cups, with ceramic and PE material properties, has been simulated, and the severity of the crack patterns produced in the cement has been analysed. Furthermore, the fixation strength has been analysed by simulating a pull-out test prior to and after fatigue testing. All ceramic cups produced much larger amounts of cement damage during fatigue testing than any PE cup, caused by stress concentrations in the cement that were attributable to the high stiffness of the ceramic. Even a completely smooth ceramic cup produced more damage than a sharp-grooved PE cup. Owing to the excessive cement cracking, the fixation strength of the ceramic cups dropped after fatigue loading. It is concluded that cemented ceramic cups have an increased risk of long-term mechanical failure by comparison with PE cups, and that a ceramic cup design that combines sufficient fixation strength with low cement failure may be difficult to achieve.

Contains fulltext : 49896.pdf (publisher's version ) (Closed access), Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] <75% of predicted value) and 18 without (FEV(1) >85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P

Contains fulltext : 49482.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Contains fulltext : 49896.pdf (publisher's version ) (Closed access), Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] <75% of predicted value) and 18 without (FEV(1) >85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P

Contains fulltext : 49482.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Berichten over de huidige stand van zaken van een roofmijten-proef en een GNO-proef uitgevoerd in proefkassen door PPO Glastuinbouw, en van het praktijkonderzoek op vijf chrysantenbedrijven door van Iperen en Syngenta bioline.

Purpose. To examine the relevance of physical disabilities for self-worth and perceived competence in children with cerebral palsy (CP), and to examine associations between behaviour problems and self-worth and perceived competence. Methods. The Harter scales for self-worth and perceived competence and a new scale for perceived motor competence were used in a sample of 80 children with CP. Their motor functioning was assessed with the Gross Motor Functioning Measure (GMFM) and behaviour problems with the Child Behaviour Check List administered to parents. Results. Self-worth and perceived competence for children with CP were comparable to the Dutch norm sample, except for perceived athletic competence. Within the CP sample, the GMFM showed a domain-specific effect on perceived motor competence. In the multivariate analysis, internalizing problems were associated negatively with all perceived competence scales and self-worth, whereas aggression was positively associated with perceived motor competence, physical appearance, and self-worth. Conclusions. Children with CP appear resilient against challenges posed to their self-worth caused by their disabilities. The relevance of the physical disability appears to be domain specific. For internalizing problems and aggression, different theoretical models are needed to account for their associations with self-worth and perceived competence.

Contains fulltext : 48199.pdf (publisher's version ) (Closed access), The beneficial effect of porosity reduction on the fatigue life of bone cement has been demonstrated in numerous experimental studies. Clinically, however, it seems that the beneficial effect of porosity reduction of cement around total hip replacement components can only be found in large follow-up studies. Little is known about the actual mechanical effect of a pore on fatigue crack formation in cement mantles. We studied the effect of pores on the crack formation process in a finite element model of a transverse slice of a total hip reconstruction. We created models with a single large pore and models with multiple pores at levels of 2, 4, and 9%. The models were cyclically torque-loaded, causing macrocracks to appear in the cement mantle. In all models, we found that pores acted as microcrack initiators. However, pores could have both a detrimental and a beneficial effect on the macrocrack propagation in the cement mantle. Both effects were seen in the models with a single large pore and in the models with multiple pores. Pores would either accelerate, deviate, or decelerate the macrocrack propagation in the cement mantle. The effect of the pores depended on the location of the pores with respect to the stress intensities in the model, but was independent of the pore size or the level of porosity. The results may explain why the beneficial effect of vacuum mixing is difficult to demonstrate clinically. Stress intensities that are present in a cement mantle in an in vivo situation may overshadow the detrimental effect of a pore, while the beneficial effect may become more pronounced.

Contains fulltext : 47857.pdf (publisher's version ) (Closed access), The Capital Hip implant was a Charnley-based system which included a flanged and a roundback stem, both of which were available in stainless steel and titanium. The system was withdrawn from the market because of its inferior performance. However, all four of the designs did not produce poor rates of survival. Using a simulated-based, finite-element analysis, we have analysed the Capital Hip system. Our aim was to investigate whether our simulation was able to detect differences which could account for the varying survival between the Capital Hip designs, thereby further validating the simulation. We created finite-element models of reconstructions with the flanged and roundback Capital Hips. A loading history was applied representing normal walking and stair-climbing, while we monitored the formation of fatigue cracks in the cement. Corresponding to the clinical findings, our simulation was able to detect the negative effects of the titanium material and the flanged design in the Capital Hip system. Although improvements could be made by including the effect of the roughness of the surface of the stem, our study increased the value of the model as a predictive tool for determining failure of an implant.

Contains fulltext : 48191.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Item does not contain fulltext, Laboratory bench tests have shown that porosity reduction increases the fatigue life of bone cement specimens. Clinically, however, the effect porosity reduction is subject to debate. We hypothesized that the discrepancy between clinical and experimental findings is related to differences in the stress distribution, which is typically uniform in experimental test specimens, while stress concentrations exist in cement around hip implants. We simulated fatigue failure of cement in a finite element model of an experimental test specimen and of a transverse slice of a total hip arthroplasty with a sharp-cornered stem. Four levels of porosity were introduced. In the fatigue test specimen model, the fatigue life clearly was dependent on the level of porosity, while in the transverse slice model, the level of porosity had virtually no effect on failure of the cement mantle. The results of the simulations confirmed our hypothesis. In simulations of laboratory tests, pores clearly acted as crack initiators, while in the simulation of a real total hip reconstruction, crack formation was governed by local stress singularities. This explains why the beneficial effect of cement porosity reduction on the lifetime of total hip reconstructions may be hard to detect clinically.

Large discrepancies have sometimes been found between the quality of life (QOL) experienced by clients with intellectual disabilities and their QOL as described by their caregivers. Olsen and Schober (Soc Indi Res 1993; 28: 173-193) may have provided a framework useful to conceptualize such discrepancies. They suggested that lack of concordance between objective circumstances (i.e. poverty) and perceived QOL must not be treated as measurement noise, but as a source of information. They speculated on the psychological processes that underly and explain this lack of concordance; particularly processes that try to deal with the stress induced by cognitive dissonance and learned helplessness. In this study low to moderate agreement was found between caregivers judgement of QOL of individual clients and clients' own perception of QOL. In some areas and for some clients the discrepancies indicated dissonance (caregivers are satisfied, clients are not) and in other areas and for other clients adaptation (clients are satisfied, caregivers are not). There were systematic differences between clients falling in these groups with respect to their personal characteristics and with respect to factual conditions of care. These outcomes are interpreted with respect to Olson and Schober's contentions regarding the psychological processes that underly a person's experience of QOL. The Olson and Schober framework appears to be a fruitful way to combine different sources of information regarding QOL.

Contains fulltext : 48199.pdf (publisher's version ) (Closed access), The beneficial effect of porosity reduction on the fatigue life of bone cement has been demonstrated in numerous experimental studies. Clinically, however, it seems that the beneficial effect of porosity reduction of cement around total hip replacement components can only be found in large follow-up studies. Little is known about the actual mechanical effect of a pore on fatigue crack formation in cement mantles. We studied the effect of pores on the crack formation process in a finite element model of a transverse slice of a total hip reconstruction. We created models with a single large pore and models with multiple pores at levels of 2, 4, and 9%. The models were cyclically torque-loaded, causing macrocracks to appear in the cement mantle. In all models, we found that pores acted as microcrack initiators. However, pores could have both a detrimental and a beneficial effect on the macrocrack propagation in the cement mantle. Both effects were seen in the models with a single large pore and in the models with multiple pores. Pores would either accelerate, deviate, or decelerate the macrocrack propagation in the cement mantle. The effect of the pores depended on the location of the pores with respect to the stress intensities in the model, but was independent of the pore size or the level of porosity. The results may explain why the beneficial effect of vacuum mixing is difficult to demonstrate clinically. Stress intensities that are present in a cement mantle in an in vivo situation may overshadow the detrimental effect of a pore, while the beneficial effect may become more pronounced.

Contains fulltext : 47857.pdf (publisher's version ) (Closed access), The Capital Hip implant was a Charnley-based system which included a flanged and a roundback stem, both of which were available in stainless steel and titanium. The system was withdrawn from the market because of its inferior performance. However, all four of the designs did not produce poor rates of survival. Using a simulated-based, finite-element analysis, we have analysed the Capital Hip system. Our aim was to investigate whether our simulation was able to detect differences which could account for the varying survival between the Capital Hip designs, thereby further validating the simulation. We created finite-element models of reconstructions with the flanged and roundback Capital Hips. A loading history was applied representing normal walking and stair-climbing, while we monitored the formation of fatigue cracks in the cement. Corresponding to the clinical findings, our simulation was able to detect the negative effects of the titanium material and the flanged design in the Capital Hip system. Although improvements could be made by including the effect of the roughness of the surface of the stem, our study increased the value of the model as a predictive tool for determining failure of an implant.

Contains fulltext : 48191.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Item does not contain fulltext, Laboratory bench tests have shown that porosity reduction increases the fatigue life of bone cement specimens. Clinically, however, the effect porosity reduction is subject to debate. We hypothesized that the discrepancy between clinical and experimental findings is related to differences in the stress distribution, which is typically uniform in experimental test specimens, while stress concentrations exist in cement around hip implants. We simulated fatigue failure of cement in a finite element model of an experimental test specimen and of a transverse slice of a total hip arthroplasty with a sharp-cornered stem. Four levels of porosity were introduced. In the fatigue test specimen model, the fatigue life clearly was dependent on the level of porosity, while in the transverse slice model, the level of porosity had virtually no effect on failure of the cement mantle. The results of the simulations confirmed our hypothesis. In simulations of laboratory tests, pores clearly acted as crack initiators, while in the simulation of a real total hip reconstruction, crack formation was governed by local stress singularities. This explains why the beneficial effect of cement porosity reduction on the lifetime of total hip reconstructions may be hard to detect clinically.

Item does not contain fulltext, Laboratory bench tests have shown that porosity reduction increases the fatigue life of bone cement specimens. Clinically, however, the effect porosity reduction is subject to debate. We hypothesized that the discrepancy between clinical and experimental findings is related to differences in the stress distribution, which is typically uniform in experimental test specimens, while stress concentrations exist in cement around hip implants. We simulated fatigue failure of cement in a finite element model of an experimental test specimen and of a transverse slice of a total hip arthroplasty with a sharp-cornered stem. Four levels of porosity were introduced. In the fatigue test specimen model, the fatigue life clearly was dependent on the level of porosity, while in the transverse slice model, the level of porosity had virtually no effect on failure of the cement mantle. The results of the simulations confirmed our hypothesis. In simulations of laboratory tests, pores clearly acted as crack initiators, while in the simulation of a real total hip reconstruction, crack formation was governed by local stress singularities. This explains why the beneficial effect of cement porosity reduction on the lifetime of total hip reconstructions may be hard to detect clinically.

Contains fulltext : 48191.pdf ( ) (Open Access), BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

Contains fulltext : 47857.pdf (publisher's version ) (Closed access), The Capital Hip implant was a Charnley-based system which included a flanged and a roundback stem, both of which were available in stainless steel and titanium. The system was withdrawn from the market because of its inferior performance. However, all four of the designs did not produce poor rates of survival. Using a simulated-based, finite-element analysis, we have analysed the Capital Hip system. Our aim was to investigate whether our simulation was able to detect differences which could account for the varying survival between the Capital Hip designs, thereby further validating the simulation. We created finite-element models of reconstructions with the flanged and roundback Capital Hips. A loading history was applied representing normal walking and stair-climbing, while we monitored the formation of fatigue cracks in the cement. Corresponding to the clinical findings, our simulation was able to detect the negative effects of the titanium material and the flanged design in the Capital Hip system. Although improvements could be made by including the effect of the roughness of the surface of the stem, our study increased the value of the model as a predictive tool for determining failure of an implant.

Large discrepancies have sometimes been found between the quality of life (QOL) experienced by clients with intellectual disabilities and their QOL as described by their caregivers. Olsen and Schober (Soc Indi Res 1993; 28: 173-193) may have provided a framework useful to conceptualize such discrepancies. They suggested that lack of concordance between objective circumstances (i.e. poverty) and perceived QOL must not be treated as measurement noise, but as a source of information. They speculated on the psychological processes that underly and explain this lack of concordance; particularly processes that try to deal with the stress induced by cognitive dissonance and learned helplessness. In this study low to moderate agreement was found between caregivers judgement of QOL of individual clients and clients' own perception of QOL. In some areas and for some clients the discrepancies indicated dissonance (caregivers are satisfied, clients are not) and in other areas and for other clients adaptation (clients are satisfied, caregivers are not). There were systematic differences between clients falling in these groups with respect to their personal characteristics and with respect to factual conditions of care. These outcomes are interpreted with respect to Olson and Schober's contentions regarding the psychological processes that underly a person's experience of QOL. The Olson and Schober framework appears to be a fruitful way to combine different sources of information regarding QOL.

Item does not contain fulltext, The long-term fixation of cemented femoral components may be jeopardised by the presence of a fibrous tissue layer at the bone-cement interface. This study used both experimental and finite element (FE) methods to investigate the load transfer characteristics of two types of cemented hip replacements (Lubinus SPII and Muller-Curved) with a fibrous tissue layer.The experimental part investigated six stems of each type, where these were implanted in composite femurs with a specially selected silicone elastomer modelling the soft interfacial layer. Two fibrous tissue conditions were examined: a layer covering the full cement mantle, representing a revision condition; and a layer covering the proximal portion of the cement mantle, representing a non-revised implant with partial debonding and fibrous tissue formation. The FE method was used to model the full fibrous tissue layer condition, for both implants. The layer was modelled as a homogeneous, linearly isotropic material. A cross-comparison was performed of the experimental and FE findings.Agreement between experimental and FE models was verified to be within 15%. Varying the stiffness parameter of the FE soft tissue layer had little influence on the cortical bone strains, though had considerable effect on the cement strains. Stress shielding occurred for both stems under both fibrous tissue conditions, with the greatest reduction around the calcar. However, the cortical bone strains were generally larger than those for the equivalent well-fixed stems. The fibrous tissue layer was not found to increase the general strain pattern of the cement mantle, though localised regions of high stress were detected.

Contains fulltext : 58284.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the number of proliferating (Ki-67-positive) epithelial cells was analyzed by immunohistochemistry in bronchial epithelium from subjects with (n = 15) or without (n = 14) chronic obstructive pulmonary disease (COPD). RESULTS: Our data demonstrate higher numbers of defensin-positive (p = 0.0001), elastase-positive (p = 0.0001) and Ki-67-positive (p = 0.0001) cells in areas with squamous cell metaplasia as compared to areas with intact or damaged epithelium, while the reverse was observed for SLPI expression (p = 0.002). No differences were observed between subjects with or without COPD, nor between current smokers and those that had stopped smoking. CONCLUSIONS: These data are in line with a role of defensins in the hyperproliferative phenotype of squamous metaplastic lesions in the airways. This role does not seem to be restricted to patients with COPD.

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Item does not contain fulltext, The long-term fixation of cemented femoral components may be jeopardised by the presence of a fibrous tissue layer at the bone-cement interface. This study used both experimental and finite element (FE) methods to investigate the load transfer characteristics of two types of cemented hip replacements (Lubinus SPII and Muller-Curved) with a fibrous tissue layer.The experimental part investigated six stems of each type, where these were implanted in composite femurs with a specially selected silicone elastomer modelling the soft interfacial layer. Two fibrous tissue conditions were examined: a layer covering the full cement mantle, representing a revision condition; and a layer covering the proximal portion of the cement mantle, representing a non-revised implant with partial debonding and fibrous tissue formation. The FE method was used to model the full fibrous tissue layer condition, for both implants. The layer was modelled as a homogeneous, linearly isotropic material. A cross-comparison was performed of the experimental and FE findings.Agreement between experimental and FE models was verified to be within 15%. Varying the stiffness parameter of the FE soft tissue layer had little influence on the cortical bone strains, though had considerable effect on the cement strains. Stress shielding occurred for both stems under both fibrous tissue conditions, with the greatest reduction around the calcar. However, the cortical bone strains were generally larger than those for the equivalent well-fixed stems. The fibrous tissue layer was not found to increase the general strain pattern of the cement mantle, though localised regions of high stress were detected.

Contains fulltext : 58284.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the number of proliferating (Ki-67-positive) epithelial cells was analyzed by immunohistochemistry in bronchial epithelium from subjects with (n = 15) or without (n = 14) chronic obstructive pulmonary disease (COPD). RESULTS: Our data demonstrate higher numbers of defensin-positive (p = 0.0001), elastase-positive (p = 0.0001) and Ki-67-positive (p = 0.0001) cells in areas with squamous cell metaplasia as compared to areas with intact or damaged epithelium, while the reverse was observed for SLPI expression (p = 0.002). No differences were observed between subjects with or without COPD, nor between current smokers and those that had stopped smoking. CONCLUSIONS: These data are in line with a role of defensins in the hyperproliferative phenotype of squamous metaplastic lesions in the airways. This role does not seem to be restricted to patients with COPD.

Item does not contain fulltext

Item does not contain fulltext

Item does not contain fulltext, The long-term fixation of cemented femoral components may be jeopardised by the presence of a fibrous tissue layer at the bone-cement interface. This study used both experimental and finite element (FE) methods to investigate the load transfer characteristics of two types of cemented hip replacements (Lubinus SPII and Muller-Curved) with a fibrous tissue layer.The experimental part investigated six stems of each type, where these were implanted in composite femurs with a specially selected silicone elastomer modelling the soft interfacial layer. Two fibrous tissue conditions were examined: a layer covering the full cement mantle, representing a revision condition; and a layer covering the proximal portion of the cement mantle, representing a non-revised implant with partial debonding and fibrous tissue formation. The FE method was used to model the full fibrous tissue layer condition, for both implants. The layer was modelled as a homogeneous, linearly isotropic material. A cross-comparison was performed of the experimental and FE findings.Agreement between experimental and FE models was verified to be within 15%. Varying the stiffness parameter of the FE soft tissue layer had little influence on the cortical bone strains, though had considerable effect on the cement strains. Stress shielding occurred for both stems under both fibrous tissue conditions, with the greatest reduction around the calcar. However, the cortical bone strains were generally larger than those for the equivalent well-fixed stems. The fibrous tissue layer was not found to increase the general strain pattern of the cement mantle, though localised regions of high stress were detected.

Contains fulltext : 58284.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the number of proliferating (Ki-67-positive) epithelial cells was analyzed by immunohistochemistry in bronchial epithelium from subjects with (n = 15) or without (n = 14) chronic obstructive pulmonary disease (COPD). RESULTS: Our data demonstrate higher numbers of defensin-positive (p = 0.0001), elastase-positive (p = 0.0001) and Ki-67-positive (p = 0.0001) cells in areas with squamous cell metaplasia as compared to areas with intact or damaged epithelium, while the reverse was observed for SLPI expression (p = 0.002). No differences were observed between subjects with or without COPD, nor between current smokers and those that had stopped smoking. CONCLUSIONS: These data are in line with a role of defensins in the hyperproliferative phenotype of squamous metaplastic lesions in the airways. This role does not seem to be restricted to patients with COPD.

Item does not contain fulltext, Peak stress levels predicted in finite element analysis (FEA) usually depend on mesh density, due to singular points in the model. In an earlier study, an FEA algorithm was developed to simulate the damage accumulation process in the cement mantle around total hip replacement (THR) implants. It allows cement crack formation to be predicted, as a function of the local cement stress levels. As the simulation is driven by mesh-dependent peak stresses, predicted crack formation rates are also likely to be mesh dependent. The aim of this study was to evaluate the mesh dependence of the predicted crack formation process, and to present a method to reduce the mesh dependence. Crack-propagation experiments were simulated. Experimental specimens, representing transverse slices of cemented THR reconstructions, were subjected to cyclic torsional loading. Crack development around the corners of the stem was monitored. The experiments were simulated using three meshes with increasing levels of mesh refinement. Crack locations and orientations were accurately predicted, and were virtually independent of the level of mesh refinement. However, the experimental crack propagation rates were overestimated considerably, increasing with mesh refinement. To eliminate the effect of stress singularities around the corners of the stem, a stress averaging algorithm was applied in the simulation. This algorithm redistributed the stresses by weighted spatial averaging. When damage accumulation was computed based on averaged stresses, the crack propagation rates predicted were independent of the level of mesh refinement. The critical distance, a parameter governing the effect of the averaging algorithm, was optimized such that the predicted crack propagation rates accurately corresponded to the experimental ones. These results are important for the validity and standardization of pre-clinical testing methods for orthopaedic implants.

Item does not contain fulltext, Rigorous preclinical testing of cemented hip prostheses against the damage accumulation failure scenario will reduce the incidence of aseptic loosening. For that purpose, a finite element simulation is proposed that predicts damage accumulation in the cement mantle and prosthetic migration. If the simulation is to become a convincing preclinical test, it should be able to distinguish between implants in a clinically relevant way, based on accurate predictions of long-term failure mechanisms of cemented hip prostheses. The algorithm was used to simulate long-term fatigue experiments on femoral reconstructions with Mueller Curved and Lubinus SPII stems. Clinically, the Mueller Curved system performs inferior to the Lubinus SPII system. The finite element simulation predicted much more cement damage around the Mueller Curved stem and showed that the entire cement mantle was involved in the failure process, which was not the case around the Lubinus SPII stem. In addition, the Mueller Curved stem was predicted to migrate more than the Lubinus SPII. The predictions showed excellent agreement with the experimental findings: similar damage locations in the cement, more damage for the Mueller Curved, similar prosthetic migration directions, and more migration for the Mueller Curved stem. This is the first time that a finite element simulation is able to differentiate between a clinically superior and an inferior implant, based on accurate simulation of the long-term failure mechanisms in a cemented reconstruction. Its use for preclinical testing purposes is corroborated.

Item does not contain fulltext, OBJECTIVE: To determine the load transfer patterns of femurs in the intact, immediate post-operative and long-term (remodelled) post-operative implanted conditions for Lubinus SPII and Muller-Curved cemented hip prostheses, and to examine to what extent remodelling may influence the long-term outcome. DESIGN: Experimental and finite element (FE) methods were applied to composite femurs under loads representing the heel-strike phase of gait, determining cortical bone and cement strains for the different femur conditions. BACKGROUND: The authors previously developed protocols to measure bone and cement strains, and to produce remodelled femur specimens, yet these have not been applied together to compare strain patterns of different femur conditions. The Lubinus SPII is clinically more successful than the Muller-Curved stem, with failure mainly due to aseptic loosening. METHODS: Cortical bone strains were determined in intact femurs. Six femurs each were implanted with the two stem types and cortical bone and cement strains were measured. Bone remodelling was recreated using a validated CAD-CAM procedure to remove a layer of proximal cortical bone, replicating a typical scenario found in stable clinical retrievals. Strains were remeasured. FE methods were used to compliment the experiments. RESULTS: Stress shielding was reduced with remodelling, though bone strains did not return to their intact values, particularly around the calcar. Cement strains increased with remodelling. Differences occurred between the two stems; the Muller-Curved produced a more severe strain transition. CONCLUSIONS: Procedures were successfully combined together to investigate in vitro the performance of two cemented stems, in immediate and long-term post-operative conditions. The increase of cement strains with remodelling is a potential indicator for in vivo cement failure. RELEVANCE: The consequences of femoral bone remodelling on the long-term success of joint replacements are not well un

Item does not contain fulltext, Peak stress levels predicted in finite element analysis (FEA) usually depend on mesh density, due to singular points in the model. In an earlier study, an FEA algorithm was developed to simulate the damage accumulation process in the cement mantle around total hip replacement (THR) implants. It allows cement crack formation to be predicted, as a function of the local cement stress levels. As the simulation is driven by mesh-dependent peak stresses, predicted crack formation rates are also likely to be mesh dependent. The aim of this study was to evaluate the mesh dependence of the predicted crack formation process, and to present a method to reduce the mesh dependence. Crack-propagation experiments were simulated. Experimental specimens, representing transverse slices of cemented THR reconstructions, were subjected to cyclic torsional loading. Crack development around the corners of the stem was monitored. The experiments were simulated using three meshes with increasing levels of mesh refinement. Crack locations and orientations were accurately predicted, and were virtually independent of the level of mesh refinement. However, the experimental crack propagation rates were overestimated considerably, increasing with mesh refinement. To eliminate the effect of stress singularities around the corners of the stem, a stress averaging algorithm was applied in the simulation. This algorithm redistributed the stresses by weighted spatial averaging. When damage accumulation was computed based on averaged stresses, the crack propagation rates predicted were independent of the level of mesh refinement. The critical distance, a parameter governing the effect of the averaging algorithm, was optimized such that the predicted crack propagation rates accurately corresponded to the experimental ones. These results are important for the validity and standardization of pre-clinical testing methods for orthopaedic implants.

Item does not contain fulltext, Rigorous preclinical testing of cemented hip prostheses against the damage accumulation failure scenario will reduce the incidence of aseptic loosening. For that purpose, a finite element simulation is proposed that predicts damage accumulation in the cement mantle and prosthetic migration. If the simulation is to become a convincing preclinical test, it should be able to distinguish between implants in a clinically relevant way, based on accurate predictions of long-term failure mechanisms of cemented hip prostheses. The algorithm was used to simulate long-term fatigue experiments on femoral reconstructions with Mueller Curved and Lubinus SPII stems. Clinically, the Mueller Curved system performs inferior to the Lubinus SPII system. The finite element simulation predicted much more cement damage around the Mueller Curved stem and showed that the entire cement mantle was involved in the failure process, which was not the case around the Lubinus SPII stem. In addition, the Mueller Curved stem was predicted to migrate more than the Lubinus SPII. The predictions showed excellent agreement with the experimental findings: similar damage locations in the cement, more damage for the Mueller Curved, similar prosthetic migration directions, and more migration for the Mueller Curved stem. This is the first time that a finite element simulation is able to differentiate between a clinically superior and an inferior implant, based on accurate simulation of the long-term failure mechanisms in a cemented reconstruction. Its use for preclinical testing purposes is corroborated.