Meeting Report: Ninth and Tenth Workshops of the European Paediatric Network for Haemophilia Management (PedNet)

This meeting report presents an overview of the discussions at the ninth and tenth workshops of the European Paediatric Network for Haemophilia Management (PedNet) that occurred in 2005 and 2006. Among numerous topics, a major theme of these workshops was the formation of inhibitors to replacement factor.     

Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment

Objective. Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients’ well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20?mg) and omeprazole (20?mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. Material and methods. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20?mg (n=358) or omeprazole 20?mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Results. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Conclusions. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20?mg) and omeprazole (20?mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.     

Differences in restenosis propensity of devices for transluminal coronary intervention: A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty

With the increasing clinical application of new devices forpercutaneous coronary revascularization, maximization of theacute angiographic result has become widely recognized as akey factor in maintained clinical and angiographic success.What is unclear, however, is whether the specific mode of actionof different devices might exert an additional independent effecton late luminal renarrowing. The purpose of this study was toinvestigate such a difference in the degree of provocation ofluminal renarrowing (or ‘restenosis propensity’)by different devices, among 3660 patients, who had 4342 lesionssuccessfully treated by balloon angioplasty (n=3797), directionalcoronary atherectomy (n= 200), Palmaz-Schatz stent implantation(n= 229) or excimer laser coronary angioplasty (n= 116) andwho also underwent quantitative angiographic analysis pre- andpost-intervention and at 6-month follow-up. To allow valid comparisonsbetween the groups, because of significant differences in coronaryvessel size (balloon angioplasty=2.62±0.55 mm, directionalcoronary atherectomy= 3.28±0.62 mm, excimer laser coronaryangioplasty= 2.51±0.47 mm, Palmaz-Schatz=3.01±0.44mm;P<0.0001), the comparative measurements of interest selectedwere the ‘relative loss’ in luminal diameter (RLoss=losslvessel size) to denote the restenosis process, and the‘relative lumen at follow-up’ (RLfup=minimal luminaldiameter at follow uplvessel size) to represent the angiographicoutcome. For consistency, lesion severity pre-intervention was representedby the ‘relative lumen pre’ (RLpre=minimal luminaldiameter prelvessel size) and the luminal increase at interventionwas measured as ‘relative gain’ (relative gain=gainl vessel size). Differences in restenosis propensity betweendevices was evaluated by univariate and multivariate analysis.Multivariate models were constructed to determine relative lossand relative lumen at follow-up, taking account of relativelumen pre-intervention, lesion location, relative gain, vesselsize and the device used. In addition, model-estimated relativeloss and relative lumen at follow-up at given relative lumenpre-intervention relative gain and vessel size, were comparedamong the four groups. Significant differences were detectedamong the groups both with respect to these estimates, as wellas in the degree of influence of progressively increasing relativegain, on the extent of renarrowing (relative loss) and angiographicoutcome (relative lumen at follow-up), particularly at higherlevels of luminal increase (relative gain). Specifically, lesionstreated by balloon angioplasty or Palmaz-Schatz stent implantation(the predominantly ‘dilating’ interventions) wereassociated with more favourable angiographic profiles than directionalatherectomy or excimer laser (the mainly ‘debulking’interventions). Significant effects of lesion severity and location,as well as the well known influence of luminal increase on bothluminal renarrowing and late angiographic outcome were alsonoted. These findings indicate that propensity to restenosis afterapparently successful intervention is influenced not only bythe degree of luminal enlargement achieved at intervention,but by the device used to achieve it. In view of the clinicalimplications of such findings, further evaluation in largerrandomized patient populations is warranted.     

Human leukocyte cathepsin G and elastase specifically suppress thrombin- induced prostacyclin production in human endothelial cells

Polymorphonuclear leukocytes (PMN) when activated release products that can potentially injure endothelial cells or alter endothelial function. Exposure of cultured human umbilical vein endothelial cells to cathepsin G and elastase isolated from human PMN at concentrations reached in vivo (100 ng/mL to 10 micrograms/mL) selectively inhibited thrombin-induced prostacyclin production and the thrombin-induced rise in cytosolic free calcium ([Ca++]i) concentration. These proteases also blocked thrombin-induced release of arachidonic acid from prelabeled endothelial cells (EC). In contrast, induction of prostacyclin (PGI2) production by arachidonate, histamine, or the calcium ionophore A23187 was not altered by treatment of EC with these proteases. The effects of the proteases were concentration-dependent, were blocked by serum or serum protease inhibitors, and were reversed when the endothelial cells were further cultured for 24 hours in the absence of the proteases. Elastase, but not cathepsin G, also produced detachment of endothelial cells. Thus, the major leukocyte proteases selectively suppress thrombin-induced prostacyclin production by human vascular endothelial cells and may alter the hemostatic balance at sites of PMN activation.     

Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism

BACKGROUND: Lifetime estrogen exposure has been related to breast cancer risk, osteoporosis, and cardiovascular disease but data on venous thromboembolism (VTE) risk are limited. METHODS: Data from a hospital-based case-control study among 608 postmenopausal women (191 with a first episode of idiopathic VTE and 417 age-matched controls) were used to determine whether estrogen exposure, as assessed by age at menopause [classified as early (< or = 45 years), normal (46-54 years) and late menopause (> or = 55 years)] and parity, was associated with the risk of VTE. RESULTS: After adjustment for potential confounding variables, the risk of VTE was increased with each year's delay in the menopause [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.02-1.10, P < 0.0075]. When compared with women with normal menopause used as a reference, the adjusted OR for VTE was 0.59 (95% CI = 0.36-0.97) and 2.53 (95% CI = 1.28-4.99) for women with early menopause and late menopause, respectively (P = 0.001). Adjusted OR for VTE was also higher for women with more than two children when compared with those with less than or equal to two children (1.56, 95% CI = 1.03-2.34, P = 0.03). The lowest risk of VTE was observed in women with early menopause and lower parity (adjusted OR = 0.60, 95% CI = 0.30-1.24), the highest risk was among women with late menopause who have had more than two children (adjusted OR = 3.41, 95% CI = 1.46-9.25). CONCLUSION: These results show that the longer exposure to endogenous estrogen is associated with an increased VTE risk.     

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea–hypopnoea index (AHI) 5–15 h^?1] and 40 controls (AHI <5 h^?1). Serum concentrations of pro‐ and anti‐inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non‐steroidal anti‐inflammatory medication, the mean level of tumour necrosis factor‐α was significantly elevated (1.54 versus 1.17 pg mL^?1, P = 0.004), whereas the level of interleukin‐1β (IL‐1β) was reduced (0.19 versus 0.23 pg mL^?1, P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti‐inflammatory cytokines, interleukin‐10 (1.28 versus 0.70 pg mL^?1, P < 0.001) and interleukin‐1 receptor antagonist (478 versus 330 pg mL^?1, P = 0.003) were elevated in the OSA group. The concentrations of C‐reactive protein increased, but IL‐1β decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro‐inflammatory, but also with the anti‐inflammatory systems.