bluuebunny/crossref_metadata_2025 huggingface dataset:
Heightened aberrant deposition of hard-wearing elastin in conduit arteries of prehypertensive SHR is associated with increased stiffness and inward remodeling
Authors: Arribas Silvia M. , Briones Ana M. , Bellingham Catherine , González M. Carmen , Salaices Mercedes , Liu Kela , Wang Yanting , Hinek Aleksander
Published: October 2008

Elastin is a major component of conduit arteries and a key determinant of vascular viscoelastic properties. Aberrant organization of elastic lamellae has been reported in resistance vessels from spontaneously hypertensive rats (SHR) before the development of hypertension. Hence, we have characterized the content and organization of elastic lamellae in conduit vessels of neonatal SHR in detail, comparing the carotid arteries from 1-wk-old SHR with those from Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats. The general structure and mechanics were studied by pressure myography, and the internal elastic lamina organization was determined by confocal microscopy. Cyanide bromide-insoluble elastin scaffolds were also prepared from 1-mo-old SHR and WKY aortas to assess their weight, amino acid composition, three-dimensional lamellar organization, and mechanical characteristics. Carotid arteries from 1-wk-old SHR exhibited narrower lumen and greater intrinsic stiffness than those from their WKY and SD counterparts. These aberrations were associated with heightened elastin content and with a striking reduction in the size of the fenestrae present in the elastic lamellae. The elastin scaffolds isolated from SHR aortas also exhibited increased relative weight and stiffness, as well as the presence of peculiar trabeculae inside the fenestra that reduced their size. We suggest that the excessive and aberrant elastin deposited in SHR vessels during perinatal development alters their mechanical properties. Such abnormalities are likely to compromise vessel expansion during a critical period of growth and, at later stages, they could compromise hemodynamic function and participate in the development of systemic hypertension.
Regulation of ACE2 in cardiac myocytes and fibroblasts
Authors: Gallagher Patricia E. , Ferrario Carlos M. , Tallant E. Ann
Published: October 2008

Angiotensin-converting enzyme 2 (ACE2) preferentially forms angiotensin-(1-7) [ANG-(1-7)] from ANG II. We showed that cardiac ACE2 is elevated following treatment of coronary artery-ligated rats with AT1 receptor blockers (ARBs). Cardiac myocytes and fibroblasts were isolated from neonatal rats to determine the molecular mechanisms for the ACE2 upregulation by ARB treatment. ANG II significantly reduced ACE2 activity and downregulated ACE2 mRNA in cardiac myocytes, effects blocked by the ARB losartan, indicating that ANG II regulates ACE2. ANG II also reduced ACE2 mRNA in cardiac fibroblasts; however, no enzyme activity was detected, reflecting the limited expression of ACE2 in these cells. Endothelin-1 (ET-1) also significantly reduced myocyte ACE2 mRNA. The reduction in ACE2 mRNA by ANG II or ET-1 was blocked by inhibitors of mitogen-activated protein kinase kinase 1, suggesting that ANG II or ET-1 activates extracellular signal-regulated kinase (ERK) 1/ERK2 to reduce ACE2. Although ACE2 mRNA was not affected by ANG-(1-7), both the ANG II- and ET-1-mediated reductions in ACE2 mRNA were blocked by the heptapeptide. The ANG-(1-7) modulatory effect was prevented by the ANG-(1-7) receptor antagonist [d-Ala7]-ANG-(1-7), indicating that the ANG-(1-7) response was mediated by a specific AT(1-7) receptor. Myocyte treatment with atrial natriuretic peptide (ANP) also reversed the ACE2 mRNA downregulation by ANG II or ET-1, whereas treatment with ANP alone was ineffective. These results indicate that multiple hypertrophic and anti-hypertropic peptides regulate ACE2 production in myocytes, suggesting that ACE2 expression in the heart is dependent upon the compliment and concentration of regulatory molecules.
Ventricular activation is impaired in aged rat hearts
Authors: Rossi Stefano , Baruffi Silvana , Bertuzzi Andrea , Miragoli Michele , Corradi Domenico , Maestri Roberta , Alinovi Rossella , Mutti Antonio , Musso Ezio , Sgoifo Andrea , Brisinda Donatella , Fenici Riccardo , Macchi Emilio
Published: October 2008

Ventricular arrhythmias are frequently observed in the elderly population secondary to alterations of electrophysiological properties that occur with the normal aging process of the heart. However, the underlying mechanisms remain poorly understood. The aim of the present study was to determine specific age-related changes in electrophysiological properties and myocardial structure in the ventricles that can be related to a structural-functional arrhythmogenic substrate. Multiple unipolar electrograms were recorded in vivo on the anterior ventricular surface of four control and seven aged rats during normal sinus rhythm and ventricular pacing. Electrical data were related to morphometric and immunohistochemical parameters of the underlying ventricular myocardium. In aged hearts total ventricular activation time was significantly delayed (QRS duration: +69%), while ventricular conduction velocity did not change significantly compared with control hearts. Moreover, ventricular activation patterns displayed variable numbers of epicardial breakthrough points whose appearance could change with time. Morphological analysis in aged rats revealed that heart weight and myocyte transverse diameter increased significantly, scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium, and gap junction connexin expression decreased significantly in ventricular myocardium compared with control rats. Our results show that in aged hearts delayed total ventricular activation time and abnormal activation patterns are not due to delayed myocardial conduction and suggest the occurrence of impaired impulse propagation through the conduction system leading to uncoordinated myocardial excitation. Impaired interaction between the conduction system and ventricular myocardium might create a potential reentry substrate, contributing to a higher incidence of ventricular arrhythmias in the elderly population.
Hemodynamic sensing using subcutaneous photoplethysmography
Authors: Turcott Robert G. , Pavek Todd J.
Published: October 2008

Pacemakers and implantable defibrillators presently operate without access to hemodynamic information. If available, such data would allow tailoring of delivered therapy according to perfusion status, optimization of device function, and enhancement of disease monitoring and management. A candidate method for hemodynamic sensing in these devices is photoplethysmography (PPG), which uses light to noninvasively detect changes in blood volume. The present study tested the hypotheses that PPG can function in a subcutaneous location, that the acute changes in blood volume it detects are directly proportional to changes in arterial pressure, and that optimum pacing intervals identified by it are concordant with those determined by arterial pressure. Aortic pressure and PPG were simultaneously recorded in 10 dogs under general anesthesia during changes in atrioventricular (AV) delay and bursts of rapid pacing to simulate tachyarrhythmias. Direct proportionality between transient changes in pressure and PPG waveforms was tested using regression analysis. Scatter plots had a linear appearance, with correlation coefficients of 0.95 (SD 0.03) and 0.72 (SD 0.24) for rapid-pacing and AV delay protocols, respectively. The data were well described by a directly proportional relationship. Optimum AV delays estimated from the induced changes in aortic pressure and PPG waveforms were concordant. This preliminary canine study demonstrates that PPG can function subcutaneously and that it may serve as a surrogate for acute changes in arterial pressure.
Subject-specific profiles of QT/RR hysteresis
Authors: Malik Marek , Hnatkova Katerina , Novotny Tomas , Schmidt Georg
Published: October 2008

The time lag of the QT interval adaptation to heart rate changes (QT/RR hysteresis) was studied in 40 healthy subjects (18 females; mean age, 30.4 ± 8.1 yr) with 3 separate daytime (>13 h) 12-lead electrocardiograms (ECG) in each subject. In each recording, 330 individual 10-s ECG segments were measured, including 100 segments preceded by 2 min of heart rate varying greater than ±2 beats/min. Other segments were preceded by a stable heart rate. In segments preceded by variable rate, QT/RR hysteresis was characterized by λ parameters of the exponential decay models. The intrasubject SDs of λ values were compared with the intersubject SD of the individual means. The λ values were also correlated to individually optimized parameters of heart rate correction. Intrasubject SDs of λ were substantially smaller than the population SD of individual means (0.390 ± 0.197 vs. 0.711, P < 0.0001). The λ values were unrelated to the QT/RR correction parameters. When compared with the corrected QT (QTc) for averaged RR intervals in 10-s ECGs and with the averaged RR intervals in 2-min history, QTc for QT/RR hysteresis led to a substantially smaller SD of QTc values (11.4 ± 2.00, 6.33 ± 1.31, and 4.66 ± 0.85 ms, respectively, P < 0.0001). Thus the speed with which the QT interval adapts to heart rate changes is highly individual with intrasubject stability and intersubject variability. QT/RR hysteresis is independent of the static QT/RR relationship and should be considered as a separate physiological process. The combination of individual heart rate correction with individual hysteresis correction of the QT interval is likely to lead to substantial improvements of cardiac repolarization studies.
Racial differences in central blood pressure and vascular function in young men
Authors: Heffernan Kevin S. , Jae Sae Young , Wilund Kenneth R. , Woods Jeffrey A. , Fernhall Bo
Published: October 2008

Young African-American men have altered macrovascular and microvascular function. In this cross-sectional study, we tested the hypothesis that vascular dysfunction in young African-American men would contribute to greater central blood pressure (BP) compared with young white men. Fifty-five young (23 yr), healthy men (25 African-American and 30 white) underwent measures of vascular structure and function, including carotid artery intima-media thickness (IMT) and carotid artery β-stiffness via ultrasonography, aortic pulse wave velocity, aortic augmentation index (AIx), and wave reflection travel time (Tr) via radial artery tonometery and a generalized transfer function, and microvascular vasodilatory capacity of forearm resistance arteries with strain-gauge plethysmography. African-American men had similar brachial systolic BP (SBP) but greater aortic SBP ( P < 0.05) and carotid SBP ( P < 0.05). African-American men also had greater carotid IMT, greater carotid β-stiffness, greater aortic stiffness and AIx, reduced aortic Tr and reduced peak hyperemic, and total hyperemic forearm blood flow compared with white men ( P < 0.05). In conclusion, young African-American men have greater central BP, despite comparable brachial BP, compared with young white men. Diffuse macrovascular and microvascular dysfunction manifesting as carotid hypertrophy, increased stiffness of central elastic arteries, heightened resistance artery constriction/blunted resistance artery dilation, and greater arterial wave reflection are present at a young age in apparently healthy African-American men, and conventional brachial BP measurement does not reflect this vascular burden.
Adenosine A2Aand β-adrenergic calcium transient and contractile responses in rat ventricular myocytes
Authors: Dobson James G. , Shea Lynne G. , Fenton Richard A.
Published: October 2008

The adenosine A2Areceptor (A2AR) enhances cardiac contractility, and the adenosine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic β1receptor (β1R)-elicited increase in contractility. In this study we compared the A2AR-, A1R-, and β1R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile responses involving PKA and PKC. Stimulation of A2AR with 2 μM (∼EC50) CGS-21680 (CGS) produced a 17–28% increase in the Ca transient ratio (CTR) and maximum velocities ( Vmax) of transient ratio increase (+MVT) and recovery (−MVT) but no change in the time-to-50% recovery (TTR). CGS increased myocyte sarcomere shortening (MSS) and the maximum velocities of shortening (+MVS) and relaxation (−MVS) by 31–34% with no change in time-to-50% relengthening (TTL). β1R stimulation using 2 nM (∼EC50) isoproterenol (Iso) increased CTR, +MVT, and −MVT by 67–162% and decreased TTR by 43%. Iso increased MSS, +MVS, and −MVS by 153–174% and decreased TTL by 31%. The A2AR and β1R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-adenosine 3′,5′-cyclic monophosphorothioate triethylamonium salt prevented both the CGS- and Iso-elicited contractile responses. The PKC inhibitors chelerythrine and KIE1-1 peptide (PKCε specific) prevented the antiadrenergic action of A1R but did not influence A2AR-mediated increases in contractile variables. The findings suggest that cardiac A2AR utilize cAMP/PKA like β1R, but the Ca transient and contractile responses are less in magnitude and not equally affected. Although PKC is important in the A1R antiadrenergic action, it does not seem to play a role in A2AR-elicited Ca transient and contractile events.
LXA4stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells
Authors: Grumbach Yael , Quynh Nga Vu Thi , Chiron Raphaël , Urbach Valérie
Published: October 2008

Lipoxin A4(LXA4) is a biologically active eicosanoid produced in human airways that displays anti-inflammatory properties. In cystic fibrosis and severe asthma, LXA4production has been reported to be decreased, and, in such diseases, one of the consequences of airway inflammation is disruption of the tight junctions. In the present study, we investigated the possible role of LXA4on tight junction formation, using transepithelial electrical resistance (TER) measurements, Western blotting, and immunofluorescence. We observed that exposure to LXA4(100 nM) for 2 days significantly increased zonula occludens-1 (ZO-1), claudin-1, and occludin expression at the plasma membrane of confluent human bronchial epithelial 16HBE14o- cells. LXA4(100 nM) stimulated the daily increase of the 16HBE14o- cell monolayer TER, and this effect was inhibited by boc-2 (LXA4receptor antagonist). LXA4also had a rapid effect on ZO-1 immunofluorescence at the plasma membrane and increased TER within 10 min. In conclusion, our experiments provide evidence that LXA4plays certainly a new role for the regulation of tight junction formation and stimulation of the localization and expression of ZO-1 at the plasma membrane through a mechanism involving the LXA4receptor.
Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model
Authors: Dodd-o Jeffrey M. , Hristopoulos Maria , Scharfstein Daniel , Brower Roy , Hassoun Paul , King Landon S. , Becker Patrice , Liu Manchang , Wang Weiwei , Hassoun Heitham T. , Rabb Hamid
Published: October 2008

We hypothesized that the influence of acute kidney injury (AKI) on the sensitivity of the lung to an injurious process varies with the severity of the injurious process. Thus, we thought that AKI would exacerbate lung injury from low degrees of lung trauma but attenuate lung injury from higher degrees of lung trauma. C57BL/6 mice underwent AKI (30-min kidney ischemia) or sham surgery, followed at 24 h by 4 h of spontaneous breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared with LTV, median bronchoalveolar lavage (BAL) protein leak was significantly lower with SB and greater with HTV in both sham and AKI mice. Compared with LTV, median Evans blue dye-labeled albumin extravasation in lungs (L-EBD) was also significantly lower with SB and greater with HTV. L-EBD showed a significant interaction between ventilatory mode and kidney health, such that AKI attenuated the L-EBD rise seen in HTV vs. LTV sham mice. An interaction between ventilatory mode and kidney health could also be seen in BAL neutrophil number (PMN). Thus, AKI attenuated the BAL PMN rise seen in HTV vs. LTV sham mice. These data support the presence of a complex interaction between mechanical ventilation and AKI in which the sensitivity of the lung to trauma varies with the magnitude of the trauma and may involve a modification of pulmonary neutrophil activity by AKI.
Interleukin-1β mediates human airway epithelial cell migration via NF-κB
Authors: White Steven R. , Fischer Bernard M. , Marroquin Bertha A. , Stern Randi
Published: October 2008

Migration of airway epithelial cells (AEC) is a necessary component of airway mucosal repair after injury. The cytokine IL-1β, present in airway inflammation, has protean effects on constituent cells within the mucosa, but its effects on epithelial repair are not known. We examined migration in differentiated primary human AEC grown in air-liquid interface culture for up to 3 wk and in the 16HBE14o−cell line. Wounds were created by mechanical abrasion and followed to closure using digital microscopy. Concurrent treatment with IL-1β (≤10 ng/ml) significantly accelerated migration in primary differentiated cells and in the 16HBE14o−cell line but did not accelerate migration in primary differentiated AEC collected from asthmatic donors. IL-1β treatment did not augment phosphorylation of stress-activated protein kinases normally activated by mechanical injury, such as heat shock protein 27, ERK1/2, and JNK, and did not elicit phosphorylation of signal transducer and activator of transcription-3. However, introduction of a silencing RNA to block expression of the p65 component of NF-κB blocked IL-1β-accelerated migration substantially. Our data demonstrate that IL-1β accelerates migration of normal, but not asthmatic, differentiated AEC by a mechanism that requires activation of the NF-κB signaling complex and suggests a trophic role for this cytokine in airway epithelial repair after injury.
The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties
Authors: Le Saux O. , Teeters K. , Miyasato S. , Choi J. , Nakamatsu G. , Richardson J. A. , Starcher B. , Davis E. C. , Tam E. K. , Jourdan-Le Saux C.
Published: October 2008

Caveolin-1 (cav1) is a 22-kDa membrane protein essential to the formation of small invaginations in the plasma membrane, called caveolae. The cav1 gene is expressed primarily in adherent cells such as endothelial and smooth muscle cells and fibroblasts. Caveolae contain a variety of signaling receptors, and cav1 notably downregulates transforming growth factor (TGF)-β signal transduction. In pulmonary pathologies such as interstitial fibrosis or emphysema, altered mechanical properties of the lungs are often associated with abnormal ECM deposition. In this study, we examined the physiological functions and the deposition of ECM in cav1−/−mice at various ages (1–12 mo). Cav1−/−mice lack caveolae and by 3 mo of age have significant reduced lung compliance and increased elastance and airway resistance. Pulmonary extravasation of fluid, as part of the cav1−/−mouse phenotype, probably contributed to the alteration of compliance, which was compounded by a progressive increase in deposition of collagen fibrils in airways and parenchyma. We also found that the increased elastance was caused by abundant elastic fiber deposition primarily around airways in cav1−/−mice at least 3 mo old. These observed changes in the ECM composition probably also contribute to the increased airway resistance. The higher deposition of collagen and elastic fibers was associated with increased tropoelastin and col1α2 and col3α1 gene expression in lung tissues, which correlated tightly with increased TGF-β/Smad signal transduction. Our study illustrates that perturbation of cav1 function may contribute to several pulmonary pathologies as the result of the important role played by cav1, as part of the TGF-β signaling pathway, in the regulation of the pulmonary ECM.
Total Parenteral Nutrition Is a Major Risk Factor for Central Venous Catheter-Related Bloodstream Infection in Colorectal Cancer Patients Receiving Postoperative Chemotherapy
Authors: Ishizuka M. , Nagata H. , Takagi K. , Kubota K.
Published: October 2008

Purpose: To clarify the risk factors for central venous catheter-related bloodstream infection (CVCR-BSI) in patients receiving chemotherapy after surgery for colorectal cancer (CRC). Methods: CVCR-BSI was evaluated retrospectively from a database of patients who had received postoperative chemotherapy using central venous catheters (CVC). Results: One hundred and nine patients received 542 CVC for a total of 5,558 catheter-days. There were no significant differences in background between the patients who had CVCR-BSI and those who did not, except for the administration of total parenteral nutrition (TPN) (p < 0.0001). Moreover, univariate analyses (using factors including type of catheter, sex, age, troubles with insertion, kinds of disinfectant, kinds of catheter, length of inserted catheter, term of catheter insertion and administration of TPN) revealed that the administration of TPN (odds ratio, 12.74; 95% CI, 2.489–62.26; p = 0.0023) was the only risk factor for CVCR-BSI. Conclusions: TPN is a major risk factor for CVCR-BSI in CRC patients receiving postoperative chemotherapy.
Birth of a Healthy Histocompatible Sibling following Preimplantation Genetic Diagnosis for Chronic Granulomatous Disease at the Blastocyst Stage Coupled to HLA Typing
Authors: Pangalos Constantinos G. , Hagnefelt Birgitta , Kokkali Georgia , Pantos Konstantinos , Konialis Christopher P.
Published: October 2008

Objective: To perform preimplantation genetic diagnosis (PGD) for chronic granulomatous disease with simultaneous HLA typing in a family case with an affected male child, with the aim of selecting unaffected and HLA-matched embryos to act as donors for hematopoietic stem cell transplantation from umbilical cord blood. Methods: A flexible, indirect HLA haplotyping protocol, based on single-cell multiplex PCR analysis of multiple polymorphic short tandem repeat (STR) markers within the human HLA complex, was optimized for the simultaneous amplification of the informative STR markers together with the gp91-phox gene region containing the mutation and the sexing marker amelogenin. Detection of the c.469C>T disease mutation was performed by minisequencing. Biopsy was performed at the blastocyst stage on day 5 by removal of trophectoderm cells. Results: A total of 11 blastocysts were biopsied on day 5 and a successful result for the informative STR markers and for the mutation detection was obtained for all 11 blastocyst samples. Two healthy and HLA-matched embryos were identified and transferred resulting in a singleton pregnancy. The results of the PGD were confirmed following standard prenatal diagnosis, and cord blood hemopoietic stem cells were obtained from the newborn for subsequent transplantation into the affected sibling. Conclusions: This study demonstrates the feasibility and first successful application of this complex PGD approach as a therapeutic option in families with children affected with X-linked chronic granulomatous disease.
C-Reactive Protein: Vascular Risk Marker in Elderly Patients with Mental Illness
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: October 2008

Background: There is increasing evidence that vascular disease contributes to cognitive impairment and dementia. Clarification of the role of vascular risk factors in dementia is important because most are modifiable, in contrast to other risk factors such as age and genetics. Methods: In 428 patients with mental illness we have investigated the relation of vascular disease to diagnoses, and a biochemical parameter, C-reactive protein (CRP), which is associated with inflammation and vascular disease. Results: Patients with vascular disease showed higher CRP levels than patients without vascular disease. Furthermore, patients with Alzheimer’s disease showed lower CRP levels than patients with vascular dementia, mild cognitive impairment or depression. There is no obvious reason for this finding, since it could not be attributed to drug treatment. Conclusion: The findings indicate that the control of conventional vascular risk factors and therapy could be guided by the level of CRP
Cognitive Functioning in Elderly Persons with Type 2 Diabetes and Metabolic Syndrome: the Hoorn Study
Authors: van den Berg Esther , Dekker Jacqueline M. , Nijpels Giel , Kessels Roy P.C. , Kappelle L. Jaap , de Haan Edward H.F. , Heine Robert J. , Stehouwer Coen D.A. , Biessels Geert Jan
Published: October 2008

Background/Aims: Type 2 diabetes mellitus (DM2) is associated with mild decrements in cognitive functioning, particularly in the elderly. It is often preceded by a ‘prediabetic stage’, characterized by the co-occurrence of insulin resistance and vascular risk factors, usually referred to as the metabolic syndrome. Cognitive decrements may already develop in these early stages. Methods: Cognitive functioning was compared cross-sectionally between DM2 patients (n = 64), patients with metabolic syndrome but without DM2 (n = 83) and control subjects (n = 100) participating in the prospective population-based Hoorn study. Participants performed an extensive neuropsychological examination. Vascular and metabolic determinants were recorded. Results: Both the DM2 group and the metabolic syndrome group performed worse than controls on the domains of information processing speed and attention and executive functioning (mean differences in z-scores 0.2–0.3, all p < 0.05). There were no significant differences in performance between the DM2 and metabolic syndrome group. None of the individual risk factors of the metabolic syndrome, measured at either the present or the previous examination, was a key determinant of cognitive functioning. Conclusion: These results show that DM2-associated cognitive decline may develop in early stages of the disease, possibly in relation to risk factors clustered in the metabolic syndrome.
Prevalence of Dementia and Its Subtypes in an Elderly Urban Korean Population: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA)
Authors: Jhoo Jin Hyeong , Kim Ki Woong , Huh Yoonseok , Lee Seok Bum , Park Joon Hyuk , Lee Jung Jae , Choi Eun Ae , Han Changsu , Choo Il Han , Youn Jong Chul , Lee Dong Young , Woo Jong Inn
Published: October 2008

Background/Aims: We estimated the prevalence of dementia and its major subtypes in an elderly urban Korean population. Methods: A study population of 1,118 Korean elders was randomly sampled from the residents aged 65 years or older living in Seongnam, Korea. Standardized face-to-face interviews, and neurological and physical examinations were conducted on 714 respondents. Dementia was diagnosed according to the DSM-IV diagnostic criteria, and its subtypes were determined according to the criteria of the NINCDS-ADRDA, the NINDS-AIREN, and the consensus guideline proposed by McKeith et al. [Neurology 1996;47:1113–1124]. Results: The estimated age- and gender-standardized prevalences were 6.3% for dementia (95% CI = 4.5–8.1), 4.8% for Alzheimer’s disease (AD; 95% CI = 3.3–6.4), 1.0% for vascular dementia (VD; 95% CI = 0.3–1.8), and 0.4% for dementia with Lewy bodies (DLB; 95% CI = 0.0–0.9). The prevalence of AD consistently increased with age, whereas that of VD peaked at age 75–79 years and decreased thereafter. Of the dementia patients, 72.0% were in the very mild or mild stages of the disease. Conclusions: The prevalence of dementia in a typical urban area of Korea was estimated to be 6.3%, and AD was the most prevalent subtype. DLB was less prevalent than VD among these community-dwelling Korean elders.
Timing Variability during Gait Initiation Is Increased in People with Alzheimer’s Disease Compared to Controls
Authors: Wittwer Joanne E. , Andrews Peta T. , Webster Kate E. , Menz Hylton B.
Published: October 2008

Background/Aims: Variability of constant speed walking is closely related to falls risk in people with Alzheimer’s disease (AD) who fall at 3 times the rate of normal elders. Falls are likely to be provoked during gait initiation, so this study aimed to determine if people with mild-moderate AD have greater variability of gait at initiation. Methods: Measures of step and stride length and time, step width and double support time were recorded during gait initiation for 10 males and 10 females with AD and 20 age- and gender-matched controls. Variability was calculated using the coefficient of variation (CV). Effect size was calculated using Cohen’s d. Results: During gait initiation AD participants had greater variability than controls in stride timing (AD CV = 4.65, Control CV = 3.64; p < 0.05, d = 0.71) and double support proportion (AD CV = 9.40, Control CV = 7.62; p < 0.05, d = 0.8). Conclusion: Increased timing variability in people with AD occurs during gait initiation as well as during constant speed walking and is evident in the early disease stages.
Electroencephalogram Variability in Dementia with Lewy Bodies, Alzheimer’s Disease and Controls
Authors: Andersson M. , Hansson O. , Minthon L. , Rosén I. , Londos E.
Published: October 2008

Background/Aim: Dementia with Lewy bodies (DLB) is probably still underdiagnosed in the clinical setting. Previous studies have suggested a relationship between fluctuations in attention and electroencephalogram (EEG) measures. Since fluctuation in attention is a core symptom of DLB, we sought to further explore whether EEG measures could help differentiate DLB from Alzheimer’s disease (AD) and healthy controls. Methods: The EEGs of 20 patients with DLB, 64 patients with AD and 54 elderly controls were assessed in regard to frequencies, coherence, and variability. Results: Greater variability was seen in delta-band power over 2-second intervals in parietal electrodes of DLB patients. The DLB group had a higher degree of overall coherence in the delta band and a lower degree of overall coherence in the alpha band than the other groups. Finally, EEG measures could distinguish DLB patients from AD patients and controls with areas under the receiver operating characteristic curves ranging between 0.75 and 0.80 and between 0.91 and 0.97, respectively. Conclusions: We suggest that the difference in variability may be associated with the fluctuating cognition seen in DLB. This might have clinical implications as guidance in the diagnosis of DLB. The EEG analysis is simple enough to be possible to apply in clinical practice.
Hydrops Fetalis Caused by Homozygous Alpha-Thalassemia and Kidd Antigen Alloimmunization in a Chinese Woman
Authors: Li Dong-Zhi , Zhong Hui-Zhu , Li Jian , Liao Can
Published: October 2008

We report a case with hydrops fetalis resulting from homozygous α-thalassemia and alloimmune hemolytic anemia due to anti-JK3. This is one of the few cases with immune- and nonimmune-induced hydrops fetalis
Intermediate Interstitial Deletion of Chromosome 7q Detected by First-Trimester Down’s Syndrome Screening
Authors: Cheong Mei-Leng Joy , Tsai Ming-Song , Cortes Raul A. , Harrison Michael R.
Published: October 2008

We report a case of prenatally diagnosed chromosome 7q intermediate interstitial deletion with the aid of first-trimester Down’s syndrome (DS) screening. After detection of a significantly diminished maternal serum pregnancy-associated plasma protein A and correspondingly high DS risk, the pregnant woman underwent amniocentesis for fetal chromosomal analysis. Amniocytes revealed a 46,XY,del(7) (q21.2q31.1) karyotype and 21 weeks’ sonography revealed fetal growth restriction, elevated nuchal fold thickness and cardiomegaly. After therapeutic induction at 22 weeks of gestation, a 310-gram male fetus was born with multiple gross abnormalities including hypertelorism, wide nasal bridge, low-set ears, cleft palate, prominent cheeks, prominent nuchal skin, simian crease and postaxial polydactyly. We review the associated prenatal screening findings, the sonographic profile and phenotypical features associated with chromosome 7q intermediate interstitial deletion.
Anti-Inflammatory Activity of Curcumin in Macrophages Stimulated by Lipopolysaccharides from Porphyromonas gingivalis
Authors: Chen Dong , Nie Min , Fan Ming-wen , Bian Zhuan
Published: October 2008

Background:Porphyromonas gingivalis, a major periodontopathic bacterium, is necessary for periodontitis to take place. The lipopolysaccharide (LPS) of P. gingivalis stimulates cytokine secretion in immune cells, and thereby initiates the inflammation related to periodontitis. Macrophages are the important ones of the immune cells that are prominent at inflammatory periodontal sites. Curcumin, a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory properties. The aim of this study was to investigate the anti-inflammatory effect and the mechanism of action of curcumin in macrophages stimulated by P. gingivalis LPS. Methods: RAW264.7 cells pre-treated with various concentrations of curcumin were stimulated by P. gingivalis LPS. TNF-α and IL-1β expressions were separately detected by RT-PCR and ELISA. Next, activation of NF-ĸB-dependent transcription was examined by luciferase assay. Results: Curcumin dose-dependently inhibited TNF-α and IL-1β gene expression and protein synthesis in RAW264.7 cells stimulated with P. gingivalis LPS. P. gingivalis LPS activated NF-ĸB-dependent transcription in RAW264.7 cells, which were down-regulated by pre-treatment with curcumin as well. Conclusion: Our data suggest that curcumin can inhibit P. gingivalis LPS-induced cytokine expression, and that this could be due to the inhibition of the NF-ĸB pathway.
Cardiac and Extracardiac Abnormalities Detected by Cardiac Magnetic Resonance in a Post-Myocardial Infarction Cohort
Authors: Weir Robin A.P. , Martin Thomas N. , Petrie Colin J. , Murphy Aengus , Clements Suzanne , Steedman Tracey , Wagner Galen S. , McMurray John J.V. , Dargie Henry J.
Published: October 2008

Objectives: All patients should undergo formal assessment of ventricular function following acute myocardial infarction (AMI). Cardiac magnetic resonance (CMR) is not widely used as a test before discharge in AMI patients. This study sought to determine the impact of contrast-enhanced CMR (ceCMR) scanning before discharge in addition to standard transthoracic echocardiography (TTE) on patient care following AMI. Methods: 100 patients admitted with AMI, all of whom had a left ventricular ejection fraction (LVEF) <40% on TTE, underwent ceCMR imaging before discharge. Abnormalities of clinical relevance detected on ceCMR, which influenced patient management, are reported. Results: Each patient (77% male, mean age 58.9 years, SD 12) underwent TTE and ceCMR at a mean 1.4 (range 0.8–3.2) and 4.2 days (range 2–11), respectively, following admission. ceCMR significantly influenced the management of 24/100 (24%) of the patient cohort, through detection of LV thrombus, right ventricular infarction, intracardiac neoplasia, and a variety of intrathoracic and intra-abdominal pathology. There were no issues regarding safety in this high-risk group of patients. Conclusion: In a cohort of AMI patients with reduced LVEF, ceCMR scanning before discharge improved the management of 24% of the cohort. ceCMR is a useful and safe adjunct to standard care after AMI.
Transmeatal Low-Level Laser Therapy for Chronic Tinnitus with Cochlear Dysfunction
Authors: Teggi R. , Bellini C. , Piccioni L.O. , Palonta F. , Bussi M.
Published: October 2008

Objectives: To establish the efficacy of low-level laser therapy for tinnitus. Methods: We performed a prospective, randomized double-blind study on 60 outpatients with tinnitus presenting sensorineural hearing loss in the affected ear. They were randomly divided into two groups, the first performing active laser therapy 20 min a day for 3 months with a 650-nm, 5-mW soft laser (group L), the second using a dummy device which duplicated all aspects of active laser therapy except for the activation of the laser beam (group C). One subject in both groups dropped out due to an increase in tinnitus loudness. Two more patients in each group ceased to comply with the protocol due to familiar problems. Results: The Tinnitus Handicap Inventory (THI) was considered the main outcome measure; no statistical difference was detected between the 2 groups in the THI total score (p = 0.97), and its functional (p = 0.89), emotional (p = 0.89) and catastrophic (p = 0.89) subscales. Moreover, a visual analog scale for self-perceived loudness of the tinnitus showed no difference between the groups (p = 0.69). Regarding psychoacoustic parameters, the minimum masking level showed no difference (p = 0.42), while loudness expressed in sensation level exhibited lower values in group L (p = 0.0127). Group L subjects also presented a decreased rate of hyperacusis (p = 0.02). No changes were detected in the audiometric threshold in both groups. Conclusions: Soft laser therapy demonstrated no efficacy as a therapeutic measure for tinnitus.
Interobserver Variability of the Würzburg Bleb Classification Score
Authors: Klink Thomas , Schrey Sybille , Elsesser Uta , Klink Janine , Schlunck Günther , Grehn Franz
Published: October 2008

Background: The Würzburg bleb classification score (WBCS) serves to assess filtering blebs in a standardized fashion. The purpose of this prospective masked agreement study was to evaluate the WBCS interobserver variability. Methods: The WBCS provides a scheme to grade clinical bleb morphology. It evaluates the following parameters: vascularity, corkscrew vessels, encapsulation, microcysts and bleb height. Thus, 113 eyes of 104 consecutive patients at various times after surgery were examined (slit lamp biomicroscopy) by 3 ophthalmologists with each observer being unaware of the findings reported by the others. To calculate the interobserver variability of the WBCS, the interobserver consistency and absolute agreement were determined with an intraclass correlation coefficient (ICC) using a 2-way random model. Results: The ICC values of a single rater’s judgment were: vascularity +0.62, corkscrew vessels +0.67, encapsulation +0.63, bleb height +0.53, microcysts +0.52 and total score +0.74. The ICC values of the mean of all 3 raters were: +0.83 vascularity, +0.86 corkscrew vessels, +0.84 encapsulation, +0.77 bleb height, +0.76 microcysts and +0.90 total score. Conclusion: The WBCS is a bleb morphology score with high levels of interobserver consistency and absolute agreement in clinical practice.
Effect of Volume Used in Sub-Tenon’s Anesthesia on Efficacy and Intraocular Pressure in Vitreoretinal Surgery
Authors: Sohn Hee Jin , Moon Hyun Seung , Nam Dong Heun , Paik Hae Jung
Published: October 2008

Purpose: To compare the effect of volumes used in sub- Tenon’s anesthesia on efficacy and intraocular pressure (IOP) in vitreoretinal surgery. Methods: A prospective clinical trial was conducted on patients undergoing sub-Tenon’s anesthesia for vitreoretinal surgery. Patients were randomized to receive either 3-, 5- or 7-ml volumes of anesthetic solution. IOP were measured immediately prior to injection, immediately after injection and at 2, 5 and 10 min after injection. Pain scores were assigned using a numerical visual analogue scale immediately after surgery, and again on postoperative day 1. Results: A total of 108 patients (119 eyes) were studied, including 35 eyes in the 3-ml group, 48 eyes in the 5-ml group, and 36 eyes in the 7-ml group. There were significant elevations in mean IOP following injection in all groups, and a trend for larger rises in IOP with larger volumes of anesthesia (p < 0.01). Mean IOP were elevated after injection, and reduced at all time intervals. However, the reduction in the 3-ml group took levels to preinjection amounts. There were no significant differences in patient-reported pain scores among the groups when assessed immediately after surgery or on postoperative day 1. The incidence of chemosis and high IOP elevations (≥40 mm Hg) were more frequent in the 7-ml group (p < 0.05). Conclusions: Sub-Tenon’s anesthesia is effective in vitreoretinal surgery. It would appear that a 3–5-ml volume of anesthetic is safe, when considering the associated complications.
‘Spontaneous’ Periocular Hemorrhage and Macrohematuria
Authors: Jaggi Gregor P. , Killer Hanspeter E.
Published: October 2008

Purpose: To report on a 19-year-old man with ‘spontaneous’ periocular hemorrhage and macrohematuria as the first signs of a bone-marrow-infiltrating rhabdomyosarcoma of the left superior rectus muscle. Procedures: Clinical eye examination, magnetic resonance imaging, laboratory workup and bone marrow biopsy were performed. Results: Magnetic resonance imaging showed a mass lesion in the left superior rectus muscle. While funduscopy had initially been normal, optic disc swelling, retinal hemorrhage and vitreous cell infiltration could be seen in the further course of disease. Laboratory work-up showed macrohematuria, thrombocytopenia and decreased concentration levels of plasma fibrinogen. Thromboplastin time was decreased. A bone marrow biopsy revealed small cell infiltration; using immunohistochemistry, a rhabdomyosarcoma was diagnosed. Unfortunately, the patient died few months later, in spite of chemotherapy. Conclusion: ‘Spontaneous’ periocular hemorrhage and macrohematuria were the first signs of a bone-marrow-infiltrating rhabdomyosarcoma in this young and otherwise healthy patient.
Mixed Brain Pathologies in Dementia: The BrainNet Europe Consortium Experience
Authors: Kovacs Gabor G. , Alafuzoff Irina , Al-Sarraj Safa , Arzberger Thomas , Bogdanovic Nenad , Capellari Sabina , Ferrer Isidro , Gelpi Ellen , Kövari Viktor , Kretzschmar Hans , Nagy Zoltan , Parchi Piero , Seilhean Danielle , Soininen Hilkka , Troakes Claire , Budka Herbert
Published: October 2008

Background: Dementia results from heterogeneous diseases of the brain. Mixed disease forms are increasingly recognized. Methods: We performed a survey within brain banks of BrainNet Europe to estimate the proportion of mixed disease forms underlying dementia and age- and gender-specific influences. Results: Data collected in 9 centres from 3,303 individuals were analysed. The proportion of patients with mixed diagnoses among all cases with Alzheimer disease (AD), vascular pathology (VP), argyrophilic grain dementia (AGD), and synucleinopathies, such as Lewy body dementia (LBD), Parkinson disease (PD) and synuclein pathology only in the amygdala, was 53.3%. Mixed pathology was more frequently reported with LBD, PD, AGD, and VP than with AD. The percentage of mixed diagnoses for AGD and VP significantly differed between centres. In patients younger than 75 years, synucleinopathies, and pure forms of AD, VP, and AGD were more frequent in men. Above 75 years of age, more women had pure AD and pure AGD. Conclusions: The most obvious neuropathological alteration should not terminate the diagnostic procedure since copathology is likely to be found. Neuropathological interpretation of AGD and VP has not been sufficiently established in a consensus. Pure forms of synucleinopathies are unlikely sole substrates for dementia.
Effect of Fetal Sex on Apoptosis-Regulating Proteins in Trophoblasts of Full-Term Human Placenta
Authors: Gol Mert , Tuna Burcin
Published: October 2008

Objective: Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels compared to those pregnant women with male fetuses. Apoptosis in the placenta has a role in hCG secretion. In the present study, we examined the effect of fetal gender on apoptosis-regulating proteins in the trophoblast cells of human term placenta. Study Design: 34 uncomplicated, singleton, term pregnancies, 17 had male and 17 had female fetuses, were recruited in the study. Apoptosis-regulating proteins of the trophoblast cells were measured by using immunohistochemistry for Bcl-2 and Bax. Staining index values were compared between the female and male pregnancies. Results: There were no sex differences in Bcl-2 and Bax proteins. There were no correlations between maternal serum and cord blood hCG levels, and staining index values of two proteins in trophoblast cells. Conclusions: The difference in maternal serum and cord blood hCG levels in correlation with fetal sex is not associated with apoptosis-regulating proteins in the trophoblast cells of human term placenta.
Sulfatase Activity in Normal and Neoplastic Endometrium
Authors: Abulafia Ovadia , Lee Yi-Chun , Wagreich Alison , Economos Kathy , Serur Eli , Nacharaju Vijaya L.
Published: October 2008

Background: Dehydroepiandrosterone sulfate (DHEAS) is metabolized to active androgens and estrogens, which may have a role in the development of endometrial cancer. Methods: We studied DHEAS conversion to dehydroepiandrosterone (DHEA) in normal and neoplastic endometrium utilizing gas chromatography-mass spectral (GC-MS) analysis. Endometrial homogenate was incubated with known amounts of DHEAS for 4 h at 37°C. Methanol extract was separated from debris by centrifugation, concentrated to 200 μl and 1 μl injected into the GC-MS instrument, equipped with a CP-Sil 8 column. DHEAS and DHEA areas were calculated by autoquantization and DHEA/DHEAS ratio was used for comparing sulfatase activity among normal endometrium (n = 6), Stage I endometrioid carcinoma (EC) (n = 15), Stage I mixed mesodermal Müllerian tumor (MMMT) (n = 6) and Stage I uterine papillary serous carcinoma (UPSC) (n = 7). Results: DHEA/DHEAS ratios in normal endometrium, EC, MMMT and UPSC were 1.45 ± 1.10, 5.63 ± 3.27, 2.88 ± 0.99, and 3.04 ± 1.76, respectively. Sulfatase activity was significantly higher in EC when compared with normal endometrium (p < 0.001), MMMT (p < 0.05), and UPSC (p < 0.05). The enzyme activity did not differ significantly between low-grade and high-grade EC tumors (5.8 ± 2.77 and 5.49 ± 3.84, respectively, p > 0.05). Conclusion: Stage I EC have higher sulfatase activity than normal endometrium, and Stage I MMMT and UPSC tumors.
Obstetric Risk Factors Associated with the Development of Periventricular Leukomalacia in Preterm Infants Born to Mothers Complicated by Placenta Previa
Authors: Oda Nanae , Takeuchi Kyousuke , Tanaka Ayumi , Maruo Takeshi
Published: October 2008

Objectives: This study was designed to evaluate the effect of antenatal risk factors on the occurrence of periventricular leukomalacia (PVL) in preterm infants from pregnancies complicated by placenta previa. Study Design: The association between obstetric risk factors and PVL was assessed in 30 singleton live births complicated with placenta previa delivered between 24 and 33 completed weeks of gestation. Each infant underwent at least two cranial ultrasounds: the first before 72 h and the second around 14 days of life. Analysis of variance was used to compare continuous variables across groups. Comparison of groups for categorical data was analyzed with Pearson χ2 test. Results: The obstetric factors in infants with PVL were compared to those in infants with negative cranial ultrasonographic findings. The main risk factors for PVL in preterm placenta previa were initial antepartum hemorrhage <28 weeks of gestation (OR 13.7; 95% CI 1.38–136.2), although the differences of gestational age of delivery between two groups were not statistically significant. Low Apgar score (<7) at 1 min increased the risk of PVL (OR 8.89; 95% CI 12.9–61.1), while no associations with PVL were observed in low Apgar score at 5 min, neonatal acidosis (pH <7.2), and neonatal anemia (Hb <14 g/dl). Conclusions: This study demonstrates that initial antepartum hemorrhage during the second trimester and low Apgar score at birth increase the risk of PVL in preterm infants born to mothers with placenta previa. We speculate that the pathophysiologic mechanisms for this finding may be due to decreased placental perfusion in the second trimester of pregnancy, which is the developmental window of vulnerability for PVL.