Alexandra Kaider

ELEVATED SERUM COBALT WITH METAL-ON-METAL ARTICULATING SURFACES

We determined serum cobalt levels in 55 patients by atomic absorption spectrophotometry before and after implantation of uncemented total hip arthroplasties. In a randomised, prospective trial 27 wrought Co-28Cr-6Mo-0.2C metal-on-metal articulations were compared with 28 ceramic-on-polyethylene hips which did not contain cobalt. Other sources of iatrogenic cobalt loading were excluded. The metal-on-metal group produced detectable serum cobalt levels (median 1.1 microg/l after one year) which were significantly different (p < 0.0001) from those of the ceramic-on-polyethylene control group (median below detection limit of 0.3 microg/l after one year). Our findings indicate that metal-on-metal bearings generate some systemic release of cobalt.

Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis

Summary.  Background: Limited data exist on the risk of pregnancy‐associated venous thromboembolism (VTE) in women with a history of VTE. Objective: To evaluate the risk of recurrent pregnancy‐associated thrombosis in women with previous VTE in a large retrospective cohort study. Patients and methods: One hundred and fifty‐nine women with at least one pregnancy (293 pregnancies in total) after a VTE were included into the study. The patients underwent a standardized interview on their history of thrombosis and pregnancy‐associated complications. Results: Eight recurrent events occurred during 197 pregnancies without thrombosis prophylaxis. The probability of VTE during pregnancy without thrombosis prophylaxis was 6.2% (95% confidence interval 1.6–10.9%). The risk was constant over the whole period of pregnancy. Of the eight women with VTE during pregnancy four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53 (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138 (6.5%) after live birth. Conclusions: Without thrombosis prophylaxis the risk for recurrent symptomatic VTE is substantial during the whole period of pregnancy in women with previous VTE. The majority of events occurred after delivery, reflecting the very high risk during the postpartum period. Prospective and comparative trials to ascertain efficacy and safety of prophylactic heparin are urgently needed.

Cementless total hip arthroplasty with a tapered, rectangular titanium stem and a threaded cup: a minimum ten-year follow-up.

Background: We report the results of cementless total hip arthroplasty with a tapered, rectangular titanium stem that was introduced in 1979 and continues to be used today with only minor changes. The aim of the design is to achieve primary stability to resist rotational and axial forces through precision rasping and press-fit implantation of a tapered, rectangular femoral component.Methods: Between October 1986 and November 1987, 208 total hip arthroplasties with insertion of a tapered, rectangular titanium stem and a threaded cup without cement were performed in 200 consecutive patients (average age, sixty-one years; range, twenty-two to eighty-four years).Results: At the time of the latest follow-up, fifty-one patients (fifty-two hips) had died and sixteen patients had been lost to follow-up, leaving 133 patients. Twelve hips had been revised, two in patients who subsequently died, leaving 123 living patients without revision. The median follow-up time was 120.7 months. Five cups needed revision surgery because of aseptic loosening; two, because of massive polyethylene wear; one, because of posttraumatic migration; and one, because of breakage. Three femoral stems were revised: one because of malpositioning (the reoperation was done five days after implantation); one, because of infection; and the third, after multiple failed acetabular revisions. The mean Harris hip score for the patients who did not have revision was 85.4 points (range, 46 to 100 points) at the time of the latest follow-up. Four patients (3%) complained of thigh pain that was not associated with another disorder. According to the criteria of Engh et al., all femoral implants were graded as stable bone-ingrown. The probability of survival of both the femoral and the acetabular component at ten years, with any revision as the end point, was 0.92 (95% confidence interval, 0.88 to 0.97). The probability of survival of the cup was 0.93 (95% confidence interval, 0.89 to 0.97), and that of the stem was 0.99 (95% confidence interval, 0.97 to 1.00).Conclusions: The results of arthroplasty with a tapered, rectangular titanium stem combined with a conical threaded cup inserted without cement were excellent at a minimum of ten years. Our data suggest that femoral stem fixation continues to be secure, while the threaded cup is prone to aseptic loosening.

Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients.

Summary.  Background:  Tissue factor (TF) expression by tumors contributes to tumor growth. Release of TF‐positive microparticles (MPs) may contribute to venous thromboembolism (VTE).

Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study

Background Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches.Methods Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3–6 weeks or 3–4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy.Results A total of 60 patients were treated. The mean changes in infarct size at 3 months were −3.5 ± 5.1% (95% CI −5.5% to −1.5%, P = 0.001) in the early group and −3.9 ± 5.6% (95% CI −6.1% to −1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 ± 5.6% (95% CI 1.3–5.6%, P = 0.003) and 3.4 ± 7.0% (95% CI 0.7–6.1%, P = 0.017), respectively. At 9–12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 ± 68.7 × 106 and 194.8 ± 60.4 × 106 stem cells, respectively, were delivered to the myocardium, and 1.30 ± 0.68 × 109 and 1.29 ± 0.41 × 109 cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points.Conclusions Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis.

Plasma plasminogen activator inhibitor-1 (PAI-1) level was observed to be associated with sequence variations at the PAI-1 locus. Therefore, PAI-1 gene promoter was screened for possibly new polymorphisms and to investigate the contribution of these sequence variations to PAI-1 levels in patients with deep vein thrombosis (DVT). DNA was isolated from blood of 83 consecutive unrelated patients (42 +/- 11 years old) and from 50 apparently healthy subjects of similar age and gender distribution. Six fragments covering DNA sequence- 1523 base pairs (bp) upstream from the start of PAI-1 gene transcription to +90 bp in the first exon, were amplified by polymerase chain reaction and analyzed by single-strand conformation polymorphisms. Two polymorphisms were found: a previously described 4G/5G deletion/insertion polymorphism -675bp upstream from the start of transcription and a novel G/A single base substitution polymorphism further upstream at -844 bp. The two polymorphisms were in strong linkage disequilibrium. Significant differences between patients and controls were observed neither for the frequencies of the 4G/5G alleles (0.60/0.40 and 0.59/0.41, respectively) nor for the frequencies of the G/A alleles (0.33/0.67 and 0.41/0.59, respectively). The distribution of both polymorphisms was similar in idiopathic and secondary DVT as well as in first and recurrent DVT. In patients association between the 4G/5G genotypes and PAI activity was observed, with the highest values in the 4G/4G genotype (13.3 U/mL), median values in the 4G/5G genotype (9.8 U/mL) and the lowest values in the 5G/5G genotype (2.0 U/mL). Despite the lack of association between the G/A genotypes and plasma PAI-1 levels, electrophoretic mobility shift assay showed specific binding of a nuclear protein from human vascular endothelial cells extracts to both the G and the A variant, suggesting functional importance of this novel G/A polymorphism in regulating the expression of PAI-1 gene.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9 years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7 years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4 pmol/L) and aBMD values at the total hip (0.989 vs 0.971 g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Cementless Total Hip Arthroplasty with the Rectangular Titanium Zweymüller Stem

In 2002 and 2006, we reported the long-term results of 208 total hip replacements performed with the Zweymuller stem and a threaded cup in 200 patients. The present study gives an update on this patient cohort. At a minimum of twenty years postoperatively, seventy-three patients (seventy-five hips) were available for follow-up; twelve patients were lost to follow-up. The key findings of our previous reports were the absence of aseptic femoral stem loosening and a poor rate of survival of the threaded cup. Since then, two revisions have been performed because of aseptic stem loosening. We observed osteolytic lesions around the proximal part of the femoral component on twenty-four (47%) of fifty-one radiographs, but no stem was deemed at risk for loosening. The probability of survival of the stem at twenty years was 0.96 (95% confidence interval, 0.91 to 0.99), and the probability of survival of the cup at twenty years was 0.67 (95% confidence interval, 0.57 to 0.75). The Zweymuller femoral stem, a tapered, rectangular implant, continues to give excellent long-term results.

Melatonin and adolescent idiopathic scoliosis

Scoliosis seen in the chicken after pinealectomy resembles adolescent idiopathic scoliosis in man. It has been suggested that in both species, deficiency of the pineal hormone, melatonin, is responsible for this phenomenon. In nine patients with adolescent idiopathic scoliosis and in ten age- and gender-matched controls, the circadian levels of serum melatonin and the excretion of urinary 6-hydroxy-melatonin-sulphate, the principal metabolite of melatonin, were determined. There were no statistically significant differences in the secretion of serum melatonin or the excretion of urinary 6-hydroxy-melatonin-sulphate between the patients and the control group. The hypothesis of melatonin deficiency as a causative factor in the aetiology of adolescent idiopathic scoliosis cannot be supported by our data.

Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis

Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation.