bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Periodontitis and the Incidence of Head and Neck Squamous Cell Carcinoma
Authors: Tezal Mine , Sullivan Maureen A. , Hyland Andrew , Marshall James R. , Stoler Daniel , Reid Mary E. , Loree Thom R. , Rigual Nestor R. , Merzianu Mihai , Hauck Linda , Lillis Cheryl , Wactawski-Wende Jean , Scannapieco Frank A.
Published: September 2009

Substantial evidence supports an association between chronic infections/inflammation, and cancer. The aim of this study was to assess the effect of chronic periodontitis on head and neck squamous cell carcinoma (HNSCC). The study population consisted of new patients at the Department of Dentistry and Maxillofacial Prosthetics, Roswell Park Cancer Institute between 1999 and 2005. Cases were patients diagnosed with primary HNSCC. Controls were all patients seen during the same time period but negative for malignancy. Patients age <21 years, edentulous, immunocompromised, and those with history of cancer were excluded. Periodontitis was measured by alveolar bone loss (ABL) from panoramic radiographs by one examiner blind to cancer status. A total of 473 patients (266 cases and 207 controls) were included in the study. Each millimeter of ABL was associated with >4-fold increased risk of HNSCC (odds ratio, 4.36; 95% confidence interval, 3.16-6.01) after adjustment for age, gender, race/ethnicity, marital status, smoking status, alcohol use, and missing teeth. The strength of the association was greatest in the oral cavity, followed by oropharynx and larynx. The association persisted in subjects who never used tobacco and alcohol. There was a significant interaction between smoking and ABL (P = 0.03). Patients with periodontitis were more likely to have poorly differentiated oral cavity SCC than those without periodontitis (32.8% versus 11.5%; P = 0.038). This study suggests that chronic periodontitis is an independent risk factor for HNSCC and smoking modifies this association. These results have implications for practical and safe strategies for prevention, diagnosis, and treatment of HNSCC. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2406–12)
Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy
Authors: Gupta Samir , Tong Liyue , Allison James E. , Carter Elizabeth , Koch Mark , Rockey Don C. , Anderson Paula , Ahn Chul , Argenbright Keith , Skinner Celette Sugg
Published: September 2009

Background: Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer screening efforts. Such data are sparse for safety-net health systems.

Methods: A retrospective cohort study of individuals ages 50 to 75 served by a safety-net health system in Tarrant County, TX was conducted to determine (a) the size of the potential screen-eligible population ages 50 to 75, (b) the rate of screening over 5 years among individuals ages 54 to 75, and (c) the potential predictors of screening, including sex, race/ethnicity, insurance status, frequency of outpatient visits, and socioeconomic status.

Results: Of 28,708 potential screen-eligible individuals, 20,416 were ages 54 to 75 and analyzed for screening; 22.0% were screened within the preceding 5 years. Female gender, Hispanic ethnicity, ages 65 to 75, insurance status, and two or more outpatient visits were independently associated with screening. Access to care was an important factor: adjusted odds ratio, 2.57 (95% confidence interval, 2.23-2.98) for any insurance; adjusted odds ratio, 3.53 (95% confidence interval, 3.15-3.97) for two or more outpatient visits.

Conclusions: The screen-eligible population served by our safety-net health system was large, and the projected deficit in screen rates was substantial. Access to care was the dominant predictor of screening participation. If our results are replicable in similar health systems, the data suggest that screening guidelines and policy efforts must take into account the feasibility of proposed interventions. Strong advocacy for more resources for colorectal cancer screening interventions (including research into the best manner to provide screening for large populations) is needed. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2373–9)
Functional and Clinical Significance of Variants Localized to 8q24 in Colon Cancer
Authors: Cicek Mine S. , Slager Susan L. , Achenbach Sara J. , French Amy J. , Blair Hilary E. , Fink Stephanie R. , Foster Nathan R. , Kabat Brian F. , Halling Kevin C. , Cunningham Julie M. , Cerhan James R. , Jenkins Robert B. , Boardman Lisa A. , Petersen Gloria M. , Sargent Daniel J. , Alberts Steven R. , Limburg Paul J. , Thibodeau Stephen N.
Published: September 2009

Multiple genome-wide association studies have identified several susceptibility variants for colon cancer at 8q24. However, the functional roles of these variants have yet to be elucidated. Here, we evaluated the potential role of these markers in tumor progression and examined association with commonly observed structural abnormalities in this region, c-MYC amplification and chromosome fragility at FRA8C and FRA8D. We first replicated the previously reported association by testing 1,178 cases and 1,009 clinic-based controls with eight markers localized to three specific regions at 8q24. We observed significant associations with colon cancer risk with markers rs13254738 (ordinal odds ratio, 0.82; 95% confidence interval, 0.072-0.94; Ptrend = 0.0037) and rs6983267 (ordinal odds ratio, 1.17; 95% confidence interval, 1.03-1.32, Ptrend = 0.013). Survival analysis was done using a separate set of 460 cases to evaluate the clinical significance of these markers. Overall, univariate analysis did not detect survival differences for any of the markers. We also tested a subset of the 460 cases (n = 380) for structural abnormalities at or near the c-MYC locus using fluorescence in situ hybridization analysis. Furthermore, we evaluated a small number of cases homozygous for the rs6983267 alleles to test for differences in fragile site induction. None of the 8q markers correlated with amplification at the c-MYC locus as detected by fluorescence in situ hybridization, and no clear pattern of breakage was observed at the FRA8C and FRA8D sites. In this study, we confirm the association for several single nucleotide polymorphisms at 8q24 in colon cancer but have not detected any structural role relating to c-MYC amplification or chromosomal fragility. Finally, these risk alleles do not seem to be associated with survival. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2492–500)
Hidden X Chromosomal Mosaicism in a 46,XX Male
Authors: Chernykh V.B. , Kurilo L.F. , Shilova N.V. , Zolotukhina T.V. , Ryzhkova O.P. , Bliznetz E.A. , Polyakov A.V.
Published: September 2009

We report on a 37-year-old XX male with complex hidden X chromosomal mosaicism. The patient had fully mature male genitalia with hypoplastic testes descended in the scrotum and no sign of undervirilization. Hormonal examination demonstrated hypergonadotropic hypogonadism, semen analysis showed severe oligoasthenoteratozoospermia. In situ hybridization revealed the presence of 3 SRY-positive cell lines bearing 1, 2 or 3 X chromosomes. Skewed inactivation of the paternal SRY-bearing X chromosome was detected by molecular analysis of the androgen receptor gene.
Body Composition and Metabolic Profile in Women with Complete Androgen Insensitivity Syndrome
Authors: Dati E. , Baroncelli G.I. , Mora S. , Russo G. , Baldinotti F. , Parrini D. , Erba P. , Simi P. , Bertelloni S.
Published: September 2009

Clinical and experimental data suggest that androgen receptor (AR) signaling plays a role on body composition, glucose homeostasis and lipid metabolism. The effect of AR disruption on such parameters was not extensively investigated in human people. A group of young to middle-age adult women with complete androgen insensitivity syndrome (CAIS, n = 18, age 32.2 ± 9.3 years; women with testes removed n = 14) was investigated for body mass index (BMI), body composition (dual energy X-ray absorptiometry), serum glucose levels, insulin sensitivity (HOMA-IR) and lipid profile. Mean BMI (24.2 ± 7.4 kg/m2) was not significantly increased (T-score 1.0 ± 2.5, p = NS vs Italian female reference values), but prevalence of obesity was higher in women with CAIS than that reported in age-related Italian females (16.7% vs 3.6%, respectively). The majority of obese individuals with CAIS was in the subgroup with intact testes (3/4). DXA assessment (n = 15) demonstrated values of total free fat mass similar to that of 46,XX female controls. Increased body fat was found in CAIS women in comparison with both female and male controls. Abnormal values of cholesterol (total and LDL) and HOMA-IR were present in a large subset of patients. Our data suggest that in women with CAIS disruption of AR signaling may increase body fat and affect some metabolic parameters. Assessment of body composition, metabolic profile and, likely, cardiovascular risk seems to be advisable with ageing in these individuals.
A Prospective Randomised Trial of Extended Core Prostate Biopsy Protocols Utilizing 12 versus 15 Cores
Authors: Rochester M.A. , Griffin S. , Chappell B. , McLoughlin J.
Published: September 2009

Objective: To prospectively evaluate the diagnostic yield of 12 versus 15 core ultrasound-guided needle prostate biopsy protocol for detection of prostate cancer. Patients and Methods: 244 patients were prospectively randomized to undergo 12 (group A), or 15 (group B) biopsies. The cancer detection rate was compared between these groups and within group B. Results: There were no differences in the age, PSA, prostate volume or Gleason score of diagnosed cancers between groups. 113 (46%) of all patients were found to have carcinoma. The number of cancers diagnosed in each group was: 63 (51.6%) in group A, and 50 (41.0%) in group B. In both groups, performing 12 biopsies increased the number of cancer cases identified by around 10% compared to 6. The frequency of cancer cases increased when 15 biopsies were performed, but not significantly (1.7%). The probability of finding a cancer after 12 biopsies was the same as after 15 biopsies (p = 0.125, McNemar’s test). Conclusions: There was no advantage in increasing the number of biopsy cores from 12 to 15 for the diagnosis of prostate cancer in men with an elevated PSA but normal digital rectal examination.
Statistical Analysis of Symptoms, Endoscopy and Urothelial Morphology in 58 Female Bladder Pain Syndrome/Interstitial Cystitis Patients
Authors: Zámečník L. , Hanuš T. , Pavlík I. , Dundr P. , Povýšil C.
Published: September 2009

Introduction: The goal of the study was to assess the course of painful syndrome in patients with bladder pain syndrome/interstitial cystitis and to assess the changes in endoscopic and histopathological findings in relation to the type of treatment. Patients and Methods: We included a total of 58 patients with histologically diagnosed interstitial cystitis. Out of these, 31 patients were treated with oral pharmacotherapy and 27 patients were treated by intravesical application of heparin. The patients were followed from time of diagnosis for 6.9 ± 2.5 and 6.6 ± 2.7 years, respectively. Results: Treatment – irrespective of its type – had a clear demonstrable effect on the monitored parameters; intravesical treatment was more effective than oral. Statistically significant (p < 0.05) changes could be observed in both groups (with two exceptions). When evaluating the relationship between subjective symptoms and objective criteria, and patients’ age and time to diagnosis, it is clear that the higher the age and the longer the time from symptoms to diagnosis, the more severe the symptoms. Conclusions: When evaluating the monitored parameters, we found significant correlations (both positive and negative). However, these relationships cannot be used to simplify the evaluation algorithm (according to ESSIC) and the initial criteria cannot predict the course of the disease.
‘Evaluation of Residencies’ in Turkey
Authors: Huri Emre , Acar Cenk , Binbay Murat , Erikson Stina , Müslümanoğlu Ahmet Yaser , Esen Tarık
Published: September 2009

Introduction: We aimed to evaluate the general status of last-year residents in Turkey by filling in the questionnaire ‘Evaluation of Residencies in Europe’. Subjects and Methods: The questionnaire ‘Evaluation of Residencies in Europe’, designed by the European Society of Residents in Urology (ESRU), was applied to 91 last-year urology residents. It consisted of 7 sections; ‘Introduction’, ‘Membership’, ‘Residency’, ‘Life and Financial Conditions’, ‘Future Practice’, ‘Training’ and ‘Research Activities and Contribution to Scientific Literature’. The results were determined and reviewed as well. Statistical analysis was performed using ANOVA and the Kruskal-Wallis Test. Results: More than 40 parameters were evaluated. The level of English was average or good for 86%. Half of the residents were aware of ESRU activities, 91% knew national ESRU representatives. Fifty-seven percent of the residents wanted to subspecialize in urology, nephrectomy or andrology, and general urology procedures had a high rate being performed by a first surgeon. Transurethral prostate resection, transurethral resection of bladder and extracorporeal shock wave lithotripsy were well known, with a rate of 76%. Conclusions: Although the Turkish resident number is one of the most excessive in Europe, we have a well-trained homogenous resident group especially in the field of endourology; most of those in the last year of their training period were satisfied with their general condition.
Inversion, Hydration and Diuresis during Extracorporeal Shock Wave Lithotripsy: Does It Improve the Stone-Free Rate for Lower Pole Stone Clearance?
Authors: Albanis Stefanos , Ather Hammad M. , Papatsoris Athanasios G. , Masood Junaid , Staios Dimitrios , Sheikh Taufiq , Akhtar Sobia , Buchholz Noor
Published: September 2009

Objective: It was the aim of this study to assess the efficacy and safety of combined forced hydration and diuresis with limited inversion during shock wave lithotripsy (SWL) by comparing this treatment modality with conventional SWL for lower calyceal nephrolithiasis. Patients and Methods: In this prospective, non-randomized study, we included 100 patients with lower calyceal calculi ≤2 cm. Fifty of them received conventional SWL and the other 50 underwent SWL combined with oral hydration, diuresis and 12° inversion position during SWL. Intravenous urography was performed for all patients prior to their treatment. Patients in both groups were treated on Dornier™ MPL 9000. Blood pressure monitoring was applied during the SWL session. Follow-up was performed the first and the third month after treatment with plain kidney-ureter-bladder X-ray and kidney-ureter-bladder ultrasound. Results: Clinical outcomes were available in 90 patients. Follow-up at 3 months showed that 83.3% of the patients belonging to the study group were rendered stone free, whereas 71.5% were stone free in the control (p > 0.05). Complications were minimal and not statistically significant. Conclusions: Forced diuresis and inversion therapy is very well tolerated; however, the stone-free rate was not significantly improved.
Prevention of Free Fatty Acid-Induced Hepatic Lipotoxicity in HepG2 Cells by Magnesium Isoglycyrrhizinate in vitro
Authors: Cheng Yuan , Zhang Juan , Shang Jing , Zhang Luyong
Published: September 2009

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that threatens public health, and current therapies remain limited. This study investigated the protective effect of magnesium isoglycyrrhizinate (MGL), a novel compound, against free fatty acid (FFA)-induced lipotoxicity in a cellular model of steatosis. Methods: HepG2 cells were incubated with 1 mmol/l FFAs together with MGL for 24 h. Cell viability was assessed using the MTT assay. Cell apoptosis was determined by Hoechst staining. Intracellular lipids were measured by flow cytometry using Nile red. Mitochondrial function was analyzed by detecting transmembrane potential, cytochrome c release and reactive oxygen species’ production. Results: MGL protected cell viability and dramatically decreased FFA-induced cell apoptosis and lipid accumulation. MGL was found to inhibit mitochondrial transmembrane polarization, and decrease mitochondrial cytochrome c release and the generation of reactive oxygen species. Conclusion: This study demonstrated that MGL attenuates FFA-induced lipotoxicity by reducing mitochondrial damage, which indicates a promising therapeutic intervention for NAFLD.
Wire Tethering or ‘Bowstringing’ as a Long-Term Hardware-Related Complication of Deep Brain Stimulation
Authors: Miller Peter M. , Gross Robert E.
Published: September 2009

Background: Widely reported long-term complications following implantation of deep brain stimulation (DBS) hardware include breakage of electrode leads, internal pulse generator (IPG) failure, skin erosions and infection. Here we report on a rarely described problem that arises from formation of scar tissue adhesions around the DBS extension wire(s). Over time, this scar tissue can become tight and pronounced, protruding noticeably beneath the skin (‘bowstringing’ in reference to its tight bow-like appearance) and leading to significant limitation of movement and discomfort. We term this ‘wire tethering’. Results:We describe 6 patients with moderate to severe wire tethering. Review of our experience suggests an association of wire tethering with the passage of two extension wires on the same side as is done when using a dual-channel IPG. Five of the patients required surgical revision of the extension wires due to the magnitude of the discomfort, limitation of movement and appearance. Removing the wires was insufficient in the most severe case, necessitating transection of the scar in several places, which was done with the extension wires in situ in 2 patients. Two patients were treated with removal of the wires alone, and 1 patient did not opt for surgery and the tethering has persisted. Conclusion: Wire tethering, or ‘bowstringing’, is an underrecognized complication of DBS hardware implantation often necessitating surgical revision. The possible etiology of wire tethering is discussed as well as suggestions for its avoidance.
Stereotactic Radiosurgery of Residual or Recurrent Craniopharyngioma: New Treatment Concept Using Leksell Gamma Knife Model C with Automatic Positioning System
Authors: Yomo Shoji , Hayashi Motohiro , Chernov Mikhail , Tamura Noriko , Izawa Masahiro , Okada Yoshikazu , Hori Tomokatsu , Iseki Hiroshi
Published: September 2009

Background/Aims: The present study analyzed the initial experience with the application of the original concept of ‘robotic microradiosurgery’ using Leksell Gamma Knife Model C with automatic positioning system for management of craniopharyngiomas. Methods: Eighteen patients with residual or recurrent craniopharyngiomas underwent radiosurgery with the use of multiple isocenters, mainly of smaller size, which were positioned compactly within the border of the lesion with resultant improved dose homogeneity, increased average dose within the target, and sharp dose fall outside the treated volume. Treatment planning was mainly guided by constructive interference in steady state images with and without gadolinium enhancement. Mean tumor volume was 1.8 cm3. In 12 cases the anterior visual pathways were either compressed or attached to the lesion. The average number of isocenters was 8.7 per cubic centimeter of target volume. Mean marginal irradiation dose was 11.6 Gy. Mean maximal dose to the anterior visual pathways was 8.4 Gy. Mean follow-up was 26.8 months, and median follow-up was 24 months. Results: Tumor growth was controlled in 17 cases (94%), and its volume reduction was attained in 13 cases (72%). In 3 patients significant shrinkage of the neoplasm after radiosurgery was accompanied by improvement of the visual functions. Their impairment was not marked in any case, nor was there any new endocrinopathy. Conclusion: Application of robotic microradiosurgery to the management of residual and recurrent craniopharyngiomas showed promising results during short- to intermediate-term follow-up, providing early tumor shrinkage in the majority of cases as well as sparing of visual and pituitary functions.
Quantitative Motor Activity Differentiates Schizophrenia Subtypes
Authors: Walther Sebastian , Horn Helge , Razavi Nadja , Koschorke Philipp , Müller Thomas J. , Strik Werner
Published: September 2009

Background: Motor symptoms are frequent in schizophrenia and relevant to the diagnosis of subtypes. However, the assessment has been limited to observations recorded in scales and experimental designs. The aim of this study was to use wrist actigraphy to obtain motor activity data in 3 schizophrenia subtypes. Methods: In total, 60 patients with schizophrenia (35 paranoid, 12 catatonic, 13 disorganized) were investigated using continuous wrist actigraphy over 24 h in an inpatient setting on average 38 days after admission. Data of the wakeful hours of the day were analyzed. Results: The activity level was predicted by schizophrenia subtype and by the type of antipsychotic medication. The movement index and mean duration of uninterrupted immobility were found to be predicted only by the schizophrenia subtype. Age, gender, duration of illness and chlorpromazine equivalents did not contribute to the variance of the activity data. A MANOVA demonstrated the significant differences in the 3 parameters between schizophrenia subtypes (p = 0.001). Patients with catatonic schizophrenia had lower activity levels, a lower movement index and a longer duration of immobility than those with paranoid schizophrenia. Conclusions: Schizophrenia subtypes can be differentiated using objective measures of quantitative motor activity. The increased duration of immobility appears to be the special feature of catatonic schizophrenia.
Characterization of Two Models of Drug-Induced Constipation in Mice and Evaluation of Mustard Oil in These Models
Authors: Kojima Ryosuke , Doihara Hitoshi , Nozawa Katsura , Kawabata-Shoda Eri , Yokoyama Toshihide , Ito Hiroyuki
Published: September 2009

Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 μg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.
Burden and Perceived Health Status Among Caregivers of Stroke Patients
Authors: Carod-Artal Francisco Javier , Ferreira Coral Luciane , Trizotto Daniele Stieven , Menezes Moreira Clarissa
Published: September 2009

Objective: To identify the main determinants of burden and perceived health status in caregivers of Brazilian stroke survivors. Methods: Cross-sectional study. Caregivers answered the Hospital Anxiety and Depression Scale (HADS), Zarit caregiver burden interview (ZCBI) and EuroQol. Patients were assessed with the National Institute of Health Stroke Scale, Barthel index (BI), modified-Rankin scale (m-RS), Mini Mental State Examination and HADS. Results: 200 caregiver-patient dyads were assessed. Caregivers were significantly younger (42 vs. 57.7 years) and had more years of formal education (10 vs. 7.8 years); p < 0.0001. Seventy-seven percent of caregivers were females, and 41% were spouses. The prevalence of anxiety disorders was significantly higher in female caregivers than in males (26.1 vs. 10.9%; p = 0.04). ZCBI mean score was 27.2, and female caregivers had significantly worse scores (28.7 vs. 22.3, p = 0.003). ZCBI mean score significantly increased (worsened) as the severity of the disease, based on m-RS, increased. ZCBI mean scores were significantly higher in wives than in other relatives (31.4 vs. 22.6; ANOVA, p < 0.0001). The EuroQol-5D and EuroQol-Visual Analog Scale mean scores were 0.7 (range: 0.04–0.85) and 75.2 (range: 1–100), respectively. Adequate convergent validity (r = –0.38 to –0.40) between EuroQol and ZBCI mean scores was observed. Patient´s disability (as measured by the BI) and caregiver’s factors (female sex, depression as measured by HADS-depression) were independent predictors of caregiver’s burden (r2 adjusted = 0.48; p < 0.0001) in the multivariate regression analysis. Conclusions: Caregiver’s mood was the most consistent factor influencing caregiver burden and perceived health in stroke caregivers.
Spontaneous Reattachment of the Margins of a Macular Retinal Pigment Epithelium Tear: Optical Coherence Tomography Documentation of a Case
Authors: Pece Alfredo , Vitale Lucia , Milani Paolo , Pierro Luisa
Published: September 2009

Purpose: To document by optical coherence tomography (OCT) the reattachment of the margins of a retinal pigment epithelium (RPE) tear. Methods: Single case report, documented by OCT scans, autofluorescence and fluorescein angiography. Results: A 67-year-old male presented with a spontaneous RPE tear due to age-related macular degeneration in his right eye. Three months later we observed that the focal RPE tear had healed and there was a new intraretinal fluid, well documented by OCT imaging. Conclusions: OCT scans show the reattachment of the margins of an RPE tear healed by tissue remodelling, and illustrate how the disease can recur.
Transcriptome-Wide Characterization of Gene Expression Associated with Unruptured Intracranial Aneurysms
Authors: Li Li , Yang Xinjian , Jiang Fan , Dusting Gregory J. , Wu Zhongxue
Published: September 2009

Background: The biological mechanisms by which cerebral aneurysms emerge, enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays. Methods: Affymetrix HU133 Plus 2.0 microarrays were used to compare gene expression levels between human cerebral aneurismal samples and normal blood vessels. Raw data were evaluated by GeneSpring software version 9.05. Differentially expressed genes were further classified according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Quantitative real-time polymerase chain reaction was used to confirm the microarray results. Results: Clustering analysis demonstrated that the aneurysm tissues and control tissues were clearly separated into two distinct groups according the differential expression patterns. The levels of 1,160 genes were significantly changed. Of these genes, 164 were upregulated and 996 were downregulated. A cluster of extracellular matrix related genes, including collagens (type I, III, V, and XI) and metalloproteinases were significantly upregulated. In contrast to previous reports, we found that a number of immune/inflammation-related genes were downregulated in intracranial aneurysms. Conclusion: Human cerebral aneurysms appeared to show a similarity in the global gene expression profile. Our results support the notion that disrupted homeostasis of the extracellular matrix components may be involved in the pathogenesis of intracranial aneurysms. Our data of the differentially regulated genes may benefit future studies on the cellular mechanisms of cerebral aneurysms.
The Randomized Controlled Trial
Authors: Stel Vianda S. , Zoccali Carmine , Dekker Friedo W. , Jager Kitty J.
Published: September 2009

Until recently, high-quality randomized controlled trials (RCTs) have rarely been performed in nephrology, because of several difficulties in conducting an RCT. The purpose of this article is to describe several issues related to the design and to the quality of RCTs in their conduct, analysis, interpretation, and reporting of the results. The advantage of an RCT is that, as a result of randomization, selection by prognosis by the clinician is prevented. However, not all RCTs provide a definitive answer on the research question that the investigators try to answer because of potential problems in their design, conduct and analysis. For example, the results of an RCT could be biased if the physicians and patients in the experimental and control groups were not sufficiently ‘blinded’. Nevertheless, if conducted properly, RCTs remain the gold standard for studying the effects of therapy and other interventions.
Prognostic Factors in Stage D Heart Failure in the Very Elderly
Authors: Martin-Pfitzenmeyer Isabelle , Gauthier Sophie , Bailly Michèle , Loi Nathalie , Popitean Laura , d’Athis Philippe , Bouvier Anne-Marie , Pfitzenmeyer Pierre
Published: September 2009

Background: The clinical characteristics of frail older patients with advanced heart failure have scarcely been studied. Objective: To describe this population and to identify some prognostic factors of mortality. Methods: 104 patients aged 75 years and older hospitalized with refractory heart failure were enrolled in a prospective multicentric study. Results: Mean age was 87.2 ± 5.3 years. Dyspnea (79.8%), crepitant rales (76.9%) and peripheral edema (73.1%) were particularly frequent. Signs of low cardiac output such as renal insufficiency (46.9%), cutaneous low flow (40.4%), and systolic hypotension (≤100 mm Hg) (24.3%) were observed less often. Signs of cognitive impairment including anxiety (55.4%), sleep disorders (43.7%) and delirium (35.5%) were frequent. Asthenia and chronic pain were noted in 92.3 and 37.5% of cases, respectively. Mortality rates were 32.7, 59.6 and 71.2% during hospitalization, at 6 months and at 12 months, respectively. According to the multivariate Cox model, six significant factors suggesting a poor prognosis were observed: chronic renal insufficiency, past neuropsychological pathology, long-term treatment with nitrates, presence of edema, low cutaneous flow, and pain. The ability to sit on a chair was the only significant factor associated with a good prognosis. Conclusion: Our study identified some clinical and prognostic factors which had been observed in very old patients with refractory heart failure. Pain management has to be a priority in these patients in order to improve their quality of life.
Circulating CD4+CD25brightFOXP3+ T Cells Are Up-Regulated by Biological Therapies and Correlate with the Clinical Response in Psoriasis Patients
Authors: Quaglino P. , Ortoncelli M. , Comessatti A. , Ponti R. , Novelli M. , Bergallo M. , Costa C. , Cicchelli S. , Savoia P. , Bernengo M.G.
Published: September 2009

Background: Regulatory T-cell (Treg) modulation is one of the potential mechanisms of anti-tumour-necrosis-factor biological agents. However, literature data on psoriasis patients are lacking. Objective: To analyse the circulating CD4+CD25brightFOXP3+ subset in 30 patients with psoriasis vulgaris/arthropathic psoriasis treated with biologicals and to investigate its relationship with the clinical response. Methods: The CD25brightFOXP3+ expression within the CD4+ subset was determined by multi-parameter flow cytometry at baseline and during treatment. FOXP3 mRNA expression was analysed by real-time reverse transcription PCR. Results: A response was obtained in 16/17 patients (91.1%) with increased CD25brightFOXP3+ values and in only 3/11 patients (27.3%) who showed a CD25brightFOXP3+ decrease during biological treatment (p = 0.0001). Responders showed significantly higher values than did non-responders as from the first 2 months of treatment (p = 0.0032). A significantly higher posttreatment expression of mRNA FOXP3 was observed in responders compared to non-responders. Conclusion: Biological drugs induce a circulating Treg up-regulation in a significant percentage of patients; such an increase is an early predictive marker of response.
Arterial Stiffness in Hemodialysis: Which Parameter to Measure to Predict Cardiovascular Mortality?
Authors: El Hadj Othmane Taha , Nemcsik János , Fekete Bertalan Cs. , Deák György , Egresits József , Fodor Erzsébet , Logan Alexander G. , Németh Zsófia K. , Járai Zoltán , Szabó Tamás , Szathmári Miklós , Kiss István , Tislér András
Published: September 2009

In previous studies, different parameters of arterial stiffness were related to cardiovascular mortality in hemodialysis patients, but their relative prognostic value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality were assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 25 patients died of cardiovascular causes. Increasing pre- and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; < 0.001 for AMP). Neither the carotid augmentation index nor carotid pulse pressure were related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis AMP was 1.41 (1.03–1.92). When included in the same model, both predialysis PWV and AMP remained significantly associated with cardiovascular mortality. Among different stiffness parameters, PWV is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis AMP seems to provide additional prognostic information.
Mapping 3-Dimensional Neovessel Organization Steps Using Micro-Computed Tomography in a Murine Model of Hindlimb Ischemia–Brief Report
Authors: Oses Pierre , Renault Marie-Ange , Chauvel Rémi , Leroux Lionel , Allières Cécile , Séguy Benjamin , Lamazière Jean-Marie Daniel , Dufourcq Pascale , Couffinhal Thierry , Duplàa Cécile
Published: September 2009

Objectives—

Studying the mechanisms of neovascularization and evaluating the effects of proangiogenic strategies require accurate analysis of the neovascular network. We sought to evaluate the contribution of the microcomputed tomography (mCT) providing high-resolution 3-dimensional (3D) structural data, to a better comprehension of the well-studied mouse hindlimb postischemic neovascularization.

Methods and Results—

We showed a predominant arteriogenesis process in the thigh and a predominant angiogenesis-related process in the tibiofibular region, in response to ischemia during the first 15 days. After 15 days, mCT quantitative analysis reveals a remodeling of arterial neovessels and a regression depending on the restoration of the blood flow. We provided also new mCT data on the rapid and potent angiogenic effects of mesenchymal stem cell therapy on vessel formation and organization. We discussed the contribution of this technique compared with or in addition to data generated by the more conventional approaches.

Conclusion—

This study demonstrated that optimized mCT is a robust method for providing new insights into the 3D understanding of postischemic vessel formation.
Ablation of Angiotensin IV Receptor Attenuates Hypofibrinolysis via PAI-1 Downregulation and Reduces Occlusive Arterial Thrombosis
Authors: Numaguchi Yasushi , Ishii Masakazu , Kubota Ryuji , Morita Yasuhiro , Yamamoto Koji , Matsushita Tadashi , Okumura Kenji , Murohara Toyoaki
Published: September 2009

Objectives—Reduced fibrinolytic activity is associated with adverse cardiovascular events. Although insulin-regulated aminopeptidase (IRAP) was recently identified as the angiotensin (Ang) IV receptor (AT4R), the impact of AngIV-AT4R signaling distal to AngII on the activation of type-1 plasminogen activator inhibitor (PAI-1) in the fibrinolytic process and subsequent formation of thrombosis remains unclarified.

Methods and Results—To determine whether AngIV would inhibit fibrinolysis via PAI-1 activation and promote thrombosis, we evaluated the degree of fibrinolysis in thrombosis models and investigated the roles of AT4R after vascular injury using IRAP knockout mice (IRAP−/−). In endothelial cells from control mice (WT; C57Bl6/J), both AngII and AngIV treatments increased PAI-1 mRNA expression in a dose-dependent manner, whereas the response was blunted in endothelial cells fromIRAP−/−mice. FeCl3-induced thrombosis was suppressed in the carotid arteries ofIRAP−/−mice when compared with WT mice. Similarly, in a model of carotid artery ligation and cuff placement,IRAP−/−mice demonstrated accelerated fibrinolysis 7 days after surgery and reduced occlusive thrombosis with negative remodeling at 28 days.

Conclusions—AngIV-AT4R signaling has a key role in fibrinolysis and the subsequent formation of arterial thrombosis after vascular injury. AT4R may be a novel therapeutic target against cardiovascular disease.
Ventricular Tachycardia Arising From the Aortomitral Continuity in Structural Heart Disease
Authors: Steven Daniel , Roberts-Thomson Kurt C. , Seiler Jens , Inada Keiichi , Tedrow Usha B. , Mitchell Richard N. , Sobieszczyk Piotr S. , Eisenhauer Andrew C. , Couper Gregory S. , Stevenson William G.
Published: September 2009

Background—

The aortomitral continuity (AMC) has been described as a site of origin for ventricular tachycardias (VT) in structurally normal hearts. There is a paucity of data on the contribution of this region to VTs in patients with structural heart disease.

Methods and Results—

Data from 550 consecutive patients undergoing catheter ablation for VT associated with structural heart disease were reviewed. Twenty-one (3.8%) had a VT involving the peri-AMC region (age, 62.7�11 years; median left ventricular ejection fraction, 43.6�17%). Structural heart disease was ischemic in 7 (33%), dilated cardiomyopathy in 10 (47.6%), and valvular cardiomyopathy in 4 (19%) patients, respectively. After 1.9�0.8 catheter ablation procedures (including 3 transcoronary ethanol ablations) the peri-AMC VT was not inducible in 19 patients. The remaining 2 patients underwent cryosurgical ablation. Our first catheter ablation procedure was less often successful (66.7%) for peri-AMC VTs compared with that for 246 VTs originating from the LV free wall (81.4%,
P
=0.03). During a mean follow-up of 1.9�2.1 years, 12 (57.1%) patients remained free of VT, peri-AMC VT recurred in 7 patients, and 1 patient had recurrent VT from a remote location. Three patients died. Analysis of 50 normal coronary angiograms demonstrated an early septal branch supplying the peri-AMC area in 58% of cases that is a potential target for ethanol ablation.

Conclusions—

VTs involving the peri-AMC region occur in patients with structural heart disease and appear to be more difficult to ablate compared with VTs originating from the free LV wall. This region provides unique challenges for radiofrequency ablation, but cryosurgery and transcoronary alcohol ablation appear feasible in some cases.
Shear Stress Inhibits Homocysteine-Induced Stromal Cell–Derived Factor-1 Expression in Endothelial Cells
Authors: Sung Mao-Lin , Wu Chia-Ching , Chang Hsin-I , Yen Chia-Kuang , Chen Heng Jung , Cheng Ju-Chien , Chien Shu , Chen Cheng-Nan
Published: September 2009

Rationale
:

Hyperhomocysteinemia contributes to vascular dysfunction and risks of cardiovascular diseases. Stromal cell–derived factor (SDF)-1, a chemokine expressed by endothelial cells (ECs), is highly expressed in advanced atherosclerotic lesions. The interplays among homocysteine, chemokines, and shear stress in regulating vascular endothelial function are not clearly understood.

Objective
:

To investigate the mechanisms for modulations of EC SDF-1 expression by homocysteine and shear stress.

Methods and Results
:

Homocysteine stimulation induced dose- and time-dependent SDF-1 expression and phosphorylation of mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. By using specific inhibitors, small interfering (si)RNA, and dominant negative mutants, we demonstrated that activation of JNK pathway is critical for the homocysteine-induced SDF-1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that homocysteine increased Sp1- and AP-1–DNA binding activities in ECs. Inhibition of Sp1 and AP-1 activations by specific siRNA blocked the homocysteine-induced SDF-1 promoter activity and expression. Preshearing of ECs for 1 to 4 hours at 20 dyn/cm
2
inhibited the homocysteine-induced JNK phosphorylation, Sp1 and AP-1 activation, and SDF-1 expression. The homocysteine-induced SDF-1 expression was suppressed by NO donor. Inhibitor or siRNA for endothelial NO synthase abolished the shear inhibition of SDF-1 expression.

Conclusions
:

Our findings serve to elucidate the molecular mechanisms underlying the homocysteine induction of SDF-1 expression in ECs and the shear stress protection against this induction.
Statin Treatment and Stroke Outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial
Authors: Goldstein Larry B. , Amarenco Pierre , Zivin Justin , Messig Michael , Altafullah Irfan , Callahan Alfred , Hennerici Michael , MacLeod Mary J. , Sillesen Henrik , Zweifler Richard , Michael K. , Welch A.
Published: September 2009

Background and Purpose—

Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial designed to determine whether treatment with atorvastatin reduces strokes in subjects with recent stroke or transient ischemic attack (n=4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the distribution of severities of ischemic cerebrovascular outcomes.

Methods—

Severity was assessed with the National Institutes of Health Stroke Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial.

Results—

Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5 or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (
P
<0.001 unadjusted and adjusted). Results were similar for all outcome events (ischemic and hemorrhagic,
P
<0.001 unadjusted and adjusted) with no effect on outcome hemorrhagic stroke severity (
P
=0.174 unadjusted,
P
=0.218 adjusted). If the analysis is restricted to those having an outcome ischemic stroke (ie, excluding those having a transient ischemic attack or no event), there was only a trend toward lesser severity with treatment based on the modified Rankin Scale score (
P
=0.0647) with no difference based on the National Institutes of Health Stroke Scale or Barthel Index.

Conclusion—

The present exploratory analysis suggests that the outcome of recurrent ischemic cerebrovascular events might be improved among statin users as compared with nonusers.
Type 2 Diabetes in the Pediatric Population: Are We Meeting ADA Clinical Guidelines in Ohio?
Authors: Valent David , Pestak Katie , Otis Megan , Shubrook Jay
Published: September 2009

Several studies have demonstrated the importance of achieving the American Diabetes Association (ADA) clinical guidelines in adults. However, research is limited on adherence to these guidelines in the pediatric population. This retrospective chart review examined 56 charts from 6 physician offices and 1 multispecialty health care system in Ohio. Variables of interest included recommendations from the 2007 ADA Standards of Medical Care in Diabetes. HgA1c was measured every 3 months in 44.6% of patients, while 55% achieved A1c goal. Blood pressure was monitored in all patients, with 57% meeting goal. Lipids and urine microalbumin were tested annually in 51.7% and 26.7% of patients, respectively. Dilated eye and foot exams were performed on 53.5% and 37.5% of patients, respectively. Adherence to ADA clinical guidelines for pediatric patients with type 2 diabetes is suboptimal. The authors recommend that specific evidence-based guidelines be evaluated for children with type 2 diabetes.
The Development of Indigenous Counseling in Contemporary Confucian Communities
Authors: Hwang Kwang-Kuo
Published: September 2009

In view of the limitations of mainstream Western psychology, the necessity of indigenous psychology for the development of global community psychology is discussed in the context of multiculturalism. In addition to this general introduction, four articles underlying a common theme were designed to discuss (a) various types of value conflicts between Confucian cultural heritage and Western individualism in an age of globalization; (b) the psychometric approach for measuring collectivistic conflict; (c) a counseling model of situational self-relation coordination for Chinese clients to handle interpersonal conflicts; and (d) the psychotherapeutic implications of various self-cultivation practices originating from the cultural traditions of Confucianism, Taoism, and Buddhism. The articles in this special issue may contribute to the development of indigenous counseling practice in multicultural Chinese communities.
Counseling Psychology in Chinese Communities in Asia
Authors: Leung S. Alvin , Chen Ping-Hwa
Published: September 2009

This article examines the need to develop an indigenous counseling psychology in Chinese communities in Asia. The cross-cultural limitations and applications of counseling psychology are discussed, using the literature on multicultural counseling and competence as illustrations. The authors elaborate on the scope and nature of indigenous counseling psychology and discuss how indigenization of counseling psychology could be carried out in Chinese communities in Asia at the local, national, and application levels. Meanwhile, several multicultural themes in Chinese communities in Asia were identified as possible focus of indigenous research and practice efforts.
Collectivistic Conflict of Chinese in Counseling
Authors: Kwan Kwong-Liem Karl
Published: September 2009

Rapid Westernization and modernization in most Chinese societies has triggered a process of acculturation to Western value orientations, which induced conflicts between Confucian-based collectivism and Western individualism at both the societal and individual levels. A review of research instruments indicated that a cultural conflict approach is often used when assessing the personality and psychological functioning of Chinese people within and outside the United States. In spite of the receptiveness toward Western influences, family and collectivistic orientation are Confucian virtues and remain dominant values that govern the interpersonal and normative relationships in Chinese societies. Within this cultural conflict context, the concept of collectivistic conflict is proposed to conceptualize the psychological adaptation and counseling concerns of the Chinese. The development of a compromising self and the reintegration of the indigenous coping mechanism of self-cultivation (i.e., striving to be a cultivated, cultured person) are postulated as therapeutic tasks when helping Chinese clients resolve collectivistic conflict.