bluuebunny/crossref_metadata_2025 huggingface dataset:
Balloon-Distension Studies in the Gastrointestinal Tract: Current Role
Authors: Gregersen Hans , Drewes Asbjørn M. , McMahon Barry P. , Liao Donghua
Published: July 2006

Balloon distension is a commonly used technique in visceral organs. Research studies take advantage of this technique for studying organ physiology, e.g. for studying the force-deformation relationship and mechanosensitive receptors in the gastrointestinal wall. Balloon distension is also used for diagnostic purposes, e.g. in the diagnostics of non-cardiac chest pain and for treatment of diseases such as bleeding esophageal varices caused by liver disease and lower esophageal sphincter occlusion caused by achalasia. Balloon distension can be carried out with concomitant measurements of pressure, volume and cross-sectional area alone or in combination. Furthermore, balloon-distension techniques can be combined with various imaging techniques such as B-mode ultrasonography and MRI to obtain three-dimensional geometric data about the three-dimensional surface with subsequent calculation of the tension or stress in the gastrointestinal organs. This article describes balloon-distension techniques, in particular new developments of the impedance planimetric technique including methods for studying gastrointestinal muscle function.
Ambulatory Esophageal pH Monitoring: New Directions
Authors: Dickman Ram , Fass Ronnie
Published: July 2006

pH testing remains a commonly used evaluative tool in clinical practice. However, the original tool that included a nasally placed pH catheter was plagued with a variety of shortcomings, primarily the effect of the procedure on patients’ lifestyle and thus on reflux-provoking activities. The miniaturization of evaluative techniques in gastroenterology was the impetus for the development of the wireless pH capsule and the SmartPill. These modalities improve patients’ tolerability of the required test and provide a unique opportunity for expansion of indications and data collection. The introduction of the multichannel intraluminal impedance with a pH sensor allowed the detection of gastroesophageal reflux that is non-acidic. However, the value of the technique beyond the realm of academic gastroenterology remains to be elucidated. Recently, there was a renewal of interest in Bilitec 2000. The technique, which has never found a clear clinical role, has been recommended as an important tool in evaluating patients who failed proton pump inhibitor therapy. However, data to support its clinical value in this situation have remained scant.
Palatine Mucosa of Aging and Experimentally Induced Diabetic Aging Rabbits: Light-Microscopic, Scanning Electron Microscopic and Transmission Electron Microscopic Qualitative Study
Authors: Kronka M.C. , Watanabe I. , Lopes M.G.O. , Silva M.C.P.
Published: July 2006

Background: Data associating palatine mucosa, microvascular architecture, aging and diabetes mellitus are few, so the aim of the present study was to examine these conditions structurally and ultrastructurally. Methods: We used 18 female rabbits, aged about 2 years at the beginning of the experiment, distributed into 2 groups: aging diabetic and aging animals, prepared by three different methodologies: light microscopy, scanning electron microscopy and transmission electron microscopy. The samples were stained with hematoxylin-eosin for light microscopy, and for scanning electron microscopy, we used Mercox® Cl-2B vascular corrosion casts. For transmission electron microscopy, the specimens were fixed and embedded in Epon 812 resin. Results: Under light microscopy, we noted small amounts of underdeveloped connective papillae and significant flattened areas through the epithelium-connective tissue interface in the aging diabetic group. Larger blood vessels were deeply located in the palatine mucosa, branching off in the direction of the epithelium-connective tissue interface. Capillaries followed the interface contour. In both groups, vascular corrosion casts revealed capillaries sprouting out in disorganized rows but parallel between themselves. ‘Hair-pin’ capillary loops and convoluted capillary loops were noted. Conclusion: The aging diabetic group showed rarefying microvasculature areas with complex tortuous capillary loops. Transmission electron microscopy results showed that the aging diabetic group presented small cytoplasmatic projections directed to the vessel lumen and micropinocytic vesicle, i.e. caveolas. Epithelium-connective tissue interface, connective papillae, microangioarchitecture, and information about endothelial cells alterations were observed in the aging diabetic and aging animals.
Postural Balance in a Random Sample of 7,979 Subjects Aged 30 Years and Over
Authors: Era P. , Sainio P. , Koskinen S. , Haavisto P. , Vaara M. , Aromaa A.
Published: July 2006

Background: Reliable normative data for force platform measurements of postural balance have not been available. Methods: Data on postural balance were collected from a representative nationwide sample of a Finnish population aged ≧30 years (n = 7,979). As part of a comprehensive health survey (Health 2000), postural balance was measured with the help of a force platform system in four test conditions: normal standing with eyes open and closed (both for 30 s), semi-tandem (20 s) and tandem stand with eyes open (20 s). In addition, balance abilities were also evaluated by a non-instrumented field test. Results: The main findings of this study indicated that the differences in balance between subjects belonging to different age categories were apparent already among young and middle-aged subjects. This is true, however, only for the more accurate force platform measurements, as the field test showed a clear ceiling effect up to 60 years of age. At higher ages both methods indicated a further, accelerating decline in balance function. In most cases, males tended to have more pronounced sway, as indicated by the speed and amplitude aspects of the movement of the center of pressure during the force platform registrations and these differences were larger in the older age groups. In contrast, in the field test a larger proportion of males were able to achieve the highest category (10 s in tandem stand) and the proportion of subjects unable to stand for a minimum of 10 s feet side by side was larger among females than males. These observations may partly be due to differences in the participation/acceptable performance in the different tests. In addition, the field test and force platform measurements may partially reflect different aspects of balance abilities. Conclusion: The results of the present study provide normative values for force platform balance tests at an age of 30 years and above. Deterioration in balance function clearly starts at relatively young ages and further accelerates from at about 60 years upwards. Due to systematic differences between males and females, separate normative values for both sexes are needed. Due to marked ceiling effects the field test can only be recommended for older individuals, aged ≧60. On the other hand, force platform registrations in the more demanding tests (semi-tandem and tandem stands) suffer from floor effects in the oldest age groups.
Aerobic-Anaerobic Profiles, Heart Rate and Match Analysis in Old Basketball Players
Authors: Tessitore Antonio , Tiberi Monica , Cortis Cristina , Rapisarda Emiliano , Meeusen Romain , Capranica Laura
Published: July 2006

Background: Scientific information on master competitions is mainly in individual sports and there is a lack of information on the senior team sport matches. Objective: To provide aerobic and anaerobic profiles of senior (55 ± 5 years) basketball players (n = 10), and to evaluate the physiological load and the match analysis of a senior basketball match. Methods: Participants were administered a maximal oxygen consumption (VO2 max) and anaerobic tests (jump tests: counter movement jump (CMJ) and bounce jump (BJ), and running tests: 10-m sprint and running 10 m while bouncing the ball (10-mBB)). During a senior basketball match, the players’ heart rate (HR), electrocardiogram (ECG), blood lactate concentration (LA) and motor activities were recorded. Results: The maximal aerobic test values were: HRpeak 149 ± 9 beats·min–1; power 187 ± 23 W; VO2peak 22.9 ± 2.2 ml·kg–1·min–1; LApeak 8.3 ± 1.9 mM. Jump test values were: CMJ = 24.9 ± 6.5 cm and BJ = 20.5 ± 4.75 cm. Running performances were: 10-m sprint in 2.26 ± 0.18 s; 10-mBB in 2.34 ± 0.14 s; 10-mBB/10-m sprint ratio 1.1 ± 0.1. During the match, no adverse event or ST-segment changes or complex arrhythmias occurred. HR exceeded 85% of HRpeak for 59 ± 37%. LA values were 3.7 ± 1.8 mM. Players spent 48% walking, 19% positioning, 17% running, 15% inactive, and 1% jumping. A limited number of fouls (2 ± 1.5) was observed and players performed only 2-point shots. Conclusion: Older basketball players undergoing a training regimen of 1.5 h·week–1 showed good anaerobic characteristics and a moderate aerobic capacity. Although the senior basketball match required high intensities (only 3% of total match time spent at HR <70% of HRmax), the ECG Holter monitoring showed no adverse event, ST-segment changes or complex arrhythmias. Finally, their play did not include the technical skills recently introduced to basketball.
Randomised Trial of In-Hospital Geriatric Intervention: Impact on Function and Morale
Authors: Saltvedt Ingvild , Jordhøy Marit , Opdahl Mo Ellen-Sofie , Fayers Peter , Kaasa Stein , Sletvold Olav
Published: July 2006

Background: In two previous publications, we have shown that treatment of acutely sick, frail elderly patients in a Geriatric Evaluation and Management Unit (GEMU) compared to treatment in the general Medical Wards (MW) reduced mortality and improved the chances of living at home in contrast to living in nursing homes or being dead. Objective: The aim of this presentation was to study the impact on function, symptoms of depression and general well-being of treatment in the GEMU as compared to treatment in MW. Methods: Acutely sick, frail patients aged ≧75 years, admitted as emergencies to the Department of Internal Medicine, were randomised either to treatment in the GEMU (n = 127) or the MW (n = 127). In the GEMU the treatment strategy emphasised comprehensive interdisciplinary assessment of all relevant disorders, prevention of complications and iatrogenic conditions, early mobilisation, rehabilitation and discharge planning. The control group received treatment as usual from the Department of Internal Medicine. After discharge neither group received specific follow-up. Activities of daily living (ADL), instrumental ADL, cognitive function, symptoms of depression and general well-being were assessed 3, 6 and 12 months after discharge from hospital. Results: There was no difference in function, depression or general well-being in the GEMU as compared to the MW group. If the dead were included in the analysis at the highest ADL dependency level, there was better function in the GEMU group at 3 months (p = 0.03). Conclusion: Treatment in the GEMU had no measurable beneficial impact on function, morale or symptoms of depression. Taken the previously shown mortality reduction into consideration an additional effect on function was less likely and the overall treatment effect was considered to be positive.
Sarcopenia – A Potential Target for Angiotensin-Converting Enzyme Inhibition?
Authors: Sumukadas Deepa , Struthers Allan D. , McMurdo Marion E.T.
Published: July 2006

Society is ageing. There has been a steady increase in the number of people aged 65 years and over throughout the 20th century and this trend is predicted to continue worldwide. This has resulted in an increase in the incidence of sarcopenia, which is a loss of muscle mass and function with age. Maintenance of muscular function into old age is critical to sustaining normal daily activity and functional independence. Sarcopenia is associated with increased morbidity and mortality. Till now most efforts to counteract sarcopenia have met with limited success. We postulate that targeting the renin-angiotensin system through angiotensin-converting enzyme (ACE) inhibition could play a role in countering sarcopenia. ACE inhibitors could work by preventing mitochondrial decline and improving endothelial function and muscle metabolism. We describe the literature to support our hypothesis that sarcopenia may be a potential therapeutic target for ACE inhibitors.
Factors Associated with Perceived Health of Very Old Inhabitants of Japan
Authors: Kawada Tomoyuki , Suzuki Shosuke , Tsukioka Tokio , Iesaki Satoru
Published: July 2006

Background: Perceived health or self-rated subjective health of the oldest inhabitants of Japan was studied to identify its associated impact on their lives. Objective: The health status of the aged was evaluated to elucidate the correlation between their health complaints and perceived health status as expressed on a comprehensive rating scale. Methods: A health questionnaire including the Todai Health Index (THI) was applied to 529 inhabitants of Central Japan, aged 85 years or older. THI is a symptom checklist composed of 130 questions. Twelve scale scores and two discriminant function values were calculated. Response rate was 99.8% (528/529). Other items included sex, age, prevalence of chronic disease and its treatment, marital status, academic career, and friendship. A question ‘How is your health?’ with five ordinal response options was used to assess perceived health. Results: The mean values of THI scale scores of lie and aggression of poor (poor or extremely poor) perceived health were significantly lower than those of good (extremely good or good) perceived health. The mean values of other THI scale scores of poor perceived health except impulsiveness and nervousness in male subjects were significantly higher than those of good perceived health. Spearman’s rank correlation coefficients between perceived health score and THI scale scores were all statistically significant. Furthermore, multiple logistic regression analysis was conducted to identify significant factors predicting perceived health. THI scale scores of physical symptoms, depressive state, and irregular daily life were significant. Odds ratios and 95% confidence intervals in parentheses on each factor were 1.15 (1.07–1.23), 1.14 (1.02–1.30), and 1.15 (1.02–1.30), respectively. Conclusions: Poor perceived health was significantly associated with irregular lifestyle, physical and mental complaints. Perceived health reflects the health status of the oldest inhabitants of Japan.
Creatine Kinase Elevation in Creutzfeldt-Jakob Disease
Authors: Finsterer Josef , Gelpi Ellen
Published: July 2006

Objectives: Creutzfeldt-Jakob disease (CJD) is not only a disorder of the central nervous system but also affects the skeletal muscle. Subclinical skeletal muscle involvement, manifesting as hyper-creatine-kinase (CK)-emia, is rare. Case Report: The patient, a 60-year-old male, developed progressive dementia, accompanied by dysphagia and bursts of aggression, disorientation and optic hallucinations. Five months after onset of the cognitive decline, hyper-CK-emia of 117 U/l (normal: <81 U/l) was noted for the first time. During 12 months until decease, hyper-CK-emia was permanently present and reached a maximum of 354 U/l. Hyper-CK-emia was attributed to subclinical involvement of the skeletal muscle in CJD. Hyper-CK-emia due to progressive brain damage, double trouble of an additional primary myopathy or due to excessive myoclonic jerking was excluded. Conclusions: This case shows that CJD may be present with mild hyper-CK-emia in individual patients, most likely due to concomitant undiagnosed involvement of the skeletal muscle in the primary disease.
Diarrhées intraitables dues à des anomalies congénitales des entérocytes
Authors: Phillips Alan D.
Published: July 2006

Contexte: Les diarrhées intraitables du nourrisson sont des affections sévères responsables d’une morbidité et d’une mortalité élevées. Ces cas demandent beaucoup de soins de la part des parents et des soignants, car il n’existe aucun traitement simple. Le petit nombre de ces patients laisse penser que seule une collaboration internationale regroupant les ressources et les sujets atteints, permettra de faire progresser la compréhension de ces affections. Des analyses régulières de la littérature dans ce domaine sont nécessaires pour faire connaître les progrès et discuter des hypothèses et critères diagnostiques. Méthodes: Le présent article est une analyse de la littérature concernant les anomalies congénitales des entérocytes. Résultats: Des diagnostics précis sont possibles dans ce groupe de maladies, et les critères en sont de plus en plus acceptés. Les cas publiés au plan mondial font apparaître des différences d’évolution clinique, certains de moindre sévérité. La morbidité et la mortalité demeurent cependant élevées. Conclusions: Un long chemin reste encore à parcourir afin de déterminer l’origine de ces troubles. La biologie moléculaire ouvre des perspectives prometteuses de détermination des anomalies génétiques de ces maladies. Il s’agit d’une priorité, car il serait ainsi possible de disposer de critères diagnostiques plus précis, de préciser les relations de ces maladies entre elles et d’apporter les informations nécessaires sur leurs mécanismes.
Entéropathies congénitales et transplantation intestinale
Authors: Goulet Olivier
Published: July 2006

Une insuffisance intestinale nécessite une nutrition parentérale. Les cas d’insuffisance intestinale sévère prolongée incluent le syndrome du grêle court, des troubles sévères de la motilité (aganglionnose totale ou subtotale ou syndrome de pseudo-occlusion intestinale chronique) et des anomalies congénitales du développement des entérocytes. Une hépatopathie sévère peut se développer chez les patients atteints d’une insuffisance intestinale tant en raison de l’affection digestive sous-jacente que d’une nutrition parentérale inadaptée. Une septicémie liée au cathéter et/ou une thrombose vasculaire étendue peuvent nuire à la poursuite d’une nutrition parentérale sûre et efficace. La prise en charge des patients atteints d’une insuffisance intestinale nécessite donc l’identification précoce de l’affection et l’analyse de son risque d’irréversibilité. La détermination du moment auquel adresser le patient pour une transplantation intestinale demeure un problème capital. En conséquence, la prise en charge doit inclure des traitements adaptés à chaque stade d’insuffisance intestinale sur la base d’une approche multidisciplinaire dans des centres assurant des soins de gastro-entérologie pédiatrique, une expertise en nutrition parentérale, un programme de nutrition parentérale à domicile, des interventions de chirurgie pédiatrique et un programme de transplantation hépato-intestinale.
Correlated Expression of High-Sensitivity C-Reactive Protein in Relation to Disease Activity in Inflammatory Bowel Disease: Lack of Differences between Crohn’s Disease and Ulcerative Colitis
Authors: Zilberman Liaz , Maharshak Nitsan , Arbel Yaron , Rogowski Ori , Rozenblat Meirav , Shapira Itzhak , Berliner Shlomo , Arber Nadir , Dotan Iris
Published: July 2006

Background/Aims: As opposed to regular C-reactive protein (CRP) assays, the introduction of high-sensitivity ones has enabled us to detect low grade inflammation in patients with inflammatory bowel disease (IBD). We addressed the subject of the degree of correlation between the concentration of high-sensitivity CRP (hs-CRP) and the inflammatory IBD activity score. Methods: Included were 90 patients with Crohn’s disease (CD), 70 with ulcerative colitis (UC) and 160 controls. Disease activity was determined using CD activity index (CDAI) for CD and Mayo score for UC. The Dade Boering BNII Nephelometer was used to determine the hs-CRP concentrations. Results: The coefficient of correlation between hs-CRP and the disease activity score was similar for both UC (0.26) and CD (0.36). Conclusions: These findings are relevant for therapeutic intervention in which a greater absolute reduction in the hs-CRP concentration in CD patients (who generally present higher CRP concentrations than those found in UC) might be interpreted as a better response compared to the same absolute reduction in UC patients. This information is needed for clinicians using the hs-CRP assay to estimate IBD disease activity in daily practice.
Association Study of Promoter Polymorphisms within the NOS3 Gene and Allergic Diseases
Authors: Holla Lydie Izakovicova , Stejskalova Andrea , Znojil Vladimír , Vasku Anna
Published: July 2006

Background: Nitric oxide (NO) is an important mediator of physiologic and pathologic processes in the airways. On this basis, we hypothesized that polymorphisms in the NOS3 gene could be associated with the disease process. Methods: Two promoter variants (–786C/T and –691C/T) were examined in a Caucasian Czech population of allergic patients [n = 671, with a subgroup of asthmatics (n = 305)] and healthy controls (n = 334) using PCR-RFLP analyses. Results: NOS3 –786C/T and –691C/T were not associated with allergic diseases or asthma. However, the –786 variant was significantly associated with asthma in men (p < 0.01, pcorr < 0.05) but not in women. NOS3 –691C/T was found to be in strong linkage disequilibrium with –786C/T, and the distribution of combined genotypes was marginally different between the asthmatic and control men. Conclusion: Our results suggest that NOS3 gene variants may be one of the factors that participate in the pathogenesis of asthma in men.
Expression of the High-Affinity Fluoropyrimidine-Preferring Nucleoside Transporter hCNT1 Correlates with Decreased Disease-Free Survival in Breast Cancer
Authors: Gloeckner-Hofmann Katharina , Guillén-Gómez Elena , Schmidtgen Claudia , Porstmann Romy , Ziegler Ralf , Stoss Oliver , Casado F. Javier , Rüschoff Josef , Pastor-Anglada Marçal
Published: July 2006

Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. Methods: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. Results: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. Conclusions: These results indicate thatthe expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy.
Do Olfactory Ensheathing Cells Play a Role in the Defense of the Brain against Infection?
Authors: Chuah Meng Inn , Vincent Adele J. , West Adrian K.
Published: July 2006

Olfactory ensheathing cells (OECs), also known as olfactory neuroglia, are widely accepted to play a role in the ontogeny of the primary olfactory pathway. Their expression of numerous growth factors and extracellular matrix molecules is consistent with a role in guiding elongating olfactory axons from the nasal cavity to their termination in the olfactory bulb. In recent years, researchers have attempted to exploit these phenotypic features by utilizing these cells as a therapeutic agent to induce repair of the injured nervous system. However, their strategic placement along olfactory nerves, spanning the region between the external nasal cavity and the olfactory bulb (part of the central nervous system), and their expression profile of immunomodulatory proteins support a possible involvement in the protection of the brain against infection. This commentary will briefly outline the relationship between OECs and developing olfactory nerves, and recent experimental evidence that suggests a remarkable functional plasticity of OECs including a possible active role in the immune system.
Successful Verbal Retrieval in Elderly Subjects Is Related to Concurrent Hippocampal and Posterior Cingulate Activation
Authors: Heun Reinhard , Freymann Katrin , Erb Michael , Leube Dirk T. , Jessen Frank , Kircher Tilo T. , Grodd Wolfgang
Published: July 2006

Objective: Memory decline and hippocampal atrophy are two major aspects of Alzheimer’s disease. Using a response-related fMRI design, we investigated the relationship between successful verbal retrieval and concurrent cerebral activation in elderly subjects in different stages of cognitive decline. We chose a correlational over the more traditional categorical approach to increase the power of detecting relevant activations. Methods: Eleven subjects with Alzheimer’s disease, 21 elderly subjects with mild cognitive impairment, and 29 age-matched cognitively unimpaired subjects learned 180 nouns. While measuring brain activation with fMRI, the subjects had to classify these 180 learned plus 180 new distractor words as known or new. Response-related fMRI analysis was used to identify cerebral activation by correctly remembered words (hits) that correlated with retrieval success in the whole group. Results: Successful verbal retrieval was significantly correlated with concurrent activation of the left hippocampus and posterior cingulate gyrus. Conclusion: The study confirms the importance of adequate hippocampal function for successful verbal retrieval in the elderly. In addition, our study supports connectivity studies indicating a functional relationship between the hippocampus and the posterior cingulate gyrus during successful verbal retrieval in the elderly in different stages of cognitive decline.
Rho/Rho Kinase Pathway Regulates Maintenance of the Differentiated Tubular Epithelial Cell Phenotype on Laminin-1
Authors: Reuters Irith , Weber Manfred , Schulze-Lohoff Eckhard
Published: July 2006

Background: Maintenance of a polarized tubular epithelium by appropriate intracellular signaling and extracellular matrix is critical both in normal renal function as well as in acute and chronic tubular injury. We examined the hypothesis that maintenance of a differentiated epithelial phenotype on the basement membrane glycoprotein laminin-1 is controlled by the Rho/Rho kinase pathway. Methods: Using the tubular epithelial cell lines LLC-PK1 and MDCK which were cultured on laminin-1 vs. collagen IV, we analyzed cell morphology and motility (cohort migration assay) as well as expression of differentiation and dedifferentiation markers (immunofluorescence microscopy). Results: Cohort migration of LLC-PK1 cells was significantly slowed down on laminin-1 (10.7 ± 2.2 m.u. (migratory units)) compared with collagen IV (16.6 ± 2.3 m.u.; BSA control: 2.8 ± 2.5 m.u.). Inhibition of the Rho/Rho kinase pathway by C3 exotoxin (1 µg/ml) or the Rho kinase inhibitor Y27632 (10 µM) significantly augmented cohort migration on laminin-1 (14.5 ± 1.4 and 16.0 ± 1.8 m.u. vs. 10.7 ± 2.2 m.u.). In parallel to the increased migratory activity, inhibition of the Rho/Rho kinase pathway resulted in a more mesenchymal phenotype of LLC-PK1 cells on laminin-1 with increased formation of lamellopodia and filopodia, distinct loss of focal contacts and stress fibers, upregulation of the dedifferentiation marker vimentin, and loss of cell-cell contacts with translocation of β-catenin from the adherens junctions to the cytosol and nucleus. Similarly, cohort migration of MDCK cells was retarded on laminin-1 when compared with collagen IV, and addition of the Rho kinase inhibitor Y27632 resulted in enhanced motility and a change in cell morphology. Conclusion: The study demonstrates that the Rho/Rho kinase pathway is required to maintain a non-migratory epithelial phenotype of cultured renal tubular LLC-PK1 and MDCK cells on the basement membrane glycoprotein laminin-1.
Is the Efficacy of LDL Apheresis in Ischemic Optic Neuropathy Linked to a Reduction in Endothelial Activation Markers?
Authors: Ramunni A. , Ranieri G. , Giancipoli G. , Guerriero S. , Ria R. , Saliani M.T. , Sborgia L. , Ranieri P. , Coratelli P.
Published: July 2006

Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by nonarteritic ischemic optic neuropathy. Statistically significant reductions were achieved in all parameters: total cholesterol (44.6%), LDL cholesterol (54.6%), fibrinogen (60.9%), von Willebrand factor (38.6%), sE-Selectin (22.6%), sICAM-1 (14%) and sVCAM-1 (15.5%), each of which was correlated with an improvement in the mean deviation of the visual field, although statistical significance for the single parameters was not reached. However, analysis of variance between the mean deviation improvement and the set of parameters taken together yielded highly significant results (p < 0.0001). LDLA was effective in reducing the values of all evaluated endothelial activation markers, and this trend was correlated with an improvement in the visual field.
Pharmacokinetics of Two Novel Bicalutamide Formulations in Healthy Male Volunteers
Authors: Cantarini Mireille , Fuhr Rainard , Morris Thomas
Published: July 2006

The oral bioavailability of two investigational formulations of bicalutamide was compared with the current clinical formulation. The first formulation was amorphous R-/S-bicalutamide in solid dispersion with a polymeric matrix of hydroxypropyl methylcellulose phthalate (HP55S) (R-/S-bicalutamide/HP55S); the second was R-bicalutamide alone in a solid dispersion with HP55S (R-bicalutamide/HP55S). Study 1 was a two-period, incomplete crossover study comparing a single dose of bicalutamide 150 mg with single 150 and 450 mg doses of R-/S-bicalutamide/HP55S in healthy male volunteers. Study 2 was a two-period, dose-escalation study of single doses of R-bicalutamide/HP55S in healthy male volunteers. Compared with bicalutamide 150 mg, both formulations appeared more bioavailable, with a faster rate of systemic absorption. The Cmax and AUC of R-bicalutamide/HP55S increased approximately proportionally with dose. The inter-subject variability of R-bicalutamide exposure for R-/S-bicalutamide/HP55S 150 mg increased 2.19-fold compared with bicalutamide 150 mg. Clinically insignificant increases in circulating luteinizing hormone and testosterone plasma concentrations were observed for both R-bicalutamide/HP55S and R-/S-bicalutamide/HP55S compared with bicalutamide 150 mg. Both new bicalutamide formulations were well tolerated.
Impact of Organ Preservation Using HTK for Graft Flush and Subsequent Storage in UW in Rat Kidney Transplantation
Authors: Schmitz Volker , Klawitter Jost , Bendrick-Peart Jamie , Haschke Manuel , Beckey Virginia E. , Laudi Sven , Neumann Ulf , Schoening Wenzel , Neuhaus Peter , Christians Uwe , Puhl Gero
Published: July 2006

Background: In kidney transplantation, preservation has a significant influence on organ function. Since previous reports have indicated a benefit of combining histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution, we evaluated the effects of initial flush with low viscosity HTK, followed by storage in UW. Material and Methods: Kidneys from inbred Lewis rats were procured using HTK or UW for initially perfusion and re-flushed after 30 min with either solution. In a third group, after perfusion with HTK, organs were re-flushed with UW. Organs were stored for 16–24 h (4°C). Study parameters were high-energy phosphates, histology, apoptosis, recipient survival and urine excretion of 15-F2t-isoprostanes (oxidative stress marker). Results:Prior to transplantation, tissue ATP/ADP concentrations were: HTK/UW>UW-only >HTK-only. In transplanted kidneys, histological damage was highest after preservation in HTK-only. Twenty-four hours after transplantation (24 h cold ischemia time – CIT), cleaved-PARP was most abundant using UW-only. 16 h of CIT resulted in higher urine concentrations of isoprostanes in the order HTK-only (368 ± 308) > UW-only (157 ± 105) > HTK/UW (67 ± 26), and was lower in HTK/UW after 24 h of CIT (146 ± 38) vs. UW-only (507 ± 33 pg/mg creatinine). Survival (24 h CIT) was significantly reduced, and percentage of initial non-functioning (INF) kidneys highest in HTK-only (2.6 ± 0.3 days, 100%), compared to UW-only (13 ± 4.4 days, 75%) and HTK/UW (18.5 ± 4.6 days, 33%). Conclusions: In long-term preservation, UW is superior over HTK. However, our results indicate that perfusion with HTK prior to storage in UW may improve the results of UW alone which is reflected by better survival, lower rate of INF, higher cellular energy conservation and a decrease of free radicals.
Intracranial Haemorrhage in Patients on Antithrombotics: Clinical Presentation and Determinants of Outcome in a Prospective Multicentric Study in Italian Emergency Departments
Authors: Baldi G. , Altomonte F. , Altomonte M. , Ghirarduzzi A. , Brusasco C. , Parodi R.C. , Ricciardi A. , Remollino V. , Spisni V. , Saporito A. , Caiazza A. , Musso G. , Cervellin G. , Lamberti S. , Buzzalino M. , De Giorgi F. , Del Prato C. , Golinelli M.P. , Gai V. , Monsù R. , Gioffre’ M. , Giovanardi D. , Cattaneo S. , Frumento F. , Caporrella A. , Re G. , De Iaco F. , Bologna G. , Nocenti F. , Lorenzi C. , Zoratti R. , Sciolla A. , Tiscione V. , Pastorello M. , Vandelli A. , Villa A. , Zanna M. , De Palma A. , Iorio A.
Published: July 2006

Background: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). Methods: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. Results: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8and 19.4%, respectively, while <30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3–6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73–4.00) in the whole population and 2.80 (95% CI 1.77–4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. Conclusion: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.
Effect of Moderate White Wine Consumption on Serum IgA and Plasma Insulin under Fasting Conditions
Authors: Kokavec Anna , Crowe Simon F.
Published: July 2006

Background/Aims: The present study aims to investigate the contribution of alcohol toxicity to the development of malnutrition by assessing the effect of consuming a moderate amount of white wine on plasma insulin and serum IgA under fasting conditions. Methods: A total of 5 non-alcoholic males aged between 19 and 22 years participated in the current investigation. The experimental procedure required participants to undergo a 6-hour fast before ingesting 4 standard units of alcohol (40 g) in the form of white wine over a 120-min period. The level of blood alcohol, plasma insulin and serum IgA was assessed at 30-min intervals across the 120-min experimental period. Results: Consuming alcohol promotes a significant increase in serum IgA in the absence of any change in plasma insulin or ketone production in fasted individuals. Conclusion: White wine prior to a meal does not promote glucose metabolism and utilization and may increase the risk of developing a transient diabetic condition due to an alteration in energy metabolism.
Homocysteine, Folate and Vitamin B12 in Patients with Coronary Heart Disease
Authors: Genser Dieter , Prachar Herbert , Hauer René , Halbmayer Walter-Michael , Mlczoch Johannes , Elmadfa Ibrahim
Published: July 2006

Background/Aims: Homocysteine and possibly also folate and vitamin B12 are involved in the pathogenesis of cardiovascular disease. We investigated the prevalence of hyperhomocysteinemia in patients with coronary heart disease (CHD), as well as folate and vitamin B12, the main nutritional factors determining the level of homocysteine. Methods: Patients with angiographically documented CHD were prospectively investigated (n = 315, 70% male, mean age 61 [range 36–81] years). Fasting total serum homocysteine was determined by high-performance liquid chromatography and fluorescence detection. Folic acid and vitamin B12 were measured with AxSYM® Systems. Results: Median homocysteine concentrations for homocysteine, folate and vitamin B12 were 12.8 µmol/l, 6.8 ng/ml and 345 pg/ml, respectively. Homocysteine levels >10 µmol/l were found in 82% of men and 73% of women. In 19% of the patients serum folate was <3 ng/ml and 22% of the patients had serum vitamin B12 values <250 pg/ml. In a multivariate linear regression model, folate and vitamin B12 showed significant negative correlations to homocysteine, explaining 5 and 3% of its variability. Age and creatinine were the most important determinants for serum homocysteine, contributing 12 and 7%, respectively. Discussion: The main determinants of total homocysteine in patients with CHD are higher age and increased creatinine. The association of lower levels of folate and vitamin B12 with higher levels of homocysteine may indicate poor dietary habits in these patients.
Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy
Authors: Fadini Gian Paolo , Sartore Saverio , Albiero Mattia , Baesso Ilenia , Murphy Ellen , Menegolo Mirko , Grego Franco , Vigili de Kreutzenberg Saula , Tiengo Antonio , Agostini Carlo , Avogaro Angelo
Published: July 2006

Objective—

Peripheral arterial disease (PAD) is a threatening complication of diabetes. As endothelial progenitor cells (EPCs) are involved in neovasculogenesis and maintenance of vascular homeostasis, their impairment may have a role in the pathogenesis of diabetic vasculopathy. This study aimed to establish whether number and function of EPCs correlate with PAD severity in type 2 diabetic patients.

Methods and Results—

EPCs were defined by the expression of CD34, CD133 and KDR, and quantified by flow cytometry in 127 diabetic patients with and without PAD. PAD severity has been assessed as carotid atherosclerosis and clinical stage of leg atherosclerosis obliterans. Diabetic patients with PAD displayed a significant 53% reduction in circulating EPCs versus non-PAD patients, and EPC levels were negatively correlated with the degree of carotid stenosis and the stage of leg claudication. Moreover, the clonogenic and adhesion capacity of cultured EPCs were significantly lower in diabetic patients with PAD versus patients without.

Conclusions—

This study demonstrates that EPC decrease is related to PAD severity and that EPC function is altered in diabetic subjects with PAD, strengthening the pathogenetic role of EPC dysregulation in diabetic vasculopathy. EPC count may be considered a novel biological marker of peripheral atherosclerosis in diabetes.
Transforming Growth Factor-α Mediates Nuclear Factor κB Activation in Strained Arteries
Authors: Lemarié Catherine A. , Tharaux Pierre-Louis , Esposito Bruno , Tedgui Alain , Lehoux Stéphanie
Published: July 2006

Mechanical factors regulate both blood vessel growth and the development and progression of vascular disease. Acting on apoptotic and inflammatory signaling, the transcription factor nuclear factor κB (NF-κB) is a likely mediator of these processes. Nevertheless, pressure-dependent NF-κB activation pathways remain mostly unknown. Here we report that high intraluminal pressure induces reactive oxygen species (ROS) in arteries and that inhibition of NADPH oxidase prevents both the generation of ROS and the activation of NF-κB associated with high pressure. We also identify the epidermal growth factor receptor (EGFR) as a ROS-dependent signaling intermediate. In arteries from EGFR mutant mice (waved-2), pressure fails to activate NF-κB. Moreover, using vessels from EGFR ligand-deficient mice, we show that transforming growth factor (TGF)-α, but neither heparin-binding EGF-like growth factor nor epiregulin, transduces NF-κB activation by high pressure. Preventing the release of the active form of TGF-α also abolishes NF-κB induction by strain. The role of TGF-α signaling in vascular remodeling is substantiated in vivo; angiotensin II-induced activation of NF-κB and associated cell proliferation and wall thickening are much reduced in TGF-α–mutant mice compared with wild-type, despite equivalent hypertension in both groups. Conversely, apoptotic cells are detected only in vessels from hypertensive TGF-α–mutant mice, outlining the role of NF-κB in cell survival. Finally, the NF-κB activation pathway contrasts with that of extracellular signal-regulated kinase 1/2, which is activated by stretch through the EGFR but does not implicate TGF-α. Hence, our data identify TGF-α as a potential specific target to modulate mechanosensitive NF-κB activation and associated vascular remodeling.
Watershed Strokes After Cardiac Surgery
Authors: Gottesman Rebecca F. , Sherman Paul M. , Grega Maura A. , Yousem David M. , Borowicz Louis M. , Selnes Ola A. , Baumgartner William A. , McKhann Guy M.
Published: July 2006

Background and Purpose—

Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype.

Methods—

From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and χ
2
analyses to compare detection by MRI versus CT of watershed infarcts.

Results—

Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (
P
<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (
P
=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns.

Conclusions—

Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient’s baseline. These findings have implications for future clinical practice and research.
Advancing the Study of Stroke in Women
Authors: Bushnell Cheryl D. , Hurn Patricia , Colton Carol , Miller Virginia M. , del Zoppo Gregory , Elkind Mitchell S.V. , Stern Barney , Herrington David , Ford-Lynch Gwendolyn , Gorelick Philip , James Andra , Brown Candice M. , Choi Emily , Bray Paul , Newby L. Kristin , Goldstein Larry B. , Simpkins James
Published: July 2006

Background and Purpose—

Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according to results of the Women’s Health Initiative clinical trials. Based on the current understanding of the mechanisms of action of estrogen, the reasons for this increased risk are uncertain. One method to better understand the reasons for this increased risk is to re-evaluate estrogen’s role in the neurovascular unit, simplistically comprised of the neurons, glia, and endothelial cells, as well as the processes of inflammation, and hemostasis/thrombosis. Besides the role of estrogen there are many gaps of knowledge about issues specific to women and stroke.

Summary of Review—

A multidisciplinary workshop was held in August 2005 to summarize the current evidence for estrogen and, more generally, stroke in women, and to provide recommendations for future basic, preclinical, and clinical research studies.

Conclusions—

These studies may ultimately change the approach to stroke prevention and treatment in women.
Role of Fibrinogen Levels and Factor XIII V34L Polymorphism in Thrombolytic Therapy in Stroke Patients
Authors: González-Conejero Rocio , Fernández-Cadenas Israel , Iniesta Juan A. , Marti-Fabregas Joan , Obach Victor , Alvarez-Sabín José , Vicente Vicente , Corral Javier , Montaner Joan
Published: July 2006

Background and Purpose—

The identification of genetic and environmental factors that could improve the benefit/risk ratio of thrombolytic therapy in patients with ischemic stroke is crucial.

Methods—

We studied the role in the efficacy and side-adverse effects of thrombolytic therapy in stroke of 2 factors involved in the structure and stability of fibrin clot: fibrinogen levels and factor XIII (FXIII) V34L, a common and functional polymorphism. Our study enrolled 200 consecutive patients with stroke who received intravenous recombinant tissue plasminogen activator.

Results—

Patients with FXIII V/V genotype and low fibrinogen (<3.6 g/L) displayed the best clinical outcome. In contrast, carriers of the L34 variant and high fibrinogen levels showed almost no clinical response. Moreover, patients with high fibrinogen levels at admission displayed higher mortality than patients with lower fibrinogen levels (22.6% versus 9.7%,
P
=0.027; OR=2.72). The FXIII V34L polymorphism also associated with mortality: 20.0% of L34 carriers but 9.1% of patients with V/V genotype died after thrombolytic therapy (
P
=0.034; OR=2.50). The deleterious effect of this variant seemed to be exacerbated by high levels of fibrinogen, supporting the role of fibrinogen levels in determining the hemostatic consequences of the FXIII polymorphism.

Conclusions—

Our study identifies 2 markers involved in fibrin formation associated with the efficacy of thrombolytic therapy and early mortality rates in patients with ischemic stroke. These markers could be useful to identify patients with stroke suitable for a safe thrombolytic therapy.