bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging
Authors: Drummond Micah J. , Dreyer Hans C. , Pennings Bart , Fry Christopher S. , Dhanani Shaheen , Dillon Edgar L. , Sheffield-Moore Melinda , Volpi Elena , Rasmussen Blake B.
Published: March 2008

Skeletal muscle loss during aging leads to an increased risk of falls, fractures, and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia; however, the muscle protein synthesis (MPS) response to resistance exercise is less in elderly compared with young subjects. On the other hand, essential amino acids (EAA) increase MPS equally in both young and old subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion following a bout of resistance exercise would stimulate anabolic signaling and MPS similarly between young and old men. Each subject ingested 20 g of EAA 1 h following leg resistance exercise. Muscle biopsies were obtained before and 1, 3, and 6 h after exercise to measure the rate of MPS and signaling pathways that regulate translation initiation. MPS increased early in young (1–3 h postexercise) and later in old (3–6 h postexercise). At 1 h postexercise, ERK1/2 MNK1 phosphorylation increased and eIF2α phosphorylation decreased only in the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups at all time points, but MNK1 phosphorylation was lower at 3 h and AMP-activated protein kinase-α (AMPKα) phosphorylation was higher in old 1–3 h postexercise. We conclude that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men; however, the response is delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old muscle may be playing a role in the delayed activation of MPS. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia.
Scaling of myocardial mass to flow and morphometry of coronary arteries
Authors: Choy Jenny Susana , Kassab Ghassan S.
Published: March 2008

There is no doubt that scaling relations exist between myocardial mass and morphometry of coronary vasculature. The purpose of this study is to quantify several morphological (diameter, length, and volume) and functional (flow) parameters of the coronary arterial tree in relation to myocardial mass. Eight normal porcine hearts of 117–244 g (mean of 177.5 ± 32.7) were used in this study. Various coronary subtrees of the left anterior descending, right coronary, and left circumflex arteries were perfused at pressure of 100 mmHg with different colors of a polymer (Microfil) to obtain rubber casts of arterial trees corresponding to different regions of myocardial mass. Volume, diameter, and cumulative length of coronary arteries were reconstructed from casts to analyze their relationship to the perfused myocardial mass. Volumetric flow was measured in relationship with perfused myocardial mass. Our results show that arterial volume is linearly related to regional myocardial mass, whereas the sum of coronary arterial branch lengths, vessel diameters, and volumetric flow show an ∼3/4, 3/8, and 3/4 power-law relationship, respectively, in relation to myocardial mass. These scaling laws suggest fundamental design principles underlying the structure-function relationship of the coronary arterial tree that may facilitate diagnosis and management of diffuse coronary artery disease.
Effects of Pitavastatin on Adiponectin in Patients with Hyperlipidemia
Authors: Inami N. , Nomura S. , Shouzu A. , Omoto S. , Kimura Y. , Takahashi N. , Tanaka A. , Nanba M. , Shouda Y. , Iwasaka T.
Published: March 2008

The effects of treatment with pitavastatin on inflammatory and platelet activation markers and adiponectin in 117 patients with hyperlipidemia were investigated to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the low-density lipoprotein cholesterol decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with or without type 2 diabetes exhibited a significant increase in adiponectin levels 6 months after pitavastatin treatment (diabetes: 3.52 ± 0.80 vs. 4.52 ± 0.71 µg/ml, p < 0.001; no diabetes: 3.48 ± 0.71 vs. 4.23 ± 0.82 µg/ml, p < 0.05). However, high-sensitivity C-reactive protein, platelet-derived microparticle and soluble P-selectin did not exhibit any differences before or after pitavastatin administration. Levels of adiponectin significantly increased after pitavastatin administration in the group of lower soluble P-selectin (soluble P-selectin before pitavastatin treatment <200 ng/ml). These results suggest that pitavastatin possesses an adiponectin-increasing effect in patients with hyperlipidemia and this effect is influenced by intensive platelet activation.
Reverse Effect of Aspirin: Is the Prothrombotic Effect after Aspirin Discontinuation Mediated by Cyclooxygenase 2 Inhibition?
Authors: Doutremepuich Christian , Aguejouf Omar , Eizayaga Francisco X. , Desplat Vanessa
Published: March 2008

Background: While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. Objectives: We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. Methods and Results: We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. Conclusions: We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient’s blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway.
A Transgenic Mouse Model for Gene–Nutrient Interactions
Authors: Kang Jing X.
Published: March 2008

Diets or nutritional supplements contain many nutrients and other components that may interact, which adds a layer of complexity to their evaluation. A well-controlled experimental model that can eliminate or minimize the confounding factors of diet is critical for addressing nutrient–gene interactions. The newly generated fat-1 transgenic mouse was genetically engineered to carry a gene, namely fat-1, from the round worm Caenorhabditis elegans and is capable of converting n–6 to n–3 fatty acids (which is naturally impossible in mammals), leading to an increase in n–3 fatty acid content with a balanced n–6/n–3 fatty acid ratio in all tissues, independent of diet. Recent studies using this model indicate that balancing the tissue n–6/n–3 ratio could exert a significant effect on gene expression. The fat-1 mouse model allows carefully controlled studies to be performed in the absence of restricted diets, which can create confounding factors that limit studies of this nature.
Successful Use of Steroids and Ureteric Stents in 24 Patients with Idiopathic Retroperitoneal Fibrosis: A Retrospective Study
Authors: Fry Andrew C. , Singh Sadmeet , Gunda Smita S. , Boustead Greg B. , Hanbury Damian C. , McNicholas Thomas A. , Farrington Ken
Published: March 2008

Background/Aims: Retroperitoneal fibrosis (RPF) is a chronic inflammatory disorder causing obstructive nephropathy and renal failure. We reviewed our management of this condition. Method: All patients with RPF treated at a single center over a 15-year period were identified. A full review of notes and computer records was undertaken. Results: Data was available on 27 patients, 3 of which were excluded from later analysis. Diagnosis was based on clinical history and cross-sectional imaging. Retroperitoneal biopsy was undertaken in 3 patients. 96% had significant renal impairment at presentation with a mean serum creatinine of 688 µmol/l. 46% required emergency hemodialysis. All patients were treated with a combination of ureteric stents and/or steroids with an excellent clinical response. The mean best creatinine reached by the cohort was 136 µmol/l, and renal function remained stable in the long term. No patients required chronic dialysis. Ureteric stents were removed within 12 months and low-dose steroids were continued for a mean of 34 months. Recurrent disease was observed in 25% of patients, who all responded well to further steroid therapy. Mean duration of follow-up was 76 months. Conclusions: RPF is very effectively treated by a combination of ureteric stents and steroids, with excellent long-term results using this approach. Continued follow-up is advised because of the possibility of recurrent disease.
Mesangial Proliferative Glomerulonephritis with or without IgA Deposits: The Morphological Characters in Psoriasis Vulgaris
Authors: Jiao Yang , Xu Hong , Li Hang , Li Xuewang
Published: March 2008

Background/Aim: Chronic glomerulonephritides associated with psoriasis vulgaris have been reported in the literature. However, because of the limited number of cases and the lack of specific histological findings, the existence of psoriatic nephropathy remains controversial. This study was performed to investigate the clinical and morphological characteristics of renal involvement in psoriasis vulgaris. Methods: We studied retrospectively 11 patients with psoriasis vulgaris. All patients had nephritic urinary sediments and underwent percutaneous renal biopsy between January 1997 and December 2006. To fulfill the criteria for the study, none of them had any other discernible chronic disease as a second cause of nephropathy, except for long-standing psoriasis vulgaris. Results: Of the 11 patients, 2 (18%) had impaired renal function and 9 (82%) presented with hematuria. Proteinuria was noted in all patients. Their mean peak ESR was 28.3 ± 29.1 mm/1st h. Renal biopsy specimens revealed common histological features of slight-to-moderate mesangial proliferative glomerulonephritis, with (73%) or without IgA depositions in the mesangial area. Inflammation and vascular lesions were unremarkable in the biopsy specimens. Conclusion: The results from this study demonstrate that mesangial proliferative glomerulonephritis with or without IgA deposits might be the major morphological pattern associated with psoriasis vulgaris.
Myelin Expression Is Altered in the Brains of Neonatal Rats Reared in a Fluctuating Oxygen Atmosphere
Authors: Sedowofia Kofi , Giles David , Wade Jean , Cunningham Steve , McColm Janet R. , Minns Robert , McIntosh Neil
Published: March 2008

Background: Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants. Objective: Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen. Methods: Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air. Results: Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls. Conclusion: We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants.
Routine Skin Cultures in Predicting Sepsis Pathogens among Hospitalized Preterm Neonates in Bangladesh
Authors: Choi Yoonjoung , Saha Samir K. , Ahmed A.S.M. Nawshad Uddin , Law Paul A. , Chowdhury M.A.K. Azad , Islam Maksuda , Darmstadt Gary L.
Published: March 2008

Background: Few studies from developing countries have examined sensitivity, specificity, positive and negative predictive values of routine surface cultures. Objectives: The purpose of the study was to determine sensitivity, specificity, and positive predictive value (PPV) of skin cultures among preterm neonates admitted to Dhaka Shishu Hospital, Bangladesh. Methods: The study was nested within a prospective, randomized, controlled trial of emollient treatment in Dhaka Shishu Hospital, Bangladesh. A total of 497 preterm infants <33 weeks gestational age and <72 h of chronological age were enrolled, and the sensitivity, specificity, and PPV of skin cultures were analyzed among 3,765 blood-skin culture pairs, wherein the skin culture was obtained within 13 days before the blood culture. Results: Overall sensitivity, specificity, and PPV were 16, 38, and 5%, respectively. PPV during Klebsiella pneumoniae outbreaks was about 9%, and the inguinal site had the highest PPV (6%) among the three skin sites. Acinetobacter spp.- and K. pneumoniae-specific PPVs were 28 and 23%, respectively. PPV was <2% for Candida spp., Enterobacter spp., and Salmonella spp. Conclusion: Routine skin culture is inefficient in predicting the pathogen responsible for sepsis among premature neonates, even in a developing country setting, where the burden of bacterial infection is relatively high. Skin cultures are also of limited utility during K. pneumoniae outbreaks, and are not recommended.
Paclitaxel Induces Vascular Endothelial Growth Factor Expression through Reactive Oxygen Species Production
Authors: Kim Hyun Sun , Oh Jin Mi , Jin Dong Hoon , Yang Kyu-Hwan , Moon Eun-Yi
Published: March 2008

The antineoplastic drug paclitaxel is known to block cells in the G2/M phase of the cell cycle through stabilization of microtubules. The development of paclitaxel resistance in tumors is one of the most significant obstacles to successful therapy. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of neovascularization. HIF-1 regulates VEGF expression at the transcriptional level. Here, we investigated whether paclitaxel treatment affects VEGF expression for the development of paclitaxel resistance. Paclitaxel treatment induced dose-dependent cell death and increased VEGF expression. Paclitaxel also induced nuclear factor-ĸB activation and stabilized HIF-1α, which stimulated luciferase activity of HIF-1α response element on VEGF gene. As paclitaxel treatment produced reactive oxygen species (ROS), VEGF expression was increased by H2O2 treatment and reduced by various ROS scavengers such as N-acetyl-L-cysteine, pyrrolidine dithiocarbamate and diphenylene iodonium. Paclitaxel-induced cell death was aggravated by incubation with those ROS scavengers. Collectively, this suggests that paclitaxel-induced VEGF expression could be mediated by paclitaxel-induced ROS production through nuclear factor-ĸB activation and HIF-1α stabilization, which could affect resistance induction to antitumor therapeutics during cancer treatment.
Dandy-Walker Cyst Upward Herniation: The Role of Magnetic Resonance Imaging and Double Shunts
Authors: Pillay Premkumar , Barnett Gene H. , Lanzeiri Charles , Cruse Robert
Published: March 2008

Upward transtentorial herniation of a Dandy-Walker cyst is a potentially fatal complication, particularly after solitary shunting of the lateral ventricle for associated hydrocephalus. Two patients with upward transtentorial herniation of their Dandy-Walker cysts are presented to illustrate the diagnostic value of magnetic resonance (MR) imaging with the demonstration of unique ‘keyhole’ and ‘snail’ signs on the axial and sagittal MR images, respectively. In both patients, double and simultaneous shunting en-Y of a lateral ventricle and the posterior fossa cyst resulted in the resolution of the herniation syndrome.
Ectopic Immature Renal Tissue in a Lumbosacral Lipoma: Pathologic and Radiologic Findings
Authors: Alston Sebastian R. , Fuller Gregory N. , Boyko Orest B. , Goscin Stephen A. , DiSclafani Antonio
Published: March 2008

Ectopic immature renal tissue was found in a lumbosacral subcutaneous lipoma with intradural extension in a 6-day-old female with spina bifida. No additional neurologic or renal anomalies were found. Ectopic renal tissue is an extremely rare finding. Histopathologic and MRI results from this case are presented and the possible significance of ectopic renal tissue in relation to the origin of extrarenal Wilms’ tumors is discussed.
Cerebrospinal Fluid Shunt Infections
Authors: Quigley Matthew R. , Reigel Donald H. , Kortyna Ricky
Published: March 2008

All shunt procedures performed at our institution from July 1982 to December 1987 were analyzed for factors possibly related to shunt infection. There were 41 infections detected in 31 patients for an overall rate of 6.9%. Only intraventricular hemorrhage (IVH) as an etiology of the hydrocephalus and internalization of an external ventricular drain (EVD) were found to correlate with septic risk. An extensive review of all the English language literature concerning shunt infections over the last 15 years was undertaken. Little consensus could be found among the 35 publications in regard to factors predisposing to shunt sepsis. Even the issue of antibiotic prophylaxis remains clouded as all papers examined exhibited methodologic flaws.
Candida albicans Shunt Infection
Authors: Shapiro Scott , Javed Tareq , Mealey, Jr. John
Published: March 2008

Seven cases of successfully treated Candida albicans cerebrospinal fluid shunt infections are reported. Treatment consisted of shunt removal and intravenous Amphoteracin B in all cases and intraventricular Amphoteracin B in 4 cases. Serious underlying medical illness, recent antibiotic therapy, indwelling intravascular and/or Foley catheters, coincident candidiasis and low birth weight prematurity are major risk factors for Candida shunt infection. Candida shunt infection appears to occur by either contamination at the time of shunt placement or by hematogenous dissemination.
Intracranial Lymphoblastic Sarcoma Mimicking a Primary Brain Tumor
Authors: Kowal-Vern Areta , Almanaseer Imad , Bleyer Archie
Published: March 2008

A lymphoblastic sarcoma mimicked a medulloblastoma in a 15-year old girl with a history of acute lymphoblastic leukemia diagnosed at age of 2 years. There was no evidence of leukemic infiltration in the brain during the 13-year latency period after the original diagnosis. She had received both prophylactic intrathecal methotrexate and central nervous system irradiation. This case emphasizes the need to consider leukemia as the cause of a ‘brain tumor’ in any patient that has a prior history of leukemia, regardless of the tumor manifestations or the remission duration of the leukemia.
Technique for the Replacement of a Peritoneal Catheter
Authors: Selman Jose Miguel , Basauri Luciano
Published: March 2008

A simple method for the replacement of a peritoneal catheter is described. The old catheter is disconnected from the valve and exteriorized from the peritoneal cavity, using a straight connector. The new catheter is anchored to the cranial or peritoneal end of the old catheter. A gentle traction allows the new catheter to follow the previous subcutaneous tunnel.
Correction of the Prominent Occiput in Beckwith-Wiedemann Syndrome
Authors: Piatt, Jr. Joseph H.
Published: March 2008

A peculiar prominence of the occiput is a variable feature of Beckwith-Wiedemann syndrome. Careful examination of the anatomy of this calvarial deformity in a recent case permitted an uncomplicated and gratifying surgical correction.
Clinicopathological and Radiological Features of Two Cases of Intraventricular Meningioma in Childhood
Authors: Byard Roger W. , Bourne Anthony J. , Clark Bruce , Hanieh Ahmed
Published: March 2008

The clinical, radiological and pathological features of two cases of intraventricular meningioma in a 9-year-old boy and a 9-year-old girl are reported. Presenting features included headache, vomiting and somnolence with no localizing neurological signs on physical examination. Neither patient showed evidence of neurofibromatosis. CT scans were helpful in establishing the preoperative diagnoses with uniformly hyperdense, well-circumscribed lesions showing bright enhancement after contrast within the lateral and third ventricles respectively. Histological examination revealed mixed fibroblastic/angioblastic and fibroblastic patterns, with typical electron-microscopic and immunohistochemical features of meningioma. Successful surgical removal was achieved in both cases.
Current Neurosurgical Treatment of Medulloblastomas in Children
Authors: Albright Leland , Wisoff Jeffrey H. , Zeltzer Paul M. , Deutsch Melvin , Finlay Jonathan , Hammond Denman
Published: March 2008

To determine the current neurosurgical treatment of children with medulloblastomas, we reviewed the operative reports and neurosurgical report forms from 141 children with posterior fossa medulloblastomas treated on two current Children’s Cancer Study Group (CCSG) protocols, CCG-921 for high-stage and CCG-923 for low-stage medulloblastoma. Most medulloblastoma operations were performed in major medical centers: 61% of the operations were performed in CCSG member institutions, 23% in CCSG affiliates and 16% in other institutions. The tumor T stage distribution was as follows: T1 – 4%, T2 – 15%, T3A – 35%, T3B – 36%, and T4 – 10%. Tumors infiltrated the brainstem in 38% of cases and were associated with hydrocephalus in 91% of cases. Hydrocephalus was managed by external ventricular drains in 50% and by shunts in 60%. Adjunctive instruments (e.g., microscope, ultrasonic aspirator) were used in 93% of the operations. Tumor removals were as follows: biopsy only 3%, partial removals 13%, subtotal removals 13%, near total removals 41% and gross total removals in 40%; 90% or more of the tumor was removed in 81% of the operations. Forty-seven percent of the operations were performed by pediatric neurosurgeons. Near total and gross total removals were performed significantly more often (p < 0.05) by pediatric neurosurgeons than by general neurosurgeons. Postoperative morbidity was reported in 46% of cases, including neurologic morbidity in 26% of cases. There was no significant difference in patient morbidity between pediatric and general neurosurgeons.
Management of Hydrocephalus Complicating Childhood Posterior Fossa Tumors
Authors: Dias Mark S. , Albright Leland
Published: March 2008

We examined the treatment of hydrocephalus in children with posterior fossa tumors to (1) compare the use of external ventricular drainage (EVD) with ventriculoperitoneal shunts (VPS), (2) determine the frequency of postoperative hydrocephalus requiring permanent shunts, and (3) determine which factors predict the need for a permanent shunt. The records of 58 children with posterior fossa tumors and associated hydrocephalus treated at our institution from 1979 to 1987 were retrospectively reviewed. Initial management of hydrocephalus included VPS in 25 patients, EVD in 17, and no treatment in 16. Patients in the ‘VPS’, ‘EVD’, and ‘no treatment’ groups differed only in the severity of hydrocephalus (less severe in the no treatment group than in the VPS and EVD groups) and in the method of dural closure following tumor resection (dura was left open more often in the EVD and no treatment groups). Of the 33 patients not initially shunted, only 9 (27%) subsequently required a shunt. These patients were compared with the remaining 24 patients who did not require a shunt. Two features predicted the need for a subsequent shunt: (1) resection of only a small volume of tumor and (2) leaving the dura open following tumor resection. Complications of EVD were few; no patient deteriorated neurologically during or after ventricular catheter removal. We conclude that between two thirds and three quarters of patients with childhood posterior fossa tumors and associated hydrocephalus may be managed with perioperative EVD and will not require shunts. Patients in whom only a minimal tumor resection is performed and those in whom the dura is left open are more likely to need permanent VPS.
Tension Hydrothorax from Intrapleural Migration of a Ventriculoperitoneal Shunt
Authors: Dickman Curtis A. , Gilbertson Debra , Pittman Hal W. , Rekate Harold L. , Daily William J.R.
Published: March 2008

A male newborn underwent a myelomeningocele repair, with subsequent placement of a ventriculoperitoneal shunt for treatment of hydrocephalus. Five days after shunt surgery, the infant acutely developed a deeply sunken fontanel, pallor, tachypnea, bradycardia, and irritability. Chest radiographs revealed intrathoracic migration of the distal shunt tubing and a tension hydrothorax. Treatment consisted of tube thoracostomy and temporary externalization of the distal shunt tubing. The patient fully recovered. The acute onset of shock in association with a sunken fontanel in a neonate with a shunt should raise the suspicion of tension hydrothorax. For critically ill infants immediate needle aspiration or thoracostomy is suggested. In less severely ill children, exposure of the shunt tubing in the neck and withdrawal of the pleural effusion by the distal shunt tubing may be performed as an emergency measure. The early recognition and urgent management of this problem are emphasized.
Coffee Consumption and Coronary Calcification
Authors: van Woudenbergh Geertruida J. , Vliegenthart Rozemarijn , van Rooij Frank J.A. , Hofman Albert , Oudkerk Matthijs , Witteman Jacqueline C.M. , Geleijnse Johanna M.
Published: March 2008

Background—

The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort.

Methods and Results—

The study involved 1570 older men and women without coronary heart disease who participated in the Rotterdam Study. Coffee intake was assessed with a semiquantitative food frequency questionnaire. Coronary calcification was detected with electron beam computed tomography. Severe calcification was defined as an Agatson calcium score >400. Sex-specific odds ratios (ORs) with 95% confidence intervals (95% CI) were obtained by logistic regression with adjustment for age, smoking, body mass index, education, and intake of energy and alcohol. In multivariable analysis, coronary calcification in women was significantly reduced for moderate (>3 to 4 cups) and high (>4 cups) coffee intake, compared with a daily intake of 3 cups or less (OR of 0.41 [95% CI: 0.25 to 0.65] and 0.54 [0.33 to 0.87], respectively). The association persisted after additional adjustment for tea and other dietary confounders, and was not modified by smoking. A nonsignificant inverse relationship was also found in men who smoked, whereas in nonsmoking men a direct association was observed.

Conclusion—

The present study suggests a beneficial effect of coffee drinking against coronary calcification, particularly in women. More research is needed to confirm these findings and to clarify possible effect modification by gender and smoking.
Differential Regulation of VEGF Signaling by PKC-α and PKC-ε in Endothelial Cells
Authors: Rask-Madsen Christian , King George L.
Published: March 2008

Objective—

Vascular endothelial growth factor (VEGF) stimulates proangiogenic signal transduction and cell function in part through activation of protein kinase C (PKC). Our aim was to examine how individual isoforms of PKC affect VEGF action.

Methods and Results—

Transfection of bovine aortic endothelial cells with small interfering RNA (siRNA) targeting either PKC-α, δ, or ε caused a reduction in the cognate PKC protein by 76% to 89% without changing expression of nontargeted isoforms. Downregulation of PKC-ε abrogated VEGF-stimulated phosphorylation of Akt at Ser473 and eNOS at Ser1179 and decreased VEGF-stimulated NO synthase activity in intact cells. In contrast, PKC-α knockdown increased Akt and eNOS phosphorylation, whereas PKCδ knockdown had no significant effect. PKC-ε knockdown also decreased VEGF-stimulated Erk1/2 phosphorylation and abolished VEGF-stimulated DNA synthesis. Consistent with an effect on several pathways of VEGF signaling, VEGF receptor-2 (VEGFR2) tyrosine phosphorylation and expression of VEGFR2 protein and mRNA was decreased by 81, 90, and 84%, respectively, during knockdown of PKC-ε, but increased during PKC-α knockdown.

Conclusions—

By regulating VEGFR2 expression and activation, PKC-ε expression is critical for activation of Akt and eNOS by VEGF and contributes to VEGF-stimulated Erk activation, whereas PKC-α has opposite effects.
Variants of the Interferon Regulatory Factor 5 Gene Regulate Expression of IRF5 mRNA in Atherosclerotic Tissue But Are Not Associated With Myocardial Infarction
Authors: Mälarstig Anders , Sigurdsson Snaevar , Eriksson Per , Paulsson-Berne Gabrielle , Hedin Ulf , Wallentin Lars , Siegbahn Agneta , Hamsten Anders , Syvänen Ann-Christine
Published: March 2008

Background—

Signaling events after activation of toll-like receptors (TLRs) are important mechanisms promoting inflammation in the atherosclerotic plaque. INF regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs. Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found to be associated with systemic lupus erythematosus.

Methods and Results—

We examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the case-control association between SNPs in the IRF5 gene with myocardial infarction (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among unstable CAD patients, association of IRF5 SNPs with recurrent coronary events (n=401) was also investigated. The IRF5 mRNA expression was increased in atherosclerotic tissue compared with control tissue (
P
<0.001). Significant associations with IRF5 expression was observed for 6 of 10 SNPs in the study. However, the IRF5 SNPs examined were neither associated with the risk of precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events in unstable CAD patients.

Conclusions—

IRF5 mRNA is expressed in cells in atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene. Genetic variation at the IRF5 locus was, however, not associated with CAD or related phenotypes.
Genetic Variation in Members of the Leukotriene Biosynthesis Pathway Confer an Increased Risk of Ischemic Stroke
Authors: Bevan Steve , Dichgans Martin , Wiechmann H. Erich , Gschwendtner Andreas , Meitinger Thomas , Markus Hugh S.
Published: March 2008

Background and Purpose—

The recent finding that genetic variants in 5-lipoxygenase activating protein and leukotriene A4 hydrolase may confer an increased risk of ischemic stroke has implicated the leukotriene family as potential mediators of cardiovascular disease. Using a case control replication methodology, all members of the leukotriene synthesis pathway and their receptors were examined for genetic variants, which may act as risk factors for all ischemic stroke and stroke subtypes.

Methods—

A case control methodology using a UK stroke cohort (872 cases, 933 controls) was adopted, with additional 5-lipoxygenase activating protein genotyping and replication of positive findings undertaken in an independent stroke population from Germany (601 cases, 736 controls).

Results—

Association was identified with variants in 5-lipoxygenase activating protein, leukotriene C4 synthase (leukotriene A4 hydrolase),and the leukotriene B4 receptor complex. Differing risks were identified for ischemic stroke subtypes. A variant in leukotriene C4 synthase was found to confer a 1.5-fold increase in risk of small vessel disease (RR, 1.515; 1.041 to 2.262;
P
=0.043) with replication in an independent cohort showing a similar risk (RR, 1.687; 1.065 to 2.675;
P
=0.026). A haplotype in the leukotriene B4 receptor complex was found to confer a 2.3-fold increase in risk of cardioembolic stroke (RR, 2.118; 1.194 to 3.760;
P
=0.01) and replication in a German cohort revealed a similar risk with a second distinct haplotype (RR, 2.060; 1.162 to 3.665;
P
=0.013).

Conclusions—

Genetic variation in leukotriene pathway members and their receptors confer an increased risk of ischemic stroke in 2 independent populations. These risks show different magnitudes depending on ischemic stroke subtype.
Rapid Morphologic Plasticity of Peri-Infarct Dendritic Spines After Focal Ischemic Stroke
Authors: Brown Craig E. , Wong Charles , Murphy Timothy H.
Published: March 2008

Background and Purpose—

Focal stroke is associated with cell death, abnormal synaptic activity, and neurologic impairments. Given that many of these neuropathologic processes can be attributed to events that occur shortly after injury, it is necessary to understand how stroke affects the structure of neurons in surviving peri-infarct regions, particularly at the level of the dendritic spines, which transmit normal and potentially abnormal and injurious synaptic signaling. Recently, we described ischemia-induced changes in the structure of layer 1 dendritic tufts of transgenic mice expressing YFP in layer 5 cortical neurons. However, these in vivo imaging experiments could not address ischemia-related phenomena that occur in deeper cortical structures/layers, other cortical regions, or submicron changes in dendritic spine structure.

Methods—

Focal stroke was induced in the forelimb sensorimotor cortex by the photothrombotic method. Two, 6, and 24 hours after stroke, brains were processed for Golgi-Cox staining to permit a detailed analysis of primary apical dendritic spine structure from layer 2/3 and 5 cortical pyramidal neurons.

Results—

Photothrombotic stroke caused a rapid deterioration of neurons, as revealed by Golgi-Cox labeling, in the infarct core that could be readily distinguished from surviving peri-infarct regions. Analysis of >15 000 dendritic spines revealed that although many spines were lost in the peri-infarct cortex during the first 24 hours after stroke (≈38% lost), spines that remained were significantly longer (≈25% at 6 hours). Furthermore, these effects were found in both layer 2/3 and 5 neurons and were restricted primarily to peri-infarct regions (<200 μm from the infarct border).

Conclusions—

These rapid changes in dendritic spine number and length may reflect an early adaptive response of potentially vulnerable peri-infarct neurons coping with postischemic spreading depression-like depolarizations and the loss of presynaptic contacts.
Applications and Advantages of Power Motion-Mode Doppler in Acute Posterior Circulation Cerebral Ischemia
Authors: Tsivgoulis Georgios , Sharma Vijay K. , Hoover Steven L. , Lao Annabelle Y. , Ardelt Agnieszka A. , Malkoff Marc D. , Alexandrov Andrei V.
Published: March 2008

Background and Purpose—

Evaluation of posterior circulation with single-gate transcranial Doppler (TCD) is technically challenging and yields lower accuracy parameters in comparison to anterior circulation vessels. Transcranial power motion-mode Doppler (PMD-TCD), in addition to spectral information, simultaneously displays in real-time flow signal intensity and direction over 6 cm of intracranial space. We aimed to evaluate the diagnostic accuracy of PMD-TCD against angiography in detection of acute posterior circulation stenoocclusive disease.

Methods—

Consecutive patients presenting to the emergency room with symptoms of acute (<24 hours) cerebral ischemia underwent emergent neurovascular evaluation with PMD-TCD and angiography (computed tomographic angiography, magnetic resonance angiography, or digital subtraction angiography). Previously published diagnostic criteria were prospectively applied for PMD-TCD interpretation independent of angiographic findings.

Results—

A total of 213 patients (119 men; mean age 65±16 years; ischemic stroke 71%, transient ischemic attack 29%) underwent emergent neurovascular assessment. Compared with angiography, PMD-TCD showed 17 true-positive, 8 false-negative, 6 false-positive, and 182 true-negative studies in posterior circulation vessels (sensitivity 73% [55% to 91%], specificity 96% [93% to 99%], positive predictive value 68% [50% to 86%], negative predictive value 95% [92% to 98%], accuracy 93% [90% to 96%]). In 14 patients (82% of true-positive cases), PMD display showed diagnostic flow signatures complementary to the information provided by the spectral display: reverberating or alternating flow, distal basilar artery flow reversal, high-resistance flow, emboli tracks and, bruit flow signatures.

Conclusions—

PMD-TCD yields a satisfactory agreement with urgent brain angiography in the evaluation of patients with acute posterior circulation cerebral ischemia. PMD display can depict flow signatures that are complimentary to and can increase confidence in standard single-gate TCD spectral findings.
Dual-Modality Monitoring of Targeted Intraarterial Delivery of Mesenchymal Stem Cells After Transient Ischemia
Authors: Walczak Piotr , Zhang Jian , Gilad Assaf A. , Kedziorek Dorota A. , Ruiz-Cabello Jesus , Young Randell G. , Pittenger Mark F. , van Zijl Peter C.M. , Huang Judy , Bulte Jeff W.M.
Published: March 2008

Background and Purpose—

In animal models of stroke, functional improvement has been obtained after stem cell transplantation. Successful therapy depends largely on achieving a robust and targeted cell engraftment, with intraarterial (IA) injection being a potentially attractive route of administration. We assessed the suitability of laser Doppler flow (LDF) signal measurements and magnetic resonance (MR) imaging for noninvasive dual monitoring of targeted IA cell delivery.

Methods—

Transient cerebral ischemia was induced in adult Wistar rats (n=25) followed by IA or intravenous (IV) injection of mesenchymal stem cells (MSCs) labeled with superparamagnetic iron oxide. Cell infusion was monitored in real time with transcranial laser Doppler flowmetry while cellular delivery was assessed with MRI in vivo (4.7T) and ex vivo (9.4T).

Results—

Successful delivery of magnetically labeled MSCs could be readily visualized with MRI after IA but not IV injection. IA stem cell injection during acute stroke resulted in a high variability of cerebral engraftment. The amount of LDF reduction during cell infusion (up to 80%) was found to correlate well with the degree of intracerebral engraftment, with low LDF values being associated with significant morbidity.

Conclusions—

High cerebral engraftment rates are associated with impeded cerebral blood flow. Noninvasive dual-modality imaging enables monitoring of targeted cell delivery, and through interactive adjustment may improve the safety and efficacy of stem cell therapy.
Cerebral Ischemic Lesions on Diffusion-Weighted Imaging Are Associated With Neurocognitive Decline After Cardiac Surgery
Authors: Barber P. Alan , Hach Sylvia , Tippett Lynette J. , Ross Linda , Merry Alan F. , Milsom Paget
Published: March 2008

Background and Purpose—

Improvements in cardiac surgery mortality and morbidity have focused interest on the neurological injury such as stroke and cognitive decline that may accompany an otherwise successful operation. We aimed to investigate (1) the rate of stroke, new ischemic change on MRI, and cognitive impairment after cardiac valve surgery; and (2) the controversial relationship between perioperative cerebral ischemia and cognitive decline.

Methods—

Forty patients (26 men; mean [SD] age 62.1 [13.7] years) undergoing intracardiac surgery (7 also with coronary artery bypass grafting) were studied. Neurological, neuropsychological, and MRI examinations were performed 24 hours before surgery and 5 days (MRI and neurology) and 6 weeks (neuropsychology and neurology) after surgery. Cognitive decline from baseline was determined using the Reliable Change Index.

Results—

Two of 40 (5%) patients had perioperative strokes and 22 of 35 (63%) tested had cognitive decline in at least one measure (range, 1 to 4). Sixteen of 37 participants (43%) with postoperative imaging had new ischemic lesions (range, 1 to 17 lesions) with appearances consistent with cerebral embolization. Cognitive decline was seen in all patients with, and 35% of those without, postoperative ischemic lesions (
P
<0.001), and there was an association between the number of abnormal cognitive tests and ischemic burden (
P
<0.001).

Conclusion—

We have provided a reliable estimate of the rate of stroke, postoperative ischemia, and cognitive impairment at 6 weeks after cardiac valve surgery. Cognitive impairment is associated with perioperative ischemia and is more severe with greater ischemic load.
MRI Detection of Secondary Damage After Stroke
Authors: Justicia Carles , Ramos-Cabrer Pedro , Hoehn Mathias
Published: March 2008

Background and Purpose—

Iron plays a central role in many metabolic processes. Under certain pathological situations it accumulates, producing negative effects such as increasing damage by oxidative stress. The present study examined long-term iron accumulation in a stroke model with secondary degeneration, using MRI and histological techniques.

Methods—

Male Wistar rats (n=22) were subjected to 60 minutes MCA occlusion. MR images (T2- and T2*-weighted) were obtained weekly between weeks 1 and 7 after reperfusion, and at weeks 10, 14, 20, and 24. Histological iron detection and immunohistochemical examination for different markers (NeuN, GFAP, OX-42, HO-1, and APP) were performed at the 3 survival time points (3, 7, and 24 weeks).

Results—

Infarcts affecting MCA territory were evident on T2-weighted imaging, and all animals showed deficits on behavioral tests. In the thalamus, T2 hyperintensity was detected 3 weeks after stroke, and disappeared around week 7 when T2*-weighted images showed a marked hypointensity in that area. Histology revealed neuronal loss in the thalamus, accompanied by strong microglial reactivity and microglial HO-1 expression. APP deposits were detected in the thalamus from week 3 on and persisted until week 24. Iron storage was detected in microglia at week 3, in the parenchyma at week 7, and around APP deposits at week 24.

Conclusions—

T2*-weighted MRI allows the detection of secondary damage in the thalamus after MCAO. Iron accumulation in the thalamus is mediated by HO-1 expression in reactive microglia.
Clinical and Tissue Response to Intravenous Thrombolysis in Tandem Internal Carotid Artery/Middle Cerebral Artery Occlusion
Authors: Thomalla Götz , Kruetzelmann Anna , Siemonsen Susanne , Gerloff Christian , Rosenkranz Michael , Röther Joachim , Fiehler Jens
Published: March 2008

Background and Purpose—

The benefit of intravenous thrombolysis in tandem internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion remains unclear. We studied clinical and imaging outcome of intravenous thrombolysis in MRI-selected patients with tandem ICA/MCA occlusion as compared to isolated MCA occlusion.

Methods—

We analyzed data of MRI-selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. Initial perfusion and diffusion lesion volumes were calculated. Final infarct volume was assessed on follow-up imaging after 5 to 8 days. Recanalization/reperfusion was assessed after 24 hours using MRA. Favorable outcome was defined as a modified Rankin scale score of 0 to 1 after 90 days.

Results—

Of 38 patients with proximal MCA occlusion, 14 (37%) had a tandem ICA/MCA occlusion. Median NIHSS on admission (15 vs 15), initial perfusion (246 vs 246 mL), and diffusion lesion volume (22 vs 21 mL), final infarct volume (30 vs 39 mL), and the proportion of patients with a favorable outcome after 3 months (50% vs 46%) were similar in tandem ICA/MCA occlusion versus isolated MCA occlusion.

Conclusion—

The presence of tissue at risk appears to play a key role for the likelihood of clinical recovery after intravenous tissue plasminogen activator treatment in acute stroke patients with tandem ICA/MCA occlusion. There appears to be no evidence to exclude patients with tandem ICA/MCA occlusion from intravenous thrombolysis.
Cerebrospinal Fluid Tenascin-C Increases Preceding the Development of Chronic Shunt-Dependent Hydrocephalus After Subarachnoid Hemorrhage
Authors: Suzuki Hidenori , Kinoshita Noriaki , Imanaka-Yoshida Kyoko , Yoshida Toshimichi , Taki Waro
Published: March 2008

Background and Purpose—

The possible cause of chronic hydrocephalus after subarachnoid hemorrhage (SAH) has been reported to be meningeal fibrosis. We examined whether the induction of tenascin-C (TN-C), an extracellular matrix glycoprotein known to promote tissue fibrosis, was associated with chronic hydrocephalus after SAH.

Methods—

We prospectively measured cerebrospinal fluid TN-C levels in 7 control patients with unruptured cerebral aneurysms and in 29 consecutive patients with aneurysmal SAH on days 1 to 12.

Results—

Cerebrospinal fluid TN-C levels were less than the diagnostic threshold level in control patients but markedly increased after SAH. Higher TN-C levels were observed in patients with more severe SAH on admission CT, ventricular drainage for acute obstructive hydrocephalus, and a worse outcome. Independent of these factors, however, cerebrospinal fluid TN-C levels were significantly higher in patients with than without subsequent chronic shunt-dependent hydrocephalus on days 1 to 9.

Conclusions—

These findings suggest the possible involvement of TN-C in the development of chronic hydrocephalus after SAH and encourage further studies.