bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats
Authors: Rector R. Scott , Thyfault John P. , Morris R. Tyler , Laye Matthew J. , Borengasser Sarah J. , Booth Frank W. , Ibdah Jamal A.
Published: January 2008

Exercise training is commonly prescribed for treatment of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether exercise training prevents the development of NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats and to elucidate the molecular mechanisms underlying the effects of exercise on hepatic steatosis. Four-week-old OLETF rats were randomly assigned to either a sedentary control group (Sed) or a group given access to voluntary running wheels for 16 wk (Ex). Wheels were locked 2 days before euthanasia in the Ex animals, and both groups were euthanized at 20 wk old. Voluntary wheel running attenuated weight gain and reduced serum glucose, insulin, free fatty acids, and triglycerides in Ex animals compared with Sed ( P < 0.001). Ex animals exhibited significantly reduced hepatic triglyceride levels and displayed fewer lipid droplets (Oil Red O staining) and reduced lipid droplet size compared with Sed. Wheel running increased by threefold the percent of palmitate oxidized completely to CO2in the Ex animals but did not alter AMP-activated protein kinase-α (AMPKα) or AMPK phosphorylation status. However, fatty acid synthase and acetyl-coenzyme A carboxylase (ACC) content were significantly reduced (∼70 and ∼35%, respectively), and ACC phosphorylation and cytochrome c content were significantly elevated (∼35 and ∼30%, respectively) in the Ex animals. These results unequivocally demonstrate that daily physical activity attenuates hepatic steatosis and NAFLD in an obese rodent model and suggest that this effect is likely mediated, in part, through enhancement of hepatic fatty acid oxidation and reductions in key protein intermediates of fatty acid synthesis.
Reduced susceptibility of muscle-specific insulin receptor knockout mice to colon carcinogenesis
Authors: Ealey Kafi N. , Lu Suying , Lau Dominic , Archer Michael C.
Published: January 2008

Insulin resistance is a risk factor for colon cancer, but it is not clear which of its metabolic sequelae are involved. The objective of this study was to determine whether increased adiposity and elevated circulating lipids commonly seen in insulin resistance promote colon carcinogenesis independent of changes in insulin. We made use of muscle-specific insulin receptor knockout (MIRKO) mice that exhibit elevated serum triglycerides (TG), free fatty acids (FFA), and fat mass but have similar body weights, circulating glucose, and insulin and insulin sensitivity to their wild-type littermates used as controls. Seven-week-old male MIRKO mice and controls received four weekly intraperitoneal injections of either 5 mg/kg azoxymethane (AOM) to induce aberrant crypt foci (ACF) or 10 mg/kg AOM to induce tumors and were killed at 24 or 40 wk of age, respectively. The MIRKO mice displayed hyperinsulinemia at 7 wk of age and reduced insulin sensitivity at 16 wk of age compared with controls. The previously reported MIRKO phenotype developed between 16 and 24 wk of age. By 40 wk of age, however, MIRKO mice were again insulin resistant. ACF development did not differ between MIRKO mice and controls, but MIRKO mice developed significantly fewer colon tumors. Our results suggest that circulating TG and FFA are not promoters of colon tumor development. Indeed, we show that the cumulative effects of the metabolic changes that occur with knockout of the insulin receptor in muscle are associated with reduced susceptibility to colon tumorigenesis.
FOLFIRI Is Tolerable after Subtotal Colectomy – A Patient with Familial Adenomatous Polyposis Who Developed Advanced Rectal Cancer
Authors: Mori Mitsue , Kiba Takayoshi , Oikawa Mika , Hokkoku Kengou , Watanabe Yuri , Shintaku Kimiko , Yoshimitsu Yutaka , Sakuma Hiroshi , Ueda Hiroshi , Nakai Masuo
Published: January 2008

A 40-year-old female with familial adenomatous polyposis (FAP) had a subtotal colectomy at 16 years of age. At 39 years, she had low anterior resection due to advanced rectal carcinoma. Thereafter, we administrated per os uracil and tegafur for 9 months. Metastatic rectal carcinoma was detected in the liver (S8) by computed tomography (CT). 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) data did not show any other metastasis. This report presents a first case of a patient undergoing subtotal colectomy administered FOLFIRI (CPT-11 180 mg/m2 as a 90-minute infusion on day 1; leucovorin 400 mg/m2 as a 2-hour infusion during CPT-11, immediately followed by 5-FU bolus 400 mg/m2 and 46-hour continuous infusion of 2,400 mg/m2 every 2 weeks). This regimen was administered without grade 3 or 4 of any adverse reaction for 6 months, although there was a possibility that this patient with subtotal colectomy may have the cause for severe diarrhea. Further investigations are needed to assess the safety in clinical trials of FOLFIRI regimen for patients with subtotal colectomy.
Ume (Japanese Apricot)-Induced Small Bowel Obstruction with Chronic Radiation Enteritis
Authors: Hashimoto Takuya , Kitayama Joji , Hidemura Akio , Ishigami Hironori , Kaizaki Shoichi , Fukushima Noriyoshi , Miyata Tetsuro , Nagawa Hirokazu
Published: January 2008

Stricture formation is recognized as one of the complications of chronic radiation enteritis. Here, we present a case of a 73-year-old woman who presented with small bowel obstruction 16 years after pelvic irradiation for uterine cancer. Computed tomographic (CT) scan of the abdomen demonstrated a 1-cm foreign body in the terminal ileum. Laparotomy revealed a stone of ume (Japanese apricot) stuck in an ileal stricture, leading to complete impaction and perforation. She was successfully treated with ileocecal resection and ileocolic anastomosis without any complication. Pathological study revealed that the low compliance caused by fibrosis of the bowel wall prevented the small ume stone from passing through the irradiated ileum. Our case implies the specific risk of food-induced small bowel obstruction in patients with a history of pelvic irradiation.
Red Blood Cells Are the Major Source of Alpha-Synuclein in Blood
Authors: Barbour Robin , Kling Kristin , Anderson John P. , Banducci Kelly , Cole Tracy , Diep Linnea , Fox Michael , Goldstein Jason M. , Soriano Ferdie , Seubert Peter , Chilcote Tamie J.
Published: January 2008

Background: α-Synuclein has been directly linked to Parkinson’s disease etiology by mutations in and multiplication of its gene that result in a familial form of Parkinson’s disease. α-Synuclein has been detected in blood, and was found to be elevated in the blood of those individuals with the α-synuclein gene multiplication. Objective: A complete analysis of the level of α-synuclein in blood has not been performed. In this report, we determine the quantitative distribution of α-synuclein in the plasma and different cellular fractions of human blood. The levels of α-synuclein in human and mouse blood are compared. Methods: α-Synuclein levels in the different fractions of blood were quantified by a sandwich ELISA with purified recombinant α-synuclein as an assay standard. Samples were further characterized by Western immunoblot analysis. Results: More than 99% of the α-synuclein resides in the red blood cells (RBCs) with less than 1% of the total detected in the plasma, platelets and peripheral blood mononuclear cells. Conclusions: More than 99% of the α-synuclein in human blood is present in the peripheral blood cells, with the remainder in plasma. Fractionation of peripheral blood cells from human blood and quantification of α-synuclein revealed that only a very small amount of the total α-synuclein is present in peripheral blood mononuclear cells, and platelets, with the majority of α-synuclein in blood being present in RBCs. Considering the abundance and fragility of RBCs, α-synuclein levels in these other blood fractions or other bodily fluids such as cerebrospinal fluid may be artificially elevated by contamination with intact or lysed RBCs.
Antibody Capture of Soluble Aβ Does Not Reduce Cortical Aβ Amyloidosis in the PDAPP Mouse
Authors: Seubert Peter , Barbour Robin , Khan Karen , Motter Ruth , Tang Pearl , Kholodenko Dora , Kling Kristin , Schenk Dale , Johnson-Wood Kelly , Schroeter Sally , Gill Davinder , Jacobsen J. Steven , Pangalos Menelas , Basi Guriqbal , Games Dora
Published: January 2008

Background: In vivo administration of antibodies against the amyloid-β (Aβ) peptide has been shown to reduce and reverse the progressive amyloidosis that develops in a variety of mouse models of Alzheimer’s disease (AD). This work has been extended to clinical trials where subsequent autopsy cases of AD subjects immunized against Aβ showed similar reductions in parenchymal amyloid plaques, suggesting this approach to reduce neuropathology in man is feasible. Objective: Multiple hypotheses have been advanced to explain how anti-Aβ antibodies may lower amyloid burden. In this report, we compare approaches utilizing either plaque-binding or peptide-capturing anti-Aβ antibodies for effectiveness in reducing amyloidosis in a mouse model of AD. Methods: A plaque-binding monoclonal antibody (3D6) and an Aβ peptide-capturing monoclonal antibody (266) were compared in chronic treatment and prevention paradigms using a transgenic mouse model of AD. The effects of antibody therapy on plaque burden and plasma clearance of Aβ were investigated by quantitative imaging and clearance studies of intravenously injected 125I-Aβ. Results: The plaque-binding antibody 3D6 was highly effective in either treatment or prevention of amyloidosis. In these studies, the peptide-capture antibody 266 showed no reduction in amyloidosis in either paradigm and showed trends towards increasing amyloidosis. Antibody 266 was also found to greatly prolong (>180-fold) the normally rapid peripheral clearance of Aβ, in contrast to that found with 3D6 (>24-fold). Conclusion: Reversing and preventing Alzheimer’s type amyloidosis is most effectively accomplished with anti-amyloid antibodies that avidly bind plaque.
Evaluation Tools and Animal Models of Peripheral Neuropathies
Authors: Fricker B. , Muller A. , René F.
Published: January 2008

Peripheral neuropathies are common and frequently debilitating disorders linked to degeneration of peripheral nerves that supply mainly the distal muscles of the extremities. Due to the diverse origin of the pathology (genetic, systemic or environmental), peripheral neuropathies exhibit different clinical forms: acute or chronic, symmetrical or asymmetrical, demyelinating or axonal. In the last 30 years, to gain insight into cellular and molecular mechanisms underlying neuropathies, numerous animal models – either spontaneous or induced by chemical compounds, physical injury or genetic engineering – have been extensively developed and used. In this review, we present (1) the methods used to assess the peripheral neuropathies in the major available animal models and their main pathological characteristics and (2) the main models and their relevance to the human pathology, and, consequently, their usefulness for preclinical studies. Finally, we discuss the emerging, recently developed tools, that should allow to gain a better insight into the mechanisms underlying the peripheral neuropathies.
Acquired Factor VIII Inhibitor in a Patient with Dermatomyositis – A Case Study
Authors: Ayoola Ayodele , Mohsini Wajahath , Aung Sein
Published: January 2008

Background: Acquired factor VIII inhibitor is an antibody formed against FVIII and seen in patients without FVIII replacement therapy. This entity has been associated with both autoimmune disease and infections. Case Study: We report the case of a 65-year-old man with dermatomyositis who presented with a bleeding episode following venipuncture and hematuria. His coagulation parameters were followed as well as the inhibitor level. His acquired FVIII inhibitor was managed successfully with rituximab. Conclusion: Our patient’s bleeding episodes resolved and the inhibitor level was undetectable after 12 months. This is the first case of acquired FVIII inhibitor in association with dermatomyositis.
Association of Familial Pernicious Anaemia and Hereditary Haemochromatosis
Authors: Bonafoux Béatrice , Henry Laurent , Delfour Christophe , Arnaud Anne , Brun Sophie , Mercier Eric , Jourdan Eric , Carillo Serge , Funakoshi Nathalie , Bureau Jean Paul , Blanc Pierre , Lavabre-Bertrand Thierry
Published: January 2008

We report the case of a 54-year-old patient presenting with a typical pernicious anaemia. His mother was diagnosed with unquestionable pernicious anaemia 5 years previously. Serum ferritin was strongly increased (1,160 µg/l, normal range 29–380), with a transferrin saturation of 95%. We found a homozygous C282Y mutation of the HFE gene in our patient, his mother being heterozygous. The son of our patient was compound C282Y/H63D heterozygous without detectable pernicious anaemia. This seems to be the first report of an association between familial pernicious anaemia and hereditary haemochromatosis. The simultaneous occurrence of the 2 diseases in the same patient helps to delineate the relative contribution of each of them to iron metabolism and erythropoiesis: iron overload was only moderately increased and responded rapidly to phlebotomies, whereas haemochromatosis did not modify the cytologic presentation of pernicious anaemia.
Observations on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy
Authors: Berliner Adam R. , Fine Derek M. , Lucas Gregory M. , Rahman M. Hafizur , Racusen Lorraine C. , Scheel Paul J. , Atta Mohamed G.
Published: January 2008

Aims: This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in HIV-infected patients. Method: Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy, while 111 had not. A group comparison was performed. Results: The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis (22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By multivariate logistic regression, CD4 counts >200 cells/mm3 and higher estimated glomerular filtration rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p < 0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent corticosteroid treatment (29 vs. 3.6%, p = 0.001). Conclusion: These findings may reflect more severe acute and/or chronic disease at the time of biopsy and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially in light of the changing spectrum of renal disease in this group.
EndoCinch® Treatment for Gastro-Oesophageal Reflux Disease
Authors: Mahmood Z. , Ang Y.S.
Published: January 2008

Gastro-oesophageal reflux disease (GORD) is a common disorder which significantly impairs the quality of life. Recently an EndoCinch® system has been described, with an approach to the treatment of GORD that would obviate the need for long-term proton pump inhibitors and the cost and potential risk of laparoscopic Nissen fundoplication. We set outto evaluate the status of this new technique for the management of GORD. We review the literatures (publications and abstracts) regarding safety, efficacy, and durability of this new antireflux procedure. On the whole, this new antireflux technique produced significant improvement in GORD symptomatology and quality of life and reduced the use of antireflux medication. However, it failed to normalize acid reflux, long-term durability data are lacking, and some serious side effects have been reported. In conclusion, EndoCinch has the potential to treat patients with this common ailment. However, further studies are necessary to determine what modifications to this antireflux technique are required in order to produce the maximum clinical benefit.
Merkel Cell Carcinoma of the Skin: A Retrospective Study of 24 Cases by the Hellenic Cooperative Oncology Group
Authors: Pectasides D. , Papaxoinis G. , Pectasides E. , Galani H. , Razi E. , Katodrytis N. , Fountzilas G. , Economopoulos T.
Published: January 2008

Background: The purpose of this retrospective study was to present the epidemiological and clinical characteristics of 24 patients with Merkel cell carcinoma of the skin (MCC) and their response to various therapeutic modalities. Methods: The tumor registry of the Hellenic Cooperative Oncology Group was used to identify patients with MCC diagnosed between 1986 and 2006. Results: The most frequent primary sites were the extremities (50%), followed by the head (33%) and the trunk (17%). Median time of follow-up was 24 months. Sixteen patients were initially diagnosed with stage I, 5 patients with stage II, and 3 patients with stage III (metastatic) disease. Six patients with stage I disease received adjuvant chemotherapy (CT) and/or radiotherapy (RT). All patients with stage I disease treated only with surgery relapsed, whereas 33% of the patients treated with adjuvant therapy recurred. All patients with stage II disease received adjuvant treatment. Among them, 2 patients relapsed. Disease-free survival (DFS) and overall survival (OS) did not differ significantly between patients with stage I and II disease (stage I: 4-year DFS 27%, 4-year OS 56%; stage II: 4-year DFS 60%, 4-year OS 80%). Patients treated with adjuvant therapy had significantly better DFS than those treated only with surgery (p = 0.012), but OS did not differ significantly (adjuvant group: 4-year DFS 59%, 4-year OS 74%; surgery group: 4-year DFS 10%, 4-year OS 50%). Eleven patients with locally advanced or metastatic disease received CT. The response rate was 73% (complete remission 18%), median progression-free survival was 10 months and median OS was 14 months. Complete remission was achieved in 2 other cases, with the addition of RT after CT. Conclusions: MCC is an aggressive neoplasm with significant chemosensitivity and radiosensitivity, but poor outcome. The role of adjuvant treatment should be further investigated.
Phase I/II Study of a Combination of S-1 and Weekly Paclitaxel in Patients with Advanced or Recurrent Gastric Cancer
Authors: Kawabata Ryohei , Fujiwara Yoshiyuki , Doki Yuichiro , Fujita Junya , Tsukahara Yasuo , Yamasaki Makoto , Miyata Hiroshi , Takiguchi Shuji , Monden Morito
Published: January 2008

Objective: A phase I/II study of a combination of S-1 and weekly paclitaxel was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs) and objective response rate (RR) in patients with advanced or recurrent gastric cancer. Methods: S-1 was administered orally at a fixed dose of 80 mg/m2 per day on days 1–14. Paclitaxel was injected intravenously on days 1, 8, and 15, starting with a dose of 50 mg/m2. The dose was increased in a stepwise manner. Results: In phase I, level 2 (60 mg/m2) was considered the MTD, because 2 of 3 patients in level 2 developed DLTs (grade 3 neutropenia and anemia, and grade 4 diarrhea and stomatitis). Therefore, the RD was determined to be level 1 (50 mg/m2). In phase II, efficacy and safety were assessed in 18 patients treated with the RD. The RR was 64.7% and the median survival time was 13.5 months. The most severe toxicities were grade 3 leukopenia (5.5%) and grade 3 neutropenia (5.5%). Conclusion: Our study showed that S-1 combined with 50 mg/m2 paclitaxel is effective and safe in patients with advanced or recurrent gastric cancer.
Prognostic Factors for Gefitinib-Treated Postoperative Recurrence in Non-Small Cell Lung Cancer
Authors: Okami Jiro , Taniguchi Kazuya , Higashiyama Masahiko , Maeda Jun , Oda Kazuyuki , Orita Naoki , Koizumi Kyoko , Kodama Ken , Kato Kikuya
Published: January 2008

Background and Objectives: The association between epidermal growth factor receptor (EGFR) mutations and response to EGFR tyrosine kinase inhibitor (TKI) has been consistently confirmed in a number of studies. However, it is still unclear whether a response to TKI treatment translates into increased survival for patients with non-small cell lung cancer (NSCLC). Methods: EGFR mutations were analyzed in 169 primary lung cancer tissues by RT-PCR and sequencing of multiple clones. The association between EGFR mutation status and the clinical outcome of gefitinib treatment was investigated. For mutation-positive cases, the percentage of mutated clones from the total number of clones was calculated. This ratio was used as the quantitative index of EGFR mutations. Results: We identified mutations in 71 of 169 patients with NSCLC. 46 patients were treated with gefitinib for postoperative recurrence. Progression-free survival and overall survival after initial gefitinib were significantly longer in patients with mutation than with wild type (univariate analysis, p < 0.001 for both). Multivariate analyses identified EGFR mutations and longer disease-free intervals after surgery as significant prognostic factors for survival. By quantitative analysis of mutation-positive cases, the increased ratio of mutated EGFR transcripts significantly associated with longer survival after gefitinib. Conclusions: EGFR mutation status and disease-free interval were associated with prolonged progression-free survival and overall survival after gefitinib treatment for postoperative recurrence of NSCLC. Quantitative analysis of mutated EGFR transcripts provided additional information for the stratification of patients with mutated EGFR.
VEGFR1 Tyrosine Kinase Signaling Promotes Lymphangiogenesis as Well as Angiogenesis Indirectly via Macrophage Recruitment
Authors: Murakami Masato , Zheng Yujuan , Hirashima Masanori , Suda Toshio , Morita Yohei , Ooehara Jun , Ema Hideo , Fong Guo-Hua , Shibuya Masabumi
Published: January 2008

Objective—

Angiogenesis and lymphangiogenesis are complex phenomena that involve the interplay of several growth factors and receptors. Recently, we have demonstrated that in
Keratin-14
(
K14
) promoter-driven
Vegf-A
transgenic (Tg) mice, not only angiogenesis but also lymphangiogenesis is stimulated. However, the mechanism by which VEGFR1 is involved in lymphangiogenesis remains unclear.

Methods and Results—

To examine how important the tyrosine kinase (TK) of VEGFR1 is in lymphangiogenesis in
K14 Vegf-A
Tg mice, we crossed the
K14 Vegf-A
Tg mice with VEGFR1-TK–deficient mice to generate double mutant
K14 Vegf-A
Tg
Vegfr1 tk
−/−
mice.
K14 Vegf-A
Tg
Vegfr1 tk
−/−
mice exhibit a remarkable decrease in lymphangiogensis as well as angiogenesis in subcutaneous tissues. To address the mechanism underlying the decrease in lymphangiogensis, we investigated the recruitment of monocyte-macrophage-lineage cells into the skin. The recruitment of VEGFR1-expressing macrophages driven by VEGF-A was reduced in
K14 Vegf-A
Tg
Vegfr1 tk
−/−
mice.
Vegf-A
Tg mice that received VEGFR1-TK–deficient bone marrow showed a reduction of macrophage recruitment, lymphangiogenesis and angiogenesis compared with those in
K14 Vegf-A
Tg mice.

Conclusions—

VEGFR1 signaling promotes lymphangiogenesis as well as angiogenesis mainly by increasing bone marrow–derived macrophage recruitment.
Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women
Authors: Lamon-Fava Stefania , Herrington David M. , Reboussin David M. , Sherman Michelle , Horvath Katalin V. , Cupples L. Adrienne , White Charles , Demissie Serkalem , Schaefer Ernst J. , Asztalos Bela F.
Published: January 2008

Objective—

The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women.

Methods and Results—

Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis, and plasma remnant-like particle cholesterol (RLP-C) concentrations were measured in 256 postmenopausal women with established CHD and in 126 CHD-free postmenopausal women. Coronary artery disease was assessed in women with CHD by quantitative coronary angiography. Plasma RLP-C and preβ1 HDL concentrations were higher and α1 and α2 HDL concentrations were lower in CHD than in CHD-free women. After adjustment for conventional CHD-risk factors, plasma levels of RLP-C were positively associated with the degree of coronary artery disease. In similar analyses, plasma preβ1 HDL particle concentrations were positively associated and α2 HDL particle concentrations were inversely associated with the extent of coronary atherosclerosis. Plasma TG, low density lipoprotein cholesterol, and HDL cholesterol levels were not associated with the degree of coronary atherosclerosis.

Conclusions—

The degree of coronary atherosclerosis in postmenopausal women is linked to a dysregulation of the TG/HDL metabolism. Subpopulations of TG-rich and HDL lipoproteins are better predictors of disease than TG and HDL cholesterol concentrations.
The Cerebral Vasculopathy of PHACES Syndrome
Authors: Heyer Geoffrey L. , Dowling Michael M. , Licht Daniel J. , Tay Stacey Kiat-Hong , Morel Kimberly , Garzon Maria C. , Meyers Philip
Published: January 2008

Background and Purpose—

PHACES syndrome is a neurocutaneous disorder of unknown etiology. We studied the spectrum of associated congenital and progressive cerebral vascular anomalies.

Methods—

The medical records of 7 patients with PHACES syndrome were reviewed and combined with an additional 108 PHACES cases identified from the literature. We reviewed the clinical characteristics, calculated the relative frequencies of each type of vascular anomaly, and assessed site of vessel involvement relative to hemangioma location.

Results—

Among a total of 115 PHACES cases, 89 (77.4%) had congenital and/or progressive cerebral vascular anomalies. The most commonly detected congenital arterial anomalies included dysplasia, aberrant origin or course, hypoplasia, and absence or agenesis. Arterial occlusions and stenoses were detected in 24 (20.9%) and 21 (18.3%) cases, respectively. Twenty (17.4%) had persistent embryonic arteries; 15 (13%) had saccular aneurysms. There appears to be a close relation between the regional distributions of cervicofacial hemangiomas and the locations of intracranial and extracranial vascular (and cardiac) anomalies.

Conclusion—

The vasculopathy of PHACES chiefly comprises a spectrum of congenital and progressive large artery lesions. Based on known embryology and the relative frequencies of specific congenital vascular anomalies, we can predict that the initial cerebral vascular changes occur early in embryogenesis, by the fifth gestational week or earlier. There appears to be both a temporal and a regional link between the arterial anomalies of PHACES and the cutaneous infantile hemangioma.
Statin Treatment and the Occurrence of Hemorrhagic Stroke in Patients With a History of Cerebrovascular Disease
Authors: Vergouwen Mervyn D.I. , de Haan Rob J. , Vermeulen Marinus , Roos Yvo B.W.E.M.
Published: January 2008

Background and Purpose—

The recently published Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study showed that statins exert a marginally beneficial effect on stroke prevention in patients with a history of cerebrovascular disease. Interestingly, the magnitude of the beneficial effect shown in this study is smaller than in similar studies, which included patients without a history of cerebrovascular disease. In SPARCL, an increased occurrence of hemorrhagic strokes in patients on statin treatment was observed, an effect that was also earlier described in the Heart Protection Study in a subgroup of patients with a history of cerebrovascular disease. The purpose of this systematic review was therefore to investigate the effect of statin treatment on the occurrence of ischemic and hemorrhagic strokes in patients with a history of cerebrovascular disease.

Methods—

We systematically searched the PUBMED database for the combination of the variables “statin” AND “stroke.” Furthermore, we searched for relevant studies in the Cochrane Library and Cochrane Central Register of Controlled Trials and handsearched citations. Pooled effect sizes were expressed in relative risk estimates with corresponding 95% CIs.

Results—

Four studies were included investigating the effect of statins in 8832 patients with a history of cerebrovascular disease. The pooled relative risk for statin users of overall stroke during follow-up was 0.88 (95% CI: 0.78 to 0.99). The pooled relative risk of ischemic stroke was 0.80 (95% CI: 0.70 to 0.92) and of hemorrhagic stroke 1.73 (95% CI: 1.19 to 2.50).

Conclusion—

In patients with a history of cerebrovascular disease, statins clearly decrease the risk of ischemic stroke. However, this beneficial effect is partly lost by an increased risk of hemorrhagic stroke.
A Very Early Rehabilitation Trial for Stroke (AVERT)
Authors: Bernhardt Julie , Dewey Helen , Thrift Amanda , Collier Janice , Donnan Geoffrey
Published: January 2008

Background and Purpose—

Very early rehabilitation, with an emphasis on mobilization, may contribute to improved outcomes after stroke. We hypothesized that a very early rehabilitation protocol would be safe and feasible.

Methods—

We performed a randomized, controlled trial with blinded outcome assessment. Patients at <24 hours after stroke were recruited from 2 Melbourne metropolitan stroke units. Patients were randomly assigned to receive standard care (SC) or SC plus very early mobilization (VEM) until discharge or 14 days (whichever was sooner). The primary safety outcome was the number of deaths at 3 months. The primary feasibility outcome was a higher “dose” of mobilization achieved in VEM. Secondary safety outcomes included adverse events (including falls and early neurologic deterioration), compliance with physiologic monitoring criteria, and patient fatigue after interventions. Secondary feasibility outcomes included “contamination” of standard care.

Results—

Overall, 18% of patients screened were suitable for recruitment. Seventy-one patients were recruited and randomized, with 2 dropouts by 12 months. The majority experienced ischemic strokes (87%). The group mean±SD age was 74.7±12.5 years, and 58% (n=41) had a National Institutes of Health Stroke Scale score >7. There was no significant difference in the number of deaths between groups (SC, 3 of 33; VEM, 8 of 38;
P
=0.20). Almost all deaths occurred in patients with severe stroke. Secondary safety outcomes were similar between groups. The intervention protocol was successfully delivered, achieving VEM dose targets (double SC,
P
=0.003) and faster time to first mobilization (
P
<0.001).

Conclusions—

VEM of patients within 24 hours of acute stroke appears safe and feasible. Intervention efficacy and cost-effectiveness are currently being tested in a large randomized, controlled trial.
Serial Electrocardiographic Assessments Significantly Improve Detection of Atrial Fibrillation 2.6-Fold in Patients With Acute Stroke
Authors: Douen Andre G. , Pageau Nicole , Medic Sejla
Published: January 2008

Background and Purpose—

Previous studies have reported a low, ≈1% to 3%, rate of detection of occult atrial fibrillation (AF) with Holter monitor in patients with acute stroke. Furthermore, at least one study has reported that Holter monitoring could not always corroborate initial electrocardiographic (ECG) detection of AF suggesting underestimation of AF by Holter. We compare the detection of new-onset AF by serial ECG assessments and Holter after acute ischemic stroke.

Methods—

One hundred forty-four patients with ischemic stroke admitted to a stroke unit were studied. The number of ECGs conducted within the first 3 days up to the detection of AF as well as the time interval for Holter “hookup” and subsequent reporting of AF was documented.

Results—

ECGs were performed in 143 patients with a baseline of 10 (7%) patients having a history of AF. Serial ECGs detected 15 new AF cases in <2 days of admission, thereby increasing the total number of known AF cases to 25 (17.5%), a 2.6-fold increased realization of AF (
P
=0.011). Holter was also completed in 12 of 15 new cases of AF but surprisingly identified AF in only 50% (6 of 12). Holter monitoring was performed in 126 cases and in this subgroup, there was no statistically significant difference in the rate of AF detection with ECG or Holter.

Conclusions—

Serial ECG assessments within the first 72 hours of an acute stroke significantly improve detection of AF. The discordance regarding the corroboration of AF by Holter in ECG-positive patients with AF supports previous observations and suggests a high incidence of paroxysmal AF as a cause of ischemic stroke.
Abnormal Regional Cerebral Blood Flow in Cognitively Normal Elderly Subjects With Hypertension
Authors: Dai Weiying , Lopez Oscar L. , Carmichael Owen T. , Becker James T. , Kuller Lewis H. , Gach H. Michael
Published: January 2008

Background and Purpose—

The purpose of this study was to examine regional cerebral blood flow (rCBF) in normal cognitive-performing subjects with hypertension (HTN) using continuous arterial spin-labeled MRI. The most common explanation for the effect of blood pressure on cognition is that HTN increases the risk of cerebrovascular disease, and it may increase the risk for Alzheimer disease possibly through small vessel disease, ischemia, oxidative stress, and inflammation. However, few studies to date have examined the rCBF of cognitively normal subjects with HTN in population-based cohorts, and none have used continuous arterial spin-labeled MRI. This is a noninvasive technique that does not require either injections or ionizing radiation and can measure absolute rCBF rates over the entire brain.

Methods—

rCBF was measured at 1.5 T using continuous arterial spin-labeled MRI in 41 cognitively normal subjects who were participating in the Cardiovascular Health Study Cognition Study. A deformable atrophy-corrected registration method was used to warp the rCBF maps to the standard colin27 brain space. Image and cluster-based statistical analyses were performed between subject groups.

Results—

Cognitively normal subjects with HTN (n=19) had decreased rCBF in the putamen, globus pallidus, bilaterally, and in the left hippocampus compared with normotensives (n=22). In addition, decreased rCBF was observed in the right and left anterior cingulate gyrus with extension to the subcallosal region, left posterior cingulate gyrus and medial precuneus, left lateral inferior and superior frontal, and inferior parietal, left orbitofrontal, and left superior temporal cortices.

Conclusions—

rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.
Risk Factor Associations With the Presence of a Lipid Core in Carotid Plaque of Asymptomatic Individuals Using High-Resolution MRI
Authors: Wasserman Bruce A. , Sharrett A. Richey , Lai Shenghan , Gomes Antoinette S. , Cushman Mary , Folsom Aaron R. , Bild Diane E. , Kronmal Richard A. , Sinha Shantanu , Bluemke David A.
Published: January 2008

Background and Purpose—

Atheroma vulnerability to rupture is increased in the presence of a large lipid core. Factors associated with a lipid core in the general population have not been studied.

Methods—

The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of individuals free of clinical cardiovascular disease designed to include a high proportion of ethnic minorities. We selected MESA participants from the top 15th percentile of maximum carotid intima media thickness by ultrasound and acquired high-resolution black blood MRI images through their carotid plaque before and after the intravenous administration of gadodiamide (0.1 mmol/kg). Lumen and outer wall contours were defined using semiautomated analysis software. We analyzed only plaques with a maximum thickness ≥1.5 mm by MRI (n=214) and assessed cross-sectional risk factor associations with lipid core presence by multivariable logistic regression.

Results—

A lipid core was present in 151 (71%) of the plaques. After controlling for age, ethnicity, sex, maximum arterial wall thickness, hypertension, cigarette smoking, diabetes, and C-reactive protein, compared with participants in the lowest tertile of total plasma cholesterol, the ORs of having a lipid core for participants in the middle and highest tertiles were 2.76 (95% CI: 1.01 to 7.51) and 4.63 (95% CI: 1.56 to 13.75), respectively. None of the other risk factors was associated with lipid core.

Conclusions—

In persons with thickened carotid walls, plasma total cholesterol, but not other established coronary heart disease risk factors, is strongly associated with lipid core presence by MRI. High total cholesterol may be associated with rupture proneness of atherosclerotic lesions in the general population.
Architecture and Blocking
Authors: Embick David , Marantz Alec
Published: January 2008

We discuss theoretical approaches to blocking effects, with particular emphasis on cases in which words appear to block phrases (and perhaps vice versa). These approaches share at least one intuition: that syntactic and semantic features create possible “cells” or slots in which particular items can appear, and that blocking occurs when one such cell is occupied by one form as opposed to another. Accounts of blocking differ along two primary dimensions: the size of the objects that compete with one another (morphemes, words, phrases, sentences); and whether or not ungrammatical forms are taken into consideration in determining the correct output (relatedly, whether otherwise well-formed objects are marked ungrammatical by competition). We argue that blocking in the sense of competition for the expression of syntactic or semantic features is limited to insertion of the phonological exponents of such features (the Vocabulary items of Distributed Morphology) at terminal nodes from the syntax. There is thus no blocking at the word level or above, and no competition between grammatical and ungrammatical structures. The architectural significance of these points is emphasized throughout the discussion.
Do So and VP
Authors: Sobin Nicholas
Published: January 2008

Culicover and Jackendoff (2005) argue that VP structure with adjunct modifiers is “flat”: both complements and adjuncts are equally sisters of V. Their arguments center around the apparent misbehavior of do so as a replacement for a syntactic VP constituent. However, several of these arguments are inconclusive. The rule that Culicover and Jackendoff offer for do so does not fare better overall than does the hierarchic VP account of do so.
On Sverdrup Discontinuities and Vortices in the Southwest Indian Ocean
Authors: LaCasce J. H. , Isachsen P. E.
Published: January 2008

The southwest Indian Ocean is distinguished by discontinuities in the wind-driven Sverdrup circulation. These connect the northern and southern tips of Madagascar with Africa and the southern tip of Africa with South America. In an analytical barotropic model with a flat bottom, the discontinuities produce intense westward jets. Those off the northern tip of Madagascar and the southern tip of Africa are always present, while the strength of that off southern Madagascar depends on the position of the zero curl line in the Indian Ocean (the jet is strong if the line intersects Madagascar but weak if the line is north of the island). All three jets are barotropically unstable by the Rayleigh–Kuo criterion. The authors studied the development of the instability using a primitive equation model, with a flat bottom and realistic coastlines. The model produced westward jets at the three sites and these became unstable after several weeks, generating 200–300-km scale eddies. The eddies generated west of Madagascar are in accord with observations and with previous numerical studies. The model’s Agulhas eddies are similar in size to the observed eddies, both the anticyclonic rings and the cyclones that form to the west of the tip of South Africa. However, the model’s Agulhas does not retroflect, most likely because of its lack of stratification and topography, and so cannot capture pinching-off events. It is noteworthy nevertheless that a retroflection is not required to produce eddies here.
Rain in Shallow Cumulus Over the Ocean: The RICO Campaign
Authors: Rauber Robert M. , Stevens Bjorn , Ochs Harry T. , Knight Charles , Albrecht B. A. , Blyth A. M. , Fairall C. W. , Jensen J. B. , Lasher-Trapp S. G. , Mayol-Bracero O. L. , Vali G. , Anderson J. R. , Baker B. A. , Bandy A. R. , Burnet E. , Brenguier J.-L. , Brewer W. A. , Brown P. R. A. , Chuang R , Cotton W. R. , Di Girolamo L. , Geerts B. , Gerber H. , Göke S. , Gomes L. , Heikes B. G. , Hudson J. G. , Kollias P. , Lawson R. R , Krueger S. K. , Lenschow D. H. , Nuijens L. , O'Sullivan D. W. , Rilling R. A. , Rogers D. C. , Siebesma A. P. , Snodgrass E. , Stith J. L. , Thornton D. C. , Tucker S. , Twohy C. H. , Zuidema P.
Published: January 2008

Shallow, maritime cumuli are ubiquitous over much of the tropical oceans, and characterizing their properties is important to understanding weather and climate. The Rain in Cumulus over the Ocean (RICO) field campaign, which took place during November 2004–January 2005 in the trades over the western Atlantic, emphasized measurements of processes related to the formation of rain in shallow cumuli, and how rain subsequently modifies the structure and ensemble statistics of trade wind clouds. Eight weeks of nearly continuous S-band polarimetric radar sampling, 57 flights from three heavily instrumented research aircraft, and a suite of ground- and ship-based instrumentation provided data on trade wind clouds with unprecedented resolution. Observational strategies employed during RICO capitalized on the advances in remote sensing and other instrumentation to provide insight into processes that span a range of scales and that lie at the heart of questions relating to the cause and effects of rain from shallow maritime cumuli.
Mapping High Sea Winds from Space: A Global Climatology
Authors: Sampe Takeaki , Xie Shang-Ping
Published: January 2008

High winds at sea are feared by sailors, but their distribution is poorly known because ships have avoided them as much as possible. The accumulation of spaceborne scatterometer measurements now allows a global mapping of high winds over the ocean. Seven years of Quick Scatterometer (QuikSCAT) data gathered since July 1999 show that high-wind events, defined as wind speeds greater than 20 m s−1 (“strong gale” and higher on the Beaufort scale), mostly happen in winter. Over coastal regions, land orography is the major cause of high winds, forcing wind jets of various types. Over the open ocean, high winds tend to be collocated with the extratropical storm tracks, along which migratory low and high pressure systems travel eastward. In comparison, tropical cyclones do not leave a strong signature in the climatology of high-wind occurrence except in the western Pacific east of Taiwan. In the extratropics, sea surface temperature (SST) fronts and their meanders significantly change the frequency of high-wind events. For example, high winds occur twice as often (or more) over the warmer than the colder flank of the Gulf Stream, and over the poleward than equatorward meanders of the Antarctic Circumpolar Current. The collocation of frequent high winds and SST frontal zones is not a mere coincidence because SST gradients anchor storm tracks, which in turn sustain the surface westerlies against friction with lateral heat and momentum flux. Both the high mean speed and large variance of wind increase the probability of high winds. Implications for navigation safety and oceanographic and climate research are discussed.
Detecting Depressive Disorder With the Hopkins Symptom Checklist-25 in Tanzania
Authors: Lee Bandy , Kaaya Sylvia F. , Mbwambo Jessie K. , Smith-Fawzi Mary C. , Leshabari Melkizedek T.
Published: January 2008

Background: Assessment of the growing prevalence of depression in developing countries is hampered by a lack of valid diagnostic instruments for the local settings.

Aim and method: This study attempted to examine the validity of the 25-item Hopkins Symptom Checklist (HSCL-25) in a special primary care population in Dar es Salaam, Tanzania.

Results: 787 antenatal participants were recruited, and their responses revealed good internal consistency, interrater reliability, and test-retest reliability, and the scale was validated using content, construct, and discriminant validation methods. Factor analysis of the depression subscale, however, confirmed the need for a locally developed scale.

Conclusions: Integrating universalist and relativist approaches, through the validation and modification of scales, may help in the detection of depression in cross-cultural settings.
Stigma, Discrimination, Empowerment and Social Networks: a Preliminary Investigation of Their Influence On Subjective Quality of Life in a Swedish Sample
Authors: Lundberg Bertil , Hansson Lars , Wentz Elisabet , Björkman Tommy
Published: January 2008

Background: Studies investigating the importance of social network, empowerment and experiences of stigma on subjective quality of life among persons with mental illness are rare.

Aim: This study aimed to investigate beliefs of devaluation/discrimination, actual rejection experiences, empowerment, social network and the relationship of these factors to subjective quality of life among subjects with mental illness.

Methods: A cross-sectional study assessing beliefs of devaluation/discrimination, actual rejection experiences, empowerment, social network and subjective quality of life was performed on 150 subjects with mental illness.

Results: The factors most prominently related to subjective quality of life were overall empowerment and overall social network. For a subgroup of subjects suffering from psychotic disorders there was a significant negative relationship between subjective quality of life and rejection experiences. This group also reported more frequent rejection experiences.

Conclusion: The findings indicate that persons with mental illness are a heterogeneous group with regard to the influence of social network, stigma and empowerment on subjective quality of life. The negative impact of actual rejection experiences might express that, in order to increase subjective quality of life, stigma must be addressed as a separate and important factor in its own right.
Psychiatric Intensive Care Units: a Literature Review
Authors: Bowers Len , Jeffery Debra , Bilgin Hulya , Jarrett Manuela , Simpson Alan , Jones Julia
Published: January 2008

Background: Psychiatric Intensive Care Units (PICU) have been part of most inpatient psychiatric services for some time, although information about their functioning and outcome has not previously been collated.

Aim: To conduct a systematic literature review to assess the current state of knowledge about such services.

Method: A search of electronic databases was undertaken, followed by obtaining additional references from items obtained.

Results: Over 50 papers in English containing some empirical data were identified. Most studies were retrospective. Typical PICU patients are male, younger, single, unemployed, suffering from schizophrenia or mania, from a Black Caribbean or African background, legally detained, with a forensic history. The most common reason for admission is for aggression management, and most patients stay a week or less. Evidence of the efficacy of PICU care is very poor.

Conclusions: Most research so far has been small scale, and more substantial work using better methodologies is clearly required.