Argatroban During Percutaneous Transluminal Coronary Angioplasty: Results of a Dose-Verification Study.

Background. Thrombin is a key enzyme in thrombogenesis. In animals, specific antithrombotic therapy at the time of coronary angioplasty reduced the incidence of subacute occlusion and inhibited the restenosis response. Argatroban is a highly selective synthetic thrombin antagonist that binds in a competitive manner. This is a report of a dose-verification study, assessing the safety and feasibility of intravenous Argatroban administration in patients undergoing percutaneous transluminal coronary angioplasty. Methods. Before angioplasty an intravenous bolus of 30 g/kg argatroban was administered, followed by a continuous infusion of 3.5 g/kg/min for 72 hours. Bolus injection was repeated, and the infusion rate was increased in order to achieve an activated coagulation time (ACT) of over 300 seconds. Following interim analysis, the bolus and initial infusion rate for the subsequent treatment groups was determined. Study endpoints were the occurrence of adverse events, coagulation tests, and qualitative angiogram reading. Patients were monitored by continuous 12-lead electrocardiographic recording over 24 hours, and underwent control angiography 18–24 hours following angioplasty. Results. Four treatment groups, comprised of 2, 8, 9, and 11 patients, respectively, were studied. The first two patients were excluded from analysis, since the initial dose was ineffective to attain an ACT-authorizing coronary angioplasty. The group with the highest dosage received a 250 g/kg intravenous bolus of argatroban, followed by a 4 hour infusion of 15 g/kg/min. At 4 hours the infusion rate was lowered to 3.8 g/kg/min and was continued for 68 hours without adjustment for catheter removal. The adverse event profile included myocardial infarction, aortocoronary bypass graft, bailout procedures, and repeat coronary angioplasty. Thrombin-time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were significantly related to argatroban plasma concentration, as demonstrated by regression analyses (R-square 0.64, 0.71, and 0.84, respectively). Prothrombin fragments 1 and 2 and thrombin-antithrombin III complex did not fit into a mathematical model, but showed slightly increased levels after reduction or cessation of the infusion rate. Conclusions. This dose-verification study, including 30 patients at four dose levels, indicated that argatroban infusion in coronary angioplasty patients can be administered safely, and results in an adequate and predictable level of anticoagulation

Silent brain infarcts and the risk of dementia and cognitive decline

BACKGROUND: Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS: We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS: During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions

Angioscopic versus angiographic detection of initial detection of intimal dissection and intracoronary thrombus

AbstractObjectives. This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus.Background. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging methods have to be compared directly to assess the additional diagnostic value of angioscopy.Methods. The angiograms and videotapes of 52 patients who had undergone angioscopy were reviewed independently by two observers unaware of other findings. Classic angiographic definitions were used for dissection and thrombus. Angioscopic dissection was defined as visible cracks or fissures on the lumen surface or mobile protruding structures that are contiguous with the vessel wall. Angioscopic thrombus was defined as a red, white or mixed red and white intraluminal mass.Results. Angiography and angioscopy were in agreement in 40.4% of cases in the absence of thrombus and in 11.5% in the presence of thrombus. No fewer than 25 (48.1%) angioscopically observed thrombi remained undetected at angiography. With angioscopy as the standard, although the specificity of angiography for thrombus was 100%, sensitivity was very low at 19%. Angioscopic dissection was present in 40 patients (76.9%) versus angiographic dissection in 15 patients (28.8%). With regard to dissection, there was no correlation between the two imaging methods (rΦ= 0.15, p = 0.29).Conclusions. Coronary angiography underestimates the presence of intracoronary thrombus. Angioscopy and angiography are complementary techniques for detecting and grading intima1dissections

Serial angioscopic and angiographic observations during the first hour after successful coronary angioplasty: A preamble to a multicenter trial addressing angioscopic markers for restenosis

Percutaneous coronary angioscopy was used in 13 patients in a pilot study to assess the intracoronary changes that occur during the first hour after balloon angioplasty (PTCA). The dilated segment was studied with 4.5F angioscopes and with quantitative coronary angiography (QCA) immediately after PTCA and at 15-minute intervals for up to 1 hour after PTCA. Significant progression of intimal dissection and thrombus formation could be demonstrated with angioscopy. These dissections and thrombi remained undetected with angiography, which only showed haziness. Thus th

Homocysteine and brain atrophy on MRI of non-demented elderly

Patients with Alzheimer's disease have higher plasma homocysteine levels than controls, but it is uncertain whether higher plasma homocysteine levels are involved in the early pathogenesis of the disease. Hippocampal, amygdalar and global brain atrophy on brain MRI have been proposed as early markers of Alzheimer's disease. In the Rotterdam Scan Study, a population-based study of age-related brain changes in 1077 non-demented people aged 60-90 years, we investigated the association between plasma homocysteine levels and severity of hippocampal, amygdalar and global brain atrophy on MRI. We used axial T(1)-weighted MRIs to visualize global cortical brain atrophy (measured semi-quantitatively; range 0-15) and a 3D HASTE (half-Fourier acquisition single-shot turbo spin echo) sequence in 511 participants to measure hippocampal and amygdalar volumes. We had non-fasting plasma homocysteine levels in 1031 of the participants and in 505 of the participants with hippocampal and amygdalar volumes. Individuals with higher plasma homocysteine levels had, on average, more cortical atrophy [0.23 units (95% CI 0.07-0.38 units) per standard deviation increase in plasma homocysteine levels] and more hippocampal atrophy [difference in left hippocampal volume -0.05 ml (95% CI -0.09 to -0.01) and in right hippocampal volume -0.03 ml (95% CI -0.07 to 0.01) per standard deviation increase in plasma homocysteine levels]. No association was observed between plasma homocysteine levels and amygdalar atrophy. These results support the hypothesis that higher plasma homocysteine levels are associated with more atrophy of the hippocampus and cortical regions in elderly at risk of Alzheimer's disease

Campus NL:

Eind 2015 hebben de gezamenlijke universiteiten, verenigd in de VSNU, opdracht gegeven om onderzoek te doen naar verleden, heden en toekomst van Campus NL: huisvesting en faciliteiten van Nederlandse universiteiten. Dit rapport is het resultaat van dit onderzoek. Dit rapport bevat zowel een korte samenvatting “Campus NL in vijf kernpunten” als een lange “Managementsamenvatting” met alle conclusies. Achtergronden over het onderzoek zijn te vinden in de “Inleiding”. De volgende vier hoofdstukken beschrijven feiten en cijfers over de huidige campus (“Stap 1”), trends die universiteit en campus beïnvloeden (“Stap 2”), campusstrategieën en -projecten (“Stap 3”) en managementinformatie voor de huisvestingsopgave waarvoor universiteiten staan (“stap 4”). In de bijlagen zijn onder andere bronnen, definities, voorbeeldberekeningen, interviewvragen en stellingen over de campus te vinden. Via deze weg wil het onderzoeksteam alle universiteiten bedanken voor het aanleveren van data, tekst en beelden, de informatieve en inspirerende interviews, de actieve deelname aan de Campus NL inputbijeenkomst van 3 juni en hun commentaar op conceptversies of onderdelen van dit rapport. Bijzondere dank aan de begeleidingscommissie en de VSNU voor de intensieve begeleiding en de waardevolle discussies

Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia

BACKGROUND: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. OBJECTIVE: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular

Treatment decision for transcatheter aortic valve implantation: the role of the heart team: Position statement paper of the Dutch Working Group of Transcatheter Heart Interventions

The current paper presents a position statement of the Dutch Working Group of Transcatheter Heart Valve Interventions that describes which patients with aortic stenosis should be considered for transcatheter aortic valve implantation and how this treatment proposal/decision should be made. Given the complexity of the disease and the assessment of its severity, in particular in combination with the continuous emergence of new clinical insights and evidence from physiological and randomised clinical studies plus the introduction of novel innovative treatment modalities, the gatekeeper of the treatment proposal/decision and, thus, of qualification for cost reimbursement is the heart team, which consists of dedicated professionals working in specialised centres