bluuebunny/crossref_metadata_2025 huggingface dataset:
Existence of Possible Functional Interaction between the Saccule and the Posterior Semicircular Canal in Humans
Authors: Fujimoto Chisato , Karino Shotaro , Ito Ken , Murofushi Toshihisa
Published: January 2009

The purpose of this study was to determine the effects of stimulation of the vertical semicircular canals on vestibular evoked myogenic potentials (VEMPs). VEMPs were recorded in 14 subjects seated with their heads and necks tilted 120° forward on the interaural axis. The head was rotated 45° to the left or right from the sagittal plane; an angular acceleration around the earth’s vertical axis was then provided. When the posterior semicircular canal (PSCC) of the recording side was excited, the rotation was defined as ‘ipsilateral rotation’, and the opposite rotation was defined as ‘contralateral rotation’. The background muscle activity-corrected p13–n23 amplitude (CA) in the ipsilateral rotation was significantly smaller than CAs in the static state and the contralateral rotation. Functional interaction between the saccule and the PSCC could be detected.
Does a Reliable Decline in Mini Mental State Examination Total Score Predict Dementia?
Authors: Hensel Anke , Luck Tobias , Luppa Melanie , Glaesmer Heide , Angermeyer Matthias C. , Riedel-Heller Steffi G.
Published: January 2009

Background/Aim: Norms for change in Mini Mental State Examination (MMSE) total score suggest that only a decline of at least 2–4 points indicates a reliable change. However, it is unknown whether change norms (Reliable Change Indices, RCIs) of the MMSE total score are suitable to predict future dementia. Methods: 554 elderly individuals aged 75 and over without dementia at the first 2 visits were tested with the MMSE at a maximum of 6 visits with 1.5-year intervals. Two different RCIs for change in MMSE score (first to second visit) were computed – one RCI which corrects for practice and one RCI which corrects for regression to the mean. The main outcome measure was the diagnosis of dementia. Results: During the study, 88 persons developed dementia. RCIs were significantly associated with future dementia diagnosis. The best cutoff for raw change in MMSE total score to predict dementia was –1 point (sensitivity = 48%, specificity = 67%, relative risk = 1.6). With the RCI + regression to the mean, the diagnostic accuracy was moderate (sensitivity = 61%, specificity = 72%, relative risk = 3.2). Conclusion: A change in MMSE total score is significantly associated with future dementia, but the diagnostic accuracy for dementia prediction is rather low.
Serum Lipids Are Related to Alzheimer’s Pathology in Nursing Home Residents
Authors: Lesser Gerson T. , Haroutunian Vahram , Purohit Dushyant P. , Schnaider Beeri Michal , Schmeidler James , Honkanen Linda , Neufeld Richard , Libow Leslie S.
Published: January 2009

Background: Studies of associations between serum lipids and Alzheimer’s disease (AD) or other dementias in the elderly show conflicting results, perhaps due to misclassification of the various dementias. Methods: For 358 nursing home residents, serum lipids were studied at admission and diagnoses established at autopsy. We used defined neuropathological criteria to distinguish the presence of AD and to avoid errors of clinical dementia assessment. Results: Residents with any AD pathology, as compared to those without AD pathology, had higher mean serum total cholesterol (TC; 200.4 vs. 185.9 mg/dl; p = 0.02) and higher mean low-density lipoprotein cholesterol (LDL; 124.5 vs. 111.5 mg/dl; p = 0.03). Further, mean TC, LDL and high-density lipoprotein cholesterol levels all increased progressively with increasing pathological certainty of AD (p for trend = 0.001, 0.02 and 0.02). Conclusions: TC and LDL were significantly related to pathologically defined AD. If serum lipids have a role in the pathogenesis of AD, interventions may modify the course of disease.
Parkinson’s Disease with and without REM Sleep Behaviour Disorder: Are There Any Clinical Differences?
Authors: Yoritaka Asako , Ohizumi Hideki , Tanaka Shigeki , Hattori Nobutaka
Published: January 2009

Rapid eye movement sleep behaviour disorder (RBD) may serve as a useful indicator to approach Parkinson’s disease (PD); however, PD patients do not always exhibit RBD. We wondered whether the presence of RBD would be reflected in the expansion of PD lesions and represent the same PD entity. We examined the clinical differences between PD with and without RBD and studied the frequency of RBD-like symptoms (RBD-s) and clinical differences in 150 PD patients, including 81 patients (54.0%) who satisfied the International Classification of Sleep Disorders, Revised, minimum clinical criteria for RBD. RBD-s preceding the appearance of parkinsonism were found in 44.4% of patients. Statistically, the presence of RBD-s was associated with ages above 65 years, male gender, constipation, dopa-induced dyskinesia and ‘sleep attack’, with odds ratios of 3.709, 2.469, 2.184, 5.046 and 6.562, respectively. No differences were found between the 2 groups with regard to symptoms at PD onset, disease duration, Hoehn-Yahr stage, hallucination, dementia, wearing-off, orthostatic hypotension, cerebral blood flow and antiparkinsonism drugs. In the early stage, RBD and autonomic system dysfunction are important factors in the progression of PD.
A Prospective Study of Alterations in Balance among Patients with Parkinson’s Disease
Authors: Rossi M. , Soto A. , Santos S. , Sesar A. , Labella T.
Published: January 2009

The aim of this study is to determine whether the balance problems experienced by Parkinson’s disease (PD) patients may in part be due to dysfunctional processing of vestibular information, and to search for factors that may help predict the risk of falls. We evaluated the balance of 45 idiopathic PD patients and 20 healthy subjects by means of computerized dynamic posturography using sensory organization tests (SOT), rhythmic weight shift (RWS) tests and limits of stability (LOS) tests; and by the timed up-and-go (TUG) test. PD patients had poorer scores in the SOT than controls for overall balance and vestibular and visual inputs. They also performed worse in RWS and LOS tests, and were slower in performing the TUG test. Hoehn-Yahr stage did not correlate with vestibular input. Balance impairment in PD patients involves deteriorated processing of vestibular input, but this deterioration is independent of disease progression. Falls are related to PD patients’ reduced limits of stability.
Switching to Second-Line Therapies in Interferon-Beta-Treated Relapsing-Remitting Multiple Sclerosis Patients
Authors: Portaccio E. , Zipoli V. , Siracusa G. , Sorbi S. , Amato M.P.
Published: January 2009

Background:Interferon-β (IFNB) therapies are the most widely used as first-line intervention in the treatment of relapsing-remitting (RR) multiple sclerosis (MS). Despite long-term experience, however, the definition and prediction of response remain controversial. Aim:The objective of this study was to assess the long-term validity of the main clinical definitions of response applied after 1 and 2 years of IFNB therapy in a cohort of RRMS patients followed up for at least 5 years. Methods:We tested these different definitions against a ‘hard’ parameter of treatment failure, represented by the need to suspend IFNB and switch to an intravenous immunosuppressive (IVIS) treatment, using Kaplan-Meier and Cox survival analyses. Results:Out of 147 RRMS patients treated with IFNB therapy and followed up for 7.8 ± 2.1 years, 26 (18%) were switched to an IVIS therapy. On the whole, disability progression as indicated using the Expanded Disability Status Scale (EDSS) and a higher number of relapses in the first 2 years of therapy were related to long-term treatment failure. Conclusion:Our study highlights the role of disability and high relapse rate in the first 2 years of treatment in predicting long-term response and the switching to second-line therapies.
Case-Control Study of Early Childhood Caries in Australia
Authors: Seow W.K. , Clifford H. , Battistutta D. , Morawska A. , Holcombe T.
Published: January 2009

The aim of this case-control study of 617 children was to investigate early childhood caries (ECC) risk indicators in a non-fluoridated region in Australia. ECC cases were recruited from childcare facilities, public hospitals and private specialist clinics to source children from different socioeconomic backgrounds. Non-ECC controls were recruited from the same childcare facilities. A multinomial logistic modelling approach was used for statistical analysis. The results showed that a large percentage of children tested positive for Streptococcus mutans if their mothers also tested positive. A common risk indicator found in ECC children from childcare facilities and public hospitals was visible plaque (OR 4.1, 95% CI 1.0–15.9, and OR 8.7, 95% CI 2.3–32.9, respectively). Compared to ECC-free controls, the risk indicators specific to childcare cases were enamel hypoplasia (OR 4.2, 95% CI 1.0–18.3), difficulty in cleaning child’s teeth (OR 6.6, 95% CI 2.2–19.8), presence of S. mutans (OR 4.8, 95% CI 0.7–32.6), sweetened drinks (OR 4.0, 95% CI 1.2–13.6) and maternal anxiety (OR 5.1, 95% CI 1.1–25.0). Risk indicators specific to public hospital cases were S. mutans presence in child (OR 7.7, 95% CI 1.3–44.6) or mother (OR 8.1, 95% CI 0.9–72.4), ethnicity (OR 5.6, 95% CI 1.4–22.1), and access of mother to pension or health care card (OR 20.5, 95% CI 3.5–119.9). By contrast, a history of chronic ear infections was found to be protective for ECC in childcare children (OR 0.28, 95% CI 0.09–0.82). The biological, socioeconomic and maternal risk indicators demonstrated in the present study can be employed in models of ECC that can be usefully applied for future longitudinal studies.
Performance of a Pen-Type Laser Fluorescence Device and Conventional Methods in Detecting Approximal Caries Lesions in Primary Teeth – in vivo Study
Authors: Novaes T.F. , Matos R. , Braga M.M. , Imparato J.C.P. , Raggio D.P. , Mendes F.M.
Published: January 2009

This in vivo study aimed to compare the performance of different methods of approximal caries detection in primary molars. Fifty children (aged 5–12 years) were selected, and 2 examiners evaluated 621 approximal surfaces of primary molars using: (a) visual inspection, (b) the radiographic method and (c) a pen-type laser fluorescence device (LFpen). As reference standard method, the teeth were separated using orthodontic rubbers during 7 days, and the surfaces were evaluated by 2 examiners for the presence of white spots or cavitations. The area under the receiver-operating characteristics curve (Az) as well as sensitivity, specificity and accuracy (percentage of correct diagnosis) were calculated and compared with the McNemar test at both thresholds. The interexaminer reproducibility was calculated using the intraclass correlation coefficient (ICC-absolute values) and the kappa test (dichotomizing for both thresholds). The ICC value of the reference standard procedure was 0.94. At white-spot threshold, no methods tested presented good performance (sensitivity: visual 0.20–0.21; radiographic 0.16–0.23; LFpen 0.16; specificity: visual 0.95; radiographic 0.99–1.00; LFpen 0.94–0.96). At cavitation threshold, both LFpen and radiographic methods demonstrated higher sensitivity (0.55–0.65 and 0.65–0.70, respectively) and Az (0.92 and 0.88–0.89, respectively) than visual inspection sensitivity (0.30) and Az (0.69–0.76). All methods presented high specificities (around 0.99) and similar ICCs, but the kappa value for LFpen at white-spot threshold was lower (0.44). In conclusion, both LFpen and radiographic methods present similar performance in detecting the presence of cavitations on approximal surfaces of primary molars.
Development of a Specific Health-Related Quality of Life Test in Drug Abusers Using the Rasch Rating Scale Model
Authors: Lozano Rojas O.M. , Rojas Tejada A.J. , Pérez Meléndez C.
Published: January 2009

A test has recently been designed for the measurement of health-related quality of life in drug abusers (Health-Related Quality of Life for Drug Abusers Test – HRQOLDA Test) based on the bi-axial concept of addiction. The aim of this work is to find out the metric properties of the test by applying the polytomous Rasch Rating Scale Model (RSM). The HRQOLDA Test was given to a sample of 358 drug abusers who began treatment in a Therapeutic Community. The Rating Scale Model (RSM) and the WINSTEPS programme were used for the analysis of its metric properties. The results shown here are an overall fit of data to the model. The items are adequately distributed over the HRQOL continuum. The response categories appear to be in order except for the category ‘a little’. The test region which measures most accurately, and is most informative, is in the middle of the continuum. The test properties studied confirm the adequacy of the RSM for accurate measurement of HRQOL in drug abusers, providing a test for measuring this specific construct in this population.
Relative Contributions of Holiday Location and Nationality to Changes in Recreational Drug Taking Behaviour: A Natural Experiment in the Balearic Islands
Authors: Bellis Mark A. , Hughes Karen , Calafat Amador , Juan Montse , Schnitzer Susanne
Published: January 2009

Aim: To examine the contributions of international holiday resorts and visitors’ nationality to recruitment, relapse into, and escalation in frequency of recreational drug use. Methods: Retrospective design surveying British, German and Spanish (n = 3,003) holidaymakers aged 16–35 visiting Ibiza or Majorca (Spain). Results: Individuals’ drug use in international resorts was related to use at home, holiday destination and nationality. While visiting Ibiza, 7.2% of British tourists tried ecstasy for the first time with similar recruitment amongst Spanish (8.6%) but not Germans (1.8%) or those visiting Majorca (0.8, 1.5 and 1.2%, respectively). Recruitment into cocaine use was associated with being Spanish, male, visiting Ibiza and drunkenness. One in 5 British holidaymakers visiting Ibiza tried at least one new drug. British and Spanish were most likely to relapse into using a drug after at least 12 months’ abstinence; 6.8% of British (1.3% German, 2.9% Spanish) relapsed into using at least one drug. Across nationalities, substance use frequency increased on holiday. Conclusions: International nightlife resorts are major sources of recruitment, relapse and escalation in drug use. Such resorts contribute to the international spread of drug cultures but have been largely ignored as settings for interventions to tackle drugs.
Severity of Dependence Scale as a Diagnostic Tool for Heroin and Cocaine Dependence
Authors: González-Sáiz Francisco , Domingo-Salvany Antònia , Barrio Gregorio , Sánchez-Niubó Albert , Brugal M. Teresa , de la Fuente Luís , Alonso Jordi
Published: January 2009

Aims: Our aim was to further assess the Severity of Dependence Scale (SDS) validity and to identify the cut-off score for a DSM-IV diagnosis of heroin and cocaine dependence through a cross-sectional survey in Barcelona, Spain. Methods: The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was used as the gold standard. 146 young (18–30 years old) heroin users were recruited from outside the healthcare context, 135 of whom were also current cocaine users. SDS scores were correlated to quantity, frequency and length of drug use. Results: The SDS cut-off point at which there was optimal discrimination of a DSM-IV diagnosis presence was found to be 3 (i.e., a score of 3 or more) for heroin dependence and 4 for cocaine dependence. Conclusions: The study gives further support to SDS dimensional properties and to its validity for rapid assessment of current heroin and cocaine dependence.
Cutaneous in vivo Metabolism of Topical Lidocaine Formulation in Human Skin
Authors: Rolsted K. , Benfeldt E. , Kissmeyer A.-M. , Rist G.M. , Hansen S.H.
Published: January 2009

Little is known about the metabolising capacity of the human skin in relation to topically applied drugs and formulations. We chose lidocaine as a model compound since the metabolic pathways are well known from studies concerning hepatic metabolism following systemic drug administration. However, the enzymes involved are also expressed in the skin. Hence, the aim of the current study was to investigate the extent of the cutaneous in vivo metabolism of topically applied lidocaine in human volunteers. A dose of 5 mg/cm2 of Xylocaine® (5% lidocaine) ointment was applied onto the buttock skin of the volunteers. After 2 h, residual formulation was removed, and two 4-mm punch biopsies were taken from each volunteer. The quantity of lidocaine extracted from the skin samples (epidermis + dermis) was 109 ± 43 ng/mm2 skin. One metabolite (monoethylglycine xylidide, MEGX) was detected in skin from 7 of the 9 volunteers. The quantity of MEGX formed, relative to the quantity of lidocaine in the skin, was not consistent and ranged from <0.8 to 12.8%. No other metabolites were detected.
Effects of Various Vehicles on Skin Hydration in vivo
Authors: Wiedersberg S. , Leopold C.S. , Guy R.H.
Published: January 2009

The stratum corneum, the outermost layer of the skin, regulates the passive loss of water to the environment. Furthermore, it is well accepted that drug penetration is influenced by skin hydration, which may be manipulated by the application of moisturizing or oleaginous vehicles. Measurements of transepidermal water loss (TEWL), and of skin hydration using a corneometer, were used to assess the effect of different vehicles on stratum corneum barrier function in vivo in human volunteers. A microemulsion significantly increased skin hydration relative to a reference vehicle based on medium chain triglycerides; in contrast, Transcutol® lowered skin hydration. TEWL measurements confirmed these observations.
Angiotensin II Upregulates RAGE Expression on Podocytes: Role of AT2 Receptors
Authors: Rüster Christiane , Bondeva Tzvetanka , Franke Sybille , Tanaka Nobushige , Yamamoto Hiroshi , Wolf Gunter
Published: January 2009

Background: Advanced glycation end products (AGEs) play an important role in diabetic nephropathy. The receptor for AGEs, called RAGE, is present on podocytes. We investigated whether angiotensin II (ANG II) modulates RAGE expression on cultured differentiated podocytes. Results: Cultured podocytes expressed AT1 and AT2 receptors. Surprisingly, ANG II induced RAGE mRNA and protein expression through AT2 receptors. ANG II had no influence on proliferation or protein content of podocytes. The increase in RAGE expression depended on stimulated transcriptional activity. Using various mutant reporter constructs of the RAGE promoter region, it was shown that a NF-κB binding site at –1519 was essential for ANG II-induced transcriptional activity. Preincubation with ANG II increased the expression of tumor necrosis factor-α mRNA and protein expression induced by AGE, indicating that the ANG II-mediated upregulation of RAGE has functional consequences. AGE-BSA was incorporated into cells as measured by Western blots for Nε-carboxymethyllysine, but ANG II did not influence this process. ANG II in the absence or presence of AGE-BSA did not induce apoptosis of podocytes. Conclusion: Our study revealed aninteraction between the renin-angiotensin system and the AGE/RAGE axis in podocytes. Since intraglomerular ANG II levels are increased in diabetic nephropathy, this interaction may have pathophysiological consequences for podocyte injury and inflammation associated with the development of diabetic nephropathy.
Proteomics in Gerontology: Current Applications and Future Aspects – A Mini-Review
Authors: Schiffer E. , Mischak H. , Zimmerli L.U.
Published: January 2009

Background: Aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies, reflecting the demand for novel biomarkers to manage theses diseases. Objective: The analysis of the human proteome for biomarkers has made considerable advances in the last years. Methods: We describe the main technological approaches taken, their advantages and disadvantages. Results: We will review the different clinical sources of material and attempt to highlight the different challenges and approaches associated with these. Age-related changes in the proteome have been described and were found to be highly similar to changes associated with chronic diseases. We will give several examples on the successful application of proteomics in the diagnosis, prognosis and therapy of these chronic diseases. Conclusions: A boost in disease-related proteomic information is expected in the very near future, and will also result in its broad clinical application. However, this view appears to be dependent on the strict adherence to proper technological/analytical parameters, correct statistics, and large databases that allow comparison of datasets provided by different scientists. Clearly, the proteome is by far too complex to be tackled by one laboratory on its own.
Hyperinflation and Intrinsic Positive End-Expiratory Pressure: Less Room to Breathe
Authors: Krieger Bruce P.
Published: January 2009

Clinically, the symptoms and limited exercise capabilities of patients with chronic obstructive pulmonary disease (COPD) correlate better with changes in lung volumes than with airflow measurements. The realization of the clinical importance of hyperinflation has been overshadowed for decades by the use of forced expiratory volume during 1 s (FEV1) and the ratio of the FEV1 to the forced expiratory vital capacity (FEV1/FVC) to categorize the severity and progression of COPD. Hyperinflation is defined as an elevation in the end-expiratory lung volume or functional residual capacity. When severe hyperinflation encroaches upon inspiratory capacity and limits vital capacity, it results in elevated intrinsic positive end-expiratory pressure (PEEPi) that places the diaphragm at a mechanical disadvantage and increases the work of breathing. Severe hyperinflation is the major physiologic cause of the resulting hypercarbic respiratory failure and patients’ inability to transition (i.e. wean) from mechanical ventilatory support to spontaneous breathing. This paper reviews the basic physiologic principles of hyperinflation and its clinical manifestations as demonstrated by PEEPi. Also reviewed are the adverse effects of hyperinflation and PEEPi in critically ill patients with COPD, and methods for minimizing or counterbalancing these effects.
miR-1
Overexpression Enhances Ca
2+
Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2
Authors: Terentyev Dmitry , Belevych Andriy E. , Terentyeva Radmila , Martin Mickey M. , Malana Geraldine E. , Kuhn Donald E. , Abdellatif Maha , Feldman David S. , Elton Terry S. , Györke Sandor
Published: January 2009

MicroRNAs are small endogenous noncoding RNAs that regulate protein expression by hybridization to imprecise complementary sequences of target mRNAs. Changes in abundance of muscle-specific microRNA,
miR-1
, have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the action of
miR-1
in the heart are only beginning to emerge. In this study we investigated the effects of increased expression of
miR-1
on excitation–contraction coupling and Ca
2+
cycling in rat ventricular myocytes using methods of electrophysiology, Ca
2+
imaging and quantitative immunoblotting. Adenoviral-mediated overexpression of
miR-1
in myocytes resulted in a marked increase in the amplitude of the inward Ca
2+
current, flattening of Ca
2+
transients voltage dependence, and enhanced frequency of spontaneous Ca
2+
sparks while reducing the sarcoplasmic reticulum Ca
2+
content as compared with control. In the presence of isoproterenol, rhythmically paced,
miR-1
–overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca
2+
, events that occurred rarely in control myocytes under the same conditions. The effects of
miR-1
were completely reversed by the CaMKII inhibitor KN93. Although phosphorylation of phospholamban was not altered,
miR-1
overexpression increased phosphorylation of the ryanodine receptor (RyR2) at S2814 (Ca
2+
/calmodulin-dependent protein kinase) but not at S2808 (protein kinase A). Overexpression of
miR-1
was accompanied by a selective decrease in expression of the protein phosphatase PP2A regulatory subunit B56α involved in PP2A targeting to specialized subcellular domains. We conclude that
miR-1
enhances cardiac excitation–contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels.
ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells
Authors: Wang Yuepeng , Zheng Xiaoyu Rayne , Riddick Nadeene , Bryden Meredith , Baur Wendy , Zhang Xin , Surks Howard K.
Published: January 2009

Abnormal vascular smooth muscle cell (VSMC) contraction plays an important role in vascular diseases. The RhoA/ROCK signaling pathway is now well recognized to mediate vascular smooth muscle contraction in response to vasoconstrictors by inhibiting myosin phosphatase (MLCP) activity and increasing myosin light chain phosphorylation. Two ROCK isoforms, ROCK1 and ROCK2, are expressed in many tissues, yet the isoform-specific roles of ROCK1 and ROCK2 in vascular smooth muscle and the mechanism of ROCK-mediated regulation of MLCP are not well understood. In this study, ROCK2, but not ROCK1, bound directly to the myosin binding subunit of MLCP, yet both ROCK isoforms regulated MLCP and myosin light chain phosphorylation. Despite that both ROCK1 and ROCK2 regulated MLCP, the ROCK isoforms had distinct and opposing effects on VSMC morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility. These data support that although the ROCK isoforms both regulate MLCP and myosin light chain phosphorylation through different mechanisms, they have distinct roles in VSMC function.
Complement Regulator CD59 Protects Against Atherosclerosis by Restricting the Formation of Complement Membrane Attack Complex
Authors: Wu Gongxiong , Hu Weiguo , Shahsafaei Aliakbar , Song Wenping , Dobarro Martin , Sukhova Galina K. , Bronson Rod R. , Shi Guo-ping , Rother Russell P. , Halperin Jose A. , Qin Xuebin
Published: January 2009

Complement is a central effector system within the immune system and is implicated in a range of inflammatory disorders. CD59 is a key regulator of complement membrane attack complex (MAC) assembly. The atherogenic role of terminal complement has long been suspected but is still unclear. Here, we demonstrate that among mice deficient in apolipoprotein (Apo)E, the additional loss of murine CD59 (
mCd59ab
−/−
/
ApoE
−/−
) accelerated advanced atherosclerosis featuring occlusive coronary atherosclerosis, vulnerable plaque, and premature death and that these effect could be attenuated by overexpression of human CD59 in the endothelium. Complement inhibition using a neutralizing anti-mouse C5 antibody attenuated atherosclerosis in
mCd59ab
−/−
/
ApoE
−/−
mice. Furthermore, MAC mediated endothelial damage and promoted foam cell formation. These combined results highlight the atherogenic role of MAC and the atheroprotective role of CD59 and suggest that inhibition of MAC formation may provide a therapeutic approach for the treatment of atherosclerosis.
Detection of Intracranial Atherosclerosis
Authors: Balucani Clotilde , Leys Didier , Ringelstein E. Bernd , Kaste Markku , Hacke Werner
Published: January 2009

Background and Purpose—

The diagnosis of intracranial atherosclerosis requires availability of appropriate imaging techniques. The objective was to evaluate the proportion of European hospitals where imaging techniques necessary to detect intracranial atherosclerosis are available.

Method—

We randomly selected 886 hospitals in 25 countries and classified them in 3 categories according to the availability of 3 imaging techniques (transcranial color-coded duplex imaging, computed tomographic angiography, and magnetic resonance angiography): “all” when the 3 techniques were available, “at least 1,” and “none.” We compared the proportion of hospitals meeting these criteria, using the odds ratio method and Germany as reference.

Results—

Two hundred seventy-two hospitals (30.7%) met criteria for all, 445 (50.2%) met criteria for at least 1, and 169 (19.1%) met criteria for none. In 2005, they had admitted, respectively, 139,118, 160, 393, and 62 667 stroke patients. Brain CT or MRI were available in 820 (92.6%) hospitals, computed tomographic angiography in 619 (69.9%), magnetic resonance angiography in 498 (56.2%), and transcranial color-coded duplex in 352 (39.7%). Compared to Germany, Greece (OR, 0.11; 95% CI, 0.01–0.88), Iberic countries (OR, 0.11; 95% CI, 0.05–0.27), Baltic countries (OR, 0.13; 95% CI, 0.03–0.56), Poland (OR, 0.40; 95% CI, 0.21–0.77), and France (OR, 0.52; 95% CI, 0.31–0.89), had significantly less hospitals in the all group.

Conclusion—

In Europe, less than one-third of ischemic stroke patients are admitted in hospitals with all imaging techniques available to detect intracranial atherosclerosis. There are important differences between countries.
Oxfordshire Community Stroke Project Clinical Stroke Syndrome and Appearances of Tissue and Vascular Lesions on Pretreatment CT in Hyperacute Ischemic Stroke Among the First 510 Patients in the Third International Stroke Trial (IST-3)
Authors: Kobayashi Adam , Wardlaw Joanna M. , Lindley Richard I. , Lewis Steff C. , Sandercock Peter A.G. , Czlonkowska Anna
Published: January 2009

Background and Purpose—

The Oxfordshire Community Stroke Project (OCSP) clinical stroke syndrome classification correlates well with the stroke lesion in established ischemic stroke, but there are few data in patients with hyperacute stroke. We wished to assess whether the OCSP correlated with the site and size of the ischemic lesion and location of cerebral vessel lesion on computed tomography (CT) in hyperacute stroke.

Methods—

Prospective study of ischemic stroke patients presenting within 6 hours of onset in the Third International Stroke Trial (IST-3), a randomized, controlled trial of rt-PA. OCSP syndrome was assigned by a computer-based algorithm. The CT assessment was made by a neuroradiologist blinded to clinical details.

Results—

We assessed baseline data and CT findings for the first 510 patients; early tissue ischemic changes were present in 329/510 (65%) total anterior circulation syndrome (TACS) - 79%; partial anterior circulation syndrome (PACS) - 57%, lacunar syndrome (LACS) - 40%; posterior circulation syndrome (POCS) - 33%. The site and size of ischemic change on CT was compatible with the clinical syndrome in 79%, 37%, 2%, and 14%, respectively. Assuming that all patients with a normal CT scan will develop an incompatible lesion these numbers reflected the “worst possible scenario.” For the “best possible scenario” we presumed that those with a normal CT will develop concordant ischemic change and the proportions were 100%, 80%, 62% and 81%, respectively. The hyperattenuated artery sign was seen in 206/510 (40%); (TACS 54%; PACS 35%, LACS 5%, and POCS 19%).

Conclusions—

Within 6 hours of stroke, in patients with a nonlacunar syndrome, the OCSP syndrome correlated well with the pattern of ischemic change on CT. For clinicians who wish to restrict the use of thrombolytic therapy to large-artery ischemic stroke, concordance of clinical and CT appearances may give greater confidence in making therapeutic decisions in hyperacute stroke. In centers where immediate access to MR is limited, use of the classification may help focus use of MR on patients with suspected LACS and POCS. The utility of the classification may further increase if IST-3 establishes that the OCSP syndrome significantly modifies response to thrombolytic therapy.
A Population-Based Study of the Prevalence of Fatigue After Transient Ischemic Attack and Minor Stroke
Authors: Winward Charlotte , Sackley Catherine , Metha Ziyah , Rothwell Peter M.
Published: January 2009

Background and Purpose—

Fatigue is common after stroke and can be attributable to the increased physical effort associated with severe neurological deficits; however, its presence in those with little motor deficit raises the possibility of confounding by other factors, such as comorbidity, anxiety, and medication. To control for such factors and determine the extent of stroke-specific fatigue, we compared patients with minor stroke who had little or no residual neurological deficit with patients with TIA; both groups had undergone similar investigations and treatment.

Methods—

The prevalence of fatigue 6 months after TIA or minor stroke was assessed in consecutive patients using the Chalder fatigue scale in a population-based incidence study (Oxford Vascular Study). Patients were included if they were independent in self-care Barthel Index (≥18/20) and without major cognitive impairment (Mini-Mental State Examination ≥24/30). Stroke severity at baseline was assessed with the National Institute of Health Stroke Scale (NIHSS). Other potential causes of fatigue were assessed including anxiety, depression, recent life events, medication, and abnormalities in biochemistry or hematologic tests.

Results—

Seventy-six participants had minor stroke (mean age, 74.1 years; 42 men) and 73 had TIA (mean age, 72.5 years; 40 men). At 6-month follow-up, median Barthel Index score was 20 (interquartile range, 20–20) in both groups. However, fatigue was more common after stroke than TIA (56% vs 29%; OR, 3.14; 95% CI, 1.51–6.57;
P
=0.0008). This difference was present both in patients with modified Rankin score of 0 at 6 months (23.8% vs 10.3%) and patients with modified Rankin score ≥1 (69.2% vs 48.6%), and remained more frequent in stroke patients after adjustment for potential confounders. Within the group of patients with stroke, the prevalence of fatigue increased with initial stroke severity (87% NIHSS ≥4 vs 48% NIHSS ≤3;
P
=0.0087); however, stroke patients with initial NIHSS of 0 were still more fatigued than patients with TIA (57% vs 29%;
P
=0.015).

Conclusions—

The prevalence of fatigue after minor stroke is higher than after TIA, suggesting that it is not simply a consequence of the stress of a recent acute cerebral event, comorbidity, medication, or other potential confounders. The high levels of fatigue in stroke patients without neurological impairment suggest it has a central origin rather than being the result of increased physical effort required after stroke.
Thrombolytic Therapy for Patients Who Wake-Up With Stroke
Authors: Barreto Andrew D. , Martin-Schild Sheryl , Hallevi Hen , Morales Miriam M. , Abraham Anitha T. , Gonzales Nicole R. , Illoh Kachi , Grotta James C. , Savitz Sean I.
Published: January 2009

Background and Purpose—

Approximately 25% of ischemic stroke patients awaken with their deficits. The last-seen-normal time is defined as the time the patient went to sleep, which places these patients outside the window for thrombolysis. The purpose of this study was to describe our center’s experience with off-label, compassionate thrombolysis for wake-up stroke (WUS) patients.

Methods—

A retrospective review of our database identified 3 groups of ischemic stroke patients: (1) WUS treated with thrombolysis; (2) nontreated WUS; and (3) 0- to 3-hour intravenous tissue plasminogen activator-treated patients. Safety and clinical outcome measures were symptomatic intracerebral hemorrhage, excellent outcome (discharge modified Rankin score, 0–1), favorable outcome (modified Rankin score, 0–2), and mortality. Outcome measures were controlled for baseline NIHSS using logistic regression.

Results—

Forty-six thrombolysed and 34 nonthrombolysed WUS patients were identified. Sixty-one percent (28/46) of the treated WUS patients underwent intravenous thrombolysis alone whereas 30% (14/46) were given only intra-arterial thrombolysis. Four patients received both intravenous and intra-arterial thrombolysis (9%). Two symptomatic intracerebral hemorrhages occurred in treated WUS (4.3%). Controlling for NIHSS imbalance, treated WUS had higher rates of excellent (14% vs 6%;
P
=0.06) and favorable outcome (28% vs 13%;
P
=0.006), but higher mortality (15% vs 0%) compared to nontreated WUS. A second comparison controlling for baseline NIHSS between treated WUS and 174 intravenous tissue plasminogen activator patients treated within 3 hours of symptoms showed no significant differences in safety and clinical outcomes.

Conclusion—

Thrombolysis may be safe in WUS patients. Our center’s experience supports considering a prospective, randomized trial to assess the safety and outcome of thrombolysis for this specific patient population.
Extending Acute Trials to Remote Populations
Authors: Leira Enrique C. , Ahmed Azeemuddin , Lamb Diane L. , Olalde Heena M. , Callison R. Charles , Torner James C. , Adams Harold P.
Published: January 2009

Background and Purpose—

Methods to increase recruitment into acute stroke trials are needed. The purposes of this study were to evaluate the safety and acceptability of initiating acute stroke trials during early helicopter evacuation and to test an intervention to facilitate informed consent.

Methods—

A randomized, controlled trial was done with patients with acute stroke who were transferred by helicopter to the University of Iowa Hospitals and Clinics from February 2007 to January 2008. The intervention to be evaluated was the use of fax and a telephone call to the patient/surrogate ahead of helicopter arrival at the outside emergency department. The aim was to improve the rate of subsequent consent (primary outcome) for a pilot trial of a potentially beneficial, low-risk medical intervention (ranitidine) to prevent aspiration pneumonitis. Consenting eligible patients received the infusion during the flight to University of Iowa Hospitals and Clinics.

Results—

One hundred patients were enrolled. Consent rate was 54% in the intervention group and 50% in the control group (
P
=0.69). However, the consent rate was higher (69%) when prearrival communications between the coinvestigator and potential subjects were successful (
P
=0.04). This approach resulted in an average gain of 59 minutes as compared with initiating recruitment on arrival to University of Iowa Hospitals and Clinics.

Conclusions—

Enrollment into stroke intervention trials is feasible during helicopter transportation from a community hospital emergency department to a tertiary stroke center. This underused resource may improve trial efficiency by enabling and expediting participation of remote populations currently excluded from research. Consent rates might be further improved by communication strategies that are more successful in reaching patients at outside emergency departments.
Upregulation of Macrophage Migration Inhibitory Factor Gene Expression in Stroke
Authors: Wang Lijuan , Zis Odysseus , Ma Guixian , Shan Zhixin , Zhang Xiong , Wang Shuo , Dai Chengbo , Zhao Jiehao , Lin Qiuxiong , Lin Shuguang , Song Weihong
Published: January 2009

Background and Purpose—

MIF has been implicated to function in many inflammatory processes. This study examined whether MIF expression was affected in stroke and its underlying molecular mechanism.

Methods—

ELISA and qRT-PCR were used to detect MIF protein and mRNA in PBMCs from stroke patients, the ischemic rat brains, and controls. A MIF promoter assay under hypoxia was performed.

Results—

MIF protein and mRNA were significantly increased in stroke patients. Increasing levels of MIF were correlated to the severity of stroke and peaked 24 hours after stroke. MIF was significantly upregulated in focal ischemic rat brains. The activity of the human MIF promoter was significantly increased under hypoxia compared to normoxia.

Conclusions—

MIF gene expression is upregulated after stroke, and hypoxia signaling plays an important role in upregulation of MIF expression under stroke.
Outcome of Patients With Negative CT Angiography Results for Arterial Occlusion Treated With Intravenous Thrombolysis
Authors: Mikulik Robert , Goldemund David , Reif Michal , Aulicky Petr , Krupa Petr
Published: January 2009

Background and Purpose—

Stroke patients without evidence of arterial occlusion may not be suitable candidates for thrombolytic therapy. In our study, we investigated the outcomes of patients with negative CT angiography results for arterial occlusion.

Methods—

The study included patients treated within 3 hours after symptom onset with intravenous thrombolysis for significant neurological deficit between August 2003 and June 2007. All of the patients were documented with negative CT angiography results for arterial occlusion by independent reviews. Outcome measurements included modified Rankin score at 3 months, incidence of intracranial hemorrhage, and infarction volume on control CT. The predictors of unfavorable outcome (modified Rankin score, 2–6) were identified by multivariate logistic regression.

Results—

Altogether, 173 patients received intravenous thrombolysis; of those, 138 underwent CT angiography. The CT angiography results were negative for arterial occlusion in 39 (28%) of the patients: mean age, 71±10 years; 16 (41%) female; median baseline NIHSS, 11. At 3 months, modified Rankin score of 0 to 1 was achieved in 18 (46%) of the patients; 6 (15%) died; and 3 (8%) had symptomatic parenchymal hemorrhage. The median infarct volume was 1.5 cm
3
. The independent predictors of unfavorable clinical outcome were higher age (OR, 1.1; 95% CI, 1.01–1.27), and baseline NIHSS >12 (OR, 18.8; 95% CI, 1.4 to 261). One patient had encephalitis diagnosed.

Conclusions—

Negative baseline CT angiography is not uncommon. The risk of intracerebral hemorrhage after thrombolytic therapy for patients without evidence of arterial occlusion is similar to the risk carried in an unselected patient population. Given the prognosis, thrombolytic therapy seems justified; however, etiology other than stroke should be considered.
Concise Review: Her Name is "Lucy", Our Three-million-year-old Ancestor
Authors: Shields E.D.
Published: January 2009

Dental anthropology is a key discipline in studies to determine the evolutionary history of our hominid ancestors, to identify the origin and dispersal of modem humans, and to reconstruct the source of observed dental variation. A survey of hominid and modem human evolutionary history, emphasizing results from powerful multivariate dental morphometric methodologies, suggests a single African origin of modem humans > 150,000 years before present from a Homo heidelbergensis ancestor. A continuum among modem humanity is described, with, first, sub-Saharan Africans, then southeast Asian Negrito, and Australian aborigines at its extant root. Other interpretations of the available data are possible. Examinations of the progress of the evolution of teeth through time give significant insight into dental morphogenetics and variation, and the biology of dental evolution. The mechanisms of evolution which fashion a phenotype and the methods of molecular and dental phylogenetics are reviewed and evaluated. This is an exciting time for dental anthropology, with fascinating and challenging questions to address, but anthropologists, not dentists, dominate the field. The perspective of a dentist can meaningfully add to the dynamics of dental anthropology.
Research Reports Biomaterials & Bioengineering
Authors: Arzate H. , Alvarez-Perez M.A. , Alvarez-Fregoso O. , Wusterhaus-Chávez A. , Reyes-Gasga J. , Ximenez-Fyvie L.A.
Published: January 2009

The nature and characteristics of the mineralized-like tissue deposited by cementoblasts are not well-known due to the difficulties in obtaining and culturing cells representing the cementum phenotype. We hypothesized that a putative cementoblastic cell line derived from a human cementoblastoma could serve as a suitable model to study the physical, chemical, and morphological features of the cementum-like tissue deposited in vitro. The cementoblastoma cell line was studied by transmission electron, high resolution, scanning, and atomic force microscopy and compared with human cellular cementum, human osteoblasts, and human alveolar bone. The analyses of the crystals and mineral-like tissue in the cell line were performed by x-ray diffraction microscopy and energy-dispersive x-ray micro-analysis. TEM examination of cementoblastoma cells revealed the presence of electron-dense intracellular vesicles surrounded by a membrane that contained filaments and needle-like structures. The diffraction patterns obtained from the intracellular material and human cellular cementum were similar, with D-spacings of 3.36 and 2.8, consistent with those of hydroxyapatite (3.440 and 2.814). The composition of the mineral-like tissue had a Ca/P ratio of 1.60 for cementoblastoma cells and 1.97 for human cellular cementum. Na (5.29%) and Cl (1.47%) were present in the composition of cementoblastoma cells. Human cellular cementum additionally contained Mg (4.95%). Osteoblastic cells showed a Ca/P ratio of 1.6280. Na represented 4.52% and Cl 1.22% of its composition. Human alveolar bone had a Ca/P ratio value of 2.01. Na (6.63%), Mg (2.10%), and Cl (0.84%) were also present. All samples examined represented biological-type hydroxyapatite. Based on the compositional and morphological features, these findings indicate that cementoblastoma-derived cells express the human cellular cementum phenotype.
Composition of Plaque and Saliva Following use of an α-Tricalcium-phosphate-containing Chewing Gum and a Subsequent Sucrose Challenge
Authors: Vogel G.L. , Zhang Z. , Carey C.M. , Ly A. , Chow L.C. , Proskin H.M.
Published: January 2009

Previous studies demonstrated that the chewing of a 2.5% (mass fraction) α-tricalcium-phosphate-fortified (a-TCP) experimental chewing gum released sufficient calcium and phosphate to eliminate any fall in the tooth mineral saturation of plaque fluid after a sucrose rinse (Vogel et al., 1998). In contrast, the chewing of a conventional sugar-free gum did not eliminate this decrease in saturation. The purpose of this study was to examine if the release of ions from plaque calcium-phosphate pools induced by this gum could provide protection during subsequent exposure to cariogenic conditions. Fourteen subjects accumulated plaque for 48 hrs, fasted overnight, chewed a control or experimental gum for 15 min, and subsequently rinsed 1 min with a mass fraction 10% sucrose solution. Before gum chewing, and at 7 min and 15 min afterward, whole plaque, plaque fluid, and salivary samples were obtained and analyzed by micro-analytical techniques. Additional samples were collected and analyzed at 25 min (7 min after the sucrose rinse). Although the results confirmed the deposition of large amounts of calcium and phosphates in plaque seen in the previous study, only a small increase was seen in plaque-fluid-free calcium and phosphate before sucrose administration. This suggests that few of the mineral ions were mobilized under non-cariogenic conditions. However, 7 min after the sucrose rinsing, an increase in these concentrations was seen which, based on hydroxyapatite ion activity product calculations, indicated a decrease in the driving force for demineralization compared with that seen with the control gum. These results suggest that the chewing of the experimental gum deposits a labile mineral reservoir in plaque that can resist a subsequent cariogenic challenge.