Procedural blood pressure and contrast extravasation on dual energy computed tomography after endovascular stroke treatment.

BACKGROUND: Blood brain barrier disruption (BBBD) can be visualized by contrast extravasation (CE) after endovascular treatment (EVT) in patients with acute ischemic stroke. Elevated blood pressure is a risk factor for BBBD. However, the association between procedural blood pressure and CE post-EVT is unknown. METHODS: In this single-center retrospective study, we analyzed 501 eligible patients who received a dual energy CT (DECT) immediately post-EVT for acute ischemic stroke. Procedural blood pressure values (SBPmean, SBPmax, SBPmax-min, and MAPmean) were collected. CE was quantified by measuring the maximum parenchymal iodine concentration on DECT iodine overlay map reconstructions. As a measure for the extent of BBBD, we created CE-ASPECTS by deducting one point per hyperdense ASPECTS region on iodine overlay maps. The association between blood pressure and CE was assessed using multivariable linear regression. RESULTS: The procedural SBPmean, SBPmax, and MAPmean were 150 ± 26 mmHg, 173 ± 29 mmHg, and 101 ± 17 mmHg, respectively. The median maximum iodine concentration on post-EVT DECT was 1.2 mg/ml (IQR 0.7-2.0), and median CE-ASPECTS was 8 (IQR 5-11). The maximum iodine concentration was not associated with blood pressure. SBPmean, SBPmax, and MAPmean were significantly associated with CE-ASPECTS (per 10 mmHg, ß = -0.2, 95 % CI -0.31 to -0.09, ß = -0.15, 95 % CI -0.25 to -0.06, ß = -0.33, 95 % CI -0.49 to -0.17, respectively). CONCLUSION: In acute ischemic stroke patients undergoing EVT, particularly in patients achieving successful recanalization, SBPmean, SBPmax, and MAPmean are associated with the extent of BBBD on immediate post-EVT DECT, but not with maximum iodine concentration.

Procedural Blood Pressure and Intracranial Hemorrhage on Dual-Energy Computed Tomography After Endovascular Stroke Treatment.

PURPOSE: Optimal systolic blood pressure (SBP) management during endovascular treatment (EVT) for acute ischemic stroke remains a topic of debate. Though BP is associated with worse functional outcome, the relationship between BP and post-procedural intracranial hemorrhage (ICH) is less well-known. We aimed to investigate the association between BP during EVT and post-procedural ICH on dual-energy CT (DECT). METHODS: We included all patients who underwent EVT for an anterior circulation large vessel occlusion between 2010 and 2019, and received DECT < 3 h post-EVT. All BP measurements during the EVT procedure were used to calculate mean arterial pressure (MAPmean), mean SBP (SBPmean), and SBPmax-min (highest minus lowest). ICH was assessed using virtual post-procedural unenhanced DECT reconstructions and classified as intraparenchymal or extraparenchymal. Symptomatic ICH was scored according to the Heidelberg criteria. The association between different BP parameters and ICH was assessed using multivariable logistic regression. RESULTS: We included 478 patients. Seventy-six patients (16%) demonstrated ICH on DECT, of which 26 (34%) were intraparenchymal. Symptomatic intraparenchymal and extraparenchymal ICH occurred in 10 (38%) and 4 (8%) patients. SBPmax, SBPmean, and MAPmean were associated with intraparenchymal ICH with an adjusted odds ratio of 1.19 (95%CI, 1.02-1.39), 1.22 (95%CI, 1.03-1.46), and 1.40 (95%CI, 1.09-1.81) per 10 mmHg, while BP was not significantly associated with extraparenchymal ICH. BP did not differ between asymptomatic and symptomatic ICH. CONCLUSION: Procedural BP is associated with intraparenchymal ICH on post-EVT DECT but not with extraparenchymal ICH. Future studies should evaluate whether individual procedural BP management reduces post-EVT ICH and improves clinical outcome.

N-terminal pro-B-type natriuretic peptide and the risk of stroke and transient ischaemic attack: the Rotterdam Study.

BACKGROUND AND PURPOSE: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population-based Rotterdam Study, the association of NT-proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated. METHODS: NT-proBNP was measured in 1997-2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex. RESULTS: During 22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person-years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29-1.76] and in women (HR 1.24; 95% CI 1.05-1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26-1.82) but not in men (HR 1.02; 95% CI 0.83-1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow-up did not change the associations. CONCLUSIONS: Higher NT-proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.

Heart failure and the risk of stroke: the Rotterdam Study.

Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (1990­1993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.15­15.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.96­6.25] after 1­6 months and 0.83 [95% CI 0.53­1.29] after 0.5­6 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure.

Nationwide incidence of first stroke and TIA in the Netherlands.

BACKGROUND: Information on incidence of stroke is important for developing and maintaining public health strategies in primary and secondary prevention. Nationwide data on the incidence of stroke are scarce and absent for the Netherlands. METHODS: New cases of first stroke and stroke subtypes in the Dutch population in 2000 were identified through linkage of national registers and included hospitalized patients for first stroke and out-of-hospital deaths from first stroke. The number of non-fatal, non-hospitalized stroke patients was estimated based on data from the Rotterdam study, a population based cohort. RESULTS: We identified 26,556 patients with a first stroke (20,798 hospitalized patients, 5758 out-of-hospital deaths). The number of non-fatal, non-hospitalized first stroke patients was estimated to be 12,255. Extrapolation of the data to the total Dutch population led to an overall estimate of approximately 41,000 patients with a first stroke. Stroke incidence increased with age and was higher in men than in women, except in the lowest (< 45 years) and highest age group (> 85 years). CONCLUSIONS: The present study provides for the first time incidence estimates of first stroke (hospitalized patients, out-of hospital deaths and non-fatal, non-hospitalized patients) based upon virtually the entire Dutch population.

Depressive symptoms and risk of stroke: the Rotterdam Study.

BACKGROUND: Previous studies that have assessed whether the presence of depressive symptoms predisposes to stroke in the general elderly population have been contradictory. Moreover, they did not distinguish between men and women and did not perform psychiatric workups in those with depressive symptoms. This study examines the association between depressive symptoms, depressive disorder and the risk of stroke in the general population. METHODS: This prospective population based cohort study included 4424 participants from the third Rotterdam Study Survey (1997-1999) who, at that time, were > or =61 years of age and free from stroke. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale (CESD) and considered present if the CESD score was > or =16. Participants with depressive symptoms had a diagnostic interview for depressive disorder. Follow-up was complete until 1 January 2005. Data were analysed using Cox proportional hazards models with adjustment for relevant confounders. RESULTS: Men with depressive symptoms (n = 73) were at increased risk of stroke (adjusted hazard ratio (HR) 2.17; 95% CI 1.11 to 4.23) and ischaemic stroke (adjusted HR 3.21; 95% CI 1.62 to 6.38). These associations were at least partly attributable to men who reported depressive symptoms but who did not fulfil Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic criteria for depressive disorder (n = 32): they had a very high risk of stroke (adjusted HR 2.70; 95% CI 1.15 to 6.33) and ischaemic stroke (adjusted HR 4.01; 95% CI 1.68 to 9.57). In women there was no association between presence of depressive symptoms and risk of stroke. CONCLUSIONS: Presence of depressive symptoms is a strong risk factor for stroke in men but not in women.

Polymorphisms of the renin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology.

BACKGROUND: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGT) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease. METHODS: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT genotype as reference. RESULTS: We found that AGT-235T increased systolic (p for trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1.25-fold (95% CI 1.02-1.52) in AGT-TT carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p = 0.008). A significant interaction was found between AGT and AT1R, further increasing the effect on periventricular and subtotal WML (p for interaction = 0.02). We found a non-significant increased risk of silent brain infarction for AGT-TT carriers and AT1R-CC carriers, but no effect on stroke. CONCLUSION: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and AT1R on the development of WML. These findings raise the question of whether the renin-angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology.

Unrecognized myocardial infarction and the risk of stroke: the Rotterdam Study.

OBJECTIVE: To investigate the relationship between unrecognized myocardial infarction and the risk of stroke in a population-based cohort study. METHODS: We followed 6,439 participants from the Rotterdam Study for stroke until January 2002. Participants were free from stroke, and presence of myocardial infarction was assessed at baseline (1990-1993). We calculated hazard ratios of stroke for persons with unrecognized or recognized myocardial infarction compared with persons without myocardial infarction. Analyses were adjusted for age, sex, and cardiovascular risk factors. RESULTS: In 52,915 person-years of follow-up, 505 strokes occurred. Recognized myocardial infarction was only borderline associated with an increased risk of stroke. Unrecognized myocardial infarction increased the risk of stroke by 76% (age- and sex-adjusted hazard ratio 1.76, 95% CI 1.31 to 2.37). Stratification by sex showed that the increased risk was only found in men (hazard ratio for men 2.53, 95% CI 1.68 to 3.81; hazard ratio for women 1.27, 95% CI 0.82 to 1.96). After adjusting for cardiovascular risk factors at baseline, the risk remained significantly increased in men (hazard ratio for stroke 2.13, 95% CI 1.35 to 3.36). Subtyping of strokes revealed that unrecognized myocardial infarction was particularly associated with cortical ischemic strokes (hazard ratio for men 3.57, 95% CI 1.79 to 7.12). CONCLUSIONS: Men with unrecognized myocardial infarction have an increased risk of stroke.

Retinal vessel diameters and risk of stroke: the Rotterdam Study.

BACKGROUND: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. OBJECTIVE: To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction. METHODS: This study was based on the prospective population-based Rotterdam Study and included 5,540 participants of 55 years or over, who had gradable fundus transparencies and were free of stroke at baseline (1990 to 1993). For each participant, retinal arteriolar and venular diameters were measured on digitized images of one eye. Follow-up for first-ever stroke was complete until January 1, 2002. RESULTS: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95% CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95% CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95% CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95% CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. CONCLUSIONS: Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.

Insulin-like growth factor I promoter polymorphism, risk of stroke, and survival after stroke: the Rotterdam study.

BACKGROUND AND PURPOSE: Low levels of insulin-like growth factor I (IGF-I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. METHODS: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. RESULTS: Non-carriers had a relative risk of 0.8 (95% CI: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% CI: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% CI: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% CI: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% CI: 1.3 to 21.5). CONCLUSIONS: Our study suggests that IGF-I is a significant determinant of survival after stroke.

[Selection of medical residents for medical specialist education: experiences with a structured procedure]. / Selectie van assistent-geneeskundigen voor medisch-specialistische opleidingen: ervaringen met een gestructureerde procedure.

OBJECTIVE: Evaluation of an objective, standardised method for selection of residents for medical specialty training. DESIGN: Retrospective. SETTING: University Hospital Utrecht, department of diagnostic radiology. Utrecht University, Department of Clinical Psychology and Health Psychology. METHODS: All applicants for residency positions in 1990-1991 were requested to complete a standard application form. The applications were judged by seven staff members on six criteria. Using statistical tests the relative contribution of each criterium was calculated. A similar procedure was followed for those who were invited for an interview. RESULTS: Most of the criteria applied for the written and oral applications contributed significantly to the rank order achieved. The written and oral criteria showed some degree of overlap, whilst the criteria used for the written application were relatively independent from those used for the interview. For a balanced evaluation of the written information a selection committee of four staff members was sufficient. CONCLUSION: Structuring the selection process as described gives both staff and applicants more insight in the criteria applied, and thus allows a more objective and valid evaluation. To medical students it is beneficial to become acquainted with criteria that may be used in selection procedures for medical specialty training, so they can prepare themselves adequately.

Murine monoclonal antibodies against a unique determinant of erythrocytes, related to Rh and U antigens: expression on normal and malignant erythrocyte precursors and Rhnull red cells.

Three murine monoclonal antibodies (Mabs) MB-2D10, LA-18.18 and LA-23.40 were prepared. They reacted with red cells of all common and most rare blood-group phenotypes, with the exception of those of the RhnullU negative and RhmodU negative phenotypes. So far, only a single example of an alloantibody (Duclos or anti-Rh38) of a similar specificity has been found. Serological studies indicated that the Mabs were probably not directed against an antigenic determinant of Rh polypeptides, the LWab glycoprotein or glycophorin B, all structures absent from or aberrantly expressed on Rhnull red cells. The antigen was found to be erythrocyte-specific, and was also present on pro-erythroblasts, erythroblasts and malignant erythroblastoid cells but not on erythroid progenitors in the bone marrow. The Mabs were found to block each other in an immune rosette method and are thus probably directed against the same epitope or against neighbouring epitopes on the same structure. In immunochemical studies, MB-2D10 precipitated the 30-32 kDa Rh polypeptides from red cell membranes and a protein or proteins which formed diffuse and overlapping bands in SDS-polyacrylamide gel electrophoresis, with Mrs of 40-200 kDa (probably the Rh-related glycoproteins). Under certain experimental conditions glycophorin B appeared to be coprecipitated. The 2D10 structure, detected by the Mabs, seems to be part of a complex of proteins and/or glycoproteins, which includes Rh polypeptides, the LWab glycoprotein and glycoproteins recognized by various Mabs with Rh-related specificities. In the red cell membrane, the complex may be associated with glycophorin B.

Complement is not activated in ABO-haemolytic disease of the newborn.

We studied the lysis in vitro of group A red cells by IgG anti-A. IgG anti-A, which strongly lysed A red cells from adults, did not lyse A red cells from cord blood, if fresh cord serum from a child with blood group AB was used as a source of complement. In cases of haemolytic disease of the newborn due to A-O or B-O antagonism with a positive direct antiglobulin test with anti-IgG serum, the red cells did not react with anti-complement sera. Apparently, complement is also not activated in vivo in case of A-O haemolytic disease of the newborn.

Supraspinous ligament avulsion: a case report.

Avulsion of a supraspinous ligament is one potential cause of low back pain. Since the symptom pattern of this condition may mimic that of other, more common, conditions, a thorough biomechanical and radiological examination is necessary to ensure proper and successful management. The necessity for a thorough and complete biomechanical, laboratory and x-ray evaluation is emphasized before successful treatment can be initiated.

Neutrophil activation detected by monoclonal antibodies.

Monoclonal antibodies have been produced against three neutrophil-associated membrane proteins (p 90, p 170, and p 70) expressed at different maturation stages of the cells. The reactivity of the antibodies against p 90 (B13.9) and p 170 (CLB-gran 10), as measured by quantitative flow cytofluorometry, increased after stimulation of the neutrophils by the calcium ionophore A23187, by phorbol myristate acetate, or by the chemoattractant formylmethionyl-leucyl-phenylalanine in combination with cytochalasin B. This increase is regulated independently of the simultaneously increased expression of the C3bi receptor, because neutrophils of a patient deficient for the C3bi receptor showed a normal increase in membrane expression of p 90 and p 170. Neutrophil cytoplasts were not inducible to increased membrane expression, suggesting that the cytoplasts lack the internal pool of these proteins. The reactivity of the antibody against p 70 (CLB-gram 5) was not affected by activation. The antibodies B13.9 and CLB-gran 10 may be useful to detect neutrophil activation.

A murine monoclonal IgM antibody specific for blood group P antigen (globoside)

A murine monoclonal IgM erythrocyte antibody appeared to have anti-P (anti-globoside) specificity. The antibody was a relatively weak cold agglutinin, but a strong haemolysin and its reactivity with red cells was markedly enhanced by enzyme treatment. This antibody was used to study the cell and tissue distribution of globoside. Globoside was not only detectable on red cells and erythroblasts, but also on endothelial cells and on subsets of platelets, megakaryocytes and fibroblasts. It was not detectable on granulocytes, monocytes and most peripheral blood lymphocytes. Neither was it present on erythroblast precursors (CFU-E, BFU-E), pro-erythroblasts or on the cells of the pro-erythroblastic cell lines K562 and HEL. However, K562 cells expressed globoside when induced to mature into erythroblasts by sodium butyrate. Cells of patients with various leukaemias were also tested. A significant number of positively reacting cells was frequently (six out of 18) seen in cases with a CML blast crisis (CML-BC) and rarely in AML (four out of 37 cases). In CML-BC the P-positive cells were probably erythroblasts and/or megakaryoblasts. Thus, globoside appeared to be an interesting marker in CML-BC of the erythroblastic or mixed erythroblastic-megakaryoblastic type.

Colony-forming cells in chronic granulocytic leukemia--II. Analysis of membrane markers.

Membrane markers and functional properties in vitro of blast cells from the peripheral blood of 2 patients with chronic granulocytic leukemia were studied. Buffy-coat cells were enriched for colony-forming cells by density centrifugation (d less than or equal to 1.062 g cm-3). Upon culture, a large proportion of the (cryopreserved) low-density cells from both patients formed hemopoietic colonies that were heterogeneous with respect to size and cellular composition. Expression of membrane markers on the cells, which had the morphology of undifferentiated blasts, was studied using flow cytometry with a panel of monoclonal antibodies. A striking heterogeneity was observed in that variable numbers of cells were found to express myelomonocytic, megakaryocytic and erythroid membrane markers. Antigenic properties of colony-forming cells were studied by sorting of cells with a fluorescence activated cell sorter. Low numbers of cells (10, 4 and 1, respectively) were sorted directly into the wells of Terasaki microtest plates. With this system, it was shown that myeloid colony-forming cells from patient 1 were exclusively present in HLA-DR-positive cell fractions. Colony formation from the level of a single sorted cell was documented. Sorting of cells labeled with anti-blood-group-H antibody showed that small erythroid colony-forming cells from patient 2 were blood-group-H antigen-positive. These cells did not express HLA-DR. The other colony-forming cells from this patient and essentially all colony-forming cells from patient 1 were HLA-DR-positive and blood-group-H-negative. Although only 2 patients were tested, our studies clearly demonstrate that low-density cell fractions from the blood of patients with CGL provide distinct advantages for the study of membrane properties of hemopoietic cells and of hemopoietic differentiation in general.