Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood

The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation.     

Effect of free radical scavengers on myocardial function and Na+, K+-ATPase activity in stunned rabbit myocardium

OBJECTIVES: The role of reactive oxygen species (ROS) in the mechanism of myocardial stunning was investigated. MATERIAL AND METHODS: Isolated Langendorff-perfused rabbit hearts were subjected to 15 min normothermic ischemia followed by 10 min reperfusion with Krebs-Henseleit solution+/-mannitol or histidine. RESULTS: In hearts reperfused without free radical scavenger the left ventricular developed pressure as well as its maximal positive and negative first derivatives (+dP/dt, -dP/dt) was significantly depressed, whereas end diastolic pressure (LVEDP) increased when compared to preischemic values. Treatment with mannitol had little protective effects, whereas singlet oxygen scavenger histidine significantly improved the recovery of LVEDP and -dP/dt. Sarcolemmal Na+, K+-ATPase activity (control, 400+/-41 nmol Pi.min-1.mg-1) was depressed in untreated stunned hearts (260+/-27 nmol Pi.min-1.mg-1), but was almost completely recovered in hearts pretreated with histidine (364+/-27 nmol Pi.min-1.mg-1). The inhibition of Na+, K+-ATPase was only slightly prevented by mannitol (302+/-29 nmol Pi.min-1.mg-1l). CONCLUSIONS: The results suggest that ROS-induced inhibition of Na+, K+-ATPase activity is involved in the mechanism of postischemic contractile dysfunction and support the view that singlet oxygen may be one of the major causes of oxidative injury during ischemia and reperfusion.     

Reduction in Fracture Rate and Back Pain and Increased Quality of Life in Postmenopausal Women Treated with Teriparatide: 18-Month Data from the European Forsteo Observational Study (EFOS)

The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.     

Visualization of dedicated catheters using fast scanning techniques with potential for MR-guided vascular interventions

This paper reports the development of dedicated catheters and real-time MR scan techniques for guiding vascular interventional procedures. By way of phantom experiments, it is shown that proper modification of the magnetic properties of catheters allows their conspicuous and consistent visualization in subsecond 2D gradient echo images and phase contrast angiograms. Dynamic scan times as low as 0.5 s could be achieved by exploiting the keyhole technique and purposeful postprocessing. The temporal resolution and spatial resolution of the resultant scan protocol shows promise for adequate tracking of catheter manipulation.     

Iterative reconstruction improves evaluation of native aortic and mitral valves by retrospectively ECG-gated thoracoabdominal CTA

Objectives

To compare native aortic (AV) and mitral valve (MV) image quality on limited-dose retrospectively ECG-gated CTA of the thoracoabdominal aorta reconstructed with iterative reconstruction (IR) and filtered back projection (FBP).

Methods

Fifty patients underwent routine care retrospectively ECG-gated thoracoabdominal limited-dose 256-slice CTA. At 30 % (systole) and 75 % (diastole) of the R-R interval AV and MV were reconstructed using FBP and IR. Objective image quality [density and noise (SD of density measurement)] was measured. Two independent observers scored subjective valve image quality using four-point Likert scales.

Results

IR significantly decreased image noise, but did not alter the aorta and interventricular septum density. Interobserver variability was moderate to good. Valve image quality was scored at least moderate in most cases. IR scored one or two Likert scale points higher than FBP in 10 (first observer) and 27 (second observer) scores. Conversely, IR scored one Likert scale point lower than FBP in 1 (first observer) and 4 (second observer) scores.

Conclusions

Limited-dose retrospectively ECG-gated thoracoabdominal CTA enables moderate to excellent evaluation of AV and MV in most patients, in addition to the primary diagnostic question. Image quality is further improved by IR.

Key Points

? Thoracoabdominal computed tomographic angiography demonstrates both the aortic and mitral valves. ? Iterative reconstruction decreases image noise and increases the SNR/CNR of thoracoabdominal CTA. ? Limited-dose retrospectively gated CTA enables moderate–excellent left-sided valvular evaluation. ? Iterative CT image reconstruction improves subjective native aortic and mitral valvular evaluation.     

Particle size of bone graft and method of impaction affect initial stability of cemented cups: human cadaveric and synthetic pelvic specimen studies

We determined the effect of bone graft particle size and impaction technique on the initial stability of cemented acetabular cups. First, acetabular reconstructions were performed in human cadaveric pelvic bones in which type 2 AAOS cavitary defects were created. Reconstructions were made with small bone grafts (average 2 mm) produced by a bone mill or large bone grafts (average 9 mm) produced by hand with a rongeur. All chips were made from freshly-frozen femoral heads. Impaction was done using acetabular impactors and a hammer. We did a loading experiment with a gradually increasing dynamic load up to 3000 N. We used radiostereometric analysis (RSA) to determine cup stability. The cups were more stable when large bone grafts were used. Because of limitations of the cadaver model, we developed a synthetic acetabular model. For validation of this model, we repeated the experiments using small and large bone grafts. The results with both models were similar. In the synthetic model, we compared impaction with hammer and impactors with the reversed reaming technique using manual compression on the reamer. The latter method resulted in more migration. We recommend firm impaction with a hammer of large bone grafts for optimal stability of the cup.     

The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

Backround  

Diverticulosis is a common disease in the western society with an incidence of 33–66%. 10–25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger (< 50 years) patient. Open sigmoid resection is still the gold standard, but laparoscopic colon resections seem to have certain advantages over open procedures. On the other hand, a double blind investigation has never been performed. The Sigma-trial is designed to evaluate the presumed advantages of laparoscopic over open sigmoid resections in patients with symptomatic diverticulitis.