bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Serum High-Molecular-Weight and Total Adiponectin on Arteriosclerosis in IgA Nephropathy Patients
Authors: Iwasa Yuko , Otsubo Shigeru , Ishizuka Tsutomu , Uchida Keiko , Nitta Kosaku
Published: March 2008

Background/Aim: Adiponectin has attracted a great deal of attention because of its antiatherogenic properties. Previous studies have reported that high-molecular-weight (HMW) adiponectin may be the active form of this protein, but there have been no reports on the relationship between serum adiponectin and arteriosclerosis. The aim of our study was to determine whether HMW or total adiponectin levels are associated with arteriosclerosis in patients with IgA nephropathy. Methods: We enrolled 72 patients aged 34.3 ± 12.7 years, from whom interlobular arteries were obtained by renal biopsy in our hospital between 2003 and 2006 and who were confirmed to have IgA nephropathy. We assessed them in relation to age, gender, body mass index, presence of hypertension, serum total cholesterol, triglyceride, uric acid, high-sensitive C-reactive protein and HMW adiponectin and total adiponectin levels, creatinine clearance, and urinary protein excretion. The severity of arteriosclerosis was semiquantitatively evaluated and classified into the following four grades: 0 = none; 1 = mild; 2 = moderate, and 3 = severe. Results: Multiple stepwise regression analysis showed associations between arteriosclerosis grade and age [standard regression coefficient (st β) = 0.560, p < 0.001], total adiponectin (st β = –0.218, p = 0.026), triglyceride (st β = 0.222, p = 0.033), and presence of hypertension (yes = 1, no = 0; st β = 0.182, p = 0.036) in the IgA nephropathy patients as a whole and associations between arteriosclerosis grade and age (st β = 0.708, p < 0.001), HMW adiponectin (st β = –0.321, p = 0.035), and triglyceride (st β = 0.292, p = 0.038) in the male IgA nephropathy patients. Conclusions: Serum total adiponectin levels are an independent determinant of arteriosclerosis in IgA nephropathy patients. It was noteworthy that in males the serum HMW adiponectin levels correlated more strongly with arteriosclerosis grade than the total adiponectin levels did. Adiponectin may prevent renal arteriosclerosis.
Effects of Hyperoxia and Nitric Oxide on Endogenous Nitric Oxide Production in Polymorphonuclear Leukocytes
Authors: Hoehn Thomas , Gratopp Alexander , Raehse Katrin , Koehne Petra
Published: March 2008

Background: Exposure to hyperoxia and nitric oxide (NO) occur frequently during the treatment of neonatal hypoxic pulmonary failure. Objective: The aim of the study was to quantify the endogenous synthesis of NO in neonatal polymorphonuclear neutrophils following exposure to hyperoxia and NO in vitro. Methods: Neonatal cord blood was exposed to room air, 25, 30 and 100% oxygen and 10 or 20 ppm NO added to the different oxygen concentrations for up to 30 min. 4,5-Diaminofluorescein diacetate (DAF-2 DA) is an intracellular dye used to measure real-time changes in NO levels in vivo. The molecular structure of DAF-2 DA changes upon contact with NO to its oxidized and fluorescent form diaminofluorescein-triazol (DAF-2T) and after being hydrolyzed by intracellular esterases cannot leave the cell. DAF-2 DA signals following equilibration with room air were used as controls. Results: Exposure to 100% oxygen increased NO production significantly when compared to 20 ppm NO plus 100% oxygen (p = 0.031) and to 20 ppm NO alone (p = 0.006). 10 ppm NO produced a similar effect. Significant increases in NO production were also noticed following exposure to 25% oxygen. This increase was already present after 10 min of oxygen exposure. Conclusion: These findings support the propagated avoidance of hyperoxia not only in preterm infants, but also in term neonates.
Oxidative Stress and Proinflammatory Cytokine Levels are Increased in Premature Neonates of Preeclamptic Mothers with HELLP Syndrome
Authors: Torrance Helen L. , Krediet Tannette G. , Vreman Hendrik J. , Visser Gerard H.A. , van Bel Frank
Published: March 2008

Background: Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes. Objectives: We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome. Methods: Prospective study of 36 infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive Care Unit. ETCOc was measured at 0–12, 48–72 and 168 h postnatally using the CO-Stat™ End-Tidal Breath Analyzer. Simultaneously, blood was sampled for MDA, IL-8 and IL-6. Results: At 0–12 h, ETCOc, MDA and IL-8 values (median[range]) were significantly higher in HELLP infants than in infants from preeclamptic mothers without HELLP (ETCOc 2.2 [1.5–3.9] vs. 1.8 [0.5–2.9] ppm; MDA 2.3 [1.3–4.1] vs. 1.5 [0.4–3.1] µmol/l; IL-8 145 [24–606] vs. 62 [26–397] pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of life (2.3 [0.8–5.8] vs. 1.1 [0.8–3.7] µmol/l, p = 0.02). Conclusion: Oxidative stress and proinflammatory cytokine levels are increased in infants of preeclamptic mothers with HELLP syndrome. These processes may cause inactivation of surfactant explaining the increased RDS incidence in these infants.
No Association of TPH1 218A/C Polymorphism with Treatment Response and Intolerance to SSRIs in Japanese Patients with Major Depression
Authors: Kato Masaki , Wakeno Masataka , Okugawa Gaku , Fukuda Tsuyoshi , Azuma Junichi , Kinoshita Toshihiko , Serretti Alessandro
Published: March 2008

Background: Variability in antidepressant response is due to genetic and environmental factors. Since SSRIs exert their activity enhancing the serotonin turnover, genes coding for proteins of the serotonin system are key candidates for a possible genetic influence with response to SSRIs. Therefore tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin in the raphe nuclei could be a candidate. In the present study, we examined the possible association of the TPH1 218A/C polymorphism with response to SSRIs in a sample of Japanese patients with major depression. Methods: The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the TPH1 218A/C polymorphism. Results: Repeated-measures analysis of variance of HAM-D score change over time with baseline scores and 5-HTTLPR variants included in the model as covariate showed no significant association of this SNP with treatment response to SSRIs. Furthermore, no significant association of this SNP could be observed with both responder rate at weeks 2, 4 and 6 and intolerance to SSRIs. Conclusion: The result suggests that 218A/C variants of TPH1 cannot play a major role as predictor of treatment response as well as intolerance in Japanese patients with major depression.
Circadian Variation of Core Body Temperature in Parkinson Disease Patients with Depression: A Potential Biological Marker for Depression in Parkinson Disease
Authors: Suzuki Keisuke , Miyamoto Tomoyuki , Miyamoto Masayuki , Kaji Yoshiaki , Takekawa Hidehiro , Hirata Koichi
Published: March 2008

Background: The biological rhythm in comorbidity of depression and Parkinson disease (PD) is still unclear. For early diagnosis or clarification of the pathologic condition of comorbidity of depression and PD, the present study investigated the presence of circadian rhythm abnormalities in patients with depression. Methods: We measured the rectal temperature (RT) in 30 PD patients with or without depression during 48 consecutive hours using the maximum entropy method (MEM) and least-squares method (COSINOR). The presence of major or minor depression was evaluated by the Mini International Neuropsychiatric Interview based on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, and the Hamilton Depression Scale. Results: The RT rhythms of patients without depression predominately showed a circadian rhythm. However, 2 of 6 patients with depression showed an infradian rhythm using MEM. COSINOR revealed that PD patients with depression showed lower amplitudes of core body temperature (p = 0.012) and higher minimum RT (p = 0.031) relative to those of patients without depression. Conclusion: PD patients with depression show an altered RT circadian rhythm. The results suggest that the characteristics of core body temperature could be potentially used as a biological marker for depression in PD.
In vitro Activities of Various Antibiotics, Alone and in Combination with Colistin Methanesulfonate, against Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients
Authors: Güzel Çağla Bozkurt , Gerçeker A. Alev
Published: March 2008

Background: The in vitro activities of various antibiotics, either alone or in combination with colistin methanesulfonate, were assessed using Pseudomonas aeruginosa strains isolated from cystic fibrosis patients. Methods: Except for colistin methanesulfonate, minimum inhibitory concentrations were determined by microbroth dilution technique as described by the Clinical and Laboratory Standards Institute (CLSI); for colistin methanesulfonate, a modified method of the CLSI was used. Minimum bactericidal concentrations were determined as described by the CLSI. The in vitro activities of antibiotics in combination were determined by microbroth checkerboard technique, and results were interpreted by fractional inhibitory concentration index. Results: According to MIC values, 100, 98, 96 and 84% of the isolates were found susceptible to amikacin, colistin methanesulfonate, meropenem and ceftazidime, respectively. The minimum bactericidal concentrations were generally equal to or twice as high as those of the minimum inhibitory concentrations. With a fractional inhibitory concentration index of ≤0.5 as borderline, synergistic interactions were more frequent with combinations where amikacin was involved than with those with colistin methanesulfonate. No antagonism was observed. Conclusion: The findings of this study may play a useful role in selecting the appropriate combinations when a single agent is inadequate to treat cystic fibrosis patients with P. aeruginosa infections.
Mechanisms Leading to Increased Vasodilator Responses to Calcitonin-Gene-Related Peptide in Mesenteric Resistance Arteries of Early Pregnant Rats
Authors: van Eijndhoven H.W.F. , Janssen G.M.J. , Aardenburg R. , Spaanderman M.E.A. , Peeters L.L.H. , De Mey J.G.R.
Published: March 2008

The objective of this study was to explore the mechanism responsible for the higher relaxing responses of mesenteric arteries to calcitonin-gene-related peptide (CGRP) in pregnancy. We performed myograph and ligand binding studies to determine the role of matrix metalloproteinase-2 (MMP-2) and CGRP receptor density. MMP activity was manipulated in isolated arteries by exposing them to the blocking effects of doxycycline. Vascular activity of MMP-2 was studied by gelatin zymography, and CGRP receptor density was determined by ligand binding analysis. Compared to nonpregnant rats, CGRP elicited stronger arterial relaxation in pregnant rats. The latter effect was neither accompanied by a change in relaxing responses to direct activation of adenylyl cyclase by forskolin nor by a change in the response to stimulation of G-protein-coupled adrenergic receptors by isoproterenol. Doxycycline did not affect the stronger arterial relaxation in pregnancy in spite of the observed more than threefold higher arterial MMP-2 activity. Density of binding sites for [125I]CGRP in arteries from pregnant rats (64 ± 14 fmol/mg protein) and from virgin rats (54 ± 5 fmol/mg protein) were comparable. The results of this study provide evidence for increased coupling of CGRP receptors to adenylyl cyclase in early pregnancy.
Ependymomas in Two Sisters and a Maternal Male Cousin with Mosaicism with Monosomy 22 in Tumour
Authors: Savard Murray L. , Gilchrist Dawna M.
Published: March 2008

A family with two sisters and their mother’s male cousin had ependymomas. Of note is the fact that chromosome analysis on the tumour of the younger sister showed two cell lines, one a normal female line, the other with monosomy of chromosome 22.
Vascular Bundles and Wickerworks in Childhood Brain Tumors
Authors: Sato Kengo , Rorke Lucy Balian
Published: March 2008

We reviewed 114 childhood brain tumors and brain sections from 30 children with no nervous system lesions to determine the incidence of vascular bundles (VB) and vascular wickerworks (VW). VB consist of a group of small blood vessels running parallel to each other. VW denote spiralling or twisting of two or more small blood vessels around one another, resembling vines. By light microscopy, VB cannot be differentiated from VW; both appear as a group of small blood vessels oriented in the same direction. VB and VW have been described in normal and abnormal brains at all ages, in association with aging, in neovascularization following necrosis, and in brain tumors. They occur rarely in normal brains, but are a common histological feature of cerebellar pilocytic astrocytomas in contrast to diencephalic pilocytic astrocytomas, anaplastic astrocytomas of cerebrum and cerebellum, and meningiomas.
Intrauterine Depressed Skull Fracture
Authors: Nakahara Toshinori , Sakoda Katsuaki , Uozumi Tohru , Takeda Tetsuji , Ogorochi Toshiya , Ueda Kazuhiro , Ueda Masanori , Sasaki Tomoko
Published: March 2008

Two cases of intrauterine depressed fracture are presented. In each case, the mother had no history of abdominal trauma during pregnancy, the children were delivered normally without the use of forceps, but a round depression was present in the left frontal bone at time of delivery. CT scans demonstrated a depressed fracture of the left frontal bone and stagnation of cerebrospinal fluid around the fracture. Elevation of the depression was therefore made through a small incision along the rear edge of the frontal bone using a periosteal elevator. A review of intrauterine depressed skull fracture is made and the concept, mechanism, surgical indications and operative methods of this rare fracture are discussed.
Delayed Cerebrospinal-Fluid Shunt Infection in Children
Authors: Schiff Steven J. , Oakes Jerry
Published: March 2008

Twelve patients with shunt infection occurring more than 6 months following shunt implantation or revision were identified and their charts reviewed. These cases were accumulated over a 9-year period, and delays from shunt surgery to detection were as long as 11 years. For 5 patients, no antecedent infection or surgery could be identified as a presumptive cause of the shunt infection. Propionibacterium species and Staphylococcus epidermidis species were the most common organisms identified. The risk of late onset of infection at this institution is less than 1% per year.
Intracranial Tuberculomas
Authors: Domingo Zayne , Peter Jonathan C.
Published: March 2008

35 children with suspected tuberculomas of the brain were given a therapeutic 4-drug trial of isoniazid, rifampicin, pyrazinamide and ethambutol. Their clinical and computed tomographic (CT) appearances were analysed retrospectively: 32 responded well to treatment with recognizable improvement on CT after 6 weeks. Three patients did not respond. One of these non-responders had a surgically removed temporal cystic astrocytoma. The majority presented with focal seizures and had a single hemispheral lesion. 14% had multiple lesions, 6% were in the cerebellum. Only 2 patients had raised intracranial pressure and required ventriculoperitoneal shunting.
Late Anaplastic Gliomas in Children Previously Treated for Acute Lymphoblastic Leukemia
Authors: Shapiro Scott , Mealey, Jr. John
Published: March 2008

At least 33 cases of late anaplastic gliomas in children previously treated for acute lymphoblastic leukemia have been discussed in the literature including 20 well-documented cases. The frequency of this second malignancy is much greater than expected and may represent a ‘new syndrome’ with some genetic predisposition. Additionally, CNS prophylaxis which includes both radiation and intrathecal methotrexate appears to work synergistically in increasing the incidence of glial tumors especially multifocal tumors in these patients. The prognosis for these children is dismal but an aggressive treatment approach including surgery, interstitial radiation, and chemotherapy appears to improve survival.
Primary Primitive Neuroectodermal Tumor of the Spinal Cord Associated with Neural Tube Defect
Authors: Freyer David R. , Hutchinson Raymond , McKeever Paul E.
Published: March 2008

Certain spinal-cord (SC) neoplasms, principally lipomas and dermoid tumors, have been diagnosed in association with characteristic neuroskeletal malformations thought to result from neural-tube defects (NTD). To our knowledge, no such association has been recognized for primary primitive neuroectodermal tumor of the SC (PNET-SC), an SC malignancy which has been reported in only 3 children and 5 adults. We describe here the occurrence and treatment results of PNET-SC in a boy who exhibited several neuroskeletal malformations suggestive of an underlying NTD. By undertaking a comparative analysis of the literature with respect to both the histology and the clinical presentation of this child’s tumor, we document an occurrence of an uncommon malignancy, PNET-SC, and identify PNET-SC as another SC neoplasm which may be associated with NTD.
Management of Choroid Plexus Tumors in Children
Authors: Johnson Dennis L.
Published: March 2008

Choroid plexus tumors are most common in the first year of life and are quite large at presentation. Total resection is the treatment of choice, and many children require diversion of the cerebrospinal fluid despite removal of the tumor. Tumor size and associated hydrocephalus present formidable challenges to the pediatric neurosurgeon. The operative approaches as well as other treatment options are discussed.
Congenital Arachnoid Cysts in Children
Authors: Balsubramaniam Chidambaram , Laurent John , Rouah Emilie , Armstrong Dawna , Feldstein Neil , Schneider Steven , Cheek William
Published: March 2008

Congenital arachnoid cysts (CAC) are benign developmental disorders. A number of theories have been proposed to explain the origin and progression to the symptomatic stage. Management strategies range from not treating the asymptomatic cysts to craniotomy, excision of cyst wall and establishment of a communication with the adjacent subarachnoid cistern or ventricle. Other lesions may resemble CAC, and can be differentiated from CAC only by a critical review of the biopsy specimen. We have reviewed our experience with true CAC and similar lesions. Based on our experience we recommend craniotomy, excision of cyst wall and establishment of a communication with an adjacent subarachnoid cistern or ventricle as the primary procedure.
Chronic Dysphagia, Vomiting and Gastroesophageal Reflux as Manifestations of a Brain Stem Glioma: A Case Report
Authors: Frank Yitzchak , Schwartz Shepard B. , Epstein Nancy E. , Beresford Richard
Published: March 2008

Brain stem glioma is the third most common childhood brain tumor, comprising 10–15% of this group of neoplasms. Typical presenting symptoms include ataxia, diplopia and headache, while signs of increased intracranial pressure occur later in the clinical course. Although prolonged failure to thrive, characterized by cachexia and vomiting are rare manifestations of brain stem lesions, in this study we report a 9.5-year-old boy with failure to thrive since infancy which remitted after excision of a brain stem astrocytoma.
Neuropathology of Pediatric Liver Transplantation
Authors: Hall Walter A. , Martinez Julio
Published: March 2008

We reviewed the clinical histories and autopsy records of 35 pediatric patients (ranging in age from 9 months to 18 years) who underwent orthotopic liver transplantation using ciclosporin and corticosteroids for immunosuppression. At the time of death, 19 children (54%) had encephalopathy, 16 (46%) were lethargic or in coma, 10 (29%) had seizures, and 10 were normal. Neuropathological lesions were found on postmortem examination inall 35 patients. Vascular lesions such as infarction, ischemia, thrombosis, and hemorrhage were the most commonneuropathological findings (86%) followed by infectious processes (29%). Candida albicans (2 patients) and Aspergillusfumigatus (3 patients) were the only offending organisms identified, both causing meningoencephalitis. Alzheimer type II astrocytes, a characteristic feature of chronic liver disease, were the singlemost common autopsyfinding (69%). Central pontine myelinolysis was seen in 3 children and basilar artery thrombosis affected 1 child.Neurological complications and their subsequent neuropathology are a significant cause of morbidity and mortality after pediatric liver transplantation. Vascular insults, electrolyte abnormalities, and infections that involve thecentral nervous system are directly related to liver function and the immunosuppression necessary to maintain graftviability. Only with continued observation after surgery combined with rapid medical and surgical treatment can we hope to improve the prognosis following liver transplantation in the pediatric population.
Immunohistochemical Studies on the Development of 5-HT (Serotonin) Neurons in the Nuclei of the Reticular Formations of Human Fetuses
Authors: Shen W.Z. , Luo Z.B. , Zheng D.R. , Yew D.T.
Published: March 2008

5-HT- positive neurons were detected by the PAP immunohistochemical methods in different nuclei of the reticular formations of human fetuses as early as 10 weeks of gestation. The majority of positive 5-HT cells were located in dorsal raphe and central superior nuclei, and there was a reduction of these neurons per 40-µm section as the fetus aged.
Management of Posthemorrhagic Hydrocephalus in the Low-Birth-Weight Preterm Neonate
Authors: Brockmeyer Douglas L. , Wright Lyn C. , Walker Marion L. , Ward Robert M.
Published: March 2008

Over a period of 34 months from 1987 to 1990 we inserted ventricular catheter reservoirs (VCR) into 20 premature low-birth-weight infants who had developed progressive, symptomatic posthemorrhagic hydrocephalus following grade III or IV intraventricular hemorrhages. The mean estimated gestational age was 27.7 ±5.3 weeks and mean birth weight was 1,041 ±699 g. The ventricular catheter reservoirs were placed on day of life 30.7 ± 29.7 and tapped for a total of 3–34 days at varying frequencies and for varying volumes. Of the 20 patients, 4 died on days of life 25, 76, 88, and 187. There were two reservoir infections, both occurring in infants who eventually died. The 16 survivors have been followed from 2 to 24 months (adjusted age). Four (25%) remain shunt-free and 3 have undergone VCR removal. There have been two shunt infections in the 12 shunted patients; ten shunt revisions have been performed overall. At the time of last follow-up, 14 patients were old enough to undergo neurodevelopmental evaluation. Five patients (36%) were ‘normal’ on gross neurological screening examination, 5 (36%) had ‘mild developmental delay’ and 4 (28%) had ‘significant developmental delay’. We feel these data support the continued use of ventricular catheter reservoirs in the management of posthemorrhagic hydrocephalus and offer hope that some of these patients might remain shunt-free and most will have a normal or mildly delayed neurodevelopmental outcome.
Giant Aneurysm of the Distal Posterior Inferior Cerebellar Artery in an 11-Month-Old Child Presenting with Obstructive Hydrocephalus
Authors: Osenbach Richard K.
Published: March 2008

Intracranial aneurysms are rare in children although several features distinguish them from adult aneurysms including variation in anatomic distribution and an increased incidence of giant and posterior circulation aneurysms. Subarachnoid hemorrhage is the most frequent presenation; however, clinical presentation suggestive of intracranial tumor is not uncommon making accurate diagnosis difficult. Direct clipping is recommended whenever possible although alternative techniques may sometimes be necessary. This report of a giant aneurysm of the distal posterior inferior cerebellar artery in an 11-month-old child illustrates the occasional difficulty in diagnosis and management of these unusual aneurysms.
Regulation of Macrophage Functions by PPAR-α, PPAR-γ, and LXRs in Mice and Men
Authors: Rigamonti Elena , Chinetti-Gbaguidi Giulia , Staels Bart
Published: March 2008

Peroxisome proliferator-activated receptors (PPARs) and (liver X receptors) LXRs are ligand-activated transcription factors that control lipid and glucose metabolism, as well as the inflammatory response. Because the macrophage plays an important role in host defense and immunoinflammatory pathologies, particular attention has been paid to the role of PPARs and LXRs in the control of macrophage gene expression and function. Research over the last few years has revealed important roles for PPAR-α, PPAR-γ, and LXRs in macrophage inflammation and cholesterol homeostasis with consequences for atherosclerosis development. In this review we will discuss the role of these transcription factors in the control of macrophage activities, with particular attention to species-differences in macrophage function control by PPARs and LXR between rodents and humans.
Negative-Feedback Loop Attenuates Hydrostatic Lung Edema via a cGMP-Dependent Regulation of Transient Receptor Potential Vanilloid 4
Authors: Yin Jun , Hoffmann Julia , Kaestle Stephanie M. , Neye Nils , Wang Liming , Baeurle Joerg , Liedtke Wolfgang , Wu Songwei , Kuppe Hermann , Pries Axel R. , Kuebler Wolfgang M.
Published: March 2008

Although the formation of hydrostatic lung edema is generally attributed to imbalanced Starling forces, recent data show that lung endothelial cells respond to increased vascular pressure and may thus regulate vascular permeability and edema formation. In combining real-time optical imaging of the endothelial Ca
2+
concentration ([Ca
2+
]
i
) and NO production with filtration coefficient (
K
f
) measurements in the isolated perfused lung, we identified a series of endothelial responses that constitute a negative-feedback loop to protect the microvascular barrier. Elevation of lung microvascular pressure was shown to increase endothelial [Ca
2+
]
i
via activation of transient receptor potential vanilloid 4 (TRPV4) channels. The endothelial [Ca
2+
]
i
transient increased
K
f
via activation of myosin light-chain kinase and simultaneously stimulated NO synthesis. In TRPV4 deficient mice, pressure-induced increases in endothelial [Ca
2+
]
i
, NO synthesis, and lung wet/dry weight ratio were largely blocked. Endothelial NO formation limited the permeability increase by a cGMP-dependent attenuation of the pressure-induced [Ca
2+
]
i
response. Inactivation of TRPV4 channels by cGMP was confirmed by whole-cell patch-clamp of pulmonary microvascular endothelial cells and intravital imaging of endothelial [Ca
2+
]
i
. Hence, pressure-induced endothelial Ca
2+
influx via TRPV4 channels increases lung vascular permeability yet concomitantly activates an NO-mediated negative-feedback loop that protects the vascular barrier by a cGMP-dependent attenuation of the endothelial [Ca
2+
]
i
response. The identification of this novel regulatory pathway gives rise to new treatment strategies, as demonstrated in vivo in rats with acute myocardial infarction in which inhibition of cGMP degradation by the phosphodiesterase 5 inhibitor sildenafil reduced hydrostatic lung edema.
Aspirin Plus Dipyridamole Versus Aspirin for Prevention of Vascular Events After Stroke or TIA
Authors: Verro Piero , Gorelick Phillip B. , Nguyen Danh
Published: March 2008

Background and Purpose—

This meta-analysis systematically reviewed randomized controlled trials comparing aspirin plus dipyridamole with aspirin alone in patients with stroke and TIA to determine the efficacy of these agents in preventing recurrent cerebral and systemic vascular events.

Methods—

We performed separate analyses of the incidences of stroke alone and composite outcome of stroke, myocardial infarction, or vascular death. We also performed two subset analyses, planned a priori, to examine effect size based on trials using (1) exclusively immediate-release and (2) predominantly extended-release dipyridamole.

Results—

The summary results indicate a significant reduction in the overall risk ratio in favor of aspirin plus dipyridamole for stroke alone with relative risk 0.77 (0.67 to 0.89) and the composite end point with relative risk 0.85 (0.76 to 0.94). Studies using immediate-release dipyridamole showed a nonstatistically significant trend in favor of the combination for stroke alone with relative risk 0.83 (0.59 to 1.15) and for the composite outcome with relative risk 0.95 (0.75 to 1.19). Studies using predominantly extended-release dipyridamole showed a statistically significant difference in favor of the combination for stroke alone with relative risk 0.76 (0.65 to 0.89) and for the composite outcome with relative risk 0.82 (0.73 to 0.92).

Conclusions—

The combination of aspirin plus dipyridamole is more effective than aspirin alone in preventing stroke and other serious vascular events in patients with minor stroke and TIAs. The risk reduction was greater and statistically significant for studies using primarily extended release dipyridamole, which may reflect a true pharmacological effect or lack of statistical power in studies using immediate release dipyridamole.
Benchmarks and Determinants of Adherence to Stroke Performance Measures
Authors: Hinchey Judith A. , Shephard Timothy , Tonn Sarah T. , Ruthazer Robin , Selker Harry P. , Kent David M.
Published: March 2008

Background and Purpose—

Develop achievable benchmarks for 9 stroke performance measures (PM) and to identify organizational factors associated with adherence.

Methods—

Adherence rates and achievable benchmarks were determined for 9 PM within a study of patients (n=2294) admitted with acute ischemic stroke at 17 hospitals. Baseline information regarding hospital characteristics and stroke-specific processes of care were collected, and multi-level models were used to test the association of these factors with adherence.

Results—

Benchmarks were ≥90% for 8 of the 9 PM. After controlling for clustering, only use of standing orders was associated with adherence to PM, including: dysphagia screening, venous thrombosis prophylaxis, consideration of tPA, and provision of educational material.

Conclusion—

High levels of adherence are achievable for several acute stroke PM. Use of standing orders is associated with adherence to PM requiring immediate action on admission.
Progression of Symptomatic Intracranial Large Artery Atherosclerosis Is Associated With a Proinflammatory State and Impaired Fibrinolysis
Authors: Arenillas Juan F. , Álvarez-Sabín José , Molina Carlos A. , Chacón Pilar , Fernández-Cadenas Israel , Ribó Marc , Delgado Pilar , Rubiera Marta , Penalba Anna , Rovira Alex , Montaner Joan
Published: March 2008

Background and Purpose—

The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA.

Methods—

Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA.

Results—

During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan–Meier curves showed that high baseline level of CRP, E-selectin, intercellular adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a) predicted ILA progression independently of vascular risk factors. Of them, only CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7];
P
=0.0001) and PAI-1 (PAI-1>23.1 ng/mL; HR, 2.4 [1.0 to 5.8];
P
=0.05) predicted ILA progression also independently of the other studied molecules.

Conclusion—

Progression of symptomatic ILA is associated with a proinflammatory state, as reflected by high levels of inflammatory markers, and with defective fibrinolysis, as indicated by raised concentrations of endogenous fibrinolysis inhibitors.
Simvastatin Reduces the Association of NMDA Receptors to Lipid Rafts
Authors: Ponce Jovita , de la Ossa Natalia Pérez , Hurtado Olivia , Millan Mónica , Arenillas Juan F. , Dávalos Antonio , Gasull Teresa
Published: March 2008

Background and Purpose—

Excess brain extracellular glutamate induced by cerebral ischemia leads to neuronal death, mainly through overactivation of N-methyl-
d
-aspartate (NMDA) receptors. The cholesterol-lowering drugs statins have been reported to protect from NMDA-induced neuronal death but, so far, the mechanism underlying this protection remains unclear. Because NMDA receptors have been reported to be associated with the cholesterol-rich membrane domains known as lipid rafts, we have investigated the effect of treatments that deplete cholesterol levels on excitotoxicity and on association of NMDA receptors to lipid rafts.

Methods—

Primary neuronal cultures were pretreated with inhibitors of cholesterol synthesis and cholesterol, and NMDA-induced cell death was determined by measuring release of lactate dehydrogenase. Lipid raft fractions were isolated and Western blots were performed.

Results—

Treatment with the inhibitors of cholesterol synthesis simvastatin, which inhibits the first step of cholesterol synthesis, or AY9944, which inhibits the last step of cholesterol synthesis, protected neurons from NMDA-induced neuronal death by 70% and 54%, respectively. Treatment with these compounds reduced neuronal cholesterol levels by 35% and 13%, respectively. Simvastatin and AY9944 reduced the association of the subunit 1 of NMDA receptors (NMDAR1) to lipid rafts by 42% and 21%, respectively, and did not change total expression of NMDAR1. Addition of cholesterol reduced neuroprotection by statins and AY9944, and partially reverted the effect of simvastatin on the association of NMDAR1 to lipid rafts.

Conclusions—

These data demonstrate that reduction of cholesterol levels protects from NMDA-induced neuronal damage probably by reducing the association of NMDA receptors to lipid rafts.
The Metabolic Syndrome Predicts Incident Stroke
Authors: Wang Jianjun , Ruotsalainen Sanna , Moilanen Leena , Lepistö Päivi , Laakso Markku , Kuusisto Johanna
Published: March 2008

Background and Purpose—

Limited information is available on the role of the metabolic syndrome (MetS) to predict stroke. We investigated the relationship of the MetS and its single components, defined by 6 different criteria, with stroke in a prospective population-based study.

Methods—

The MetS was defined according to the World Health Organization, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program (NCEP), the American College of Endocrinology, the International Diabetes Federation, and the American Heart Association (updated NCEP) criteria. We investigated the relationship of the MetS with stroke using Cox regression analyses in 991 Finnish subjects without diabetes, aged 65 to 74 years at baseline, and followed-up for 14 years.

Results—

The MetS defined by the World Health Organization, European Group for the Study of Insulin Resistance, NCEP, International Diabetes Federation, and updated NCEP criteria was significantly associated with incident stroke (fatal and nonfatal) when adjusted for confounding variables (HR, 1.52 to 1.72). After exclusion of subjects with myocardial infarction, these 5 definitions still predicted stroke (HR, 1.49 to 1.80). Of the single components of the MetS, the following predicted stroke in multivariable models when subjects with myocardial infarction were excluded: impaired glucose tolerance (2-hour glucose in an oral glucose tolerance test, 7.8 to 11.0 mmol/L) by the World Health Organization and American College of Endocrinology criteria (HR, 1.66); insulin resistance (HR, 1.60) by the European Group for the Study of Insulin Resistance criteria; and central obesity (HR, 1.52) by the NCEP criteria.

Conclusions—

The MetS defined by the 6 criteria except for the American College of Endocrinology definition predicts stroke in elderly subjects. However, impaired glucose tolerance alone is as strong a predictor of stroke as is the MetS defined by the World Health Organization, NCEP and updated NCEP criteria.
Risks and Benefits of Oral Anticoagulation Compared With Clopidogrel Plus Aspirin in Patients With Atrial Fibrillation According to Stroke Risk
Authors: Healey Jeff S. , Hart Robert G. , Pogue Janice , Pfeffer Marc A. , Hohnloser Stefan H. , De Caterina Raffaele , Flaker Greg , Yusuf Salim , Connolly Stuart J.
Published: March 2008

Background and Purpose—

In ACTIVE-W, oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular events in patients with atrial fibrillation. However, because OAC carries important bleeding complications, risk stratification schemes have been devised to identify patients for whom the absolute benefits of OAC exceed its risks.

Methods—

Participants were risk-stratified with the widely-used CHADS
2
scheme. Treatment-specific rates of stroke and major bleeding were calculated for patients with a CHADS
2
=1 and compared to those with a CHADS
2
>1.

Results—

Observed stroke rates for those with a CHADS
2
=1 were 1.25% per year on C+A and 0.43% per year on OAC (RR=2.96, 95% CI: 1.26 to 6.98,
P
=0.01). Among patients with a CHADS
2
>1, the stroke rates were 3.15% per year on C+A and 2.01% per year on OAC (RR=1.58, 95% CI: 1.11 to 2.24,
P
=0.01) (
P
for interaction between stroke risk category and efficacy of OAC=0.19). The risk of major bleeding during OAC was significantly lower among patients with CHADS
2
=1 (1.36% per year) compared with CHADS
2
>1 (2.75% per year) (RR=0.49, 95% CI 0.30 to 0.79,
P
=0.003).

Conclusions—

In this clinical trial, patients with a CHADS
2
=1 had a low risk of stroke, yet still derived a modest (<1% per year) but statistically significant absolute reduction in stroke with OAC and had low rates of major hemorrhage on OAC.
Genetic Variation in Soluble Epoxide Hydrolase (
EPHX2
) Is Associated With an Increased Risk of Ischemic Stroke in White Europeans
Authors: Gschwendtner Andreas , Ripke Stephan , Freilinger Tobias , Lichtner Peter , Müller-Myhsok Bertram , Wichmann H.-Erich , Meitinger Thomas , Dichgans Martin
Published: March 2008

Background and Purpose—

Genetic variation in the
EPHX2
gene region has been reported to influence susceptibility to ischemic stroke in blacks. We assessed the role of this gene region in white Europeans and performed analyses with regard to stroke subtypes.

Methods—

Twenty-six single nucleotide polymorphisms in the
EPHX2
gene region were genotyped in 601 patients with ischemic stroke and 736 matched controls. Cases were subtyped according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system. Analyses were done on single markers and haplotypes using a sliding-window approach.

Results—

Three single nucleotide polymorphisms showed associations with an increased risk for ischemic stroke (allelic models; all
P
≤0.01). One of them retained statistical significance after correction for multiple testing. Associations were observed with large-vessel stroke and stroke of undetermined etiology but not with other stroke subtypes.

Conclusions—

Our findings confirm and extend previous studies suggesting that genetic variation in or near the
EPHX2
gene contributes to the risk of ischemic stroke. This association seems to be mediated predominantly by large-vessel disease.
Remodeling the Brain
Authors: Gauthier Lynne V. , Taub Edward , Perkins Christi , Ortmann Magdalene , Mark Victor W. , Uswatte Gitendra
Published: March 2008

Background and Purpose—

Studies on adult stroke patients have demonstrated functional changes in cortical excitability, metabolic rate, or blood flow after motor therapy, measures that can fluctuate rapidly over time. This study evaluated whether evidence could also be found for structural brain changes during an efficacious rehabilitation program.

Methods—

Chronic stroke patients were randomly assigned to receive either constraint-induced movement therapy (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was performed on structural MRI scans obtained immediately before and after patients received therapy.

Results—

The group receiving constraint-induced movement therapy exhibited far greater improvement in use of the more affected arm in the life situation than the comparison therapy group. Structural brain changes paralleled these improvements in spontaneous use of the more impaired arm for activities of daily living. There were profuse increases in gray matter in sensory and motor areas both contralateral and ipsilateral to the affected arm that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In contrast, the comparison therapy group failed to show gray matter increases. Importantly, the magnitude of the observed gray matter increases was significantly correlated with amount of improvement in real-world arm use.

Conclusions—

These findings suggest that a previously overlooked type of brain plasticity, structural remodeling of the human brain, is harnessed by constraint-induced movement therapy for a condition once thought to be refractory to treatment: motor deficit in chronic stroke patients.
Staged Escalation Therapy in Acute Basilar Artery Occlusion
Authors: Pfefferkorn Thomas , Mayer Thomas E. , Opherk Christian , Peters Nils , Straube Andreas , Pfister Hans-Walter , Holtmannspötter Markus , Müller-Schunk Stefanie , Wiesmann Martin , Dichgans Martin
Published: March 2008

Background and Purpose—

The prognosis of acute basilar artery occlusion (BAO) is poor if early recanalization is not achieved. Recanalization strategies include intravenous thrombolysis (IVT) and intra-arterial thrombolysis, as well as endovascular mechanical thrombectomy (EMT). The combination of IVT with consecutive on-demand EMT may allow for early treatment initiation with high recanalization rates but has never been systematically tested in patients with BAO.

Methods—

Starting in January 2006, we treated all eligible patients with acute BAO admitted to our academic stroke center or one of our cooperating community hospitals after a standardized protocol combining IVT with consecutive on-demand EMT. Inclusion criteria were: (1) presence of predefined symptoms clearly suggestive of BAO; (2) exclusion of intracerebral hemorrhage on CT scan; (3) evidence of BAO on CT angiography; (4) start of therapy within 6 hours after symptom onset; and (5) no contraindications for IVT. If CT angiography showed persistent BAO after IVT, EMT was performed.

Results—

Since January 2006, 16 patients have been treated. All patients received IVT; in 7 of them, EMT became necessary because of persistent BAO. Final recanalization was achieved in 15 patients. Three months after therapy, 12 of 16 patients were still alive; 7 of them had a good outcome (modified Rankin score ≤2).

Conclusions—

Our data suggest that the combination of IVT with on-demand consecutive EMT in BAO is feasible, allows for early treatment, and provides excellent recanalization rates.
Cigarette Smoking and Risk of Stroke in the Chinese Adult Population
Authors: Kelly Tanika N. , Gu Dongfeng , Chen Jing , Huang Jian-feng , Chen Ji-chun , Duan Xiufang , Wu Xigui , Chen Chung-Shiuan , He Jiang
Published: March 2008

Background and Purpose—

We studied the relationship between cigarette smoking and stroke incidence and mortality in the Chinese adult population.

Methods—

We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged 40 years and older. Data on cigarette smoking and other covariables were collected at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 to 2000, with a response rate of 93.4%.

Results—

During an average of 8.3 years follow-up, a total of 6780 stroke events (3979 fatal strokes) were observed. The multivariate-adjusted relative risks (95% confidence interval) of stroke incidence and mortality associated with present cigarette smoking were 1.28 (1.19 to 1.37) and 1.13 (1.03 to 1.25) in men and 1.25 (1.13 to 1.37) and 1.19 (1.04 to 1.36) in women, respectively. The corresponding population attributable risks were 14.2% and 7.1% in men and 3.1% and 2.4% in women. Compared to never-smokers, the multivariate-adjusted relative risks of stroke incidence (95% confidence interval) were 1.21 (1.12 to 1.31), 1.21 (1.11 to 1.32), and 1.36 (1.25 to 1.47) for those who smoked 1 to 9, 10 to 19, and ≥20 cigarettes per day; and 1.18 (1.09 to 1.28), 1.25 (1.15 to 1.35), and 1.34 (1.24 to 1.44) for those who smoked 1 to 11, 12 to 26, and >26 pack-years, respectively (both
P
<0.0001 for linear trends).

Conclusions—

Our study identified a positive and dose-response relationship between cigarette smoking and risk of stroke. Smoking prevention and cessation programs should be an important strategy for reducing the burden of stroke in Chinese adults.
Wide-Coverage Deep Statistical Parsing Using Automatic Dependency Structure Annotation
Authors: Cahill Aoife , Burke Michael , O'Donovan Ruth , Riezler Stefan , van Genabith Josef , Way Andy
Published: March 2008

A number of researchers have recently conducted experiments comparing “deep” hand-crafted wide-coverage with “shallow” treebank- and machine-learning-based parsers at the level of dependencies, using simple and automatic methods to convert tree output generated by the shallow parsers into dependencies. In this article, we revisit such experiments, this time using sophisticated automatic LFG f-structure annotation methodologies with surprising results. We compare various PCFG and history-based parsers to find a baseline parsing system that fits best into our automatic dependency structure annotation technique. This combined system of syntactic parser and dependency structure annotation is compared to two hand-crafted, deep constraint-based parsers, RASP and XLE. We evaluate using dependency-based gold standards and use the Approximate Randomization Test to test the statistical significance of the results. Our experiments show that machine-learning-based shallow grammars augmented with sophisticated automatic dependency annotation technology outperform hand-crafted, deep, wide-coverage constraint grammars. Currently our best system achieves an f-score of 82.73% against the PARC 700 Dependency Bank, a statistically significant improvement of 2.18% over the most recent results of 80.55% for the hand-crafted LFG grammar and XLE parsing system and an f-score of 80.23% against the CBS 500 Dependency Bank, a statistically significant 3.66% improvement over the 76.57% achieved by the hand-crafted RASP grammar and parsing system.