bluuebunny/crossref_metadata_2025 huggingface dataset:
Left-Ventricular Diastolic Dysfunction as a Risk Factor for Dialytic Hypotension
Authors: Rostoker Guy , Griuncelli Mireille , Loridon Christelle , Benmaadi Abbès , Illouz Eric
Published: June 2009

Objectives: Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis and thus reduce the patients’ life expectancy. The aim of this study was to assess the link between left-ventricular diastolic dysfunction and dialytic hypotension. Methods: We performed a prospective cross-sectional study of 72 hemodialysis patients with a low dialysis vintage, 36 of whom had dialysis hypotension, based on echocardiography and brain natriuretic peptide (BNP) assay. Results: There was no difference between normotensive patients and those with dialysis-associated chronic hypotension as regards BNP level, cardiac index, left-ventricular ejection fraction, or myocardial fractional shortening. Both hypotension-prone patients requiring dialysate sodium profiling and chronic refractory hypotensive patients requiring macromolecule infusion had cardiac diastolic dysfunction as shown by a similarly abnormal E/A ratio <1 in 89–91% of cases, associated with a significant decrease in color M-mode diastolic flow propagation velocity (Vp, p < 0.05 nonparametric ANOVA). The area under the ROC curve for Vp was 0.69. A Vp cutoff of 39.5 cm/s was optimal for predicting dialysis-associated hypotension. Conclusions: We conclude that diastolic dysfunction is associated with dialytic hypotension and that a low Vp – a preload-independent index – is predictive of dialysis-associated hypotension.
Inert Gas Washout: Theoretical Background and Clinical Utility in Respiratory Disease
Authors: Robinson Paul D. , Goldman Michael D. , Gustafsson Per M.
Published: June 2009

Inert gas washout was first described more than 60 years ago and 2 principal tests have been developed from it: the single breath and multiple breath washout (MBW) techniques. The invention of fast responding gas analysers almost 60 years ago and small computers 30 years later have facilitated breath-by-breath analysis and the development of sophisticated analysis techniques. It is now possible to detect not only the degree of pulmonary ventilation inhomogeneity, but also to gain important insight into the location of the underlying disease process. While single breath washout requires a full vital capacity effort, tidal breathing during the multiple breath test requires minimal co-operation and co-ordination, and is feasible in subjects of all ages. Available MBW normative data from parameters, such as the lung clearance index, appears to vary minimally with age, making MBW particularly useful to follow children longitudinally. Multiple breath inert gas washout has demonstrated improved sensitivity, in comparison to spirometry, in the early detection of a number of important disease processes, including cystic fibrosis. Despite this, these important techniques remain under-utilised in the clinical setting and there is a lack of commercially available devices currently available. The recent resurgence of research in this area has produced a large number of important studies and a pronounced international interest has developed in these techniques. This review article will provide an overview of the theoretical background of inert gas washout and analysis indices, review important physiological and clinical insights gained from research to date (as well as from our own experience) to illustrate its utility, and outline the challenges that lie ahead in incorporating these techniques into the mainstream clinical setting.
Evaluation of the Size and Area of the Corpus Callosum with the Osiris Method in Alzheimer’s Disease
Authors: Kabay Sibel Canbaz , Kabay Sibel Canbaz , Gulbandilar Eyup , Ozden Hilmi , Ozbag Davut , Guven Gul , Adapinar Baki , Durmaz Ramazan
Published: June 2009

Background/Objective: Significant corpus callosum (CC) atrophy has been demonstrated in patients with Alzheimer’s disease (AD). The aim of this study is to evaluate the size and the area of the CC with the Osiris method. The correlation between the CC measurements and Mini-Mental Status Examination (MMSE) scores in AD patients was also investigated. Methods: The results of the topographic measurements included the cross-sectional area of entire CC, body, rostral portion of the genu and splenium from a midsagittal magnetic resonance imaging section. The results of the topographic measurements of CC on MRI with the Osiris method were compared between AD (n = 29) and control subjects (n = 27). Results: In AD patients the mean value of the splenium was 9.2 ± 1.5 mm, the width of the CC body was 3.9 ± 0.2 mm, the rostral portion of the genu was 7.9 ± 0.2 mm, and the total CC area was 47.2 ± 0.9 mm2. In the control group the mean values were 12.2 ± 2.1 mm, 5.9 ± 0.2 mm, 11.2 ± 0.2 mm and 56.1 ± 0.6 mm2, respectively. Significant reduction was detected in the splenium, the CC body and the rostral part of the genu and CC area in AD patients. The MMSE score was 18.9 ± 4.5 in the AD patients and 29.1 ± 0.9 in the control subjects. A significant positive correlation between the MMSE scores and each CC measurement was seen in the AD patients. Conclusion: The results of this study suggest that callosal atrophy in AD may suggest the severity of the disease. The Osiris method for CC measurements may be used as an easy and reliable technique to assess the severity of the disease.
Oligomerization Partially Explains the Lowering of Aβ42 in Alzheimer’s Disease Cerebrospinal Fluid
Authors: Englund Hillevi , Degerman Gunnarsson Malin , Brundin Rose Marie , Hedlund Marie , Kilander Lena , Lannfelt Lars , Ekholm Pettersson Frida
Published: June 2009

Background/Objective: The lowering of natively analyzed Aβ42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer’s disease (AD). The presence of Aβ oligomers can interfere with such analyses causing underestimation of Aβ levels due to epitope masking. The aim was to investigate if the lowering of CSF Aβ42 seen in AD is caused by oligomerization. Methods: Aβ42 was analyzed under both denaturing and non-denaturing conditions. An Aβ42 oligomer ratio was calculated from these quantifications. The presence of oligomers leads to Aβ42 epitope masking during non-denaturing assays, resulting in a higher ratio. Results: The Aβ42 oligomer ratio was used for the assessment of oligomerized Aβ in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured Aβ42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Aβ42 oligomer ratio in CSF. Conclusion: Combining denaturing and non-denaturing quantifications of Aβ42 into an oligomer ratio enables the assessment of Aβ oligomers in biological samples. The increased Aβ42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured Aβ42 is caused by oligomerization.
Direct Aldosterone Action as a Profibrotic Factor via ROS-Mediated SGK1 in Peritoneal Fibroblasts
Authors: Yamahara Hideki , Kishimoto Noriko , Nakata Midori , Okazaki Akiko , Kimura Taikou , Sonomura Kazuhiro , Matsuoka Eiko , Shiotsu Yayoi , Adachi Takaomi , Matsubara Hiroaki , Iwasaka Toshiji , Mori Yasukiyo
Published: June 2009

Background/Aims: Peritoneal fibrosis leads to discontinuation of peritoneal dialysis. Although aldosterone promotes tissue fibrosis in many organs, its contribution to peritoneal fibrosis and the underlying mechanism are poorly understood. The present study investigated the direct effect of aldosterone on cultured rat peritoneal fibroblasts (RPFs). Methods: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors (MRs), 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), serum- and glucocorticoid-inducible protein kinase 1 (SGK1), and connective tissue growth factor (CTGF) mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). To determine the role of reactive oxygen species (ROS) induced by aldosterone, an active oxygen assay with several inhibitors was used. The ability of RPFs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA (siRNA) of SGK1 was transfected into cultured cells using lipofectamine. Results: CYP11B2, MRs, and 11β-HSD2 were expressed in RPFs. The release of aldosterone from RPFs into the culture medium was confirmed. Aldosterone increased the expression of SGK1 mRNA via ROS generation. Spironolactone, apocynin, and tempol significantly reduced SGK1 expression. Aldosterone upregulated CTGF transcripts significantly. SGK1 gene silencing suppressed aldosterone-induced CTGF expression. Conclusion: The local aldosterone system acts directly as a profibrotic factor via ROS-mediated SGK1 in RPFs.
Does Antineoplasm Treatment Decrease the Glomerular Filtration Rate in Children?
Authors: Stefanowicz Joanna , Owczuk Radosław , Sierota Danuta , Kaczorowska-Hać Barbara , Balcerska Anna
Published: June 2009

Background: The aim of this cross-sectional study was to test the hypothesis that children diagnosed with nephroblastoma experience increased disturbance in renal filtration even after prompt treatment compared to patients treated for other neoplastic childhood diseases. Procedures: Our study included 127 children and young adults, who were successfully treated for nephroblastoma (n = 34), oncohaematological childhood diseases (n = 58), and other solid tumours (n = 35). In each patient, serum levels of cystatin C, microalbuminuria, and C-reactive protein, and serum and urine levels of creatinine were examined, along with a urine analysis. The estimated glomerular filtration rate (eGFR) was assessed using the Schwartz formula and Filler’s formula. Results: Our studies show that patients who were successfully treated for nephroblastoma and other solid tumours have lower GFR (GFRSch 118 ± 20, p = 0.00006, and 117 ± 22, p = 0.00003; GFRFiller 99 ± 17, p = 0.0001, and 104 ± 21 ml/min/1.73 m2, p = 0.0002) than children treated for oncohaematological diseases (GFRSch 137 ± 19, GFRFiller 121 ± 18 ml/min/1.73 m2). Conclusions: Patients diagnosed with nephroblastoma and other solid tumours have lower eGFR than children with oncohaematological childhood diseases and are at higher risk for developing CKD. This study demonstrates the necessity of nephrological monitoring.
Temozolomide: A Safe and Effective Treatment for Malignant Digestive Endocrine Tumors
Authors: Maire Frédérique , Hammel Pascal , Faivre Sandrine , Hentic Olivia , Yapur Lorena , Larroque Béatrice , Couvelard Anne , Zappa Magaly , Raymond Eric , Lévy Philippe , Ruszniewski Philippe
Published: June 2009

Background: Systemic chemotherapies are associated with limited response rates and significant toxicity in patients with malignant digestive endocrine tumors (DET). Preliminary studies have reported interesting results with temozolomide in patients with DET. Aim: It was the aim of this study to assess the efficacy and safety of temozolomide in patients with malignant DET. Patients and Methods: Twenty-one patients, median age 61 years (range 56–77), with metastatic well-differentiated DET were retrospectively studied. All patients except 1 had received prior treatment (hepatic resection, chemotherapy). All patients had progressive disease in the 3 months prior to entry into the study. Temozolomide was administered at doses of 200 mg/m2 daily for 5 days, every 28 days. Treatment was assessed for safety, progression-free and overall survival. Results: The median number of temozolomide cycles was 5 (range 2–15). Grade 3 hematological toxicity occurred in 5 patients. There were no toxic deaths. According to the Response Evaluation Criteria in Solid Tumors criteria, partial response and stabilization were obtained in 1 (5%) and 17 patients (81%), respectively. The median time to progression was 9 months (range 3–26). The 1-year progression-free survival and overall survival were 42 and 77%, respectively. Conclusion: Temozolomide is a well-tolerated oral chemotherapy in patients with malignant DET, including those who have already received treatment. In patients with progressive disease, temozolomide controls tumor progression in 86% of cases.
D1-Like Receptor Antagonist Inhibits IL-17 Expression and Attenuates Crescent Formation in Nephrotoxic Serum Nephritis
Authors: Okada Hirokazu , Inoue Tsutomu , Hashimoto Kumiko , Suzuki Hiromichi , Matsushita Sho
Published: June 2009

Background/Aims: A dopamine type 1-like receptor (D1-like-R) expressed on dendritic cells was involved in Th17 cell differentiation of naive CD4+ T cells. Thus, we treated mice with nephrotoxic serum nephritis (NTN) with a D1-like-R antagonist to test whether Th17 cells play a role in this kidney disease. Methods: The SCH group of nephritic mice was administered with a D1-like-R antagonist, SCH23390, from day 0 to day 13. The kidney and spleen were collected at sacrifice on day 14. Glomerular pathology and CCR6+ cell infiltration were quantitatively evaluated. IL-4, IFN-γ and IL-17 mRNA levels in the kidney, and IFN-γ and IL-17 concentrations in the supernatants from splenocytes activated in vitro were measured. Results: Crescent formation had significantly developed in the positive control (PC) group of untreated, nephritic mice, which was suppressed in the SCH group. Glomerular infiltration of CCR6+ cells was also noted in the PC group, which was abolished in the SCH group. Renal IL-17 and IFN-γ mRNA levels were significantly reduced in the SCH group compared with the PC group. Additionally, in vitro activation augmented IFN-γ induction, but suppressed IL-17 induction by splenocytes from the SCH group compared with those from the PC group. Conclusion: We identified treatment with a D1-like-R antagonist inhibited IL-17 expression and attenuated crescent formation in NTN mice.
Imaging and Quantitative Analysis of Atherosclerotic Lesions by CARS-Based Multimodal Nonlinear Optical Microscopy
Authors: Wang Han-Wei , Langohr Ingeborg M. , Sturek Michael , Cheng Ji-Xin
Published: June 2009

Objective—

The purpose of this study was to assess the ability of label-free multimodal nonlinear optical (NLO) microscopy to characterize, and thus enable quantitative in situ analyses of, different atherosclerotic lesion types, according to the original scheme suggested by the AHA Committee.

Methods and Results—

Iliac arteries were taken from 24 male Ossabaw pigs divided into lean control and metabolic syndrome groups and were imaged by multimodal NLO microscopy where sum-frequency generation (SFG) and 2-photon excitation fluorescence (TPEF) were integrated on a coherent anti-Stokes Raman scattering (CARS) microscope platform. Foam cells, lipid deposits, matrices, and fibrous caps were visualized with submicron 3D resolution. Starting from the adaptive intimal thickening in the initial stage to the fibrous atheroma or mineralization in the advanced stages, lesions were visualized without labels. Histological staining of each lesion confirmed the lesion stages. Lipid and collagen contents were quantitatively analyzed based on the CARS and SFG signals. Lipid accumulation in thickened intima culminated in type IV whereas the highest collagen deposition was found in Type V lesions. Luminal CARS imaging showed the capability of viewing the location of superficial foam cells that indicate relatively active locus in a lesion artery.

Conclusions—

We have demonstrated the capability of CARS-based multimodal NLO microscopy to interrogate different stages of lesion development with subcellular detail to permit quantitative analysis of lipid and collagen contents.
High Levels of Myeloid-Related Protein 14 in Human Atherosclerotic Plaques Correlate With the Characteristics of Rupture-Prone Lesions
Authors: Ionita Mihaela G. , Vink Aryan , Dijke I. Esmé , Laman Jon D. , Peeters Wouter , van der Kraak Petra Homoet , Moll Frans L. , de Vries Jean-Paul P.M. , Pasterkamp Gerard , de Kleijn Dominique P.V.
Published: June 2009

Objective—

Atherosclerotic plaque rupture can lead to severe complications such as myocardial infarction and stroke. Myeloid related protein (Mrp)-14, Mrp-8, and Mrp-8/14 complex are inflammatory markers associated with myocardial infarction. It is, however, unknown whether Mrps are associated with a rupture-prone plaque phenotype. In this study, we determined the association between Mrp-14, -8, -8/14 plaque levels and plaque characteristics.

Methods and Results—

In 186 human carotid plaques, levels of Mrp-14, -8, and -8/14 were quantified using ELISA. High levels of Mrp-14 were found in lesions with a large lipid core, high macrophage staining, and low smooth muscle cell and collagen amount. Plaques with high levels of Mrp-14 contained high interleukin (IL)-6, IL-8, matrix metalloprotease (MMP)-8, MMP-9, and low MMP-2 concentrations. Mrp-8 and Mrp-8/14 showed a similar trend. Within plaques, a subset of nonfoam macrophages expressed Mrp-8 and Mrp-14 and the percentage of Mrp-positive macrophages was higher in rupture-prone lesions compared to stable ones. In vitro, this subset of macrophages does not acquire a foamy phenotype when fed oxLDL.

Conclusion—

Mrp-14 is strongly associated with the histopathologic features and the inflammatory status of rupture-prone atherosclerotic lesions, identifying Mrp-14 as a local marker for these plaques.
Phrenic Stimulation
Authors: Biffi Mauro , Moschini Carlotta , Bertini Matteo , Saporito Davide , Ziacchi Matteo , Diemberger Igor , Valzania Cinzia , Domenichini Giulia , Cervi Elena , Martignani Cristian , Sangiorgi Diego , Branzi Angelo , Boriani Giuseppe
Published: June 2009

Background—

Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices.

Methods and Results—

In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites (
P
<0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V.

Conclusions—

PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference.
National Institutes of Health Stroke Scale Certification Is Reliable Across Multiple Venues
Authors: Lyden Patrick , Raman Rema , Liu Lin , Emr Marian , Warren Margo , Marler John
Published: June 2009

Background and Purpose—

National Institutes of Health Stroke Scale certification is required for participation in modern stroke clinical trials and as part of good clinical care in stroke centers. A new training and demonstration DVD was produced to replace existing training and certification videotapes. Previously, this DVD, with 18 patients representing all possible scores on 15 scale items, was shown to be reliable among expert users. The DVD is now the standard for National Institutes of Health Stroke Scale training, but the videos have not been validated among general (ie, nonexpert) users.

Methods—

We sought to measure interrater reliability of the certification DVD among general users using methodology previously published for the DVD. All raters who used the DVD certification through the American Heart Association web site were included in this study. Each rater evaluated one of 3 certification groups.

Results—

Responses were received from 8214 raters overall, 7419 raters using the Internet and 795 raters using other venues. Among raters from other venues, 33% of all responses came from registered nurses, 23% from emergency department MD/other emergency department/other physicians, and 44% from neurologists. Half (51%) of raters were previously National Institutes of Health Stroke Scale-certified and 93% were from the United States/Canada. Item responses were tabulated, scoring performed as previously published, and agreement measured with unweighted kappa coefficients for individual items and an intraclass correlation coefficient for the overall score. In addition, agreement in this study was compared with the agreement obtained in the original DVD validation study to determine if there were differences between novice and experienced users. Kappas ranged from 0.15 (ataxia) to 0.81 (Item 1c, Level of Consciousness-commands [LOCC] questions). Of 15 items, 2 showed poor, 11 moderate, and 2 excellent agreement based on kappa scores. Agreement was slightly lower to that obtained from expert users for LOCC, best gaze, visual fields, facial weakness, motor left arm, motor right arm, and sensory loss. The intraclass correlation coefficient for total score was 0.85 (95% CI, 0.72 to 0.90). Reliability scores were similar among specialists and there were no major differences between nurses and physicians, although scores tended to be lower for neurologists and trended higher among raters not previously certified. Scores were similar across various certification settings.

Conclusions—

The data suggest that certification using the National Institute of Neurological Disorders and Stroke DVDs is robust and surprisingly reliable for National Institutes of Health Stroke Scale certification across multiple venues.
Development of the Italian Version of the National Institutes of Health Stroke Scale
Authors: Pezzella Francesca Romana , Picconi Orietta , De Luca Assunta , Lyden Patrick D. , Fiorelli Marco
Published: June 2009

Background and Purpose—

The National Institutes of Health Stroke Scale (NIHSS) is a basic component of the assessment of patients with acute stroke. To foster and standardize the use of the NIHSS among Italian health professionals, we translated the scale, dubbed into Italian the training and test videotapes devised by the National Institutes of Health researchers, and conducted a series of certification courses using the translated videos.

Methods—

Translation, text adaptation, video dubbing, and editing of the Italian NIHSS videotapes relied on a team of bilingual stroke neurologists. Three waves of training courses were organized for mixed classes of medical and nonmedical health professionals. The certification test was based on the usual set of 5 videotaped patients. Scoring rules were those provided by the National Institutes of Neurological Disorders and Stroke. Reliability of the Italian NIHSS was assessed using kappa statistics and compared with that of the original NIHSS.

Results—

During 3 years, 850 nurses, 460 nonneurologist physicians, and 246 neurologists were trained. Pass rates were respectively 44%, 75%, and 87%, respectively. Overall, 80% of scale items showed moderate to excellent reliability. Independent significant predictors of test failure at multivariate logistic regression were nurse profession (OR, 5.41; 95% CI, 4.07 to 7.20), older age (OR, 1.03; 95% CI, 1.02 to 1.05), and first edition of the course (OR, 3.13; 95% CI, 2.43 to 4.05). The agreement across all items between NIHSS and the Italian NIHSS was 80% (kappa=0.70±0.18, z<0.001).

Conclusions—

The Italian translation, supervised by experienced vascular neurologists, did not influence the clinimetric characteristics of the NIHSS. Our findings support the implementation of NIHSS video training in languages other than English.
Avoiding “Pseudo-Reversibility” of CT-CBV Infarct Core Lesions in Acute Stroke Patients After Thrombolytic Therapy
Authors: Schaefer Pamela W. , Mui Kit , Kamalian Shahmir , Nogueira Raul G. , Gonzalez R. Gilberto , Lev Michael H.
Published: June 2009

Background and Purpose—

Rarely, acute ischemic stroke (AIS) patients have pretreatment CT-CBV abnormalities larger than final infarct volumes. We sought to determine: (1) the prevalence of CT-CBV “reversibility” in AIS patients treated with thrombolytic therapy, and (2) whether the presumed tissue salvage of these CT-CBV lesions depends on the CTP software.

Methods—

We reviewed the admission CT-CBV maps (calculated with an algorithm sensitive to tracer arrival time) and follow-up images of 148 AIS patients who received thrombolytic therapy. When the follow-up infarct appeared smaller than the admission CT-CBV lesion, the CTP source images were reprocessed using “delay-correction” software (GE, CTP 4). Original and “delay-corrected” CT-CBV ischemic lesion volumes were compared to each other and follow-up infarct volumes using the Student
t
test.

Results—

11/148 (7.4%) patients had admission CT-CBV larger than follow-up lesions (mean difference −69.5 cc, range −146.0 to −14.0 cc;
P
<0.05). For all patients, the admission CT-CBV lesions were smaller on the delay- versus nondelay-corrected maps (mean difference −83.1, range −233 to −2 cc;
P
<0.05). Only 2 patients had delay-corrected CT-CBV lesions larger than follow-up infarctions, with a 12- to 17-cc difference in volume. 7/9 of the remaining patients had extracranial hemodynamic factors potentially delaying tracer arrival, including atrial fibrillation (AF; n=4), congestive heart failure (CHF; n=4), or extracranial internal carotid artery (ICA) stenosis (n=1).

Conclusion—

True “reversibility” of CT-CBV “core” lesions in AIS patients after thrombolytic therapy is rare, with small volumes of “salvaged” tissue. Pseudoreversibility of core lesions in standard CT-CBV maps can be avoided by using specific algorithmically optimized delay-correction software. Further investigation is warranted to determine whether this finding applies to algorithms provided by other vendors.
Relative Risks for Stroke by Age, Sex, and Population Based on Follow-Up of 18 European Populations in the MORGAM Project
Authors: Asplund Kjell , Karvanen Juha , Giampaoli Simona , Jousilahti Pekka , Niemelä Matti , Broda Grazyna , Cesana Giancarlo , Dallongeville Jean , Ducimetriere Pierre , Evans Alun , Ferrières Jean , Haas Bernadette , Jorgensen Torben , Tamosiunas Abdonas , Vanuzzo Diego , Wiklund Per-Gunnar , Yarnell John , Kuulasmaa Kari , Kulathinal Sangita
Published: June 2009

Background and Purpose—

Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed.

Methods—

Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses.

Results—

Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania).

Conclusions—

Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.
Preliminary Evidence That Ketamine Inhibits Spreading Depolarizations in Acute Human Brain Injury
Authors: Sakowitz Oliver W. , Kiening Karl L. , Krajewski Kara L. , Sarrafzadeh Asita S. , Fabricius Martin , Strong Anthony J. , Unterberg Andreas W. , Dreier Jens P.
Published: June 2009

Background and Purpose—

Spreading depolarizations, characterized by large propagating, slow potential changes, have been demonstrated with electrocorticography in patients with cerebral hemorrhage and ischemic stroke. Whereas spreading depolarizations are harmless under normal conditions in animals, they cause or augment damage in the ischemic brain. A fraction of spreading depolarizations is abolished by N-methyl-
d
-aspartate receptor antagonists.

Summary of Case—

In 2 patients with severe acute brain injury (traumatic and spontaneous intracranial hemorrhage), spreading depolarizations were inhibited by the noncompetitive N-methyl-
d
-aspartate receptor antagonist ketamine. This restored electrocorticographic activity.

Conclusions—

These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future neuroprotective trials.
The 1425G/A SNP in
PRKCH
Is Associated With Ischemic Stroke and Cerebral Hemorrhage in a Chinese Population
Authors: Wu Lijun , Shen Yue , Liu Xin , Ma Xu , Xi Bo , Mi Jie , Lindpaintner Klaus , Tan Xuerui , Wang Xingyu
Published: June 2009

Background and Purpose—

PRKCH
(the gene encoding protein kinase C η) has a role in the pathogenesis of ischemic stroke. The 1425G/A SNP in
PRKCH
(rs2230500) is significantly associated with ischemic stroke in Japanese. The aim of the present study is to investigate the associations in ischemic stroke and other types of stroke in the Chinese population.

Methods—

A total of 1209 patients with stroke and 1174 controls were examined using a case–control methodology. The 1425G/A SNP in
PRKCH
was genotyped by allele-specific real-time PCR assay.

Results—

The 1425G/A SNP in
PRKCH
was significantly associated with both ischemic stroke (odds ratio [OR]=1.31; 95% confidence interval [CI], 1.08 to 1.60;
P
=0.0058) and cerebral hemorrhage (OR=1.94; 95% CI, 1.21 to 3.10;
P
=0.0054) under a dominant model. Even after age- and sex-adjustment, the significant associations remained (in ischemic stroke, for AA+AG versus GG, OR=1.37, 95% CI, 1.12 to 1.67,
P
=0.0019; in cerebral hemorrhage, for AA+AG versus GG, OR=1.96, 95% CI, 1.21 to 3.19,
P
=0.0064).

Conclusions—

The 1425G/A SNP in
PRKCH
increases the risk of both ischemic stroke and cerebral hemorrhage in the Chinese population.
Randomized, Placebo-Controlled, Double-Blind Study of Ropinirole in Chronic Stroke
Authors: Cramer Steven C. , Dobkin Bruce H. , Noser Elizabeth A. , Rodriguez Rachelle W. , Enney Lori A.
Published: June 2009

Background and Purpose—

Evidence suggests the potential to improve motor status in patients with stroke by modifying brain catecholaminergic tone. The current study hypothesized that increased dopaminergic tone via the dopamine agonist ropinirole, when combined with physiotherapy (PT), would significantly and safely increase gait velocity.

Methods—

Patients with moderate motor deficits due to stroke 1 to 12 months prior were randomized (double blinded) to 9 weeks of immediate-release ropinirole or placebo, each with PT, and followed up for 3 additional weeks. Drug dose (0.25 to 4 mg once daily) was titrated weekly, as tolerated. The primary end point was gait velocity during the 12 weeks of study participation.

Results—

Patients in the ropinirole+PT group averaged 2.4 mg/d by end of week 9, although the target dose was at least 3 mg/d. Ropinirole+PT was generally safe and well tolerated, including no drug-related serious adverse events. Across all 33 enrollees, significant gains were found over time for gait velocity and for most secondary end points. However, gains did not differ by treatment assignment. PT and occupational therapy were commonly prescribed outside of the trial, although the extent of these was not correlated with study outcomes.

Conclusions—

At doses achieved in this trial, increased dopaminergic tone via ropinirole+PT was generally well tolerated but did not show any improvement over and above the effects of PT alone.
One Session of Repeated Parietal Theta Burst Stimulation Trains Induces Long-Lasting Improvement of Visual Neglect
Authors: Nyffeler Thomas , Cazzoli Dario , Hess Christian W. , Müri René M.
Published: June 2009

Background and Purpose—

Visual neglect is a frequent disability in stroke and adversely affects mobility, discharge destination, and length of hospital stay. It is assumed that its severity is enhanced by a released interhemispheric inhibition from the unaffected toward the affected hemisphere. Continuous theta burst transcranial magnetic stimulation (TBS) is a new inhibitory brain stimulation protocol which has the potential to induce behavioral effects outlasting stimulation. We aimed to test whether parietal TBS over the unaffected hemisphere can induce a long-lasting improvement of visual neglect by reducing the interhemispheric inhibition.

Methods—

Eleven patients with left-sided visual neglect attributable to right hemispheric stroke were tested in a visual perception task. To evaluate the specificity of the TBS effect, 3 conditions were tested: 2 TBS trains over the left contralesional posterior parietal cortex, 2 trains of sham stimulation over the contralesional posterior parietal cortex, and a control condition without any intervention. To evaluate the lifetime of repeated trains of TBS in 1 session, 4 trains were applied over the contralesional posterior parietal cortex.

Results—

Two TBS trains significantly increased the number of perceived left visual targets for up to 8 hours as compared to baseline. No significant improvement was found with sham stimulation or in the control condition without any intervention. The application of 4 TBS trains significantly increased the number of perceived left targets up to 32 hours.

Conclusions—

The new approach of repeating TBS at the same day may be promising for therapy of neglect.
Validation and Refinement of the ABCD2 Score
Authors: Fothergill Amy , Christianson Teresa J.H. , Brown Robert D. , Rabinstein Alejandro A.
Published: June 2009

Background and Purpose—

Transient ischemic attacks are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow-up and need for hospitalization differs widely. Recently, an effort has been made to risk-stratify patients presenting with transient ischemic attacks through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort.

Methods—

Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data.

Results—

Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (≤4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days.

Conclusions—

Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.
Sarpogrelate Versus Aspirin in Secondary Prevention of Cerebral Infarction: Differential Efficacy in Diabetes?
Authors: Shinohara Yukito , Nishimaru Katsuya
Published: June 2009

Background and Purpose—

The results of the Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS), a randomized double-blind study of sarpogrelate (selective 5-HT
2A
receptor antagonist) versus aspirin in 1510 Japanese patients, have been reported. But S-ACCESS failed to demonstrate noninferiority of sarpogrelate to aspirin for preventing the recurrence of cerebral infarction. Here we compare the characteristics of sarpogrelate and aspirin in various subgroups.

Methods—

Subgroups were predefined from patients’ baseline characteristics. Hazard ratio (HR) and 95% confidence interval (CI) for sarpogrelate versus aspirin were calculated for primary (cerebral infarction) and secondary (serious vascular events) end points. Interactions between treatment effects and subgroup variables were examined by post hoc analysis.

Results—

No significant difference in outcome between sarpogrelate and aspirin was found across multiple predefined subgroups. In post hoc analysis, a qualitative treatment interaction with diabetes mellitus was detected (
P
=0.166 for recurrence of cerebral infarction;
P
=0.098 for serious vascular events). HR for the recurrence of cerebral infarction with sarpogrelate versus that with aspirin was 0.87 (95% CI: 0.48 to 1.60) in diabetic patients and 1.51 (95% CI: 0.98 to 2.31) in nondiabetic patients. For serious vascular events, the corresponding HRs were 0.73 (95% CI: 0.42 to 1.25) and 1.28 (95% CI: 0.89 to 1.83).

Conclusions—

No specific baseline characteristic resulting in a significant difference between the effects of sarpogrelate and aspirin was identified. Aspirin was superior in most subgroups, except diabetics. Sarpogrelate may be a useful treatment option for Japanese patients with diabetes.
VEGF Receptor-2 Variants Are Associated With Susceptibility to Stroke and Recurrence
Authors: Zhang Weili , Sun Kai , Zhen Yisong , Wang Daowen , Wang Yibo , Chen Jinxing , Xu Jianfeng , Hu Frank B. , Hui Rutai
Published: June 2009

Background and Purpose—

Dysregulation of vessel wall formation, growth, and maintenance may confer susceptibility of stroke.

Methods—

We tested the hypothesis that variants in 2 genes encoding vascular endothelial growth factor and vascular endothelial growth factor receptor-2 are associated with susceptibility to stroke and its recurrence in a Chinese case–control study comprising 1849 patients with stroke and 1798 control subjects and replicated the investigation in an independent study comprising 327 cases and 327 control subjects. The correlation of variants with carotid artery intima media thickness was examined in 1123 healthy individuals.

Results—

Compared with their corresponding wild-type genotypes, one coding variant, rs2305948 (Val297Ile), in the vascular endothelial growth factor receptor-2 gene was associated with increased susceptibility to intracerebral hemorrhage (additive model: OR, 2.06; 95% CI, 1.64 to 2.59;
P
=7.6×10
−10
; dominant model: OR, 2.20; 95% CI, 1.70 to 2.84;
P
=1.5×10
−9
), a promoter variant rs2071559 (−604T>C) in the gene was associated with reduced susceptibility to atherothrombotic stroke (additive model: OR, 0.82; 95% CI, 0.71 to 0.93;
P
=0.003; dominant model: OR, 0.78; 95% CI, 0.65 to 0.92;
P
=0.004) and was reversely correlated with carotid artery intima media thickness (
P
=2.8×10
−5
). Replication in the second study yielded similar results. During a median 4.5 years of follow-up for the first stroke population, 355 recurrent strokes were documented. Subjects carrying 297Ile had a higher risk for stroke recurrence (relative risk, 1.40; 95% CI, 1.12 to 1.75;
P
=0.003), and those with −604C had a lower risk for recurrence (relative risk, 0.71; 95% CI, 0.58 to 0.89;
P
=0.002) than their wild-type carriers.

Conclusions—

The vascular endothelial growth factor receptor-2 gene variants may serve as novel genetic markers for the risk of stroke and its recurrence.
Anosmia After Perimesencephalic Nonaneurysmal Hemorrhage
Authors: Greebe Paut , Rinkel Gabriël J.E. , Algra Ale
Published: June 2009

Background and Purpose—

Anosmia frequently occurs after aneurysmal subarachnoid hemorrhage not only after clipping, but also after endovascular coiling. Thus, at least in part, anosmia is caused by the hemorrhage itself and not only by surgical treatment. However, it is unknown whether anosmia is related to rupture of the aneurysm with sudden increase in intracranial pressure or to the presence of blood in the basal cisterns. Therefore, we studied the prevalence of anosmia in patients with nonaneurysmal perimesencephalic hemorrhage.

Methods—

We included all patients admitted to our hospital with perimesencephalic hemorrhage between 1983 and 2005. Patients were interviewed with a structured questionnaire. We calculated the proportion of patients with anosmia with corresponding 95% CIs.

Results—

Nine of 148 patients (6.1%; 95% CI, 2.8% to 11%) had noticed anosmia shortly after the perimesencephalic hemorrhage. In 2, the anosmia had disappeared after 8 to12 weeks; in the other 7, it still persisted after a mean period of follow-up of 9 years.

Conclusions—

Anosmia occurs in one of every 16 patients with perimesencephalic hemorrhage, which is lower than previously reported rates after coiling in patients with subarachnoid hemorrhage but higher than rates after coiling for unruptured aneurysms. These data suggest that blood in the vicinity of the olfactory nerves plays a role in the development of anosmia.
Some Remarks on Patronage in Syria-Palestine During the Late Bronze Age
Authors: Pfoh Emanuel
Published: June 2009

Following the discussion presented in an article by R. Westbrook on patronage in the ancient Near East (JESHO 48/2, 2005), the aim of this paper is to continue with the discussion as well as to address some of the views on the topic regarding Syria-Palestine during the Late Bronze Age, using examples from the Amarna letters and Hittite treaties. Some of the critical questions that should be addressed in further discussions on the subject are related to the socio-political nature of patronage and its relationship to kinship ties in society, and why and how patronage relationships are established in society. Après l'étude du R. Westbrook sur l'évidence du patronage dans le Proche-Orient ancien, publié dans ce journal (JESHO 48/2, 2005), on veut continuer avec la discussion du thème mais donner aussi quelques révisions pour la Syrie-Palestine du l'âge du Bronce Récent à partir de exemples dans les lettres d'Amarna et les traités hittites. Questions fondamentales qu'on doit traiter sont: la nature socio-politique du patronage et son rapport avec la parenté dans la société; et pourquoi et comment les liens de patronage sont établis dans la société.
Agriculture in al-Hamdānī's Yemen: A Survey from Early Islamic Geographical Texts
Authors: Varisco Daniel Martin
Published: June 2009

The area of Yemen has been one of the most productive agricultural regions in the Arab World since the beginning of Islam. This article surveys the available knowledge from Arabic geographical and historical texts on the state of agriculture in Yemen during the early Islamic period up through the 10th century CE. The primary focus is on the work of Abū Muhammad al-Hasan al-Hamdānī, including translation of a section on Yemeni agriculture from his Sifat jazīrat al-Arab. In addition to discussion of rain periods, water resources and agricultural methods, information on the known cultivated crops is provided. Depuis le commencement de l'ère islamique le Yémen constitue la région agricole la plus fertile du monde arabe. Cette contribution étudie l'agriculture au Yémen jusqu'au Xe siècle EC en exploitant les textes géographes et historiques arabes disponibles, tout d'abord les écrits de Abū Muhammad al-Hasan al-Hamdānī, y inclut la traduction de la section qui traite de l'agriculture yéménite de son Sifat jazīrat al-Arab.Des considérations sur les pluies saisonnières, les ressources d'eau douce, et la méthode de culture, l'étude nous révèle en outre des détails sur la nature des produits agricoles connus.
Colombo versus Cannanore: Contrasting Structures of Two Colonial Port Cities (1500-1700)
Authors: Biedermann Zoltán
Published: June 2009

This article compares the urban structures of early modern Colombo and Cannanore, two South Asian port cities controlled by the Portuguese during the sixteenth and seventeenth centuries, and taken over by the Dutch in 1656 and 1663. It is argued that, whereas Cannanore was an urban complex marked by a set of walls that separated ethnically and religiously distinct neighborhoods, Colombo, less influenced by regulations emanating from Lisbon and Goa and more exposed to local politics in an unusual historical and military context, developed into a more integrated city surrounded by a single external wall. Although, after the Dutch takeover, Cannanore's urban structure did not change much, Colombo's, on the other hand, was entirely transformed. These contrasts draw our attention to the complexity of urban developments in the colonial contexts of South Asia between 1500 and 1700. Cet article compare les structures urbaines, à l'époque moderne, de Colombo et de Cannanore, deux villes portuaires sud-asiatiques contrôlées par les Portugais aux XVIe-XVIIe siècles puis, à partir de 1656 et 1663 respectivement, par les Hollandais. Tandis que Cannanore était un complexe urbain marqué par des murs séparant les uns des autres les quartiers habités par des groupes ethniques et religieux différent, Colombo, moins influencée par les régulations issues de Lisbonne et de Goa et plus exposée aux influences politiques locales dans un contexte historique et militaire particulier, devint une ville plus intégrative encadrée par une seule ligne de remparts. Après la conquête hollandaise, les structures urbaines furent peu altérées à Cannanore, mais entièrement transformée à Colombo en vue d'une organisation ségrégative de l'espace. Ces attitudes contrastées servent à nous alerter sur la complexité des développements urbains dans les contextes coloniaux d'Asie du Sud entre 1500 et 1700.
The Ottoman State and Descendants of the Prophet in Anatolia and the Balkans (c. 1500-1700)
Authors: Canbakal Hülya
Published: June 2009

Throughout the Islamic world those claiming descent from the Prophet Muhammad (T. seyyid/şerif, pl. sadat/eşraf) were (and are) accorded a special status. This article shows that the process of teseyyüd ("seyyidization") not only took place through official awards, but also through appropriation. In the Ottoman Empire registers thus began to be kept of officially recognized sadat. The examination of these, largely un(der)studied, sources argues that the state sometimes employed its capacity to seyyidize for (cultural) political purposes. The article also sheds valuable light on Ottoman policies vis-à-vis tribalism and nomadism. Dans le monde islamique entier un statut spécial était (et est) accordé à tous ceux qui revendiquent descendance du Prophète Mahomet (T. seyyid/şerif, pl. sadat/eşraf). Dans cet article on explique que le processus de tessyyüd ('seyyidisation') se passait non seulement par attribution officielle, mais aussi par appropriation. Dans l'Empire ottoman on a commencé ainsi à tenir des registres de sadat officiellement reconnu. L'examen de ces sources largement sous-étudiées démontre que l'État parfois usait de son autorité de 'seyyediser' pour des fins politiques (culturelles). Cet article jette en même temps une lumière de grande valeur sur la politique ottomane quant au tribalisme et au nomadisme.