Bending moments of zirconia and titanium abutments with internal and external implant-abutment connections after aging and chewing simulation.

OBJECTIVES: To test the fracture load of zirconia abutments with different types of implant-abutment connections after chewing simulation and to compare their bending moments to internally connected identical titanium abutments. MATERIALS AND METHODS: Forty-eight identical customized zirconia abutments with different implant-abutment connections were fabricated for four different test groups: one-piece internal implant-abutment connection (BL; Straumann Bonelevel), two-piece internal implant-abutment connection (RS; Nobel Biocare Replace Select), external implant-abutment connection (B; Brånemark MK III), two-piece internal implant-abutment connection (SP; Straumann Standard Plus). Twelve titanium abutments with one-piece internal implant-abutment connection (T; Straumann Bonelevel) served as control group. After aging by means of thermocycling (5-50°C, 120 s) and chewing simulation (1,200,000 cycles, 49 N load, 1.67 Hz), static load was applied at a 30° angle to the palatal surface until failure. Bending moments were calculated for comparison of the groups. Data were analyzed descriptively and by performing the Kruskal-Wallis test with Bonferroni correction. RESULTS: The mean bending moments of the abutments were 714.1 ± 184.9 N cm (T), 331.7 ± 57.8 N cm (BL), 429.7 ± 62.8 N cm (RS), 285.8 ± 64.4 N cm (B) and 379.9 ± 59.1 N cm (SP). The bending moments of control group T were significantly higher than those of all other groups. The values of group RS were significantly higher than those of group B but within the value range of groups SP and BL. CONCLUSION: The bending moments of the different tested types of zirconia abutments vary with different implant-abutment connections after chewing simulation. The use of a secondary metallic component might have a beneficial influence on the stability of zirconia abutments.

In vitro study of the influence of the type of connection on the fracture load of zirconia abutments with internal and external implant-abutment connections.

PURPOSE: To determine whether zirconia abutments with an internal connection exhibit similar fracture load as zirconia abutments with an external connection. MATERIALS AND METHODS: The following zirconia abutments were divided into four groups of 20 each: StraumannCARES abutments on Straumann implants (group A), Procera abutments on Branemark implants (group B), Procera abutments on NobelReplace implants (group C), and Zirabut SynOcta prototype abutments on Straumann implants (group D). The abutments were fixed on their respective implants either internally via a secondary abutment (A) or a metallic coupling (C) (two-piece) or directly externally (B) and internally (D) (one-piece). In each group, 10 abutments were left unrestored (A1 to D1). Ten received glass-ceramic crowns (A2 to D2). Static loading was performed according to the ISO norm 14801 until failure. The bending moment was calculated for comparison of the groups and subjected to statistical analysis (Student t test). RESULTS: The mean bending moments of the unrestored abutments were 371.5 +/- 142.3 Ncm (A1), 276.5 +/- 47.6 Ncm (B1), 434.9 +/- 124.8 Ncm (C1), and 182.5 +/- 136.5 Ncm (D1). Two-piece internally connected abutments exhibited higher bending moments than one-piece internally (C1 versus D1 P = .003, A1 versus D1 P = .03) or externally (C1 versus B1 P = .004) connected abutments. The groups with restorations did not show different bending moments than those without restorations. The mean bending moments of the restored abutments were 283.3 +/- 44.8 Ncm (A2), 291.5 +/- 31.7 Ncm (B2), 351.5 +/- 58 Ncm (C2), and 184.3 +/- 77.7 Ncm (D2). Group C2 exhibited the highest bending moment (P < .05). Internally connected one-piece abutments (D2) were weaker than all other groups (D2 versus A2 P = .002; D2 versus B2 P = .001; D2 versus C2 P = .0003). CONCLUSIONS: The type of connection significantly influenced the strength of zirconia abutments. Superior strength was achieved by means of internal connection via a secondary metallic component.

Clinical significance of anti-protein Z antibodies in patients with lupus anticoagulant.

INTRODUCTION: Protein Z serves as cofactor for the inactivation of factor Xa by the plasma protein Z-dependent protease inhibitor. Deficiency of protein Z was reported to exhibit a clinical manifestation like lupus anticoagulant characterised by thrombosis and fetal loss. As anti-protein Z antibodies may be associated with low protein Z levels, we hypothesised that anti-protein Z antibodies might play a role in lupus anticoagulant (LA). MATERIALS AND METHODS: Anti-protein Z antibodies were measured by commercially available ELISA in 102 LA-patients (69 with and 33 without thrombosis) and 33 healthy volunteers. RESULTS: Elevated anti-protein Z IgG and/or IgM, IgG and IgM antibody levels were more prevalent among LA-patients (62%, 35%, 45%) than among controls (50%, 25%, 25%), but the difference was only statistically significant for the IgM subtype (p=0.037). Anti-protein Z IgG (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.33-1.82) and IgM (OR 0.82, CI 0.35-1.88) antibody levels in the highest quartile of controls did not indicate an increased risk for thrombosis among LA-patients. Anti-protein Z IgG (OR 2.0, CI 0.5-7.6) and IgM (OR 1.8, CI 0.5-6.6) antibody levels in the highest quartile of controls were more prevalent in women with pregnancy loss than in those with normal pregnancy, but the difference was not statistically significant. CONCLUSION: Our data indicate that anti-protein Z antibodies are not associated with thrombosis in LA. However, women with LA and pregnancy loss show a tendency towards elevated anti-protein Z antibody levels.

The angiotensin-converting enzyme insertion/deletion polymorphism and serum levels of angiotensin-converting enzyme in venous thromboembolism. Data from a case control study.

The angiotensin-converting enzyme (ACE) has been suggested to affect blood coagulation and fibrinolysis. Results from literature on the role of the frequent insertion/deletion (I/D) polymorphism in the ACE gene in venous thromboembolism (VTE) are controversial. Only limited data on ACE serum levels inVTE exist. We determined the ACE I/D polymorphism by genotyping and ACE serum levels by an enzymatic assay in 100 high-risk patients with objectively confirmed recurrentVTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism. One hundred twenty-five age- and sex-matched healthy individuals served as controls. ACE genotype frequencies were not significantly different between patients (DD: 26.0%, ID: 52.0%, II: 22.0%) and controls (DD: 29.6%, ID: 44.8%, II: 25.6%; p = 0.56). Neither individuals with ACE DD genotype nor those with ACE ID genotype had a higher risk for VTE in comparison to those with ACE II genotype (odds ratio and [95% confidence interval]: 1.0 [0.5-2.1] and 1.4 [0.7-2.6], respectively). Serum ACE levels (U/l) did not differ between patients (median = 25.25, 25th -75th percentile: 20.20-33.70) and controls (24.20, 17.85-34.50, p = 0.49). In the total population involved in the study the ACE DD genotype (n = 63: 36.00 [26.40-43.00]) was associated with higher ACE levels than the ACE ID genotype (n = 108: 24.10 [19.80-31.48], p < 0.001) and the ACE II genotype (n = 54: 19.35 [15.00-22.95], p < 0.001). In conclusion, we found a significant association of the ACE I/D polymorphism with ACE serum levels. However, neither the serum levels nor the I/D genotype were associated with VTE.

High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant.

BACKGROUND: The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. METHODS: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. RESULTS: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) microg/L vs 36.8 (11.0) microg/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 microg/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) microg/L vs 44.1 (14.1) microg/L; P <0.001). CONCLUSIONS: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.

The clinical significance of anti-prothrombin antibodies for risk assessment of thromboembolism in patients with lupus anticoagulant.

INTRODUCTION: Thromboembolism is a common manifestation of lupus anticoagulant (LA), however only a subgroup of LA-patients is affected by thrombosis. Study objective was to investigate whether anti-prothrombin antibodies can identify LA-patients at increased risk for thrombosis. MATERIALS AND METHODS: In total 79 patients, 50 with (42 men/8 women) and 29 without thrombosis (21 men/8 women), were investigated for their presence of anti-prothrombin IgG and IgM antibodies using assays from two different manufacturers (Aeskulisa=assay I, CoaChrom=assay II). RESULTS: The prevalence of elevated levels of anti-prothrombin IgG, IgM as well as IgG and/or IgM antibodies was 66% [assayI] (36% [assayII]), 38% (24%) and 72% (50%) in patients with thrombosis and 55% (24%), 28% (28%) and 66% (41%) in patients without thrombosis, respectively. Neither anti-prothrombin IgG or IgM nor IgG and/or IgM antibodies were found to indicate an increased risk for thrombosis. In the subgroup of patients with arterial or venous thrombosis there was also no association between anti-prothrombin antibodies and thrombosis. The comparison of median levels of IgG and IgM anti-prothrombin antibodies between patients with and without thrombosis yielded a borderline statistically significant difference only for anti-prothrombin IgG antibodies by using assay II (p=0.033), all other comparisons were not statistically significant. CONCLUSIONS: In conclusion, presence of anti-prothrombin antibodies was not associated with thromboembolism in LA-patients.

The course of severe autoimmune thrombocytopenia in patients not undergoing splenectomy.

BACKGROUND AND OBJECTIVES: Splenectomy is the most effective treatment for patients with severe autoimmune thrombocytopenia (AITP) who do not have a spontaneous or drug- induced remission. However, this treatment has some short and long term risks. There is no consensus on the indications and optimal timing of splenectomy, since it is unknown up to which time from onset of symptoms a remission can be expected without splenectomy. DESIGN AND METHODS: We studied the incidence of complete or partial remissions in a cohort of 114 adult patients (68 women, 46 men, median age 49.8 years, interquartile range 28.3-68.4) with severe AITP (platelet count < 20x10(9)/L at diagnosis) using Kaplan Meier analysis. Patients who underwent splenectomy during the observation period were censored at the time of splenectomy. RESULTS: The probability of a complete remission was 61% and that of at least a partial remission was 86% at 5 years. The incidence of complete remission was highest within the first 6 months (30%), but increased up to 53% between 6 months and 3 years after diagnosis. The probability of a remission was not related to age, gender, or the presence or absence of platelet antibodies, but was higher in patients with an acute onset of symptoms in comparison to those with an insidious onset (p = 0.0003). The chance of a late remission was higher in patients with an insidious onset of disease. INTERPRETATION AND CONCLUSIONS: These data indicate that splenectomy may be delayed for up to 3 years, in particular in those patients whose AITP has had an insidious onset.

Anti-beta2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant.

The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-beta2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-beta2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite beta2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-beta2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6-56.4]. This risk was even higher in the subgroup of women (n = 16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4-126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7-17.6]. The co-existence of anti-beta2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95% CI 1.3-29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-beta2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

Inflammation in patients with lupus anticoagulant and implications for thrombosis.

OBJECTIVE: The underlying mechanism of the prothrombotic state associated with the lupus anticoagulant (LAC) has not been fully elucidated. Evidence suggests involvement of inflammation in arterial and venous thrombosis, and it may be hypothesized that subclinical inflammation aggravates the tendency to thrombosis in patients with LAC. METHODS: Levels of high sensitivity C-reactive protein (hs-CRP), fibrinogen, and factor VIII (VIII) were measured in 38 patients with LAC and a history of thrombosis, 27 with LAC and no history of thrombosis, and 33 healthy controls. RESULTS: Hs-CRP, fibrinogen, and factor VIII levels were significantly higher in patients with LAC with thrombosis (hs-CRP median = 0.3 mg/dl, interquartile range, IQR, 0.11-0.62, p < 0.001 vs controls; fibrinogen mean = 395 +/- 90 SD mg/dl, p < 0.001; factor VIII mean = 181 +/- 50%, p = 0.005) as well as in those without thrombosis (median = 0.21, IQR 0.10-0.12, p < 0.001; mean = 378 +/- 91, p = 0.003; mean = 179 +/- 39, p = 0.015) compared to controls (median = 0.07, IQR 0.03-0.12; mean = 308 +/- 48; mean = 137 +/- 39). After adjustment for age, body mass index, smoking status, and blood group (only for factor VIII) the differences between LAC groups and controls remained significant, except for the comparison of fibrinogen between patients without thrombosis and controls. The association between LAC and markers of inflammation was confirmed using linear regression analysis. Markers of systemic inflammation did not differentiate between LAC patients with and without thrombosis (p = 0.829 for hs-CRP, p = 0.649 for fibrinogen, p = 0.996 for factor VIII). CONCLUSION: Our results show that LAC is associated with an inflammatory state. However, there was no evidence for an association between inflammatory markers and thromboembolism in patients with LAC.

The Fc gammaRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIb alpha and Fc gammaRIIa and a risk for thromboembolism in lupus anticoagulant patients.

There is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not. The Fc gammaRIIa receptor is the only Fc receptor expressed by platelets. As platelets can be activated via this receptor, we have compared gene frequencies of the Fc gammaRIIa polymorphism R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively, in an exploratory study. Furthermore, we investigated the presence of autoantibodies against Fc gammaRIIa and/or GPIb alpha, which is in close proximity to the Fc gammaRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles. The Fc gammaRIIa-R/R131 genotype was significantly less frequent in patients with LA compared to controls (p<0.025). These findings were due to an increased frequency of heterozygous patients in the LA/TE+ cohort (odds ratio 6.76, 95% confidence interval 1.55-62.03, p<0.008). For the first time, heterozygosity, rather than homozygosity, can be linked to disease, which may be explained by the dual function of the Fc gammaRIIa, namely binding of antibodies to platelets and thereby their activation, and, on the other hand, clearance of antibody coated platelets by the phagocyte system. There was no correlation between the presence of anti-Fc gammaRIIa or anti-GPIb alpha autoantibodies and the Fc gammaRIIa-R/H131 polymorphism, nor the incidence of TE, nor HLA class II alleles.

Type 2 diabetes in patients with end-stage renal disease is not associated with further increased serum inflammatory parameters.

BACKGROUND: Cardiovascular morbidity and mortality is markedly increased in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and is further pronounced when diabetes mellitus is also present. As atherogenesis is mediated by inflammation of vessel walls and as evidence evolves that atherosclerosis and diabetes mellitus share a common inflammatory basis, we considered whether ESRD patients with additional diabetes mellitus exhibit increased inflammation levels exceeding those of ESRD patients without diabetes mellitus. METHODS: The study included 20 ESRD patients with type 2 diabetes mellitus and 16 non-diabetic ESRD patients on long-term HD. The patients' clinical characteristics and serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor receptor I (sTNF-RI), neopterin and fibrinogen were assessed. RESULTS: There were no significant differences in serum levels of CRP, IL-6, neopterin, sTNF-RI and fibrinogen found in ESRD patients with and without diabetes mellitus. HD duration correlated significantly with neopterin (r=0.515, p<0.001) and sTNF-RI (r=0.429, p<0.05) serum levels. HD led to a significant reduction in neopterin levels whereas CRP, IL-6 and sTNF-RI levels did not change significantly. CONCLUSIONS: With the inherent limitations of a small number of patients studied, we observed that the presence of type 2 diabetes mellitus in addition to ESRD was not associated with further increased serum levels of the examined inflammatory parameters. Our observations suggest that the worsened prognosis of diabetic ESRD patients is probably not explainable by superimposing inflammatory processes.

Mortality in severe, non aggressively treated adult autoimmune thrombocytopenia.

A total of 130 consecutive patients with severe autoimmune thrombocytopenia (AITP) who were diagnosed and treated in our institution between 1991 and 2001 were followed up. The patients were almost exclusively treated with prednisolone, immunoglobulin and/or splenectomy. The aim of the treatment was to keep the platelet count at least above 10,000 microL. None of the patients died from bleeding, two patients died from infection and seven from other unrelated causes. These data show that AITP is a relatively benign disease that does not require aggressive treatment. Bleeding can be prevented if the platelet count can be kept above 10,000 microL.