bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peak Systolic Velocities May Be Falsely Low in Young Patients with Erectile Dysfunction
Authors: Shamloul Rany 
Published: January 2006

ABSTRACT

Introduction
Introduction of duplex ultrasonography with color flow Doppler analysis after intracavernous injection of vasoactive drugs has been reported to be a minimally invasive and accurate method, and considered the gold-standard technique for evaluating penile hemodynamics. However, several studies have demonstrated that in some cases Color Doppler Ultrasound (CDU) testing may result in wrong diagnosis because of anxiety and increased sympathetic stimulation.

Aim
This study was carried out to evaluate the impact of age on the decision to repeat CDU in patients with initial low peak systolic velocities (PSVs).

Methods
This is a prospective study involving 71 patients with erectile dysfunction (ED) who presented to the Department of Andrology, Sexology and Sexually Transmitted Diseases at Cairo University between December 2000 and April 2002. An intracavernous pharmacotest and CDU with prostaglandin E1, papaverine, and phentolamine was performed. All patients in the study had poor response to intracavernous pharmacotesting and achieved a low PSV (&lt;30 cm/second) during the initial CDU examination. The CDU was repeated 2 weeks later. The 71 patients were grouped into four according to age: group A (20–29 years old) consisted of 11 patients, group B (30–39 years old) consisted of 19 patients, group C (40–49 years old) consisted of 20 patients, and group D (50–59 years old) consisted of 21 patients.

Results
The group A patients experienced a statistically significant increase (P &lt; 0.05) in their PSV measurements, which reached normal values in the second CDU. None of the patients of groups B, C, or D experienced any statistically significant change (P &gt; 0.05) in their PSV measurements in the second CDU, which remained below normal values. Also, there was a statistically significant difference between the PSV measurements of group A and the other three groups.

Conclusions
Low PSV measurements in young men (less than 30 years old) with ED should be interpreted with caution. The effect of sympathetic overtone because of the environment in the office and anxiety related to penile injection, together with any underlying psychological disturbance, should be taken into consideration during the evaluation of the results of the CDU. Repetition of the CDU is recommended before considering any additional invasive diagnostic or therapeutic modalities.
Educating Physicians to Treat Erectile Dysfunction Patients: Development and Evaluation of a Course on Communication and Management Strategies
Authors: Athanasiadis Loukas , Papaharitou Stamatis , Salpiggidis Georgios , Tsimtsiou Zoi , Nakopoulou Evangelia , Kirana Paraskevi-Sofia , Moisidis Kyriakos , Hatzichristou Dimitrios 
Published: January 2006

ABSTRACT

Purpose
To describe the development and assess the outcome of a workshop on erectile dysfunction (ED) management based on participating physicians evaluations.

Method
The study involved physicians who attended a workshop offered throughout the country, during a 3-year period. The workshop included tutorials, video-based dramatizations, and role-play sessions. A pilot study investigated the workshop's impact on physicians’ attitudes toward patient-centeredness and sexual behavior issues; Patient–Practitioner Orientation Scale (PPOS) and Cross Cultural Attitude Scale (CCAS) were administered before and after the course. New knowledge acquisition, quality of presentation, and workshop's usefulness in their clinical practice were the dimensions used for workshop's evaluation. Analysis used quantitative and qualitative methods.

Results
A total of 194 questionnaires were administered during the pilot study and the response rate was 53.6%. A shift in attitudes toward patient-centeredness and less judgmental attitude toward patients’ sexual attitudes were revealed (total PPOS score and Sharing subscale: P &lt; 0.05, CCAS: P &lt; 0.001). Six hundred physicians were asked to evaluate the workshops and the response rate was 62.3%. The tutorial session for “medical treatment of ED” (P &lt; 0.001) and the role-play on sexual history taking (P &lt; 0.05) received higher evaluation scores. Qualitative analysis showed that the most frequently reported category referred to the appropriateness of role-play as a teaching and awareness-raising technique (31.25%); a need for changes in clinical practice and communication patterns was identified by 20% of the participants who stressed the necessity for multidisciplinary approach, as well as the adoption of a nonjudgmental attitude toward patients.

Conclusion
Training courses on ED management, using a combination of tutorial and interactive sessions, constitute an effective way of providing knowledge, enhancing physicians’ communication skills with ED patients, and influencing attitudes toward patient-centeredness in sexual issues. Such results strongly support the establishment of sexual medicine courses at continuing medical education curricula.
Assessment and monitoring of glycemic control in primary diabetes care: Monitoring techniques, record keeping, meter downloads, tests of average glycemia, and point‐of‐care evaluation
Authors: Rizvi Ali A. , Sanders Michelle B. 
Published: January 2006

AbstractPurpose: To present a review of glucose monitoring methods useful in primary care.Data sources: Pertinent publications in the literature, printed materials and resources, and the clinical experience of the authors as a referral center for care of patients with diabetes.Conclusions: Regular monitoring of glucose control is an integral and important aspect of diabetes care. It allows the advanced practice nurse (APN) to assess whether diabetes goals are being met or not, involves patients in the care of their disease, and assists in making informed treatment decisions.Implications for practice: A working knowledge of glucose monitoring methods, monitors, testing devices, and laboratory tests is extremely beneficial for the APN in attaining standards of care for patients with diabetes.
Distal adenomatous polyps are rare in patients with inflammatory bowel disease
Authors: Dixon A , Wurm P , Hart A , Robinson R 
Published: January 2006

Abstract

Objective
There is an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). The aim of this study was to compare the prevalence of left sided adenomas in patients with IBD aged 55–64 years with a local age matched control population.

Method
A review of clinical notes. The prevalence of adenomas in patients with IBD attending for either sigmoidoscopy or colonoscopy was compared with local age matched controls that participated in the national screening trial for colorectal cancer with flexible sigmoidoscopy.

Results
Of 106 patients (61 male, 45 female, mean age of 59 years), 80 suffered from ulcerative colitis, 20 from Crohn's disease, and six from indeterminate colitis. All patients had undergone at least one flexible sigmoidoscopy and 75 had a colonoscopy. Distal adenomas were found in three patients with ulcerative colitis compared with 67 of 749 controls (2.8% v 8.9%, χ2 = 4.6, p = 0.03).

Conclusions
The results suggest that distal adenomatous polyps are rare in patients aged 55–64 years with IBD compared with a control population. This supports the hypothesis that lesions other than polyps are important for the development of colorectal cancer in patients with IBD.
Long term prognosis of heart failure after acute coronary syndromes without ST elevation
Authors: Shibata M C , Collinson J , Taneja A K , Bakhai A , Flather M D 
Published: January 2006

Abstract

Background
Information about long term outcomes of patients with acute coronary syndromes (ACS) who have clinically diagnosed heart failure is scarce.

Methods
In a UK registry, this study evaluated patients with non-ST elevation ACS, recording treatment, and clinical outcomes for six months. In a subgroup, a four year mortality follow up was performed to estimate the impact of the clinical diagnosis of heart failure on survival.

Results
Of 1046 patients, 139 (13%) had a history of clinically diagnosed heart failure. At discharge, ACE inhibitors were prescribed for 58% and 28%, of those with and without a history of heart failure respectively (p&lt;0.001). Rates of angiography, percutaneous intervention, and coronary artery bypass graft were 17.3% and 29.2% (p = 0.003), 5.0% and 8.4% (p = 0.17), and 5.0% and 7.5% (p = 0.3) for these groups respectively. Death or new myocardial infarction at six months occurred in 22% and 10% (p&lt;0.001) and at four years death occurred in 60% and 20% of these groups respectively (p&lt;0.001). In a multivariate analysis prior heart failure carried an odds ratio of 2.0 (p = 0.001) for death or myocardial infarction at six months and 2.4 (p&lt;0.001) for death over four years. New heart failure was associated with an increased risk of death at six months (20% compared with 5%, p&lt;0.001).

Conclusion
A clinical history of heart failure carries a substantial risk of death in patients admitted with ACS without ST elevation. Nearly 60% of those with prior heart failure are dead after four years. After adjustment for confounding factors, prior heart failure more than doubles the risk compared with those with no history.
Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells
Authors: Roccaro Aldo Maria , Hideshima Teru , Raje Noopur , Kumar Shaji , Ishitsuka Kenji , Yasui Hiroshi , Shiraishi Norihiko , Ribatti Domenico , Nico Beatrice , Vacca Angelo , Dammacco Franco , Richardson Paul Gerard , Anderson Kenneth Carl 
Published: January 2006

AbstractBone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined.In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient–derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependent inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angiopoietin 1 (Ang1), and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu. (Cancer Res 2006; 66(1): 184-91)
An Imprinted Locus Epistatically Influences Nstr1 and Nstr2 to Control Resistance to Nerve Sheath Tumors in a Neurofibromatosis Type 1 Mouse Model
Authors: Reilly Karlyne M. , Broman Karl W. , Bronson Roderick T. , Tsang Shirley , Loisel Dagan A. , Christy Emily S. , Sun Zhonghe , Diehl John , Munroe David J. , Tuskan Robert G. 
Published: January 2006

Abstract
Cancer is a complex disease in which cells acquire many genetic and epigenetic alterations. We have examined how three types of alterations, mutations in tumor suppressor genes, changes in an imprinted locus, and polymorphic loci, interact to affect tumor susceptibility in a mouse model of neurofibromatosis type 1 (NF1). Mutations in tumor suppressor genes such as TP53 and in oncogenes such as KRAS have major effects on tumorigenesis due to the central roles of these genes in cell proliferation and cell survival. Imprinted genes expressed from only one parental chromosome affect tumorigenesis if their monoallelic expression is lost or duplicated. Because imprinted loci are within regions deleted or amplified in cancer, the parental origin of genomic rearrangements could affect tumorigenesis. Gene polymorphisms can vary tumor incidence by affecting rate-limiting steps in tumorigenesis within tumor cells or surrounding stroma. In our mouse model of NF1, the incidence of tumors mutant for the tumor suppressor genes Nf1 and Trp53 is strongly modified by a linked imprinted locus acting epistatically on two unlinked polymorphic loci, Nstr1 and Nstr2. This interaction of an imprinted locus and polymorphic susceptibility loci has profound implications for human mapping studies where the parental contribution of alleles is often unknown. (Cancer Res 2006; 66(1): 62-8)
Reversal of P-glycoprotein–Mediated Multidrug Resistance in Cancer Cells by the c-Jun NH2-Terminal Kinase
Authors: Zhou Jun , Liu Min , Aneja Ritu , Chandra Ramesh , Lage Hermann , Joshi Harish C. 
Published: January 2006

Abstract
A significant impediment to the success of cancer chemotherapy is multidrug resistance (MDR). A typical form of MDR is attributable to the overexpression of membrane transport proteins, such as P-glycoprotein, resulting in an increased drug efflux. In this study, we show that adenovirus-mediated enhancement of the c-Jun NH2-terminal kinase (JNK) reduces the level of P-glycoprotein in a dose- and time-dependent manner. Protein turnover assay shows that the decrease of P-glycoprotein is independent of its protein stability. Instead, this occurs primarily at the mRNA level, as revealed by reverse transcription-PCR analysis. We find that P-glycoprotein down-regulation requires the catalytic activity of JNK and is mediated by the c-Jun transcription factor, as either pharmacologic inhibition of JNK activity or dominant-negative suppression of c-Jun remarkably abolishes the ability of JNK to down-regulate P-glycoprotein. In addition, electrophoretic mobility shift assay reveals that adenoviral JNK increases the activator protein binding activity of the mdr1 gene in the MDR cells. We further show that the decrease of P-glycoprotein level is associated with a significant increase in intracellular drug accumulation and dramatically enhances the sensitivity of MDR cancer cells to chemotherapeutic agents. Our study provides the first direct evidence that enhancement of the JNK pathway down-regulates P-glycoprotein and reverses P-glycoprotein–mediated MDR in cancer cells. (Cancer Res 2006; 66(1): 445-52)
Paclitaxel-Induced Nuclear Translocation of FOXO3a in Breast Cancer Cells Is Mediated by c-Jun NH2-Terminal Kinase and Akt
Authors: Sunters Andrew , Madureira Patricia A. , Pomeranz Karen M. , Aubert Muriel , Brosens Jan J. , Cook Simon J. , Burgering Boudewijn M.T. , Coombes R. Charles , Lam Eric W.-F. 
Published: January 2006

Abstract
The microtubule-targeting compound paclitaxel is often used in the treatment of endocrine-resistant or metastatic breast cancer. We have previously shown that apoptosis of breast cancer cells in response to paclitaxel is mediated by induction of FOXO3a expression, a transcription factor downstream of the phosphatidylinositol-3-kinase/Akt signaling pathway. To further investigate its mechanism of action, we treated MCF-7 cells with paclitaxel and showed a dose-dependent increase in nuclear localization of FOXO3a, which coincided with decreased Akt signaling but increased c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Flow cytometry revealed that paclitaxel-induced apoptosis of MCF-7 cells and of other paclitaxel-sensitive breast cancer cell lines was maintained in the presence of inhibitors of p38 (SB203580) or mitogen-activated protein/ERK kinase 1 signaling (PD98059) but abrogated when cells were treated with the JNK1/2 inhibitor SP600125. SP600125 reversed Akt inhibition and abolished FOXO3a nuclear accumulation in response to paclitaxel. Moreover, conditional activation of JNK mimicked paclitaxel activity and led to dephosphorylation of Akt and FOXO3a. Furthermore, mouse embryonic fibroblasts (MEF) derived from JNK1/2 knockout mice displayed very high levels of active Akt, and in contrast to wild-type MEFs, paclitaxel treatment did not alter Akt activity or elicit FOXO3a nuclear translocation. Taken together, the data show that cell death of breast cancer cells in response to paclitaxel is dependent upon JNK activation, resulting in Akt inhibition and increased FOXO3a activity. (Cancer Res 2006; 66(1): 212-20)
Topological and Functional Discovery in a Gene Coexpression Meta-Network of Gastric Cancer
Authors: Aggarwal Amit , Li Guo Dong , Hoshida Yujin , Tsan Yuen Siu , Chu Kent-Man , So Samuel , Boussioutas Alex , Chen Xin , Bowtell David , Aburatani Hiroyuki , Leung Suet Yi , Tan Patrick 
Published: January 2006

Abstract
Gastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we assembled and systematically analyzed a consensus gene coexpression meta-network of gastric cancer incorporating &gt;300 tissue samples from four independent patient populations (the “gastrome”). We find that the gastrome exhibits a hierarchical scale-free architecture, with an internal structure comprising multiple deeply embedded modules associated with diverse cellular functions. Individual modules display distinct subtopologies, with some (cellular proliferation) being integrated within the primary network, and others (ribosomal biosynthesis) being relatively isolated. One module associated with intestinal differentiation exhibited a remarkably high degree of autonomy, raising the possibility that its specific topological features may contribute towards the frequent occurrence of intestinal metaplasia in gastric cancer. At the single-gene level, we discovered a novel conserved interaction between the PLA2G2A prognostic marker and the EphB2 receptor, and used tissue microarrays to validate the PLA2G2A/EphB2 association. Finally, because EphB2 is a known target of the Wnt signaling pathway, we tested and provide evidence that the Wnt pathway may also similarly regulate PLA2G2A. Many of these findings were not discernible by studying the single patient populations in isolation. Thus, besides enhancing our knowledge of gastric cancer, our results show the broad utility of applying meta-analytic approaches to genome-wide data for the purposes of biological discovery. (Cancer Res 2006; 66(1): 232-41)
Consistent Rearrangement of Chromosomal Band 6p21 with Generation of Fusion GenesJAZF1/PHF1andEPC1/PHF1in Endometrial Stromal Sarcoma
Authors: Micci Francesca , Panagopoulos Ioannis , Bjerkehagen Bodil , Heim Sverre 
Published: January 2006

AbstractEndometrial stromal sarcomas (ESS) represent &lt;10% of all uterine sarcomas. Cytogenetic data on this tumor type are limited to 32 cases, and the karyotypes are often complex, but the pattern of rearrangement is nevertheless clearly nonrandom with particularly frequent involvement of chromosome arms 6p and 7p. Recently, a specific translocation t(7;17)(p15;q21) leading to the fusion of two zinc finger genes, juxtaposed with another zinc finger (JAZF1) and joined to JAZF1 (JJAZ1), was described in a subset of ESS. We present three ESS whose karyotypes were without the disease-specific t(7;17) but instead showed rearrangement of chromosomal band 6p21, twice as an unbalanced t(6p;7p) and once as a three-way 6;10;10 translocation. All three tumors showed specific rearrangement of the PHD finger protein 1 (PHF1) gene, located in chromosomal band 6p21. In the two tumors with t(6;7), PHF1 was recombined with the JAZF1 gene from 7p15, leading to the formation of a JAZF1/PHF1 fusion gene. The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia. The PHF1 gene encodes a protein with two zinc finger motifs whose involvement in tumorigenesis and/or tumor progression has not been reported before, but its rearrangement clearly defines a new pathogenetic subgroup of ESS. (Cancer Res 2006; 66(1): 107-12)
Telomere Repeat Binding Factor 2 Interacts with Base Excision Repair Proteins and Stimulates DNA Synthesis by DNA Polymerase β
Authors: Muftuoglu Meltem , Wong Heng Kuan , Imam Syed Z. , Wilson David M. , Bohr Vilhelm A. , Opresko Patricia L. 
Published: January 2006

Abstract
The ends of linear chromosomes are capped and protected by protein-DNA complexes termed telomeres. Consequences of telomere dysfunction include genomic instability that can contribute to neoplastic transformation and progression. Telomere binding proteins interact with numerous proteins involved in DNA repair, underscoring the importance of regulating DNA repair pathways at telomeres. Telomeric DNA is particularly susceptible to oxidative damage, and such damage is repaired primarily via the base excision repair (BER) pathway. Using a screen for potential interactions between telomere repeat binding factor 2 (TRF2) and proteins involved in BER of oxidized bases in vitro, we found that TRF2 physically bound DNA polymerase β (Pol β) and flap endonuclease 1 (FEN-1). The interactions with endogenous proteins in human cell extracts were confirmed by coimmunoprecipitation experiments. The primary binding sites for both Pol β and FEN-1 mapped to the TRF2 NH2-terminal and COOH-terminal domains. We further tested the ability of TRF2 to modulate BER protein partners individually on a variety of substrates in vitro. TRF2 stimulated Pol β primer extension DNA synthesis on telomeric and nontelomeric primer/template substrates, resulting in up to a 75% increase in the proportion of longer products. TRF2 also stimulated Pol β strand displacement DNA synthesis in reconstituted BER reactions and increased the percent of long-patch BER intermediates on both telomeric and nontelomeric substrates. Potential roles of TRF2 in cooperation with BER proteins for DNA repair pathways at telomeres, as well as other genomic regions, are discussed. (Cancer Res 2006; 66(1): 113-24)
Physical and Functional Interaction between hMSH5 and c-Abl
Authors: Yi Wei , Lee Tai-Hsien , Tompkins Joshua D. , Zhu Fengxue , Wu Xiling , Her Chengtao 
Published: January 2006

Abstract
Despite being a member of the mismatch repair family of proteins, the biological functions of hMSH5 in human cells are presently elusive. Here, we report a novel physical and functional interaction between hMSH5 and c-Abl; the latter is a critical non–receptor tyrosine kinase involved in many critical cellular functions including DNA damage response, in which the kinase activity is normally suppressed in the absence of biological challenges. Our data indicate that hMSH5 associates with c-Abl in vivo, which is mediated by a direct physical interaction between the NH2 terminus (residues 1-109) of hMSH5 and the c-Abl SH3 domain. This physical interaction facilitates the activation of c-Abl tyrosine kinase and the phosphorylation of hMSH5 in response to ionizing radiation. Our data also indicate that the hMSH5 P29S variant overactivates the c-Abl tyrosine kinase activity. Furthermore, it seems that the tyrosine phosphorylation of hMSH5 promotes the dissociation of hMSH4-hMSH5 heterocomplex. Together, the revealed physical and functional interaction of hMSH5 with c-Abl implies that the interplay between hMSH5 and c-Abl could manipulate cellular responses to ionizing radiation–induced DNA damages. (Cancer Res 2006; 66(1): 151-8)