Non-invasive markers to investigate vascular damage in systemic disease

While the access and quality of cardiovascular health care continues to evolve, the Western world is confronted with new challenges in the 21th century. As result of an increased overall life-expectancy, the prevalence of chronic diseases is rising. Various chronic conditions, although effecting different organs and systems, appear to be complicated by an increased risk for cardiovascular morbidity and mortality. In order to improve risk prediction and prevent CVD, its necessary to first improve our understanding of pathways involved in vascular injury and accelerated atherosclerosis. Vascular injury, as consequence of various known and unknown risk factors, precedes the occurrence of a clinical event and is a key step in its etiology. In this thesis various vascular injury related markers, obtained by new imaging and non-imaging techniques, in high-risk patients groups are investigated and discussed. For example, we investigated whether microcalcification, assed with 18F-NaF PET, differs between culprit and non-culprit atherosclerotic plaques. Furthermore, we evaluated MRI assessed plaque thickness and morphology of the carotid artery persons with hemophilia in order to better understand the relation between cardiovascular disease and hypocoagulability. New techniques and insights can help us to further improve the treatment of cardiovascular diseases in the future

Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn's Disease

Systemic presence of arthritis autoantibodies (AAb) is specific for rheumatoid arthritis (RA). AAb initiation might be triggered by chronic mucosal inflammation, such as in inflammatory bowel disease (IBD). We assessed the prevalence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in ulcerative colitis (UC) and Crohn’s disease (CD) patients, with regard to the prevalence of joint complaints in AAb+ versus AAb− IBD patients. RA patients and healthy subjects (HC) served as controls. Serum was collected from 226 UC, 165 CD and 86 RA patients, and 36 HCs. One-hundred-and-ten UC (48.7%) and 76 CD (46.1%) patients were seropositive for at least one autoantibody, compared to 4 (13.9%) HCs and 81 (94.2%) RA patients. Eighty-three (37%) UC and 52 (32%) CD patients were seropositive for the anti-cyclic citrullinated protein antibody (anti-CCP2) of the immunoglobulin A type (IgA anti-CCP2), compared to 1 (2.8%) HC and 64 (74%) RA patients. RF of the immunoglobulin G type (IgG RF) and IgA RF seropositivity in UC and CD patients was comparable to HCs and low compared to RA patients. Arthralgia was reported by 34 (18.7%) UC and 50 (33.1%) CD patients, but presence of arthralgia was not increased in AAb+ patients. AAbs are frequently present in IBD patients, supporting the hypothesis that inflammation of intestinal mucosa induces low systemic levels of ACPA

Diagnostic value of axillary artery ultrasound in patients with suspected giant cell arteritis

Objectives. To compare colour duplex ultrasonography (CDU) findings with axillary F-18-fluorodeoxyglucose (FDG) PET/CT findings and to compare the diagnostic performance of temporal and axillary artery CDU with temporal artery CDU alone. Methods. Patients suspected of GCA were retrospectively included. Presence of a halo or occlusion was considered a positive CDU finding. FDG-PET/CT-assessed axillary artery involvement was defined as axillary artery FDG uptake higher than liver uptake. The reference was the clinical diagnosis after 6 months, which was based on symptomatology and additional diagnostic tests, with the exception of CDU. Results. Of the 113 included patients, GCA was diagnosed in 41. Twenty-eight out of 41 GCA patients underwent a FDG-PET/CT. FDG-PET-assessed extra-cranial GCA was present in 20/41 patients, of which 13 showed axillary involvement on FDG-PET/CT. An axillary halo was found in eight of these 13 patients. Six out of the 20 patients with FDG-PET-assessed GCA showed no axillary involvement on CDU or FDG-PET/CT. Five of them had single artery involvement on FDG-PET/CT (two aorta; three vertebral artery). One patient had an axillary occlusion on CDU, consistent with FDG-PET/CT results. Overall, sensitivity and specificity of temporal artery CDU was 52% (95% CI: 35, 67) and 93% (95% CI: 84, 97), respectively. Adding axillary artery results improved sensitivity to 71% (95% CI: 55, 84), while specificity did not change. Conclusion. Presence of an axillary halo or occlusion on CDU is consistent with axillary artery FDG-PET/CT results, but a negative CDU does not rule out axillary involvement. Adding axillary artery assessment to temporal artery assessment may substantially increase the diagnostic performance of CDU

First results from the L3+C experiment at CERN

The L3+C experiment combines the high-precision spectrometer of the L3 detector at LEP, CERN, with a small air shower array. The momenta of cosmic ray induced muons can be measured from 20 to 2000 GeV/c. During the 1999 data taking period 5 billion muon events were recorded in the spectrometer. From April until mid Summer 2000 an additional 3 billion muon events have been recorded as well as 25 million air shower events. Here the first results on the muon momentum spectrum and charge ratio will be presented

Psychometric Performance of the Stony Brook Scar Evaluation Scale and SCAR-Q Questionnaire in Dutch Children after Pediatric Surgery

Introduction: The growing population of survivors following pediatric surgery emphasizes the importance of long-term follow-up. The impact of surgical scars on daily life can be evaluated through patient-reported outcome measurements. The Stony Brook Scar Evaluation Scale (SBSES) and SCAR-Q questionnaire are two interesting instruments for this purpose. We evaluated their psychometric performance in Dutch children after pediatric surgery. Methods: After English–Dutch translation, we evaluated—following the COSMIN guidelines—the feasibility, reliability (internal and external), and validity (construct, criterion, and convergent) of the SBSES and SCAR-Q in Dutch patients &lt; 18 years old with surgical scars. Results: Three independent observers completed the SB for 100 children (58% boys, median age 7.3 (IQR 2.5–12.1) years) in whom surgery had been performed a median of 2.8 (0.5–7.9) years ago. Forty-six of these children (61% boys, median age 12.1 (9.3–16.2) years) completed the SCAR-Q. Feasibility and internal reliability (Cronbach’s alpha &gt; 0.7) was good for both instruments. For the SB, external reliability was poor to moderate (interobserver variability: ICC 0.46–0.56; intraobserver variability: ICC 0.74). For the SCAR-Q, external reliability was good (test–retest agreement: ICC 0.79–0.93). Validity tests (construct, criterion, and convergent) showed poor to moderate results for both instruments. Conclusions: The Dutch-translated SBSES and SCAR-Q showed good feasibility and internal reliability. External reliability and validity were likely affected by differences in conceptual content between the questionnaires. Combining them would provide insight in the impact of scars on patients. Implementation of these instruments in longitudinal follow-up programs could provide new insights into the long-term psychological outcome after pediatric surgery.</p