bluuebunny/crossref_metadata_2025 huggingface dataset:
How Helpful Are Meta-Analyses in Determining the Best Therapy of Blood Diseases?
Authors: Gale Robert Peter , Lazarus Hillard M.
Published: December 2010

Meta-analyses of data from randomized clinical trials (RCTs) are often used by hematologists to compare the efficacy of therapies of blood diseases. This is especially so when results of RCTs are not decisive. This situation in RCTs arises when the magnitude of differences in treatment outcomes between therapies tested is small, when trials are unpowered to detect differences (these are confounded) and/or when RCTs reach, or seem to reach, contradictory conclusions. Contributing to these limitations of RCTs are the relative rarity of many blood diseases, poor recruitment into RCTs and the greater interest of many hematologists in therapy strategy than in a direct comparison of alternate therapies. These limitations of RCTs are solvable, but only in part, by meta-analyses. Adding data from high-quality observational database studies(ODBs) to meta-analyses is sometimes useful in resolving controversies, but this approach also has limitations: biases may be difficult or impossible to identify and/or to adjust for. However, ODBs have large numbers of diverse subjects receiving diverse therapies and adding these data to meta-analyses sometimes gives answers more useful to clinicians than meta-analyses of RCTs alone. Side-by-side comparisons suggest analyses from high-quality ODBs often give similar conclusions as meta-analyses of high-quality RCTs. Quantification of expert opinion of high quality is also sometimes useful: experts rarely disagree under precisely defined circumstances and their consensus conclusions are often concordant with results of meta-analyses of high-quality RCTs with and without ODBs. We conclude that meta-analyses are often helpful to determine the best therapy of blood diseases. Accuracy can be improved by including data from high-quality ODBs, when appropriate, and by resolving discordances, if any, with conclusions from high-quality ODBs and from quantification of expert opinion.
Immunotherapy for Patients with Follicular Lymphoma: The Contribution of Systematic Reviews
Authors: Vidal Liat , Gafter-Gvili Anat , Shpilberg Ofer
Published: December 2010

The course of follicular lymphoma has changed considerably with the introduction of immunotherapy. Systematic reviews and meta-analyses are reliable, efficient and well-established methods to summarize the vast amount of data acquired in recent years on the role of immunotherapy, including monoclonal antibodies, radio-labeled monoclonal antibodies and interferon-α in the treatment of patients with follicular lymphoma. We aimed to summarize the data from systematic reviews assessing immunotherapy for these patients. A search through Medline and the Cochrane Library for systematic reviews of randomized controlled trials of different types of immunotherapy for patients with follicular lymphoma yielded 17 reviews. Eleven of them were eligible for this review and are described herein. These systematic reviews have dramatically influenced the approach to patients with follicular lymphoma.
Management of Aplastic Anemia: The Role of Systematic Reviews and Meta-Analyses
Authors: Gafter-Gvili Anat , Ram Ron , Raanani Pia , Shpilberg Ofer
Published: December 2010

Aplastic anemia is a rare bone marrow failure disorder. Allogeneic hematopoietic cell transplantation (alloHCT) and immunosuppressive therapy (IST) are the main therapeutic modalities currently used to treat patients with aplastic anemia. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) are regarded as the highest level of evidence and as such aid practitioners in solving clinical questions. The objective of this review is to assess the base of evidence for the common practice and the current guidelines for the management of aplastic anemia. It focuses on data obtained from systematic reviews and meta-analyses of RCTs conducted in this field. Specifically, it focuses on four major therapeutic questions: the roles of alloHCT, IST, hematopoietic growth factors and supportive care.
The Use of Myeloid Colony-Stimulating Factors in Hematologic Malignancies: The Role of Systematic Reviews and Meta-Analyses
Authors: Gurion Ronit , Shacham-Abulafia Adi , Shpilberg Ofer , Raanani Pia
Published: December 2010

Myeloid colony-stimulating factors (M-CSFs), which include granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), regulate the proliferation and differentiation of myeloid cells. Their use has an important role in the treatment of hematologic malignancies. Guidelines for the use of colony stimulating factors have been published by the American Society of Oncology (ASCO) in 1996 and have been updated several times, most recently in 2006. Meta-analyses of randomized controlled trials are regarded as the highest grade of evidence in clinical research and as such, compared to individual studies, they have more power in answering unresolved clinical issues. In this review, our aim is to evaluate the role of M-CSFs in hematologic malignancies based on meta-analyses conducted in the field.
Infections in Hematogical Cancer Patients: The Contribution of Systematic Reviews and Meta-Analyses
Authors: Paul Mical , Gafter-Gvili Anat , Goldberg Elad , Yahav Dafna
Published: December 2010

Systematic reviews and meta-analyses have made a major contribution to the evidence-based management of infections in cancer patients. We review the contribution of systematic reviews with regard to antibiotic, antifungal, antiviral and Pneumocystis pneumonia prophylaxis; antibiotic and antifungal treatment of febrile neutropenia; use of intravenous immunoglobulins, and infection control strategies during neutropenia. We focus on limitations of randomized controlled trials and the way systematic reviews have addressed and resolved some of these limitations. Systematic reviews allow us to ask the right clinical question; consider the most relevant clinical outcome; address the problem of small trials and rare outcomes; address external validity and bias in randomized controlled trials, and point at gaps in evidence.
Comparison of the Use of the Halimeter and the Oral Chroma™ in the Assessment of the Ability of Common Cultivable Oral Anaerobic Bacteria to Produce Malodorous Volatile Sulfur Compounds from Cysteine and Methionine
Authors: Salako Nathanael O. , Philip Leeba
Published: December 2010

Objective: To compare the use of the Halimeter and the Oral Chroma™ to assess the ability of common oral anaerobic bacteria isolated from the Kuwaiti population to produce volatile sulfur compounds (VSCs). Materials and Methods: Broth cultures of common anaerobes isolated from supragingival plaque were centrifuged and pellets resuspended in phosphate buffer (pH 7.7) with an optical density OD550 of 0.3. 100 µl of this suspension and 870 µl of buffer were added in 2 sterile 15-ml head space vials. Reaction was initiated by addition of 30 µl of 33 mML-methionine and L-cysteine, respectively, in each vial and incubation at 37°C for 90 min. 500 µl of 3 M phosphoric acid was added to tubes and was kept aside for 10 min. Production of VSCs was measured using the Halimeter and the Oral Chroma. Results: The major VSC producers identified by both Halimeter and Oral Chroma with L-cystenine as substrate were Campylobacter ureolyticus, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Gemella morbillorum. The concentrations of hydrogen sulfide recorded by both Halimeter and Oral Chroma were essentially identical. With L-methionine as substrate, both Halimeter and Oral Chroma identified different complements of anaerobes with C. ureolyticus,P. gingivalis,Fusobacterium nucleatum and P. intermedia as major VSC producers. The concentrations of methyl mercaptan recorded by the Halimeter were lower compared to those assessed by the Oral Chroma. Conclusion: The results suggest that the Oral Chroma may produce a more comprehensive assessment of VSC production by oral microflora than the Halimeter.
Involvement of Opioid, Adenosine and 5-HT3 Receptors in Antinociceptive Effects of an Ayurvedic Polyherbal Formulation
Authors: Chandrasekar S.B. , Divakar Kalyani , Pawar A.T. , Goli Divakar , Harisha R. , Bhanumathy M. , Sushma G. , Shivaprasad H.N.
Published: December 2010

Objective: The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. Materials and Methods: With the tail immersion method, rats received two different doses (270 and 405 mg/kg BW, p.o.) of a formulation, pethidine (5.4 mg/kg BW, p.o.) as a reference standard and the combination of the higher dose of the formulation with naloxone (2 mg/kg, i.p.), an opioid receptor antagonist, and caffeine (16 mg/kg, i.p.), used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses (390 and 585 mg/kg, BW, p.o.) of formulation, diclofenac sodium (15 mg/kg, BW, p.o.) as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron (0.5 mg/kg, i.p.), a serotonin receptor antagonist. Results: The polyherbal formulation (405 mg/kg) exhibited a significant (p < 0.01) antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant (p < 0.01) dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. Conclusion: Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways.
Microbiology of Tunnelled Catheter-Related Infections in a Multi-Ethnic South-East Asian Patient Population
Authors: Teo Boon Wee , Sau Po Yi , Xu Hui , Ma Valerie , Vathsala A. , Lee Evan J.C.
Published: December 2010

Introduction: Clinical practice guidelines recommend empiric antibiotic therapy for suspected tunnelled haemodialysis catheter-related infections (CRI), and the choice of antibiotics should be adjusted according to the local microbiological profile and antimicrobial sensitivities. We aim to describe the microbiology, antibiotic sensitivities, and clinical outcomes of CRI with tunnelled haemodialysis catheters in a multi-ethnic South-East Asian population. Methods: Using a prospective vascular access registry, we identified 99 patients who had catheters removed for suspected or confirmed CRI (50.5% male, mean age 56.9 years) from January 1, 2007, till May 2009. We retrospectively retrieved microbiology, mortality and echocardiography data from the hospital electronic databases. Results: There were 115 removal-unique cultures that yielded 75.7% Gram-positive and 24.3% Gram-negative isolates (15 removals were polymicrobial). Organisms isolated were methicillin-resistant Staphylococcus aureus (MRSA) 28.6%, methicillin-sensitive S. aureus 26.5%, coagulase-negative staphylococci 21.4%, Pseudomonas aeruginosa 10.2%, and others. Out of 8 patients who died, 7 had MRSA. Risk factors associated with mortality were Chinese race (p = 0.03), MRSA infection (p < 0.001), and older age (p < 0.001). Conclusion: Gram-positive isolates accounted for most tunnelled CRI and MRSA was highly associated with death. In sick patients presenting with suspected CRI, the preferred empiric antibiotic regimen should include agents active against both MRSA and P. aeruginosa.
Cinacalcet Treatment for Secondary Hyperparathyroidism in Dialysis Patients: An Observational Study in Routine Clinical Practice
Authors: Bover Jordi , Perez Rafael , Molina Manuel , Benavides Beatriz , Ariza Francisco , Miguel José Luis , Tornero Fernando , Torregrosa Josep Vicens ,   on behalf of the Renal Osteodystrophy Group of the Spanish Society of Nephrology and all the investigators from the REHISET study
Published: December 2010

Background: Cinacalcet reduces intact parathyroid hormone (iPTH), Ca and P serum levels in patients with secondary hyperparathyroidism (SHPT). Methods: This Spanish, multicenter, observational, retrospective study collected data from SHPT dialysis patients 12 weeks before and up to 72 weeks after starting cinacalcet in clinical practice. Results: Data from 428 patients with uncontrolled SHPT despite receiving standard of care (29% with baseline iPTH 501–800 pg/ml; 51% with >800 pg/ml) were collected. Percentages of patients within National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets at baseline and 72 weeks were: iPTH, 0 versus 32.5% (p < 0.05); Ca, 40.1 versus 50% (p < 0.05); P, 47.7 versus 53.8% (p = 0.162). Vitamin D sterol use decreased from 53.3% at baseline to 36.7% at 72 weeks (p < 0.05). The mean ± SD cinacalcet dose at 72 weeks was 44.0 ± 25.8, 51.7 ± 31.3 and 57.1 ± 37.0 mg for patients with baseline iPTH 301–500, 501–800 or >800 pg/ml, respectively. The main adverse reactions were nausea (5.4%), dyspepsia (5.1%) and vomiting (3.7%). Conclusions: The introduction of cinacalcet improved the routine clinical management of SHPT in a large cohort of Spanish dialysis patients. Cinacalcet is effective and well tolerated regardless of disease severity, and maintains its efficacy over 72 weeks.
Molecular Study of Proteinuria in Patients Treated with B12 Supplements: Do Not Forget Megaloblastic Anemia Type 1
Authors: Levin-Iaina Nomy , Dinour Dganit , Morduchowicz Gabriel , Ganon Liat , Holtzman Eli J.
Published: December 2010

Background/Aims: Current consensus supports the notion that proteinuria is a marker of renal disease with prognostic implications. Whereas most chronic kidney disease patients with proteinuria would often require antiproteinuric agents, there are some exceptions. Megaloblastic anemia type 1 (MGA1) is characterized by megaloblastic anemia due to congenital selective vitamin B12 malabsorption and proteinuria. In the present study, we describe 2 Israeli Jewish patients with MGA1 and isolated proteinuria. Methods: Because of their origin, the patients were screened for the presence of the already studied Tunisian AMN mutation, by direct sequencing the corresponding region from genomic DNA. PCR products were purified and sequenced. Results: Genomic DNA sequencing of the AMN gene of both patients confirmed that the acceptor splice site in intron 3 was changed from CAG to CGG (208-2A→G). Conclusion: We determined the molecular basis of MGA1 in both patients and discuss the involvement of the cubilin/AMN complex in this pathology and its role in the development of the proteinuria. We also discuss the questionable significance of antiproteinuric treatment for these patients.
Oxaliplatin-Free Interval as a Risk Factor for Hypersensitivity Reaction among Colorectal Cancer Patients Treated with FOLFOX
Authors: Mori Yukiko , Nishimura Takafumi , Kitano Toshiyuki , Yoshimura Ken-ichi , Matsumoto Shigemi , Kanai Masashi , Hazama Megumi , Ishiguro Hiroshi , Nagayama Satoshi , Yanagihara Kazuhiro , Teramukai Satoshi , Chiba Tsutomu , Sakai Yoshiharu , Fukushima Masanori
Published: December 2010

Background: Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood. Patients and Methods: Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed. Results: Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016). Conclusions: An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.
Impact of Polymorphisms of the Genes Encoding Angiotensin II-Forming Enzymes on the Progression of IgA Nephropathy
Authors: Jung Eun Sook , Kim Sun Moon , Cha Ran-hui , Oh Yun Kyu , Kim Yon Su , Kim Suhnggwon , Lim Chun Soo
Published: December 2010

Background/Aims: Angiotensin II has been shown to play an important role in various renal diseases. Genetic polymorphisms of the renin-angiotensin system have been reported to be related to the clinical outcomes in immunoglobulin A nephropathy (IgAN). We investigated the association of polymorphisms of the genes encoding major angiotensin II-forming enzymes with the development and progression of IgAN among Korean patients. Methods: A total of 261 IgAN patients and 300 healthy controls were studied. The polymorphisms of angiotensin-converting enzyme gene (I/D, A2350G) and chymase (CMA) gene (rs1800875, rs1800876) were determined. Results: No significant difference was observed in the genotype and allele frequencies of the polymorphisms between IgAN patients and controls. The frequency of AA/AG genotypes of CMA rs1800875 and CC/CT genotype of CMA rs1800876 were significantly higher in patients with progressive disease course than in those with stable course (53.2 vs. 38.6%, p = 0.029; 89.6 vs. 78.3%, p = 0.031, respectively). In the Cox regression model with adjustment for clinical risk factors, CMA rs1800875 AA/AG genotypes remained an independent risk factor (hazard ratio 2.351; p = 0.001). Conclusion: Our results suggest that the CMA rs1800875 polymorphism is associated with the progression of IgAN in Korean patients.
Microchimeric Fetal Cells Are Recruited to Maternal Kidney following Injury and Activate Collagen Type I Transcription
Authors: Bou-Gharios George , Amin Farhana , Hill Peter , Nakamura Hiroyuki , Maxwell Patrick , Fisk Nicholas M.
Published: December 2010

Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.
Insufficient Lymph Node Dissection Is an Independent Risk Factor for Postoperative Cancer Death in Patients Undergoing Surgery for Stage II Colorectal Cancer
Authors: Ishizuka M. , Nagata H. , Takagi K. , Kubota K.
Published: December 2010

Background: Surgical resection is the most effective treatment for patients with stage II colorectal cancer (CRC). However, a few patients with early-phase CRC suffer postoperative cancer death. Aims: To investigate the risk factors for postoperative cancer death in patients who undergo surgery for stage II CRC. Methods: Prognostic significance was analyzed by χ2 test, univariate analyses, Kaplan-Meier analysis and log-rank test using clinicopathological factors from the database. Results: A total of 205 patients with stage II CRC were evaluated. Age (≤65/>65 years), venous invasion (negative/positive), number of dissected lymph nodes (≤9/≧10), grade of lymph node dissection (sufficient/insufficient) and albumin level (<3.5/≧3.5 g/dl) were associated with shorter overall survival. Univariate analysis of the clinicopathological factors revealed that only the grade of lymph node dissection (sufficient/insufficient) was associated with postoperative cancer death (odds ratio 2.993, 95% confidence interval 1.216–7.368, p = 0.017).Kaplan-Meier analysis and log-rank test revealed that the group with insufficient lymph node dissection had a higher incidence of postoperative cancer death than the group with sufficient dissection (p < 0.001). Conclusions: Insufficient lymph node dissection is an independent risk factor for postoperative cancer death in patients who undergo surgery for stage II CRC.
Avoidable Cost of Alcohol Abuse in Canada
Authors: Rehm Jürgen , Patra Jayadeep , Gnam William H. , Sarnocinska-Hart Anna , Popova Svetlana
Published: December 2010

Aims: To estimate avoidable burden and avoidable costs of alcohol abuse in Canada for the year 2002. Methods: A policy effectiveness approach was used. The impact of six effective and cost-effective alcohol policy interventions aimed to reduce alcohol consumption was modeled. In addition, the effect of privatized alcohol sales that would increase alcohol consumption and alcohol-attributable costs was also modeled. The effects of these interventions were compared with the baseline (aggregate) costs obtained from the second Canadian Study of Social Costs Attributable to Substance Abuse. Results: It was estimated that by implementing six cost-effective policies from about 900 million to two billion Canadian dollars per year could be saved in Canada. The greatest savings due to the implementation of these interventions would be achieved in the lowering of productivity losses, followed by health care, and criminality. Substantial increases in burden and cost would occur if Canadian provinces were to privatize alcohol sales. Conclusion: The implementation of proven effective population-based interventions would reduce alcohol-attributable burden and its costs in Canada to a considerable degree.
Functional Expression and Subcellular Localization of the Taurine Transporter TauT in Murine Neural Precursors
Authors: Hernández-Benítez Reyna , Pasantes-Morales Herminia , Pinzón-Estrada Enrique , Ramos-Mandujano Gerardo
Published: December 2010

Taurine addition to cultured embryonic neural precursor cells (NPC) significantly increased cell proliferation [Hernández-Benítez et al., 2010]. The medium used for NPC growing and proliferation is a fetal serum-free medium, and therefore, NPC become taurine depleted. Addition of taurine to the cultured medium fully replenished the cell taurine pool, suggesting the functional expression of a taurine transporter (TauT) in these cells. In the present study, TauT in NPC was functionally characterized and its protein expression and the subcellular distribution of immunoreactivity were determined. 3H-taurine uptake in NPC could be separated into a non-saturable component and a Na+/Cl–-dependent, saturable component. The saturable component showed an apparent 2:1:1 Na+/Cl–/taurine stoichiometry, a Vmax of 0.39 ± 0.04 nmol/mg protein/min, and a Km of 21.7 ± 2.6 µM. TauT in NPC was strongly inhibited by hypotaurine and β-alanine (92 and 79%, respectively) and reduced (71%) by γ-aminobutyric acid. TauT protein is expressed in NPC as a single band of about 70 kDa. Essentially all (98.8%) of the neurosphere-forming cells were positive to TauT immunoreactivity. Immunolocalization visualized by confocal microscopy localized TauT predominantly at the cell membrane. TauT was also found at the cytosol and only occasionally at the nuclear membrane. This study represents the first characterization of TauT in NPC.
Development of Gold Standard Ion-Selective Electrode-Based Methods for Fluoride Analysis
Authors: Martínez-Mier E.A. , Cury J.A. , Heilman J.R. , Katz B.P. , Levy S.M. , Li Y. , Maguire A. , Margineda J. , O’Mullane D. , Phantumvanit P. , Soto-Rojas A.E. , Stookey G.K. , Villa A. , Wefel J.S. , Whelton H. , Whitford G.M. , Zero D.T. , Zhang W. , Zohouri V.
Published: December 2010

Background/Aims: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. Methods: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. Results: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. Conclusion: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.
The Role of ERK1/2 Signaling Pathway in Coronary Microembolization-Induced Rat Myocardial Inflammation and Injury
Authors: Li Lang , Li Dong-Hua , Qu Nan , Wen Wei-Ming , Huang Wie-Qiang
Published: December 2010

Aim: Inflammation plays an important role in coronary microembolization (CME)-induced myocardial injury. The present study was designed to investigate the role of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of CME. Methods: Sprague-Dawley rats were randomly divided into three groups: sham-operated group (sham group), CME group and PD98059 group (15 animals per group). CME was produced by injection of 42-µm microspheres into the left ventricle with occlusion of the ascending aorta. Rats in the PD98059 group were injected with PD98059, a specific ERK1/2 inhibitor, 30 min before the CME operation. Western blotting and immunohistochemistry analysis were used to determine the activation of ERK1/2. Echocardiography was employed to evaluate cardiac function. Hematoxylin-eosin staining was performed to assay myocardial inflammation. Expression of TNF-α mRNA was determined by RT-PCR analysis, and activity of NF-ĸB was assessed by electrophoretic mobility shift assay. Results: CME dramatically induced cardiac dysfunction (left ventricular ejection fraction, LVEF, was 72.97 ± 3.20% in the CME vs. 82.69 ± 3.50% in the sham group, p < 0.05) and local myocardial inflammatory response, both of which were ameliorated significantly by PD98059 (LVEF was 76.46 ± 4.46 and p < 0.05 vs. CME group). When compared to the CME group, PD98059 markedly attenuated the increased phosphorylation of ERK1/2 (0.48 ± 0.11 vs. 0.92 ± 0.10, p < 0.05), expression of TNF-α mRNA (0.42 ± 0.06 vs. 0.94 ± 0.04, p < 0.05) and activity of NF-ĸB (104.83 ± 13.65 vs. 540.79 ± 24.95, p < 0.05) in CME rat myocardium. Conclusions: The present study demonstrates a novel role of the ERK1/2 signaling pathway in promoting myocardium inflammation and dysfunction in CME, and suggests that ERK1/2 is a novel potential therapeutic target for CME.
Sleep Quality and Quality of Life in Patients with Hypertrophic Cardiomyopathy
Authors: Pedrosa Rodrigo P. , Lima Sandro G. , Drager Luciano F. , Genta Pedro R. , Amaro Aline C.S. , Antunes Murillo O. , Arteaga Edmundo , Mady Charles , Lorenzi-Filho Geraldo
Published: December 2010

Objectives: To evaluate clinical predictors of poor sleep quality and quality of life (QOL) in patients with hypertrophic cardiomyopathy (HCM). Methods: Consecutive stable patients with HCM were evaluated for the risk of obstructive sleep apnea (OSA) by the Berlin Questionnaire, daytime sleepiness by the Epworth Sleepiness Scale, sleep quality by the Pittsburgh Sleep Questionnaire Index and QOL by the Minnesota Living with Heart Failure Questionnaire. Asymptomatic subjects without HCM were used as controls. Results: We studied 84 patients with HCM and 42 controls who were similar with regard to gender (49 vs. 50% males), age [52 (38–62) vs. 47 (33–58) years] and body mass index (27 ± 4 vs. 27 ± 5). HCM diagnosis, high risk for OSA and female gender were independently associated with poor sleep quality in the entire population. Among patients with HCM, poor QOL was independently associated with poor sleep quality, New York Heart Association functional class and diuretic therapy. Conclusion: Poor sleep quality is very common in patients with HCM and may have a negative impact on the QOL, which in turn is an important marker of prognosis in patients with cardiomyopathies.
Characteristics and Outcome of Patients with Early Complete Neurological Recovery after Thrombolysis for Acute Ischemic Stroke
Authors: Blinzler C. , Breuer L. , Huttner H.B. , Schellinger P.D. , Schwab S. , Köhrmann M.
Published: December 2010

Background: Recombinant tissue plasminogen activator (rt-PA) is the only approved specific therapy for acute ischemic stroke. This study analyzes demographic and clinical characteristics of patients with early complete neurological recovery after thrombolysis. Methods: Data of 320 consecutive patients treated with rt-PA within 3 h of stroke onset at our facility between April 2006 and March 2009 were extracted from our prospective institutional stroke and thrombolysis database. Baseline demographic parameters, risk factors, clinical characteristics as well as neuroradiologic findings of patients with complete recovery 24 h after treatment and at hospital discharge were analyzed. Outcome was evaluated using the modified Rankin Scale at 90 days. Results: Thirty patients (9.4%) were asymptomatic 24 h after thrombolysis and 70 (22%) at hospital discharge. Patients with complete recovery were younger, more often male, had milder stroke symptoms, less often cardioembolic strokes, fewer bleeding complications and more often normal follow-up imaging. In addition, in-hospital time was shorter and these patients retained a better functional outcome at 90 days. Only 1 patient who had completely recovered at hospital discharge died during the follow-up time. In multivariate regression analysis, only the National Institute of Health Stroke Score (NIHSS) on admission was predictive for complete recovery at both examined time points. Conclusion: Rapid complete recovery can be achieved in up to a fifth of acute stroke patients treated with thrombolysis. These patients are younger and have milder strokes, less often with cardioembolic origin. Better outcome and lower mortality are sustained at 3 months.
EEG Patterns and Epileptic Seizures in Acute Phase Stroke
Authors: Mecarelli O. , Pro S. , Randi F. , Dispenza S. , Correnti A. , Pulitano P. , Vanacore N. , Vicenzini E. , Toni D.
Published: December 2010

Background: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. Methods: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. Results: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. Conclusions: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures.
Surgical Outcomes for Rhinogenic Contact Point Headaches
Authors: Bektas Devrim , Alioglu Zekeriya , Akyol Nurettin , Ural Ahmet , Bahadir Osman , Caylan Refik
Published: December 2010

Objective: To evaluate the surgical outcome in patients diagnosed as having rhinogenic contact point headaches (RCPH). Subjects and Methods: Thirty-six patients (aged 17–58 years) with RCPH underwent mini functional endoscopic sinus surgery procedures. Patients’ pain complaints were evaluated with a visual analog scale (VAS) both pre- and postoperatively. Results: All patients reported a decrease in the intensity of pain postoperatively. Nineteen patients (52.7%) reported complete relief. The difference between the preoperative (mean 8.62) and postoperative VAS pain scores (mean 2.11) was statistically very significant (p = 0.0000). No major complications were encountered. Conclusion: The removal of contact points in patients with RCPH is very effective in carefully selected patients.
Sequential Expression, Activity and Nuclear Localization of Prolyl Oligopeptidase Protein in the Developing Rat Brain
Authors: Hannula Mirva J. , Männistö Pekka T. , Myöhänen Timo T.
Published: December 2010

Prolyl oligopeptidase (POP) is a serine protease that hydrolyzes peptides shorter than 30-mer. Some evidence has recently been obtained that POP can generate protein-protein interactions and therefore participate in various physiological and pathological events. Several studies have reported that POP may be involved in neurogenesis since its activity increases during development and can be found in the nucleus of proliferating tissues. In cell cultures, POP has been shown to be localized in the nucleus, but only early in the development, since during maturation it is moved to the cytosol. We have now studied for the first time the expression of POP protein, its enzymatic activity and nuclear localization in vivo in the developing rat brain. We observed that enzymatic activity of POP is highest on embryonic day 18 while the protein amounts reach their peak at birth. Furthermore, POP is located in the nucleus only early in the development but is transferred to the cytosol already before parturition. Our in vivo results confirm the previous cell culture results supporting the role of POP in neurogenesis. A discordance of antenatal protein amounts and enzymatic activities is suggesting a tight regulation of POP activity and possibly even a nonhydrolytic role at that stage.
Altitudinal Movements of Guizhou Snub-Nosed Monkeys (Rhinopithecus brelichi) in Fanjingshan National Nature Reserve, China: Implications for Conservation Management of a Flagship Species
Authors: Niu Kefeng , Tan Chia L. , Yang Yeqin
Published: December 2010

Primate movements can include a substantial altitudinal component, depending on the complexity of the landscape and the distribution of the inherent vegetation zones. We investigated altitudinal movements of Guizhou snub-nosed monkeys (Rhinopithecus brelichi) at Fanjingshan National Nature Reserve, China. The monkeys ranged at elevations between 1,350 and 1,870 m with an overall mean of 1,660 m. We did not find a significant difference in the mean elevations among seasons or evidence of winter migration to lower elevations. The monkeys exhibited a distinct daily altitudinal movement pattern that coincided with their activities. During the day, the monkeys consistently traveled from lower to higher elevations in the morning (98% of records) and then descended to lower elevations in the afternoon (96%). Hence, the mean elevation of night roosts was significantly lower (1,561 m) than those of feeding sites and day roosts (1,735 and 1,737 m, respectively). We suggest that this daily pattern of R. brelichi may reflect a trade-off between finding food and avoiding predation within the mixed evergreen and deciduous broadleaf vegetation zone at the study site, which may constitute the most important habitat for R. brelichi in the reserve.
Systematic Reviews of Topical Fluorides for Dental Caries: A Review of Reporting Practice
Authors: Ijaz S. , Croucher R.E. , Marinho V.C.C.
Published: December 2010

This paper aims to assess systematic reviews on the caries-preventive effect of topical fluorides, identifying key content and reporting quality issues to be considered by researchers planning a review in this area. Published systematic reviews and meta-analyses of any topical fluoride intervention for caries control were included. Relevant databases were searched (December 2009), along with reference lists of included publications. Thirty-eight reports were identified and assessed. A majority of these focused on the child/adolescent population, fluoride toothpastes, no treatment/placebo comparisons, and had caries increment as the main outcome. Complete reporting of eligibility criteria (PICOS) was uncommon, except in Cochrane reviews. Less than half reported searching multiple sources and only one third reported a search strategy. Duplicate study selection and data extraction was reported in 27 (71%) and 16 (42%) reviews, respectively; quality assessment of included studies was not reported in one third of the reviews. Meta-analysis was reported in 20 (52%) reviews, with six not reporting the methods of synthesis used, 17 formally assessing heterogeneity, and 12 reporting analyses for its exploration. This study shows that some content features have been covered more often than others in existing fluoride reviews, while some relevant features are yet to be addressed. Also, reporting of several methodological aspects are below an acceptable level, except for Cochrane reviews. Current reporting guidelines for systematic reviews of interventions (e.g. PRISMA) and sources of high-quality existing reviews (e.g. The Cochrane Library) should be closely followed to enhance the validity and relevance of future topical fluoride reviews.
Efficacy and Safety of Bronchoscopic Cryotherapy for Granular Endobronchial Tuberculosis
Authors: Mu Deguang , Nan Dongyan , Li Wangping , Fu Enqing , Xie Yonghong , Liu Tonggang , Jin Faguang
Published: December 2010

Background: The most important sequela of endobronchial tuberculosis (EBTB) is bronchial stenosis, which causes wheezing, dyspnea and obstructive pneumonia. But there have been no reports about applying cryotherapy for granular EBTB that did not show luminal narrowing of the bronchus at diagnosis. Whether this technique is useful for preventing granular EBTB from progressing into stenosis needs to be clarified. Objective: To investigate the efficacy and safety of bronchoscopic cryotherapy for granular endobronchial tuberculosis. Methods: In this study, we analyzed the records of 76 patients with granular EBTB. Diagnosis of TB was confirmed by microbiology or histopathology. Bronchoscopic examinations revealed that the patients had granular endobronchial tuberculosis. Thirty-eight patients received bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy and the other 38 patients received routine anti-tuberculosis chemotherapy alone. We compared the treatment effect of these 2 groups. The outcome measures were the changes of lesions, the rate of disappearance of lesions and complications of bronchoscopic cryotherapy. Results: The complete removal rate was 100% in patients with bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy; the complete removal rate was 78.9% in patients with anti-tuberculosis chemotherapy alone; the rate of disappearance of lesions in the bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy group was faster than that of the anti-tuberculosis chemotherapy alone group. There were no severe complications from bronchoscopic cryotherapy. Conclusions: Bronchoscopic cryotherapy can accelerate the healing of granular EBTB and help to prevent progressive bronchial stenosis due to granular EBTB and is a very safe method.
Intravitreal Bevacizumab and Cytokine Levels in Major and Macular Branch Retinal Vein Occlusion
Authors: Lim Ji Won
Published: December 2010

Purpose: My aim was to evaluate the effect of intravitreal bevacizumab and to determine the concentrations of inflammatory cytokines in patients with macular edema due to branch retinal vein occlusion (BRVO), according to the site of the occlusion. Methods: In a prospective interventional case series, 46 eyes of patients with macular edema due to major (n = 30) or macular BRVO (n = 16) were included. The patients were treated primarily with intravitreal bevacizumab (1.25 mg/0.05 ml) and completed 12 months of follow-up. Reinjections were performed if optical coherence tomography showed persistent or recurrent macular edema. Aqueous humor samples were collected at the time of initial intravitreal injection. Multiplex bead assays were used for the measurement of cytokines. Results: The visual acuity and central macular thickness were improved significantly in patients with major and macular BRVO at 12 months. During 12 months, the eyes with major BRVO received a mean of 3.8 intravitreal injections, whereas those with macular BRVO received a mean of 1.9 intravitreal injections (p = 0.009). Significantly increased concentrations of IL-6, IL-8 and MCP-1 were observed in the aqueous humor of BRVO patients compared with control samples. Higher concentrations of IL-6, VEGF, PDGF-AA and MCP-1 were measured in the aqueous humor of patients with major BRVO compared with macular BRVO at baseline (p < 0.05). Conclusion: Intravitreal bevacizumab was similarly effective for improving macular edema in patients with major and macular BRVO. However, macular BRVO required fewer injections and had lower cytokine levels in the aqueous humor than major BRVO.
Subjective Health and Memory Predictors of Mild Cognitive Disorders and Cognitive Decline in Ageing: The Personality and Total Health (PATH) through Life Study
Authors: Sargent-Cox Kerry , Cherbuin Nicolas , Sachdev Perminder , Anstey Kaarin J.
Published: December 2010

Aims: To investigate self-reports of memory and health as predictors of transition to mild cognitive impairment (MCI) or any mild cognitive disorder (any MCD) in a community-based study. Method: 2,082 individuals, aged 60–64 years, were assessed at 2 time points 4 years apart for MCI using either the International Consensus Criteria, the Clinical Dementia Rating scale (CDR, 0.5), or a suite of criteria sets for mild cognitive disorders (any MCD) and global cognitive change. Logistic and multiple regression was used to assess conversion to diagnosis and cognitive change from the SF-12 self-rated health (SRH) and physical health subscale measures, as well as reports of memory problems. Results: Of the 2,082 participants with no cognitive impairment at wave 1, 18 participants had a diagnosis of MCI, 32 a CDR score of 0.5, and 64 participants presented with any MCD 4 years later. After controlling for age, sex and education, SRH and physical health were significant predictors of MCD, memory interference was the only significant predictor of MCI, and cognitive change was associated with SRH, physical health and memory interference. Conclusion: Brief, short, easily collected self-reports of health, disability and memory can provide useful information on the risk of MCD and cognitive decline in young-old adults.
‘Executive’ Functions and Normal Aging: Selective Impairment in Conditional Exclusion Compared to Abstraction and Inhibition
Authors: Silver Henry , Goodman Craig , Gur Ruben C. , Gur Raquel E. , Bilker Warren B.
Published: December 2010

Background: Some executive functions may be selectively impaired in normal aging over and above the general cognitive decline. Methods: We examined the performance of healthy high functioning young (n = 77) and older (n = 57) individuals on three ‘executive’ tests: conditional exclusion, abstraction, and inhibition of prepotent responses. We compared their relationships to each other and to other cognitive functions including attention, psychomotor speed and working memory. Results: Conditional exclusion was significantly more impaired than abstraction or inhibition in the elderly compared to the younger group and unlike them, showed a nonlinear relationship with age. These findings were independent of other cognitive functions. Analysis of PCET performance characteristics showed that older individuals were particularly impaired in attaining the last of the three achievable categories, were slower, and had fewer error monitoring resources compared to the younger group. Conclusions: Conditional exclusion shows an age-related pattern of impairment distinct from inhibition and abstraction. We propose that in healthy well-functioning individuals, it taps processes integrating task set establishment and shifting in context of accumulating information. It may thus be useful as a specific marker of complex cognitive functions in studies of normal cognitive aging and in early detection of cognitive dysfunction.