bluuebunny/crossref_metadata_2025 huggingface dataset:
MELTING POINT AND LATTICE PARAMETER SHIFT IN SUPPORTED METAL NANOCLUSTERS
Authors: BORMAN V. D. , BORISYUK P. V. , TRONIN I. V. , TRONIN V. N. , TROYAN V. I. , PUSHKIN M. A. , VASILIEV O. S.
Published: August 2009

The dependencies of the melting point and the lattice parameter of supported metal nanoclusters as functions of clusters height are theoretically investigated in the framework of the uniform approach. The vacancy mechanism describing the melting point and the lattice parameter shifts in nanoclusters with decrease in their sizes is proposed. It is shown that under the high vacuum conditions (p < 10-7 torr ) the essential role in clusters melting point and lattice parameter shifts is played by van der Waals forces of cluster–substrate interaction. The proposed model satisfactorily accounts for the experimental data.
NUMERIC AND EXACT SOLUTIONS OF THE NONLINEAR CHAPMAN–KOLMOGOROV EQUATION: A CASE STUDY FOR A NONLINEAR SEMI-GROUP MARKOV MODEL
Authors: FRANK T. D.
Published: August 2009

Nonlinear Markov processes are known to arise from diffusion approximations of nonlinear master equations and generalized Boltzmann equations and have been studied in their own merit in the context of nonlinear Fokker–Planck equations. Nonlinear Markov processes can account for collective phenomena, collective oscillations, and collective chaotic behavior. Despite the importance of nonlinear Markov processes for the physics of stochastic processes, relatively little is known about the Chapman–Kolmogorov equation of nonlinear Markov processes. The manuscript derives the exact solution of the Chapman–Kolmogorov equation for a recently proposed deterministic Markov model. Numerical solutions of the Chapman–Kolmogorov equation are used to demonstrate the nonlinear semi-group property of conditional probabilities of nonlinear Markov processes.
Hepatic uptake of γ-butyrobetaine, a precursor of carnitine biosynthesis, in rats
Authors: Fujita Masaharu , Nakanishi Takeo , Shibue Yuta , Kobayashi Daisuke , Moseley Richard H. , Shirasaka Yoshiyuki , Tamai Ikumi
Published: August 2009

γ-Butyrobetaine (GBB) is a precursor in the biosynthesis of carnitine, which plays an important role in the β-oxidation of fatty acids, and is converted to carnitine by γ-butyrobetaine dioxygenase (BBD) predominantly in liver. We investigated the molecular mechanism of hepatic uptake of GBB in rat hepatocytes. Cellular localization of rat Octn2 (rOctn2:Slc22A5) was studied by Western blot analysis. Uptake of deuterated GBB (d3-GBB) was examined in HEK293 cells expressing rOctn2 (HEK293/rOctn2) and freshly isolated rat hepatocytes. d3-GBB was quantified by use of liquid chromatography-tandem mass spectrometry. Western blot analysis demonstrated an expression of OCTN2 protein in hepatic basolateral membrane but not in bile canalicular membrane fraction. Furthermore, we found that d3-GBB was taken up by rOctn2 in an Na+-dependent manner with Kmvalue of 13 μM. The apparent Kmvalue for d3-GBB transport in freshly isolated rat hepatocytes was 9 μM. d3-GBB uptake by the rat hepatocytes was inhibited by γ-aminobutyric acid (GABA) to 30% of the control, whereas it was inhibited by carnitine to 62% of the control, even at 500 μM. Furthermore, d3-GBB uptake by rat hepatocytes was decreased by 45% with rat Gat2 (Slc6A13, a major liver GABA transporter) silenced by the microRNA method. Accordingly, the present study clearly demonstrates that GBB is taken up by hepatocytes for carnitine biosynthesis not only via Octn2 but also via the GABA transporter, possibly Gat2.
In vivo assessment of blood flow patterns in abdominal aorta of mice with MRI: implications for AAA localization
Authors: Amirbekian Smbat , Long Robert C. , Consolini Michelle A. , Suo Jin , Willett Nick J. , Fielden Sam W. , Giddens Don P. , Taylor W. Robert , Oshinski John N.
Published: August 2009

Abdominal aortic aneurysms (AAA) localize in the infrarenal aorta in humans, while they are found in the suprarenal aorta in mouse models. It has been shown previously that humans experience a reversal of flow during early diastole in the infrarenal aorta during each cardiac cycle. This flow reversal causes oscillatory wall shear stress (OWSS) to be present in the infrarenal aorta of humans. OWSS has been linked to a variety of proatherogenic and proinflammatory factors. The presence of reverse flow in the mouse aorta is unknown. In this study we investigated blood flow in mice, using phase-contrast magnetic resonance (PCMR) imaging. We measured blood flow in the suprarenal and infrarenal abdominal aorta of 18 wild-type C57BL/6J mice and 15 apolipoprotein E (apoE)−/− mice. Although OWSS was not directly evaluated, results indicate that, unlike humans, there is no reversal of flow in the infrarenal aorta of wild-type or apoE−/− mice. Distensibility of the mouse aortic wall in both the suprarenal and infrarenal segments is higher than reported values for the human aorta. We conclude that normal mice do not experience the reverse flow in the infrarenal aorta that is observed in humans.
Epidemiology of Acute Renal Failure in ICUs: A Multi-Center Prospective Study
Authors: Andrikos Emilios , Tseke Paraskevi , Balafa Olga , Cruz Dinna N. , Tsinta Afrodite , Androulaki Marianthi , Pappas Michael , Ronco Claudio
Published: August 2009

Background and Aim: Acute kidney injury (AKI) is a common complication in intensive care units (ICUs). However, its incidence and outcome vary in several studies depending on definitions used or even the geographic origin of the study. We aimed to evaluate the epidemiology of AKI in ICUs in Greece. Method: Prospective multicenter study of ICU patients presented with AKI during a 3-month period. Results: One-hundred and seventy patients presented with AKI (16% of total admissions in 23 ICUs). The most common contributing factor to AKI was sepsis (45%). Half of the patients required renal replacement therapy, which was mainly managed by ICU clinicians. Nearly 65% of the AKI patients died, whereas 15% were discharged with renal impairment. Age (RR 1.01, p = 0.046), sepsis (RR 1.62, p = 0.015) and urine output (RR 0.99, p = 0.009) were independently associated with outcome. Conclusion: AKI involves a large number of patients in Greek ICUs and is associated with adverse outcomes.
Monitor Turnaround Time and Time Efficiency in Hemodialysis Delivery – A Global Comparison
Authors: Alquist Maria , Hegbrant Jörgen B.A. , Bosch Juan P.
Published: August 2009

Background/Aims: Increasing cost pressure has forced shortening of dialysis treatments. The aim of this study was to benchmark the hemodialysis (HD) delivery monitor turnaround time and time efficiency in a global comparison. Methods: 683 HD deliveries in 26 Gambro Healthcare clinics in Europe, Taiwan and the USA were assessed using the Treatment Mapping methodology. Results: Consolidated mean monitor turnaround time was 324.4 min. On average, 69% consisted of the HD treatment and 31% (102.8 min) of other activities: monitor preparation, monitor disinfection and monitor waiting – roughly one third each. USA had the shortest monitor turnaround, dialysis treatment and disinfection times. However, time efficiency – the percentage of monitor turnaround time on dialysis – was the lowest in the USA (68 vs. 69 and 74% in Europe and Taiwan) as monitor preparation, undress and waiting were the longest in USA. Conclusion: A monitor/disposable design to minimize time for preparation, undress and disinfection would reduce the cost of operational time without compromising quality.
Preliminary Report regarding the Use of Selective Sorbents in Complex Cardiac Surgery Patients with Extensive Sepsis and Prolonged Intensive Care Stay
Authors: Yaroustovsky M. , Abramyan M. , Popok Z. , Nazarova E. , Stupchenko O. , Popov D. , Plushch M. , Samsonova N.
Published: August 2009

Aims: The purpose of this publication is to evaluate the first experiences with the supplemental use of selective endotoxin adsorption cartridges in the treatment of critically ill patients complicated by severe sepsis after cardiac surgery. Methods: Thirteen patients with Gram-negative sepsis underwent the procedure of selective lipopolysaccharide (LPS) adsorption using Alteco adsorber (group I) or Toraymyxin™ columns (polymyxin-B-immobilized fiber) (group II). Results: This therapy positively influenced the course of sepsis. After the second procedure, levels of serum endotoxin and procalcitonin markedly decreased in both groups. We also discovered a positive effect on leukocytosis levels and a trend towards normalization of body temperature, improvement of hemodynamic indices and increase of the lung’s oxygenating function. Blood cultures taken several days after the procedure were negative. Conclusion: Our experience with LPS adsorption shows some evidence for the potential efficacy of this method in the treatment of critically ill patients with sepsis. Further investigations are required.
Neuroprotective Properties of Melatonin in a Model of Birth Asphyxia in the Spiny Mouse (Acomys cahirinus)
Authors: Hutton Lisa C. , Abbass Mahila , Dickinson Hayley , Ireland Zoe , Walker David W.
Published: August 2009

Birth asphyxia is associated with disturbed development of the neonatal brain. In this study, we determined if low-dose melatonin (0.1 mg/kg/day), administered to the mother over 7 days at the end of pregnancy, could protect against the effects of birth asphyxia in a precocial species – the spiny mouse (Acomys cahirinus). At 37 days of gestation (term is 38–39 days), pups were subjected to birth asphyxia (7.5 min uterine ischemia) and compared to Cesarean section-delivered controls. At 24 h of age, birth asphyxia had increased markers of CNS inflammation (microglia, macrophage infiltration) and apoptosis (activated caspase-3, fractin) in cortical gray matter, which were reduced to control levels by prior maternal melatonin treatment. Melatonin may be an effective prophylactic agent for use in late pregnancy to protect against hypoxic-ischemic brain injury at birth.
Improvement in the Detection of α0- and Deletional α-Thalassemia by Real-Time PCR Combined with Dissociation Curve Analysis
Authors: Liu Jingzhong , Tang Ning , Liu Quanzhang , Wang Lirong , Han Han , Cai Ren , Wu Xiaoyi , Xiao Bai
Published: August 2009

The prevailing cause of α-thalassemia in Southeast Asia is the presence of 3 deletion mutations in the α-globin genes (–SEA, –α3.7 and –α4.2). Current detection methods include gap polymerase chain reaction (PCR), multiplex PCR and real-time PCR with SYBR Green 1 combined with dissociation curve analysis. To improve and simplify a previously published method that requires 4 separate reactions, a duplex PCR assay was designed to detect both the nondeletional and the –SEA alleles. This duplex PCR can successfully identify the nondeletional allele and both the –SEA carrier and homozygous genotypes. The combination of the duplex PCR and 2 gap PCRs (for detection of –α3.7 and –α4.2) can diagnose all types of deletional α-thalassemia. Our method was validated by analysis of 195 DNA samples, the results of which were consistent with prior diagnoses. The developed assay can reliably diagnose α0-thalassemia and all types of deletional α-thalassemia. The diagnostic method is simple, rapid, accurate, automated, inexpensive and has a high throughput.
Mid-Dilution Hemodiafiltration: A Comparison with Pre- and Postdilution Modes Using the Same Polyphenylene Membrane
Authors: Maduell Francisco , Arias Marta , Vera Manel , Fontseré Néstor , Blasco Miquel , Barros Xoana , Garro Julia , Elena Montserrat , Bergadá Eduardo , Cases Aleix , Bedini Jose Luis , Campistol Josep M.
Published: August 2009

As a change from Diapes to polyphenylene membrane in the mid-dilution filter has recently been developed, the aim of this study was to compare mid-dilution using this new dialyzer versus pre- and postdilution. The prospective study included 20 patients who underwent 4 hemodiafiltration (HDF) sessions: 1.7 m2 polyphenylene and predilution infusion flow (Qi) 200 ml/min, 1.7 m2 and postdilution Qi 100 ml/min, 1.9 and 2.2 m2 mid-dilution both with Qi 200 ml/ min. The urea and creatinine reduction ratios were slightly higher in postdilution. The β2-microglobulin (85.8%), myoglobin (73.6%), prolactin (67.8%) and retinol-binding protein (29.2%) reduction ratios with 1.9 m2 mid-dilution, which was similar to 2.2 m2 mid-dilution, were significantly higher than with the post- and predilution modes. Mid-dilution appears to be a good HDF alternative that allows a better removal of larger molecules than postdilution and, mainly, predilution. Mid-dilution using 1.9 or 2.2 m2 dialyzers, at the same convective volume, showed a similar removal.
Epigenomics in Psychiatry
Authors: Kato Tadafumi
Published: August 2009

It is not known whether and how epigenetic factors contribute to the pathophysiology of mental disorders. As possible mechanisms, epimutations during embryogenesis, epigenetic memory of environmental effects, and the role of epigenetic gene regulation in the action mechanisms of treatment may be considered. To date, detection of DNA methylation differences between twins discordant for mental disorders, and DNA methylation differences in candidate genes in the postmortem brains between patients with mental disorders and control subjects have been reported. More recently, several findings of epigenomic studies using genome-wide DNA methylation analysis have been reported. Further studies using this comprehensive analysis will provide insight into the role of epigenetics in mental disorders.
Epigenetic Profiling in Schizophrenia and Major Mental Disorders
Authors: Iwamoto Kazuya , Kato Tadafumi
Published: August 2009

Epigenetic alterations such as DNA methylation and histone modifications are important in the etiology or pathophysiology of mental disorders. Here, we review recent studies on the relationship between DNA methylation and major mental disorders. We will focus on the role of DNA methylation in postmitotic neurons, intra- and interindividual variations in DNA methylation, the possible involvement of methionine metabolism pathways, and candidate and genome-wide DNA methylation as they relate to mental disorders.
Long-Term Outcome after Lithium Augmentation in Unipolar Depression: Focus on HPA System Activity
Authors: Adli Mazda , Bschor Tom , Bauer Michael , Lucka Claudia , Lewitzka Ute , Ising Marcus , Uhr Manfred , Mueller-Oerlinghausen Bruno , Baethge Christopher
Published: August 2009

Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings.
Subjective Memory Complaints and Awareness of Memory Functioning in Mild Cognitive Impairment: A Systematic Review
Authors: Roberts J.L. , Clare L. , Woods R.T.
Published: August 2009

Objectives: Subjective memory complaint (SMC) is central to the diagnosis of mild cognitive impairment (MCI). People with MCI are at a higher risk of progressing to dementia, and research on SMC is contradictory in terms of the accuracy of SMC and its predictive role for future dementia. One possible reason for these contradictory findings is that the level of awareness of memory function may vary among people with MCI. This review examines whether the level of awareness of memory functioning varies amongst people classified as having MCI and whether there is support for the suggestion that the level of awareness in MCI predicts future progression to dementia. Method: Sixteen studies were identified which evaluate the awareness level in people classified as having MCI in either a clinical or research setting. In addition to the outcome of each study, the conceptualization of awareness, ‘object’ of awareness and methodology were also considered. Results: There is evidence to show that the level of awareness in MCI does vary, and this may have implications for future progression to dementia. Conclusions: Given the increased risk of progression to dementia for those identified as having MCI, the role of awareness should be explored further with due consideration given to the conceptualisation of awareness and the methodology employed. The finding of variability in awareness has implications for the use of SMC in the diagnostic criteria for MCI.
Cognitive Reserve in Relation to Abeta42 in Patients Converting from MCI to Dementia – A Follow-Up Report
Authors: Rolstad S. , Nordlund A. , Eckerström C. , Gustavsson M.H. , Zetterberg H. , Wallin A.
Published: August 2009

The concept of the cognitive reserve (CR) hypothesizes that premorbid factors such as education enable compensation for the manifestation of brain pathology. Accordingly, pathology should be more prominent in individuals with higher CR before becoming clinically apparent. Previously, we found that patients subsequently converting to dementia with higher CR had lower concentrations of amyloid beta 42 (abeta42) as compared to patients with lower CR. However, the interaction between time, biomarkers, neuropsychological performance and CR is yet to be established. Objective: To study the relation between biomarkers, neuropsychological performance and CR longitudinally. Method: A mixed between-within subject analysis of variance was performed for longitudinal analysis. Paired t tests were used for within group comparisons. Results: Patients with higher CR (n = 15) had significantly lower concentrations of abeta42 at both time points compared to those with medium (n = 23) and lower CR (n = 28). Also, abeta42 concentrations decreased significantly from baseline to follow-up in patients with higher and medium CR. Groups performed comparably on neuropsychological tests. Conclusion: This study provides further support for the applicability of abeta42 as a substitute for pathology in relation to CR. Also, abeta42 reflects the disease progression in patients with higher and medium CR.
Validation of a HeLa Mx2/Luc Reporter Cell Line for the Quantification of Human Type I Interferons
Authors: Seo Young-Jun , Kim Gi-Hyun , Kwak Ho-Jung , Nam Ju-Sun , Lee Hwa Jeong , Suh Soo-Kyung , Baek Kyung-Min , Sohn Yeo-won , Hong Seung-Hwa
Published: August 2009

Although antiviral assays have been the most widely available biological assays for interferons (IFNs), they are less sensitive and provide considerable interassay variation. In this study, we demonstrate a new reporter cell line, which is based on HeLa cells transfected with a plasmid containing a human Mx2 promoter driving a luciferase (Luc) cDNA. To characterize the specific gene expression profiles induced by interferon alpha, we analyzed the microarray results of interferon response gene expression induced by IFN-α2a or IFN-α2b treatment with HeLa cells. We found that the Mx2 gene increased the most by treatment with both IFN-α2a and IFN-α2b. Based on this result, we designed a reporter cell line, HeLa-Mx2, suitable for determination of IFN-α. HeLa cells were stably transfected with the luciferase gene under the control of Mx2 promoter. The expression of luciferase can be easily measured for luminescence using a 96-well luminometer and has been correlated with the concentration of added IFN and cell density. In the validation results, our reporter cell line had specificity for type I IFN, but the significant effects of a number of other cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-2, IL-5, IL-6 and GM-CSF, or type II interferon (IFN-γ) were not observed. Moreover, the robustness of our cell line is demonstrated by the lack of an effect of the HeLa-Mx2 cell culture’s age on the performance of the reporter gene assay. The reporter gene assay demonstrated reproducible dose-response curves for IFN-α2a in the range of 1–10,000 IU/ml. The 95% confidential limit and total coefficient of variation estimates ranged between 96 and 116 and 10.51% in the reducible range mentioned above, respectively. In conclusion, we established a stable IFN-responsible HeLa-Mx2 cell line, which has advantages with regard to simplicity, selectivity, and reliability over conventional cytopathic effect reduction assays used to quantify IFN-α activity.
Cortactin Interacts with Podocalyxin and Mediates Morphological Change of Podocytes through Its Phosphorylation
Authors: Kobayashi Tatsuo , Notoya Mitsuru , Shinosaki Toshihiro , Kurihara Hidetake
Published: August 2009

Background/Aims: Morphological change of podocytes is closely correlated with the development of proteinuria. Podocalyxin is a major sialoglycoprotein of the podocytes and is thought to be involved in the maintenance of the foot processes structure. Our aim was to examine the mechanism by which podocalyxin contributes to the morphological change of podocytes. Methods: We searched protein(s) which coprecipitate with podocalyxin using rat glomerular lysate. Localization of podocalyxin and the coprecipitated protein, cortactin, was studied in a model of puromycin aminonucleoside (PAN) nephrosis by immunocytochemistry. Tyrosine phosphorylation of cortactin was examined. Association of the podocalyxin/cortactin complex with the actin cytoskeleton was evaluated by extraction with Triton-X and immunoblotting. Results: Cortactin was found to be co-immunoprecipitated with podocalyxin. Immunocytochemical analysis revealed that these 2 proteins colocalized in the apical side of podocytes. In PAN nephrosis, localization of cortactin was altered after the onset of proteinuria, with increased tyrosine phosphorylation. Simultaneously, the dissociation of the podocalyxin/cortactin complex from the actin cytoskeleton was induced. Conclusions: These results indicate that cortactin mediates interaction between podocalyxin and actin filaments in podocytes and that alteration of this interaction may play a role in the process of morphological change of podocytes.
Sympathetic Nerve Varicosities in Close Apposition to Basolateral Membranes of Collecting Duct Epithelial Cells of Rat Kidney
Authors: Loesch Andrzej , Unwin Robert , Gandhi Vanita , Burnstock Geoffrey
Published: August 2009

Background: There are reports of sympathetic innervation of the nephron and of P2 purinergic receptors on epithelial cells. Since ATP is a cotransmitter with noradrenaline in sympathetic nerves, the objective of the present study was to re-investigate basolateral innervation of rat renal collecting duct epithelial cells by sympathetic nerves in the context of recent data on the effects of ATP on this nephron segment. Methods: Kidney sections were processed for electron immunocytochemistry, using tyrosine hydroxylase rabbit polyclonal antibody, with a second layer of biotinylated donkey anti-rabbit antibody and finally extravidin-horseradish peroxidase. Immunoreactivity was visualised with 3,3′-diaminobenzidine and examined with a Philips CM120 transmission electron microscope. Results: Electron microscopic evidence is presented for close apposition of sympathetic nerve varicosities immunolabelled with tyrosine hydroxylase to principal and intercalated type epithelial cells of the collecting duct of the cortical region. Conclusions: It is suggested that ATP is released as a cotransmitter from sympathetic nerve varicosities to act on basolateral P2 purinoceptors to influence sodium and water (and potentially acid-base) transport, in conjunction with the known (typically inhibitory) actions of autocrine and/or paracrine release of ATP from collecting duct epithelial cells acting via luminal P2 receptors. It is suggested that while luminal responses may dominate under normal physiological conditions, in pathophysiological states, such as stress and dehydration, sympathetic nerves might also be involved in modulating collecting duct fluid and electrolyte transport.
Comparison of Long-Term Outcomes between Spousal Transplants and Other Living Unrelated Donor Transplants: Single-Center Experience
Authors: Yoon Hye Eun , Song Joon Chang , Hyoung Bok Jin , Hwang Hyeon Seok , Lee So Young , Jeon Youn Joo , Park Sun Cheol , Choi Bum Soon , Kim Yong Soo , Moon In Sung , Yang Chul Woo
Published: August 2009

Background/Aims: The greater use of living unrelated donors (LUDs) as kidney donors is a worldwide trend in the current era of organ shortage, and spouses are an important source of LUDs. This study was to compare the long-term outcomes of spousal donor grafts with other LUD grafts. Methods: Among 445 LUD grafts, 77 were spouses and 368 were other LUDs. The clinical characteristics and long-term survival rates for spousal transplants were compared with those for other LUD transplants, and risk factors affecting graft survival were assessed. Results: Spousal donors had a significantly higher average number of human leukocyte antigen (HLA) mismatches (4.2 vs. 3.4, p < 0.001) and were older (41 vs. 33 years, p < 0.001) than LUDs. The 10-year survival rates for spousal donor grafts were 60.6%, similar to those for LUD grafts (58.5%, p = 0.61). The 10-year biopsy-proven acute rejection-free survival rates (85.5 vs. 89.6%, p = 0.45) and patient survival rates were also similar (84.3 vs. 79.6%, p = 0.35). The degree of HLA mismatching, the spousal donor type or donor age did not affect the graft survival. Conclusion: Renal transplants from spousal donors show similar long-term outcomes to those from better HLA-matched and younger LUDs.
Volume Indicators and Left Ventricular Mass during Aggressive Volume Management in Patients on Thrice-Weekly Hemodialysis
Authors: Goldfarb-Rumyantzev Alexander S. , Chelamcharla Madhukar , Bray Bruce E. , Leypoldt John K. , Lavasani Iran , Nelson Natalia , Lavasani Tooran , Baird Bradley , Cheung Alfred K.
Published: August 2009

Objective: We examined the relationship between various volume indicators, i.e. multifrequency bioelectric impedance analysis (BIA), predialysis serum N-terminus-pro-brain natriuretic peptide (NT[-]pro[-]BNP) levels, and inferior vena cava diameter, and left ventricular mass index (LVMI) at baseline and with rigorous volume management on thrice-weekly hemodialysis. Methods: Twenty-two patients on chronic thrice-weekly hemodialysis were followed for 52 weeks. Left ventricular hypertrophy was present in 100% of the cohort at baseline. Results: There were no significant correlations among volume indicators except for a correlation between extracellular-volume-to-body-mass ratio and collapsibility index (r = 0.476; p = 0.039) at 6 months. There were no correlations between blood pressure and volume indicators. Baseline (but not follow-up) collapsibility index correlated with LVMI (r = 0.506; p = 0.038). In ‘lag-time’ analyses, there were no correlations between volume indicators at baseline or 6 months and LVMI at subsequent time points. LVMI decreased from 243.6 ± 83.3 g/m2 at baseline to 210.6 ± 62.9 g/m2 at 6 months (p = 0.104) and further to 203.2 ± 49.0 g/m2 at 12 months (p = 0.035). Conclusions: (1) Left ventricular hypertrophy was prevalent in hemodialysis patients; (2) BIA, inferior vena cava ultrasound and serum NT-pro-BNP levels yield discordant results for fluid volumes; (3) regression of LVMI could occur with rigorous fluid management, even with thrice-weekly dialysis.
Patients Aged 80 and Older Undergoing Orthopedic or Urologic Surgery: A Prospective Study Focusing on Perioperative Morbidity and Mortality
Authors: Peled Eli , Keren Yaniv , Halachmi Sarel , Soudry Michael , Zinman Chaim , Kats Yeshayahu , Barak Michal
Published: August 2009

Background: The population is progressively aging and an increasing number of elderly patients face surgical treatment. Objective: The current study was designed to examine the perioperative morbidity and mortality of elderly patients undergoing orthopedic or urologic surgery and look for predictors for adverse outcome. Methods: This is a prospective study of elderly patients, 80 years of age and older, who underwent elective or emergent orthopedic or urologic surgery in our institution during a 5-month period. Data were collected on age, gender, chronic diseases, number of regular medications, whether or not the patient was bedridden before surgery, American Society of Anesthesiologists (ASA) class, type of surgery and anesthesia, duration of hospitalization, and 30-day postoperative morbidity and mortality. We studied correlations between pre- and intraoperative parameters and postoperative complications. Results: During the study period, 39 patients underwent urologic surgery and 147 patients underwent orthopedic surgery. Age ranged from 80 to 98 years (85 ± 4.2 years, mean ± SD). One patient had an intraoperative complication, 5 patients had postoperative complications within 1 day of surgery, and 23 had complications within 1 month of surgery. Five (2.7%) patients, all of whom were operated urgently, died after surgery. Postoperative complications correlated significantly to poor ASA class (p = 0.01), urgency of the procedure (p = 0.03), and extent (p = 0.02) and duration (p = 0.01) of surgery. No significant correlation was found between outcome and any other pre- or intraoperative factors. Conclusions: Elderly surgical patients with poor ASA class or following urgent, extensive or long surgery are at a higher risk for postoperative morbidity and mortality, mandating special perioperative care.
Effects of Nicotine Exposure on Renal Function of Normal and Hypercholesterolemic Rats
Authors: Tamaoki Lie , Oshiro-Monreal Fabíola M. , Helou Claudia M.B.
Published: August 2009

Background/Aims: Renal risks of nicotine exposure associated with hypercholesterolemia are still unknown. Methods: Thus, hypercholesterolemic rats (HC) and their control (C) were evaluated by inulin clearance (InCl) measured at baseline and during nicotine infusion (100 μg/kg b.w.). Five groups were studied: (i) C; (ii) DEN (C submitted to a renal denervation); (iii) C + L-arginine (0.25% in drinking water); (iv) HC, and (v) HC + L-arginine (0.25% in drinking water). Furthermore, C and HC had their renal blood flow (RBF) measured and they have also been chronically treated with nicotine (12.5 μg/ml in drinking water) to assess InCl on the 8th day. Results: Nicotine increased blood pressure in C, DEN and HC and reduced InCl only in C. L-Arginine treatment blunted nicotine effects on blood pressure and increased InCl only in C. Moreover, nicotine did not change RBF in C but elicited in HC, whereas renal vascular resistance was increased in C and unchanged in HC. Indeed, chronic nicotine exposure has also reduced InCl in C. Conclusion: Nicotine acted on the adrenergic system and nitric oxide counteracted this action in C, but the same may not be applied to HC. An impairment in renal autoregulation may explain why InCl was unchanged in HC.
Correlation Between Carotid Intimal/Medial Thickness and Atherosclerosis
Authors: Finn Aloke V. , Kolodgie Frank D. , Virmani Renu
Published: August 2009

A widely adopted surrogate for predicting rates of cardiovascular events involves measure of carotid intimal-medial thickness (CIMT) by B mode ultrasound, a technique available since the mid 1980s. The value of this modality remains in its ability to noninvasively assess cardiovascular risk beyond traditional factors identified by the Framingham risk score, and it is among the few available techniques for monitoring the effectiveness of pharmacotherapy on plaques. There are, however, existing limitations to this methodology. Perhaps the most important distinction is that IM thickness measurements are generally acquired in the common carotid artery, whereas advanced atherosclerotic disease occurs predominantly downstream in the internal carotid. Moreover, primary contributors to IM thickening are age and hypertension, which do not necessarily reflect the atherosclerotic process. Initiation of disease-related plaques begins as what is referred to as pathological intimal thickening; lesions characterized by the formation of lipid pools in the absence of a necrotic core. The eventual development of a necrotic core, however, is considered a key indicator of significant plaque advancement and recognized feature of lesion vulnerability. Necrotic cores are thought to arise from macrophage infiltration of lipid pools followed by secondary necrosis where defective clearance of debris, tissue disruption proteases, and intraplaque hemorrhage, likely contribute to its enlargement. Therefore, one of the primary limitations to CIMT is its inability to distinguish lesions with a necrotic core. Moreover, in most cases measures of plaque area or volume are generally considered better predictors of an inflammatory process consistent with atherosclerotic disease rather than intimal medial thickness.
ENPP1
Q121 Variant, Increased Pulse Pressure and Reduced Insulin Signaling, and Nitric Oxide Synthase Activity in Endothelial Cells
Authors: Bacci Simonetta , Di Paola Rosa , Menzaghi Claudia , Di Fulvio Patrizia , Di Silvestre Sara , Pellegrini Fabio , Baratta Roberto , Marucci Antonella , Mastroianno Sandra , Fini Grazia , Formoso Gloria , Consoli Agostino , Perticone Francesco , Frittitta Lucia , Pandolfi Assunta , Trischitta Vincenzo
Published: August 2009

Objective—

Insulin resistance induces increased pulse pressure (PP), endothelial dysfunction (ED), and reduced bioavailability of endothelium-derived nitric oxide (NO). The genetic background of these 3 cardiovascular risk factors might be partly common. The
ENPP1
K121Q polymorphism is associated with insulin resistance and cardiovascular risk.

Methods and Results—

We investigated whether the K121Q polymorphism is associated with increased PP in white Caucasians and with ED in vitro. In 985 individuals, (390 unrelated and 595 from 248 families), the K121Q polymorphism was associated with PP (
P
=8.0×10
−4
). In the families, the Q121 variant accounted for 0.08 of PP heritability (
P
=9.4×10
−4
). This association was formally replicated in a second sample of 475 individuals (
P
=2.6×10
−2
) but not in 2 smaller samples of 289 and 236 individuals (
P
=0.49 and 0.21, respectively). In the individual patients’ data meta-analysis, comprising 1985 individuals, PP was associated with the Q121 variant (
P
=1.2×10
−3
). Human endothelial cells carrying the KQ genotype showed, as compared to KK cells, reduced insulin-mediated insulin receptor autophosphorylation (
P
=0.03), Ser
473
-Akt phosphorylation (
P
=0.03), and NO synthase activity (
P
=0.003).

Conclusions—

Our data suggest that the
ENPP1
Q121 variant is associated with increased PP in vivo and reduced insulin signaling and ED in vitro, thus indicating a possible pathogenic mechanism for the increased cardiovascular risk observed in
ENPP1
Q121 carriers.
Statins Block Calcific Nodule Formation of Valvular Interstitial Cells by Inhibiting α-Smooth Muscle Actin Expression
Authors: Benton Julie A. , Kern Hanna B. , Leinwand Leslie A. , Mariner Peter D. , Anseth Kristi S.
Published: August 2009

Objective—

Calcific aortic stenosis, characterized by excessive fibrosis and deposition of bone-like calcified tissue, affects roughly 2% to 3% of the U.S. population over the age of 65. Recent studies have suggested that statins have a positive effect on the progression of aoritic stenosis, likely because of their ability to affect the resident cell population, known as valvular interstitial cells (VICs). VICs are fibroblastic cells that can differentiate to form activated myofibroblasts, displaying increased alpha smooth muscle actin (αSMA) expression, contractility, and collagen production.

Methods and Results—

In culture, VICs spontaneously form multicellular aggregates that subsequently develop into calcified nodules, providing an in vitro model for aortic stenosis. Using real-time microscopic tracking, we observed that confluent VIC monolayers spontaneously contract into rounded nodules, suggesting that myofibroblastic contractility is a critical step in the process of nodule formation. Overexpression of αSMA increased VIC calcific nodule formation and contractility, whereas knockdown of αSMA with siRNAs reduced these phenotypes, suggesting that the expression and contractile properties of αSMA are essential to the formation of nodules. Statin treatment of VICs reduced αSMA expression, inhibited contractility, and decreased nodule formation. When statins were used to treat preformed nodules, no decrease in the number of calcified nodules was observed, suggesting that statins may play more of a preventative role in aortic stenosis than a cure.

Conclusions—

Our studies provide evidence of a causal relationship between VIC myofibroblastic activity and initial VIC calcific nodule formation. Furthermore, we demonstrate that pravastatin inhibition of calcific nodule formation is related to inhibition of myofibroblastic activity.
Truncation of Titin’s Elastic PEVK Region Leads to Cardiomyopathy With Diastolic Dysfunction
Authors: Granzier Henk L. , Radke Michael H. , Peng Jun , Westermann Dirk , Nelson O. Lynne , Rost Katharina , King Nicholas M.P. , Yu Qianli , Tschöpe Carsten , McNabb Mark , Larson Douglas F. , Labeit Siegfried , Gotthardt Michael
Published: August 2009

Rationale:

The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region.

Objective:

The purpose of this study was to investigate the contribution of titin’s proline–glutamate–valine–lysine (PEVK) region to biomechanics and growth of the heart.

Methods and Results:

We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element.

Conclusions:

Titin’s PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies.
Intraventricular Fibrinolysis and Lumbar Drainage for Ventricular Hemorrhage
Authors: Staykov Dimitre , Huttner Hagen B. , Struffert Tobias , Ganslandt Oliver , Doerfler Arnd , Schwab Stefan , Bardutzky Juergen
Published: August 2009

Background and Purpose—

Both intraventricular fibrinolysis (IVF) and lumbar drainage (LD) may reduce the need for exchange of external ventricular drainage (EVD) and shunt surgery in patients with intracerebral hemorrhage and severe intraventricular hemorrhage. We investigated the feasibility and safety of IVF followed by early LD for the treatment of posthemorrhagic hydrocephalus.

Methods—

This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (n=32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if “LD weaning” was unsuccessful for >10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale.

Results—

IVF resulted in fast clearance of the third and fourth ventricles (73±50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105±59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding.

Conclusions—

In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.
Reliability of the Modified Rankin Scale
Authors: Quinn Terence J. , Dawson Jesse , Walters Matthew R. , Lees Kennedy R.
Published: August 2009

Background and Purpose—

A perceived weakness of the modified Rankin Scale is potential for interobserver variability. We undertook a systematic review of modified Rankin Scale reliability studies.

Methods—

Two researchers independently reviewed the literature. Crossdisciplinary electronic databases were interrogated using the following key words: Stroke*; Cerebrovasc*; Modified Rankin*; Rankin Scale*; Oxford Handicap*; Observer variation*. Data were extracted according to prespecified criteria with decisions on inclusion by consensus.

Results—

From 3461 titles, 10 studies (587 patients) were included. Reliability of modified Rankin Scale varied from weighted κ=0.95 to κ=0.25. Overall reliability of mRS was κ=0.46; weighted κ=0.90 (traditional modified Rankin Scale) and κ=0.62; weighted κ=0.87 (structured interview).

Conclusion—

There remains uncertainty regarding modified Rankin Scale reliability. Interobserver studies closest in design to large-scale clinical trials demonstrate potentially significant interobserver variability.
Optimizing Screening and Management of Asymptomatic Coronary Artery Disease in Patients With Stroke and Patients With Transient Ischemic Attack
Authors: Ovbiagele Bruce , Liebeskind David S. , Kim Doojin , Ali Latisha K. , Pineda Sandra , Saver Jeffrey L.
Published: August 2009

Background and Purpose—

The feasibility of implementing an expert consensus guideline recommending use of a stroke patient’s profile to manage undiagnosed coronary artery disease remains unclear.

Methods—

Following a guideline-based algorithm, we screened consecutive patients with ischemic stroke and patients with transient ischemic attack for asymptomatic coronary artery disease using the Framingham Heart Study Coronary Risk Score (FCRS) cutoff of high risk (≥20%) for experiencing a hard coronary artery disease event over a 10-year period. Patients with high FCRS received dobutamine stress echocardiogram outpatient screening, additional treatment (β-blocker), or further management (cardiologist referral).

Results—

From July 2004 to September 2007, among 693 patients, 501 (72%) met study criteria, of which 80 (16%) had FCRS ≥20%. Elevated serum glucose, nonhigh-density lipoprotein, triglycerides, homocysteine, glycosylated hemoglobin as well as large vessel atherosclerotic stroke mechanism were more frequent in high versus low FCRS patients (
P
<0.05). Among high FCRS patients, 35 (44%) had dobutamine stress echocardiogram performed. Leading reasons for dobutamine stress echocardiogram nonperformance were patient noncompliance (42%) and primary care physician refusal (33%).

Conclusions—

Screening for coronary artery disease risk using FCRS is feasible in hospitalized patients with stroke, but outpatient adherence to stress testing is challenging largely due to patient and primary care physician-related factors.
Association of Symptoms of Chronic Bronchitis and Frequent Flu-Like Illnesses With Stroke
Authors: Grau Armin J. , Preusch Michael R. , Palm Frederik , Lichy Christoph , Becher Heiko , Buggle Florian
Published: August 2009

Background and Purpose—

Acute and several chronic infectious diseases increase the risk of stroke. We tested the hypothesis that chronic bronchitis and frequent flu-like illnesses are independently associated with the risk of stroke or transient ischemic attack (TIA).

Methods—

We assessed symptoms of chronic bronchitis, frequency of flu-like illnesses, and behavior during acute febrile infection in 370 consecutive patients with ischemic or hemorrhagic stroke or TIA and 370 age- and sex-matched control subjects randomly selected from the population.

Results—

Cough with phlegm during ≥3 months per year (grade 2 symptoms of chronic bronchitis) was associated with stroke or TIA independent from smoking history, other risk factors, and school education (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.17 to 5.94;
P
=0.021). There was also an independent association between frequent flu-like infections (>2 per yr) and stroke/TIA (OR 3.54; 95% CI 1.52 to 8.27;
P
=0.003). Simultaneous assessment of chronic bronchitis and frequent flu-like infections did not attenuate the effect of either factor. Patients reported more often than control subjects to continue to work despite febrile infection (OR 3.68, 95% CI 1.80 to 7.52, multivariate analysis).

Conclusions—

Our results suggest that chronic bronchitis is among those chronic infections that increase the risk of stroke. Independent from chronic bronchitis, a high frequency of flu-like illnesses may also be a stroke risk factor. Infection-related behavior may differ between stroke patients and control subjects.