bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced actions of insulin‐like growth factor‐I and interferon‐α co‐administration in experimental cirrhosis
Authors: Tutau Federico , Rodríguez‐Ortigosa Carlos , Puche Juan Enrique , Juanarena Nerea , Monreal Iñigo , García Fernández María , Clavijo Encarna , Castilla Alberto , Castilla ‐ Cortázar Inma
Published: March 2010

Background: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin‐like growth factor‐I (IGF‐I) whose plasma levels are diminished in cirrhosis. IGF‐I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon‐α (IFN‐α) therapy seems to suppress the progression of hepatic fibrosis.

Aims: The aim of this study was to investigate the effect of the co‐administration of IGF‐I+IFN‐α to Wistar rats with CCl4‐induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology.

Methods: The mechanisms underlying the effects of these agents were studied by reverse transcription‐polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor‐β (TGF‐β), α‐smooth muscle actin, collagen, tissular inhibitor of metalloproteinases‐1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection.

Results: Both IGF‐I and IFN‐α exerted significant effects on fibrogenesis. IGF‐I significantly increased serum albumin and HGF whereas IFN‐α‐therapy did not. The inhibition of TGF‐β expression was only observed by the effect of IFN‐α‐therapy. In addition, only the co‐administration of IGF‐I and IFN‐α was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture.

Conclusion: The co‐administration IGF‐I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.
Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection
Authors: Hayashi Takehiro , Tamori Akihiro , Nishikawa Manabu , Morikawa Hiroyasu , Enomoto Masaru , Sakaguchi Hiroki , Habu Daiki , Kawada Norifumi , Kubo Shoji , Nishiguchi Shuhei , Shiomi Susumu
Published: March 2010

Background/Aims: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV.

Methods: The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement‐loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation‐specific polymerase chain reaction.

Results: The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P=0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR‐HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P=0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR‐HCC.

Conclusions: Molecular alterations in hepatocarcinogenesis of patients with SVR‐HCC were different from those of patients with continuous HCV infection.
Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver
Authors: Nagatsuma Keisuke , Hayashi Yoshihiro , Hano Hiroshi , Sagara Hiroshi , Murakami Kazuhiro , Saito Masaya , Masaki Takahiro , Lu Tomoe , Tanaka Mitsugu , Enzan Hideaki , Aizawa Yoshio , Tajiri Hisao , Matsuura Tomokazu
Published: March 2010

Background: To determine the extent to which hepatic stellate cell (HSC) activation contributes to liver fibrosis, it was found necessary to develop an alternative structural and functional stellate cell marker for in situ studies. Although several HSC markers have been reported, none of those are associated with particular HSC functions.

Aim: The present study was undertaken to examine whether lecithin:retinol acyltransferase (LRAT), the physiological retinol esterification enzyme of the liver, is a potential and relevant tissue marker for HSC.

Methods: An antibody specific to mouse and human LRAT was prepared based on the amino acid sequences. Antibodies to LRAT were used for immunohistochemical studies to assess the distribution of LRAT‐positive cells in the liver with the aid of fluorescence and immunogold electron microscopy.

Results: LRAT‐positive cells were found to be confined in the space of Disse, corresponding with the location of desmin‐positive HSC in rodent liver, also in human liver. Interestingly, LRAT‐positive staining was also observed along the liver sinusoidal endothelial lining. Furthermore, immune electron microscopic studies revealed that LRAT was mainly distributed in HSC within the rough‐endoplasmic reticulum (RER) and multivesicular bodies, whereas LRAT staining within the endothelial cells was largely confined to the perinuclear area and to some extent to the RER.

Conclusion: Evidence has been accumulated that LRAT might serve as an excellent alternative HSC marker for future structural and functional studies. Furthermore, the presence of LRAT in endothelial cells might suggest a currently unknown function of this enzyme in liver endothelial biology.
Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C
Authors: Nieminen Urpo , Arkkila Perttu E. T. , Kärkkäinen Päivi , Färkkilä Martti A.
Published: March 2010

Background/Aims:The role of liver biopsy has been questioned in the management of patients with hepatitis C viral (HCV) infection. The aims of this study were to determine the impact of clinical parameters and degree of inflammation and steatosis on liver fibrosis.

Patients/Methods:Clinical data and liver histology findings in 510 HCV patients were analysed.

Results:Hepatitis C virus genotype 1 (GT‐1) was found in 38%, GT‐2 in 15% and GT‐3 in 45% of patients. In liver biopsy specimens, inflammation activity was present in 68%, increased fibrosis in 19% and marked steatosis in 17% of patients. Independent clinical risk factors for the increased fibrosis were patients' age at biopsy, body mass index (BMI) and duration of HCV. Steatosis and inflammation activity were independent histological risk factors for fibrosis only in GT‐1; in GT‐3, only inflammation correlated independently with fibrosis.

Conclusions:Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in GT‐1. When scoring liver biopsies of HCV patients, the degree of steatosis should be included in addition to fibrosis and inflammation activity.
Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells
Authors: Messner Donald J. , Sivam Gowsala , Kowdley Kris V.
Published: March 2010

Background/Aims: Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and the resulting downstream toxic effects in cultured T51B rat liver epithelial cells.

Methods: T51B cells were loaded with ferric ammonium citrate (FAC) with or without the iron delivery agent 8‐hydroxyquinoline. Cytotoxicity was measured by methylthiazolyldiphenyl‐tetrazolium bromide assay. Iron uptake and iron bioavailability were documented by chemical assay, quench of calcein fluorescence and ferritin induction. Reactive oxygen species (ROS) were measured by a fluorescence assay using 2′,7′‐dichlorodihydrofluorescein diacetate. Oxidative stress signalling to jnk, c‐jun and p38 was measured by a Western blot with phospho‐specific antibodies.

Results: Curcumin bound iron, but did not block iron uptake or bioavailability in T51B cells given FAC. However, it reduced cytotoxicity, blocked the generation of ROS and eliminated signalling to cellular stress pathways caused by iron. Inhibition was observed over a wide range of FAC concentrations (50–500 μM), with an apparent IC50 in all cases between 5 and 10 μM curcumin. In contrast, desferoxamine blocked both iron uptake and toxic effects of iron at concentrations that depended on the FAC concentration. The effects of curcumin also differed from those of α‐tocopherol, which did not bind iron and was less effective at blocking iron‐stimulated ROS generation.

Conclusions: Curcumin reduced iron‐dependent oxidative stress and iron toxicity in T51B cells without blocking iron uptake.
Model for end‐stage liver disease, model for end‐stage liver disease‐sodium and Child–Turcotte–Pugh scores over time for the prediction of complications of liver cirrhosis
Authors: Choi Pil Cho , Kim Hong Joo , Choi Woo Hyuk , Park Dong Il , Park Jung Ho , Cho Yong Kyun , Sohn Chong Il , Jeon Woo Kyu , Kim Byung Ik
Published: March 2010

Background/Aims: There has been no report concerning the predictive capability of each scoring system in determining the development of complications of liver cirrhosis such as variceal bleeding and/or hepatic encephalopathy.

Methods: We retrospectively studied 128 patients with liver cirrhosis [92 males; mean (standard deviation) 54.2 (11.2) years] admitted to our institution from March 2004 to April 2006. Seventy‐three patients (57.0%, group 1) were admitted because of complications of cirrhosis and 55 patients (43.0%, group 2) were admitted for causes unrelated to complications of cirrhosis. We calculated values for model for end‐stage liver disease (MELD), MELD‐sodium (MELD‐Na) and Child–Turcotte–Pugh (CTP) scores on admission and at 3 and 6 months before admission. Each delta score was defined as the difference in the scores of 3 and 6 months before admission.

Results: The relative risk for complications in the patients with ΔMELD/3 months ≥1.35, ΔMELD‐Na/3 months ≥1.35 and ΔCTP/3 months ≥1 was 2.05 [95% confidence intervals (CI) 1.47–2.85, P<0.01], 2.04 (95% CI 1.45–2.88, P<0.01) and 1.98 (95% CI 1.39–2.81, P<0.01) respectively. The area under the receiver‐operating characteristic curves of ΔMELD/3 months, ΔMELD‐Na/3 months and ΔCTP/3 months for the occurrence of cirrhotic complications were 0.691, 0.694 and 0.722 respectively. A higher ΔMELD/3 months (≥1.35), ΔMELD‐Na/3 months (≥1.35) and ΔCTP/3 months (≥1) was associated with decreased survival.

Conclusions: Delta model for end‐stage liver disease/3 months, ΔMELD‐Na/3 months and ΔCTP/3 months were clinically useful parameters for predicting the occurrence of cirrhotic complications.
Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis
Authors: Ryu Soo Hyung , Chung Young‐Hwa , Lee Jae Kyun , Kim Jeong A. , Shin Jung Woo , Jang Myoung Kuk , Park Neung Hwa , Lee Han Chu , Lee Yung Sang , Suh Dong Jin
Published: March 2010

Backgrounds/Aims: It has been reported that tamoxifen may affect hepatoma cell growth in vitro by suppressing transforming growth factor β‐1 (TGF‐β1) expression, suggesting that tamoxifen might also retard fibrogenesis. Thus, we examined whether tamoxifen might suppress TGF‐β1 expression and consequently inhibit the process of hepatic fibrosis in vivo.

Methods: To induce periportal hepatic fibrosis, 50 male adult Sprague–Dawley rats were injected with 0.62 mmol/kg of allyl alcohol, intraperitoneally, twice a week for 8 weeks. Hepatic fibrosis scores, intrahepatic collagen levels and plasma TGF‐β1 expression levels were evaluated in three groups of 10 rats orally administered tamoxifen at 1, 5 and 10 mg/kg, respectively, and in 20 controls. Messenger RNAs (mRNAs) encoding TGF‐β1 and TGF‐β receptors in liver tissue were semiquantified using reverse transcriptase polymerase chain reaction.

Results: Hepatic fibrosis scores decreased progressively as the dose of tamoxifen increased, resulting in a significant change in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.018). Intrahepatic collagen content was significantly less in the group treated with tamoxifen at 10 mg/kg compared with the control (P=0.045). Plasma TGF‐β1 levels were also significantly lower in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.007). All three concentrations of tamoxifen tested decreased the expression levels of hepatic TGF‐β1 mRNA and type I TGF‐β receptor (TGF‐β RI) mRNA to similar extents.

Conclusions: Tamoxifen seems to inhibit the process of hepatic fibrosis dose‐dependently by suppressing the transcription of TGF‐β1 and TGF‐β RI in an experimental model of periportal hepatic fibrosis.
Gender‐incompatible liver transplantation is not a risk factor for patient survival
Authors: Lehner Frank , Becker Thomas , Klempnauer Jürgen , Borlak Jürgen
Published: March 2010

Background/Aims: Clinical data may be suggestive for differences in patient survival in gender‐incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively linked to circulating hormones. We therefore investigated patient survival as well as metabolism of steroids to identify possible causes of improved graft survival in gender‐mismatched OLT.

Methods: We examined our single‐centre database of 1355 recipients of first liver transplants for overall patient survival by non‐parametric and parametric analysis of multivariance taking the age of recipient and donor, ischaemia time, underlying liver disease and the time period of transplantation into account. Furthermore, the metabolism of androgens in gender‐incompatible OLT was studied in cultures of primary human hepatocytes obtained from male and female patients.

Results: Unlike previous studies we were unable to determine overall significant differences in patient survival in gender‐incompatible OLT, even though a statistically significant improved patient survival was observed when male donor livers were transplanted into female recipients in univariant analysis (P=0.047). However, when the overall patient management was taken into account no difference in survival was determined in multivariant analysis. Importantly, the metabolism of testosterone did not differ between male and female hepatocyte cultures, except for the production of 6‐α‐hydroxy‐testosterone (P<0.001).

Conclusions: Taken collectively, clinical observations may tend to suggest a slightly improved patient survival in gender‐incompatible OLT but this cannot be explained on the bases of androgen metabolism. Overall, we view gender‐incompatible liver transplantation not to be a confounder in patient survival after OLT.
Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma
Authors: Kim Ji Hoon , Park Joong‐Won , Koh Dong Wook , Lee Woo Jin , Kim Chang‐Min
Published: March 2010

Background/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC.

Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored.

Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each).

Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.
Syndecan 1 (CD138) serum levels: a novel biomarker in predicting liver fibrosis stage in patients with hepatitis C
Authors: Zvibel Isabel , Halfon Phillipe , Fishman Sigal , Penaranda Guillaume , Leshno Moshe , Or Anat Bet , Halpern Zamir , Oren Ran
Published: March 2010

Background and Aims: Syndecan 1 (CD 138) is a cell surface proteoglycan shed by cells in several pathological conditions, including wound healing. The aim of this study was to test whether CD138 could serve as a non‐invasive marker for detection of liver fibrosis and thereby reduce the need for liver biopsy.

Patients and Methods: An estimation set of 134 patients and a validation set of 67 patients with chronic hepatitis C were studied. There were 80 normal healthy volunteers. Patients were staged according to liver biopsies (Metavir fibrosis staging, stage F0, n=35; F1, n=40; F2, n=37, F3, n=39; F4, n=51). Serum CD138 levels were retrospectively measured by enzyme‐linked immunoabsorbent assay the same day of the liver biopsy. The primary endpoints were the diagnostic values of CD138 for F2–F4, F3–F4 and F4.

Results: Respective areas under receiver operating characteristic curve of CD138 for F2–F4, F3–F4 and F4 diagnosis were 0.82, 0.76 and 0.81. CD138 had a positive predictive value of 82% for F2–F4 diagnosis and a high negative predictive value (86%) and specificity (84%) for exclusion of F4.

Conclusion: CD138 is a new simple non‐invasive marker for predicting liver fibrosis in patients with chronic hepatitis C. The relevance of this marker in combination with other fibrosis markers should be explored.
New aspects of liver abnormalities as part of the systemic mast cell activation syndrome
Authors: Alfter Kirsten , Von Kügelgen Ivar , Haenisch Britta , Frieling Thomas , Hülsdonk Alexandra , Haars Ulrike , Rolfs Arndt , Noe Gerhard , Kolck Ulrich W. , Homann Jürgen , Molderings Gerhard J.
Published: March 2010

Background/Aims: This study was aimed at investigating the form and prevalence of liver involvement in patients with systemic mast cell activation syndrome, a possibly common subvariant of systemic mastocytosis. An attempt was made to shed light on potential mechanisms responsible for mast cell mediator‐related liver abnormalities.

Methods: The methods used were clinical investigation, biochemical determination of cholesterol, transaminases and bilirubin in blood, determination of chitotriosidase by enzyme‐linked immunosorbent assay technique, and quantitative reverse transcribed‐polymerase chain reaction to determine chitotriosidase expression.

Results: An elevation of plasma cholesterol was detected in 75% of the patients; elevations of transaminases and bilirubin were determined in 40 and 36% of the patients respectively; hepatomegaly or morphological hepatic alterations were observed in 34%. Chitotriosidase level in blood as a surrogate parameter for Kupffer cell activation in the liver was unchanged. However, chitotriosidase expression in isolated mast cells was downregulated at the mRNA level.

Conclusions: Hypercholesterolaemia and liver abnormalities are frequently found in patients with the mast cell activation syndrome. Hence, the mast cell activation syndrome should be considered at an early stage as a possible cause of hypercholesterolaemia and of hepatic abnormalities of unknown reason. Mast cell activation may be indicated by a reduced expression of the enzyme chitotriosidase in blood‐derived mast cells as well as by an increased plasma cholesterol level.
Neuropsychological impairment in severe acute viral hepatitis is due to minimal hepatic encephalopathy
Authors: Sharma Praveen , Sharma Barjesh Chander , Tyagi Pankaj , Kumar Manoj , Sarin Shiv Kumar
Published: March 2010

Background and Aims: Minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis may have prognostic significance with regard to the development of clinical hepatic encephalopathy (HE) and deterioration in patient quality of life. Its prevalence in acute viral hepatitis (AVH) is not known.

Patients and Methods: Consecutive 20 AVH patients (age, 29.9±7.9 years; M:F 18:2, hepatitis A:B:E: 2:16:2) without overt encephalopathy were evaluated for MHE and followed up. All patients underwent number connection tests – A and B, figure connection tests – A and B, digit symbol test and object assembly test and critical flicker frequency (CFF) at baseline and after the resolution of icterus. MHE was diagnosed if two or more psychometric tests were abnormal.

Results: Prevalence of MHE (n=5) was 25%, which resolved on follow‐up during the anicteric resolution phase. Five (25%) patients had greater than two abnormal psychometry tests and four (20%) had CFF <38 Hz. CFF alone had sensitivity and specificity of 80 and 100%, respectively, in the diagnosis of MHE. There was significant difference in the performance of CFF during the icteric and resolution phase of AVH (40.6±3.4 vs 41.8±2.1 Hz, P=0.04). Arterial ammonia level were higher in patients with MHE compared with patients without MHE (88.2±23.5 vs 53.8±10.9 μmol/L, P=0.001). On univariate analysis fasting ammonia level at baseline was significantly associated with all the psychometric tests (P=0.001). None of the patients developed HE either in MHE group or in those who did not had MHE at baseline.

Conclusions: MHE occurs in 25% of patients with AVH and resolves on follow up with recovery of AVH. Raised arterial ammonia during the icteric phase is associated with development of MHE.
Immunoregulatory effects of liver ablation therapies for the treatment of primary and metastatic liver malignancies
Authors: Gravante Gianpiero , Sconocchia Giuseppe , Ong Seok Ling , Dennison Ashley R. , Lloyd David M.
Published: March 2010

Ablation of liver tissue produces in situ tumoural antigens and elicits specific immune responses. The aim of this review is to examine the available data about the local and systemic responses produced and to compare differences between the methods available. A literature search was undertaken for all papers focusing on immune responses following ablative therapy of the liver, including experimental and clinical studies. Following ablative procedures, the cellular response is elicited by the presentation of antigens by dendritic cells to specific CD4+ T cells, which in turn stimulate natural killer or CD8+ cytotoxic cells. The local release of intracellular debris activates Kupffer cells to produce cytokines, which, in the immediate vicinity, activate monocytes/macrophages or specific T cells that respond and produce systemic reactions such as fever, thrombocytopaenia or shock. The immune responses elicited by cryotherapy, both cellular and cytokine, seem far greater than those produced by radiofrequency or microwave ablation, probably as a consequence of the peculiar mechanism of cell death of the former (disruptive necrosis). This mechanism is considered central to the pathogenesis of cryoshock. Ablative techniques stimulate the immune system and provide an easy way to achieve in vivo vaccination against tumoural antigens. Immunomodulatory approaches have the potential to augment the initial immune stimulation and this combined approach could pave the way to a more selective and specific method of treating liver tumours.
Nutritional Status and Cognitive Function in Community‐Living Rural Bangladeshi Older Adults: Data from the Poverty and Health in Ageing Project
Authors: Ferdous Tamanna , Cederholm Tommy , Kabir Zarina Nahar , Hamadani Jena Derakhshani , Wahlin Åke
Published: March 2010

OBJECTIVES: To investigate the association between nutritional status and general and specific (fluid and crystallized) cognitive functioning in a group of older people living in a rural area in Bangladesh.

DESIGN: Cross‐sectional study.

SETTING: Matlab, Bangladesh.

PARTICIPANTS: Four hundred fifty‐seven randomly selected persons aged 60 and older (mean age 69.5 ± 6.8), 55% female.

MEASUREMENTS: Nutritional status was evaluated using a modified form of the Mini Nutritional Assessment (MNA). General cognitive function was assessed using the Bangla Adaptation of the Mini‐Mental State Examination, and a word synonym test was used to test semantic memory function (a crystallized ability). To assess cognitive processing speed (a fluid ability), “cross balls” and “complete boxes” tests (scores/time unit) were used. Clinical diagnoses were registered. Structured questionnaires were used to assess demographic and socioeconomic status of the participants.

RESULTS: Twenty‐six percent of the participants were undernourished, and 62% were at risk of malnutrition according to the MNA. The MNA scores were significantly lower in women than in men (P=.01). Women performed worse than men in all three cognitive tasks (P<.001). Poorer cognitive performance was independently associated with older age, female sex, illiteracy, visual impairment, severity of disease, and depressive symptoms. There were significant associations between better nutritional status and better cognitive performance tests of general ability and processing speed, whereas semantic memory appeared to be less affected.

CONCLUSION: The association between nutritional status and cognitive function involves general and specific cognitive abilities, with fluid ability seeming to be affected but crystalized functions being relatively spared.
Evaluation of the Potential for Bloodborne Pathogen Transmission Associated with Diabetes Care Practices in Nursing Homes and Assisted Living Facilities, Pinellas County
Authors: Thompson Nicola D. , Barry Vaughn , Alelis Karen , Cui Dongming , Perz Joseph F.
Published: March 2010

OBJECTIVES: To evaluate and characterize routine blood glucose monitoring practices in nursing homes and assisted living facilities (ALFs).

DESIGN: Cross‐sectional, self administered survey and facility site visit.

SETTING: Two hundred eighty‐nine licensed long‐term care facilities in Pinellas County, Florida.

PARTICIPANTS: Stratified random sample of 48 long‐term care facilities (17% overall sample).

MEASUREMENTS: Data on facility characteristics, infection control policies, staff practices, and equipment used for blood glucose monitoring. Differences between facilities in each stratum were compared and evaluated using the Pearson chi‐square or Fisher exact test.

RESULTS: Fifteen nursing homes and 17 small and 16 large ALFs participated; 53 declined (48% participation rate). Bloodborne pathogen training (P=.02), hepatitis B vaccination (P=.003), and blood glucose monitoring (P<.001) policies were reported less often at ALFs. Staff glove use during blood glucose monitoring was lowest (50%) at small ALFs (P=.02). Reusable fingerstick devices intended for personal use were most often in use at ALFs (P<.001); four of 18 facilities (including 1 nursing home) were inappropriately using them for multiple residents. At 22 facilities (including all nursing homes), multiple residents shared blood glucose meters; only six (27%) reported cleaning them after each use.

CONCLUSION: Despite existing recommendations, practices that facilitate bloodborne pathogen transmission during blood glucose monitoring were identified at nursing homes and ALFs. Infection control practices and polices were most often lacking at ALFs. Better training and oversight of blood glucose monitoring in long‐term care is needed to prevent transmission of bloodborne pathogens.
Investigation on Thermal Conductivity of Aluminum Nitride Ceramics by FT‐Raman Spectroscopy
Authors: Lee Hyeon‐Keun , Kim Do Kyung
Published: March 2010

FT‐Raman spectroscopy was used to characterize the thermal conductivity of yttria‐doped polycrystalline aluminum nitride (AlN) ceramics. Specimens with different thermal conductivity were prepared using sintering additives of different size, content, and mixing method. The broadening of the Raman mode is caused by point defects and impurities, which affect the thermal conductivity of the AlN grains (lattice thermal conductivity). The width of the Raman line was related to the c‐axis lattice parameter contraction, which was caused by aluminum vacancies produced by various defects. A correlation is suggested between the width of the E2 (high) phonon mode and the lattice thermal conductivity of AlN ceramics.
Microfracture and Limited Tribochemical Wear of Silicon Carbide During High‐Speed Sliding in Cryogenic Environment
Authors: Guha Tufan Kumar , Basu Bikramjit
Published: March 2010

In an effort to develop an understanding of the tribological properties of silicon carbide (SiC) in a cryogenic environment, this contribution reports on the results of the sliding wear properties of the self‐mated SiC in liquid nitrogen (LN2). Two sets of sliding wear tests were conducted in a planned manner in LN2 under varying combinations of operating conditions, using a specially designed high‐speed cryo‐tribometer. In the first set, the sliding velocity is varied up to 1.1 m/s, for 600 s, at a constant load of 5 N; while the second set of experiments were conducted with loads of 5, 10, and 15 N, at a constant speed of 3.3 m/s for 900 s, thereby enabling to evaluate tribological potential over a broad spectrum of operating conditions. In our experiments, high coefficient of friction (COF) (0.28–0.40) and high wear resistance (∼10−7–10−6 mm3/N m) have been measured for self‐mated SiC. The topographical observations using a scanning electron microscope reveal that limited tribochemical layer formation, as well as grain boundary microfracture‐induced damage mechanisms, contribute to the wear of self‐mated SiC. The experimental results are critically analyzed with reference to flash temperature and contact stress conditions, as well as compared with some baseline experiments, conducted under ambient conditions. A comparison with our earlier research results, obtained with self‐mated Al2O3 or ZrO2, establishes the good tribological potential of self‐mated SiC in LN2, in terms of exhibiting a better combination of COF and wear rate.
Rheumatoid Leptomeningitis: Magnetic Resonance Imaging and Pathologic Findings—A Case Report
Authors: Cianfoni Alessandro , Falcone Carlo , Faustini Francesca , Lauriola Libero , Imbesi Steven , Marca Giacomo Della , Zoli Angelo , Colosimo Cesare
Published: March 2010

BACKGROUND AND PURPOSE

Rheumatoid arthritis (RA) is a chronic inflammatory multisystem disease with articular and extra‐articular manifestations. Intracranial manifestations of RA are rare. Purpose of this article is to report on a rarely described leptomeningeal involvement in RA, and on its neuroimaging features, including diffusion‐weighted imaging (DWI).

METHODS

The authors describe the case of a 74‐year‐old woman with a 5‐year history of RA presenting with progressive left‐side weakness and hypoesthesia. The patient underwent laboratory investigation and brain contrast‐enhanced MRI, also with DWI, before undergoing brain biopsy.

RESULTS

Neuroimaging revealed abnormal high T2‐signal in right frontal and parietal lobes, restricted diffusion in the subarachnoid space, and diffuse thick linear leptomeningeal contrast‐enhancement. These findings were interpreted as rheumatoid leptomeningitis, and brain biopsy confirmed this diagnosis.

CONCLUSIONS

In summary, rheumatoid meningitis is a rare neurological complication of RA, but it should be considered in the proper clinical setting when patient presentation and laboratory results fail to support the other differential diagnostic possibilities proposed by the MR imaging findings.
Extravasating Contrast Material on Angiography Following Carotid Angioplasty and Stenting: Not Necessarily Subarachnoid Hemorrhage
Authors: Sharma Pranshu , Poppe Alexandre Y. , Eesa Muneer , Steffanhagan Nikolai , Hudon Mark , Morrish William
Published: March 2010

We describe a case of asymptomatic extravasation of iodinated contrast material into the sulci on digital subtraction angiography following carotid angioplasty and stenting resulting in sulcal hyperdensity on computed tomography (CT). We believe the mechanism for this observation is hyperperfusion injury and that in the absence of any associated clinical signs, it should not be considered alarming for subarachnoid hemorrhage.
Treatment of Vertebral Artery Origin Stenosis with Anti‐Proliferative Drug‐Eluting Stents
Authors: Edgell Randall C. , Yavagal Dileep R. , Drazin Doniel , Olivera Raul , Boulos Alan S.
Published: March 2010

BACKGROUND

Vertebral artery origin stenosis is a known cause of stroke that is treatable with angioplasty and stenting. Previous studies have demonstrated that this technique is safe but is limited by high rates of in‐stent stenosis. Anti‐proliferative drug‐eluting stents are an alternative for reducing in‐stent stenosis at the vertebral artery origin.

METHODS

This retrospective study included five consecutive patients treated with anti‐proliferative drug‐eluting stents. The patients' demographics, indications for treatment, procedural technique, and clinical and radiographic follow‐up are presented along with a review of the literature.

RESULTS

No peri‐procedural complications occurred. One patient had a transient ischemic attack (TIA) during the follow‐up period. No patients had hemodynamically significant (>50%) in‐stent stenosis at follow‐up. Among the 287 cases reported in the literature, there were two strokes (.7%), four TIAs (1.4%), and no procedurally related deaths. Among patients undergoing angiographic follow‐up, 26% were found to have >50% in‐stent stenosis.

CONCLUSIONS

Anti‐proliferative drug‐eluting stents hold promise for reducing in‐stent stenosis at the vertebral artery origin.
Pathophysiology and Long‐Term Outcome of Reversible Tumor‐Like Lesions Induced by Presenting Status Epilepticus
Authors: Canas Nuno , Soares Pedro , Calado Sofia , Pestana Ricardo , Ribeiro Constança , Vale José
Published: March 2010

BACKGROUND AND PURPOSE

Within the spectrum of reversible neuroimaging abnormalities induced by status epilepticus (SE) tumor‐like lesions (TLL) have been rarely described. Their etiology, pathophysiology, and long‐term outcome remain uncertain. These issues could be clarified by long‐term magnetic resonance imaging (MRI) studies in TLL induced by presenting SE.

METHODS

Prospective multi‐sequence MRI and clinical and electroencephalographic long‐term (18 to 60 months) follow‐up studies were performed in 3 patients with reversible TLL induced by presenting SE.

RESULTS

In the peri‐ictal MRI, TLL are hypointense in T1‐weighted, hyperintense in T2‐weighted, and fluid‐attenuated inversion recovery images with a marked subcortical component and sulci effacement. The diffusion and MR‐spectroscopy studies disclosed intermixed areas of increased/decreased diffusivity associated with a lactate peak and a decreased N‐acetylaspartate. At long‐term follow‐up, none of the patients had seizure recurrence or electroencephalographic epileptiform abnormalities; MRI showed residual focal atrophy and gliosis associated with neuronal loss/dysfunction.

CONCLUSIONS

SE per se may induce TLL. MRI multi‐sequence studies disclosed that they are mainly formed by focal vasogenic and cytotoxic edema resulting from the hypermetabolism associated with seizure activity. In spite of a clinical favorable long‐term outcome, the demonstration of irreversible brain damage argues in favor of immediate treatment of SE.
Pilot Study of New Diagnostic Criteria for Middle Cerebral Artery Stenosis by Transcranial Doppler
Authors: Hao Qing , Gao Shan , Leung Thomas Wai Hong , Guo Ming Hui , You Yong , Wong Ka Sing
Published: March 2010

BACKGROUND AND PURPOSE

Current criteria for middle cerebral artery (MCA) stenosis by transcranial Doppler were mainly based on the flow velocity acceleration, ignoring other useful parameters. We tested the accuracy of new criteria using magnetic resonance angiography (MRA) as the confirmative method.

METHODS

A compositive score for each MCA was calculated according to following parameters: Velocity Scale (score 0‐6 for peak systolic velocity <140 to ≥300 cm/second), Hemodynamic Scale (score 0‐5 for diffuse or focal velocity increase; score 0‐6 for differences between bilateral MCA; score 17 for damping velocity), and Spectrum Scale (score 0‐2 for normal spectrum, turbulence, and musical murmurs).

RESULTS

The median scores in normal‐mild, moderate, and severe groups on MRA differed significantly (P < .001). The optimal cutoff score for <50% and ≥50% stenosis was 3 with the PPV of 72.3% (95% confidence interval [CI]: 65.3% to 78.5%) and negative predictive value (NPV) of 89.5% (95% CI: 85.9% to 92.3%), for moderate and severe stenosis was 6 with the PPV of 85.9% (95% CI: 76.7% to 92.0%) and NPV of 61.9% (95% CI: 50.6% to 72.1%). Both scores performed better than peak systolic or mean velocity.

CONCLUSIONS

This new method was feasible and reliable and showed some advantages over the velocity‐only method. Further studies using digital subtraction angiography as the gold standard are needed to ameliorate the new criteria.
High‐Resolution Phased‐Array MRI of the Human Brain at 7 Tesla: Initial Experience in Multiple Sclerosis Patients
Authors: Metcalf Meredith , Xu Duan , Okuda Darin T. , Carvajal Lucas , Srinivasan Radhika , Kelley Douglas A.C. , Mukherjee Pratik , Nelson Sarah J. , Vigneron Daniel B. , Pelletier Daniel
Published: March 2010

Recent advancement for magnetic resonance imaging (MRI) involves the incorporation of higher‐field strengths. Although imagers with higher magnetic field strengths were developed and tested in research labs, the direct application to patient MR studies have been extremely limited. Imaging at 7 Tesla (7T) affords advantages in signal‐to‐noise ratio and image contrast and resolution; however, these benefits can only be realized if the correct coils exist to capture the images. The objective of this study was to develop optimized high‐resolution 7T MRI techniques using high sensitivity, specialized phased‐array coils, for improved gray matter (GM) and white matter differentiation, in an effort to improve visualization of multiple sclerosis (MS) lesions in vivo. Twenty‐three subjects were enrolled in this preliminary study, 17 with clinically definite MS (11 females, 6 males; mean age 43.4 years; range 22‐64 years) and 6 healthy controls (2 females, 4 males; mean age 39.0 years; range 27‐67 years). MR imaging of MS patients at 7T was demonstrated to be safe, well tolerated, and provided high‐resolution anatomical images allowing visualization of structural abnormalities localized near or within the cortical layers. Clear involvement of the GM was observed with improved morphological detail in comparison to imaging at lower‐field strength.
Frequency of Microemboli Signal in Stroke Patients Treated with Low Molecular Weight Heparin or Aspirin
Authors: Hao Qing , Chang Hui Meng , Wong Meng Cheong , Wong Ka Sing , Chen Christopher
Published: March 2010

BACKGROUND AND PURPOSE

Microemboli signal (MES) detected by transcranial Doppler (TCD) may represent ongoing embolic phenomenon and is a predictor of recurrent stroke or transient ischemic attack. We sought to study the frequency of MES in stroke patients with large artery occlusive diseases treated with low molecular weight heparin (LMWH) or aspirin.

METHODS

Patients participating in the Fraxiparine in Ischemic Stroke (FISS)‐tris study were recruited. MES detection was performed from middle cerebral artery on the 1st, 3rd, and 7th days after randomization. The correlation between the presence of MES and the treatment was determined by the χ2 test.

RESULTS

Among 47 patients, 26 were randomized to LMWH and 21 to aspirin. On day 1, MES were detected in 10 patients (7/26 on LMWH, 3/21 on aspirin; P= .475). On day 3, 12 patients had MES (7/25 on LMWH, 5/20 on aspirin; P= .821). On day 7, 11 patients had MES (6/25 on LMWH, 5/20 on aspirin; P= .938). The median of the number of MES on days 1, 3, and 7 was 4 (range 1‐10), 5 (range 1‐42), and 3 (range 1‐33) for the LMWH group and 1 (range 1‐15), 4 (range 1‐10), and 2 (range 1‐4) for the aspirin group.

CONCLUSIONS

There were no significant differences in the frequency of MES between patients with large artery occlusive disease treated with LMWH and aspirin.
Iron Foreign Body in the Optic Nerve without Ocular Siderosis
Authors: Hwang Yih‐Shiou , Lin Ken‐Kuo , Chen Kuan‐Jen , Lai Chi‐Chun
Published: March 2010

BACKGROUND AND PURPOSE

An intraocular iron foreign body may cause many ocular complications, sometimes even blindness. Therefore, if possible, it should be removed to avoid ocular siderosis. We report a case in which a foreign body was trapped in the optic nerve and could not be removed. After a 2‐year follow‐up, no ocular siderosis or progressive deterioration in vision was found. This is the first case report of a foreign body in the optic nerve behind the eyeball in the PubMed literature.

METHODS

The authors describe the case of a 33‐year‐old man with an ocular trauma history at work. A metal iron foreign body was trapped in the optic nerve behind the eyeball, which was demonstrated by computed tomography.

RESULTS

There was no significant vision change and ocular siderosis by electroretinogram after 2 years of follow‐up.

CONCLUSIONS

Intra‐optic‐nerve foreign body may have a better ocular prognosis. Siderosis may not be seen in patients with optic nerve iron foreign body. Intraocular foreign body should be accurately studied before surgical procedures.
Reversed Flow in the External Carotid Artery Despite a Patent but Stenosed Common Carotid Artery
Authors: Savva Elena , Sztajzel Roman , Landis Theodor , Perren Fabienne
Published: March 2010

BACKGROUND AND PURPOSE

Occlusion of the common carotid artery (CCA) is generally associated with an occlusion of the ipsilateral internal carotid artery (ICA) or of the external carotid artery (ECA) or of both. Sometimes, collateral circulation to the ECA may preserve patency of the ICA via retrograde perfusion through the bulb. We herewith report a case of reversed flow in the ECA in the presence of a patent but stenosed CCA as diagnosed with color‐coded duplex flow imaging (CDFI).

CASE REPORT

This 85‐year‐old right‐handed man was admitted for rapidly regressive acute dysarthria associated with left hemiparesis. Diffusion‐weighted magnetic resonance (MR) imaging showed an acute ischemic lesion in the territory of the right middle cerebral artery. MR angiography showed patency of the right ICA and ECA but an occlusion of the CCA was suspected. CDFI demonstrated patency of the right CCA with a high‐resistance pattern due to a large, partially calcified, stenosing atheromatous plaque. Surprisingly, reversed flow was observed in the right ECA of which signal was dampened.

CONCLUSION

Collateralization with reversed flow in the ECA may occur in a patent but stenosed CCA associated with a high‐grade stenosis of the carotid bifurcation. CDFI is a very useful tool to detect such hemodynamic conditions.
MR Atypical Wernicke Encephalopathy Showing Extensive Brain Stem and Diencephalic Involvement
Authors: Nardone Raffaele , Venturi Alessandro , Golaszewski Stefan , Caleri Francesca , Tezzon Frediano , Ladurner Gunther
Published: March 2010

Wernicke encephalopathy (WE) is a serious neurological disorder caused by thiamine (vitamin B1) deficiency. We report a case of atypical and extensive location of abnormal signal lesions on magnetic resonance imaging (MRI) in a man with alcohol abuse with WE. MRI performed on the first hospital day showed signal intensity alterations extending in the whole brain stem and diencephalon; the mismatch between diffusion‐weighted images and apparent diffusion coefficient map was highly suggestive of vasogenic edema. This report further supports the view that WE may represent a spectrum of radiological entities and can have a wide spectrum of manifestations on MRI; thus, clinical features are essential to diagnose it.
Prefrontal Compensatory Mechanism May Enable Normal Semantic Memory Performance in Mild Cognitive Impairment (MCI)
Authors: Gigi Ariela , Babai Reuven , Penker Avichen , Hendler Talma , Korczyn Amos D.
Published: March 2010

Mild cognitive impairment (MCI) is considered as a potential transitional state between normal aging and dementia. Studies addressing semantic memory in patients with incipient dementia and MCI show inconsistent results. In the current report we focused on MCI and examined memory performance (semantic, episodic, and working memory) in addition to structural and functional magnetic resonance imaging (fMRI) measurements. We studied 6 MCI, 6 normal controls, and 4 Alzheimer disease (AD) patients. MCI participants demonstrated normal semantic memory performance while fMRI examination revealed distinct patterns of activations between MCI and normal aged subjects. According to our previous study, time courses were taken from parietal, dorsolateral‐prefrontal‐cortex (DLPFC), hippocampal formation, and fusiform gyri. A small number of activated voxels in parietal regions were depicted in MCI participants and were correlated with structural changes in this region. In contrast, significantly higher activation (intensity and number of voxels) was observed in DLPFC of MCI subjects. The overactivity seen in DLPFC of MCI may represent a compensatory mechanism that enables them to perform normally. These preliminary results suggest that functional imaging may be useful for early diagnosis of dementia and call to develop reliable tests and criteria that will enable using such methods clinically.
Comprehensive flow cytometry phenotype in acute leukemia at diagnosis and at relapse
Authors: LI XIN , DU WEN , LIU WEI , LI XIAOQING , LI HONGRUI , HUANG SHI‐ANG
Published: March 2010

Li X, Du W, Liu W, Li X, Li H, Huang S‐A. Comprehensive flow cytometry phenotype in acute leukemia at diagnostic and at relapse. APMIS 2010; 118: 353–59.

Multiparameter flow cytometry (MFC) plays a vital role in the detection of minimal residual disease (MRD) and diagnosis of relapse in acute leukemia. However, application of a limited panel of antibodies in MFC leads to high rates of false‐negative and false‐positive results. Thirteen patients with acute lymphoblastic leukemia (ALL) and 12 patients with acute myeloid leukemia (AML) were immunophenotyped by MFC at diagnosis and at relapse using a comprehensive panel of monoclonal antibodies (McAbs) to 27 antigens and CD45/SSC gating. In 23 of 25 patients (92.3%), changes in at least one of progenitor‐associated, myeloid and lymphoid antigens between diagnosis and relapse were observed. Antigen changes were observed in 92 of 239 antigens (38.5%) expressed in 25 patients, in 49 of 117 antigens (41.9%) expressed in 13 ALL patients, and in 43 of 122 antigens (35.2%) expressed in 12 AML patients. Phenotypic changes were characterized by the expression of cross‐lineage antigens. The intralineage change was observed in the majority of patients. However, myeloid lineage shift was identified by MFC in two patients with T‐ALL. Multiple panels of three or more McAbs are likely to be required in the monitoring of MRD and diagnosis of relapse in acute leukemia by MFC.