Less wear in deep-dished mobile compared to fixed bearing total knee arthroplasty of the same design at 5-year follow-up: a randomised controlled model-based Roentgen stereophotogrammetric analysis trial.

PURPOSE: The aim of this prospective randomised controlled study was to compare wear characteristics and functional outcome between deep-dished mobile bearing (MB) and fixed bearing (FB) cemented total knee arthroplasty (TKA). We hypothesised that deep-dished MB reduces polyethylene wear and improves patient-reported outcome measures. METHODS: A total of 50 patients were randomised to receive a MB or FB tibia component of the same cemented TKA design. Patients were evaluated over a 5-year follow-up period. Medial and lateral wear were assessed using model-based Roentgen Stereophotogrammetric Analysis (RSA) and compared with the direct postoperative minimal joint space measurement. Functional outcome was assessed by the clinician-derived KSS and OKS, WOMAC, LEAS, and FJS-12. All data were derived using a general linear mixed model. RESULTS: At 5-year follow-up, decreased wear in the MB compared to the FB group was observed on the lateral side (0.07 ± 0.17 mm, p = 0.026), but not on the medial side (0.31 ± 0.055 mm, p = 0.665). Functional outcomes improved with a statistical significant effect over time, with no significant differences between groups (all p > 0.17). CONCLUSION: This model-based RSA study with 5-year follow-up showed that cemented deep-dished MB reduced lateral polyethylene wear as compared to FB in a single TKA system, whilst clinical outcomes were comparable. Longer follow-up is needed to establish clinical implications of these altered wear patterns and determine type of wear. LEVEL OF EVIDENCE: Level 1 randomised controlled trial.

Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects.

BACKGROUND AND OBJECTIVES: Impaired regulation of lipid oxidation (metabolic inflexibility) is associated with obesity and type 2 diabetes mellitus. Recent evidence has indicated that dietary polyphenols may modulate mitochondrial function, substrate metabolism and energy expenditure in humans. The present study investigated the effects of short-term supplementation of two combinations of polyphenols on energy expenditure (EE) and substrate metabolism in overweight subjects. SUBJECTS AND METHODS: Eighteen healthy overweight volunteers (9 women, 9 men; age 35±2.5 years; body mass index 28.9±0.4 kg m(-2)) participated in a randomized, double-blind cross-over trial. Combinations of epigallocatechin-gallate (E, 282 mg day(-1))+resveratrol (R, 200 mg day(-1)) and E+R+80 mg day(-1) soy isoflavones (S) or placebo capsules (PLA) were supplemented twice daily for a period of 3 days. On day 3, circulating metabolite concentrations, EE and substrate oxidation (using indirect calorimetry) were measured during fasting and postprandial conditions for 6 h (high-fat-mixed meal (2.6 MJ, 61.2 E% fat)). RESULTS: Short-term supplementation of E+R increased resting EE (E+R vs PLA: 5.45±0.24 vs 5.23±0.25 kJ min(-1), P=0.039), whereas both E+R (699±18 kJ 120 min(-1) vs 676±20 kJ 120 min(-1), P=0.028) and E+R+S (704±18 kJ 120 min(-1) vs 676±20 kJ 120 min(-1), P=0.014) increased 2-4 h-postprandial EE compared with PLA. Metabolic flexibility, calculated as the postprandial increase to the highest respiratory quotient achieved, tended to be improved by E+R compared with PLA and E+R+S only in men (E+R vs PLA: 0.11±0.02 vs 0.06±0.02, P=0.059; E+R+S: 0.03±0.02, P=0.009). E+R+S significantly increased fasting plasma free fatty acid (P=0.064) and glycerol (P=0.021) concentrations compared with PLA. CONCLUSIONS: We demonstrated for the first time that combined E+R supplementation for 3 days significantly increased fasting and postprandial EE, which was accompanied by improved metabolic flexibility in men but not in women. Addition of soy isoflavones partially reversed these effects possibly due to their higher lipolytic potential. The present findings may imply that long-term supplementation of these dosages of epigallocatechin-gallate combined with resveratrol may improve metabolic health and body weight regulation.

Differences in oral health behaviour between children from high and children from low SES schools in The Netherlands.

OBJECTIVE: To identify the determinants of dental caries in relation to socio-economic status (SES) within oral health, children's eating habits and parental attitudes towards oral health. BASIC RESEARCH DESIGN: Dental screening data were collected from 6- and 10-year-old schoolchildren from low and high SES schools in The Netherlands in this cross-sectional study. METHODS: The clinical examination was performed by trained dental hygiene students who collected the data on dental caries, dental plaque and duration of brushing. The paper questionnaire completed by the parents included 18 questions about oral health behaviour, eating habits and parental attitudes towards oral health. RESULTS: Two of the six parameters of oral health behaviour were statistically associated with the high caries prevalence in the low SES group (brushing frequency (p = 0.028) and age at the first visit to the dentist (p = 0.044)). High intake of fruit juices and/or soft drinks (p = 0.043) and low calcium intake (p = 0.028) were identified as risk determinants for caries with low SES. All parameters of parental attitudes towards oral health were associated with caries, but not with SES. CONCLUSIONS: This study confirmed that the high caries prevalence in children from low SES schools was associated with oral health behaviour and eating habits. The role of parents was indirectly associated with the occurrence of dental caries. Therefore, it is important to include parents in all intervention programmes in order to reduce the prevalence of caries.

Gut microbiota composition in relation to the metabolic response to 12-week combined polyphenol supplementation in overweight men and women.

BACKGROUND/OBJECTIVES: The intestinal microbiota may have a profound impact on host metabolism. As evidence suggests that polyphenols affect substrate utilization, the present study aimed to investigate the effects of polyphenol supplementation on intestinal microbiota composition in humans. Furthermore, we examined whether (changes in) gut microbiota composition may determine the metabolic response to polyphenol supplementation. SUBJECTS/METHODS: In this randomized, double-blind, placebo (PLA)-controlled trial, 37 overweight and obese men and women (18 males/19 females, 37.8±1.6 years, body mass index: 29.6±0.5 kg/m2) received either epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 and 80 mg/day, respectively) or PLA for 12 weeks. Before and after intervention, feces samples were collected to determine microbiota composition. Fat oxidation was assessed by indirect calorimetry during a high-fat mixed meal test (2.6 MJ, 61 energy% fat) and skeletal muscle mitochondrial oxidative capacity by means of ex vivo respirometry on isolated skeletal muscle fibers. Body composition was measured by dual-energy X-ray absorptiometry. RESULTS: Fecal abundance of Bacteroidetes was higher in men as compared with women, whereas other assessed bacterial taxa were comparable. EGCG+RES supplementation significantly decreased Bacteroidetes and tended to reduce Faecalibacterium prausnitzii in men (P=0.05 and P=0.10, respectively) but not in women (P=0.15 and P=0.77, respectively). Strikingly, baseline Bacteroidetes abundance was predictive for the EGCG+RES-induced increase in fat oxidation in men but not in women. Other bacterial genera and species were not affected by EGCG+RES supplementation. CONCLUSIONS: We demonstrated that 12-week EGCG+RES supplementation affected the gut microbiota composition in men but not in women. Baseline microbiota composition determined the increase in fat oxidation after EGCG+RES supplementation in men.

Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women.

Gut microbiota composition may play an important role in the development of obesity-related comorbidities. However, only few studies have investigated gender-differences in microbiota composition and gender-specific associations between microbiota or microbial products and insulin sensitivity. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), substrate oxidation (indirect calorimetry), systemic inflammatory markers and microbiota composition (PCR) were determined in male (n=15) and female (n=14) overweight and obese subjects. Bacteroidetes/Firmicutes-ratio was higher in men than in women (P=0.001). Bacteroidetes/Firmicutes-ratio was inversely related to peripheral insulin sensitivity only in men (men: P=0.003, women: P=0.882). This association between Bacteroidetes/Firmicutes-ratio and peripheral insulin sensitivity did not change after adjustment for dietary fibre and saturated fat intake, body composition, fat oxidation and markers of inflammation. Bacteroidetes/Firmicutes-ratio was not associated with hepatic insulin sensitivity. Men and women differ in microbiota composition and its impact on insulin sensitivity, implying that women might be less sensitive to gut microbiota-induced metabolic aberrations than men. This trial was registered at clinicaltrials.gov as NCT02381145.

Sera from HIV-1 infected individuals in all stages of disease preferentially recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA.

The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are predominant targets of the humoral immune response to infection by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the primary target of neutralizing antibodies directed against the envelope proteins of HIV-1. The V3 loop is also the major determinant for HIV-1 cell-specific tropism. To further characterize the humoral immune response directed against the gp120 envelope proteins, we expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2 cells. Sera from four infected adults over the course of infection [McNearney et al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 envelope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeric envelope proteins revealed that the humoral response was directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HIV-1 infected individuals in different stages of the disease were tested. Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral immune response is preferentially elicited against the V3 loop of the prototypic macrophage-tropic gp120 envelope protein ADA.

The relationship of dietary fat to plasma lipid levels as studied by factor analysis of adipose tissue fatty acid composition in a free-living population of middle-aged American men.

We have used adipose tissue biopsies to assess the quality of fat in the diet and its influence on plasma lipid levels in 413 free-living normolipidemic male subjects. Factor analysis identified three factors which separated the fatty acids on the basis of their chemical structure. F1--monounsaturates--animal fats; F2--saturates--carbohydrates; F3--polyunsaturates--vegetable oils. An increase in F1 was associated with an increase in plasma triglycerides (TG), plasma total cholesterol (TC), and VLDL-C: an increase in F2 led to a decrease in VLDL-C. A rise in F3 was associated with lowered TG, VLDL-C, and HDL-C but increased LDL-C. However, the contribution of each of these factors to the variance in TG, TC, LDL-C, and HDL-C was small, namely: 5.48, 1.30, 2.57, and 2.02%, respectively. A special relationship between F3 and VLDL-C was found such that 16.22% of its variance could be attributed to F3. Our conclusion is that adipose tissue composition and, by implication, the type of dietary fat intake, explains only a small proportion (1-19%) of the variance in plasma lipids in normolipidemic subjects.

Elevated concentrations of circulating intercellular adhesion molecule 1 (ICAM-1) in HIV-1 infection.

The membrane-bound glycoprotein intercellular adhesion molecule 1 (ICAM-1) plays an important role for many cell-contact-dependent immune functions. A soluble, circulating form of ICAM-1 (cICAM-1) has been detected in the serum of healthy persons and increased concentrations in tumor patients have been reported. We measured serum levels of cICAM-1 in HIV-1-infected individuals with a recently developed ELISA. In contrast to HIV-seronegative controls (median value of 294 ng/ml, range of 185-408 ng/ml; n = 22), significantly elevated concentrations were detected in 76 HIV-1-infected persons (median of 487 ng/ml, range of 231-1,524 ng/ml; p < 0.0001). In HIV-1-infected individuals, cICAM-1 values did not correlate with the absolute number of CD4+ T cells or with disease progression according to the Walter Reed staging classification. Concentrations of cICAM-1 correlated with the serum concentrations of IL-6 (p = 0.0015; Spearman's rank correlation analysis) and with urinary neopterin (p = 0.005), but not with the C-reactive protein. Since there is evidence that cICAM-1 can interfere with immunological functions, the high amounts circulating in HIV-1-positive individuals could contribute to the disturbance of the immune system in HIV-1 infection.

Direct demonstration of binding of aggregated mouse IgG1 to the 40-kDa Fc receptor for IgG (Fc gamma RII) in both high and low responders.

Several directly fluorochrome-conjugated murine monoclonal antibodies (mAb) of the IgG1 subclass and directed against B or T cell antigens were found to bind to monocytes via the 40-kDa Fc receptor for IgG (Fc gamma RII). As expected from the established polymorphism of Fc gamma RII, strong staining was observed in about 75% of individuals. In the remaining 25% staining was clearly weaker, but could be definitely demonstrated with a mAb against the B cell-specific CD19 differentiation antigen. Specificity of binding to Fc gamma RII was confirmed by the ability to block the binding of the CD19 mAb by pre-incubation with aggregated IgG1 or with mAb against Fc gamma RII. The extent of T cell proliferation induced with a CD3 mAb of the IgG1 isotype (a-Leu 4), which is dependent on the interaction of monocyte Fc gamma RII with the Fc portion of the CD3 mAb, exactly correlated with the amount of binding to Fc gamma RII in all individuals. Proliferation was dose-dependent for both high and low responders; cells of low responders did not proliferate at concentrations below 16 ng/ml of mAb, whereas there was a small but unequivocal proliferation at higher concentrations. These results confirm that monocytes from previously characterized "non-responders" are able to bind aggregated murine IgG1 via Fc gamma RII. They also demonstrate that directly labeled mAb can cause extensive nonspecific staining which may not be excluded by the use of control antibodies of the same isotype.

Immunomodulatory effect of sodium dodecyl sulfate on human neutrophils and the human promyelocytic HL-60 cell line.

The effect of sodium dodecyl sulfate (SDS), an anionic amphiphilic detergent, on the function of human neutrophils and of the human promyelocytic leukemia cell line HL-60 was investigated. SDS modulated the respiratory burst in human neutrophils and HL-60 cells which were stimulated with phorbol 12-myristate 13-acetate (PMA). In concentrations above 1 X 10(-6) M it also caused release of lysosomal enzymes (beta-D-glucuronidase, myeloperoxidase and lysozyme) from neutrophils. Our results demonstrate that SDS at concentrations 1 X 10(-6) M-1 X 10(-4) M strongly affect properties of human phagocytic cells.

Production and characterization of a monoclonal antibody against neopterin.

We have produced and characterized the first monoclonal antibody against neopterin (D-erythro-6-(1,2,3,-trihydroxypropyl)pterin). The antibody specifically recognizes neopterin in a modified RIA. The binding capacity in this assay is 34%, the sensitivity limit of inhibition is 0.9 nmol/l. Cross-reactivity exists with monapterin (L-threo(1,2,3,trihydroxypropyl)pterin) in 30%, with other pteridines cross-reactivity has been found in less than 5%.

[Post-exposure prevention of HIV infection]. / Die postexpositionelle Prophylaxe der HIV-Infektion.

The risk of health-care workers to become infected with HIV during professional activities is low. Prevention of exposures by obeying appropriate precautions is the most important means to lower this risk further. During the last few years it has become more and more likely that an immediate antiretroviral postexposure prophylaxis can prevent at least 80% of possible infections. Thus, each exposure to HIV-positive blood should be considered an acute medical emergency. Immediate counseling by qualified experts and possibilities to start postexposure prophylaxis as soon as possible should be available in all medical settings.

Class II antigens in Hashimoto thyroiditis. II. Expression of HLA-DR on infiltrating mononuclear cells in peripolesis.

Surgical specimens from patients with Hashimoto thyroiditis (HT) or colloid goiter (CG) were analyzed using an immunofluorescence double staining technique to characterize the infiltrating mononuclear cells (MNC) and to determine the possible expression of HLA-DR antigens by these cells. In HT the majority of infiltrating MNC were T cells. In the interstitium T cells with helper/inducer phenotype (Leu 3a+) were more abundant than those with suppressor/cytotoxic phenotype (OKT8+) and approximately 10-25% of all T cells expressed HLA-DR. Among the cells in peripolesis [i.e., protruding between thyroid epithelial cells (TEC)] OKT8+ cells were observed more frequently than Leu 3a+ cells, expression of DR antigens being 7 and 12%, respectively. The occurrence of Leu 3a+ cells in peripolesis is in marked contrast to the findings in colloid goiter where the intraepithelial population of MNC is almost exclusively composed of OKT8+ cells. The various ways in which the peripoletic Leu 3a+ cells could contribute to the special pathogenesis of HT are discussed.

Generation of multinucleated giant cells in vitro by culture of human monocytes with Mycobacterium bovis BCG in combination with cytokine-containing supernatants.

Multinucleated giant cells (MGC), a characteristic feature of tuberculous granulomas, form by fusion of monocytes or macrophages, but little is known about the mechanism of the fusion process itself. Several studies report an indirect effect of mycobacteria, i.e., induction of a soluble lymphocyte-derived fusion factor following stimulation by mycobacteria or mycobacterial products. The aim of our study was to determine whether contact with mycobacteria can induce MGC formation from human monocytes in vitro. Stimulation of monocytes with Mycobacterium bovis bacillus Calmette-Guérin (BCG) in combination with cytokine-containing supernatants of herpesvirus saimiri-transformed human T-cell clones (T-SN) led to MGC formation with fusion rates of about 27%. In contrast, stimulation with one component alone induced only low fusion rates of up to 10%. Heat-killed BCG in combination with T-SN induced monocyte fusion to the same extent as live mycobacteria. BCG culture supernatant, BCG lysate, or inert particles in combination with T-SN did not induce MGC formation. Experiments using transwell plates containing a semipermeable membrane revealed that induction of the fusion process is dependent on direct contact of monocytes and mycobacteria. MGC formation induced by BCG plus T-SN could be inhibited by addition of monoclonal antibodies to gamma interferon (but not tumor necrosis factor alpha) as well as to the beta chain (CD18) of beta2-integrins. These results demonstrate that contact with mycobacteria in combination with cytokine-containing supernatants is able to induce human monocytes to form MGC and that membrane-bound molecules of mycobacteria and monocytes are involved in the fusion process.

Class II antigens in Hashimoto thyroiditis. I. Synthesis and expression of HLA-DR and HLA-DQ by thyroid epithelial cells.

Aberrant expression of HLA-DR antigens on epithelial cells is seen in various organ-specific autoimmune disorders including Hashimoto thyroiditis (HT). Expression of HLA-DQ has so far not been demonstrated on these cells. We report here that thyroid epithelial cells (TEC) in HT, in addition to the known aberrant expression of HLA-DR, coexpress HLA-DQ antigens. Furthermore we provide evidence that class II antigens are synthesized by TEC themselves by demonstration of intracellular HLA-DR gamma-chain. These findings support the theory that TEC may be able to present (auto)antigens in vivo thus perhaps contributing to the perpetuation of thyroid destruction. As expression of class II antigens on TEC was never observed in non- or weakly infiltrated areas, we propose that infiltration by T cells is necessary to induce this aberrant expression of class II antigens.

Ca ions stabilize the binding of complement factor iC3b to the pseudohyphal form of Candida albicans.

The pseudohyphal form of Candida albicans is able to bind iC3b. This may play an important role in the pathogenesis of disseminated candidiasis and, in particular, in adherence to endothelium, protection against complement action, and iron acquisition from erythrocytes. Here we report that Ca2+ ions are required to maintain stable binding of iC3b to C. albicans pseudohyphae.