bluuebunny/crossref_metadata_2025 huggingface dataset:
Ruptured Intracranial Mycotic Aneurysm in Infective Endocarditis: A Natural History
Authors: Kuo Isabel , Long Theodore , Nguyen Nathan , Chaudry Bharat , Karp Michael , Sanossian Nerses
Published: September 2010

Mycotic aneurysms are a rare cause of intracranial aneurysms that develop in the presence of infections such as infective endocarditis. They account for a small percentage of all intracranial aneurysms and carry a high-mortality rate when ruptured. The authors report a case of a 54-year-old man who presented with infective endocarditis of the mitral valve and acute stroke. He subsequently developed subarachnoid hemorrhage during antibiotic treatment, and a large intracranial aneurysm was discovered on CT Angiography. His lesion quickly progressed into an intraparenchymal hemorrhage, requiring emergent craniotomy and aneurysm clipping. Current recommendations on the management of intracranial Mycotic Aneurysms are based on few retrospective case studies. The natural history of the patient's ruptured aneurysm is presented, as well as a literature review on the management and available treatment modalities.
Factors Associated with Overweight and Obesity among Kuwaiti Elementary Male School Children Aged 6–10 Years
Authors: Al-Isa Abdulwahab Naser , Campbell Jennifer , Desapriya Ediriweera
Published: September 2010

Background. Childhood obesity is becoming a global epidemic which may result in increased morbidity and mortality during young adulthood.Objectives. To identify factors associated with overweight and that of obesity among Kuwaiti elementary male school children aged 6–10 years.Methods. Weights and heights of 662 students at a randomly selected school were collected to obtain body mass index (BMI).Results. The prevalence of overweight and obesity among the students were 20.2% and 16.8%, respectively. There were a variety of factors associated with overweight and obesity; however, having one or more obese brother, an unemployed father, or a high (>11) number of persons living at home was significantly associated with higher risk of overweight and obesity. Increased age and school level as well as having a chronic disease were associated with the risk of overweight.Conclusion. Health education programs for families should be implemented to help control overweight and obesity in Kuwaiti children.
Two New Families of Floating FDNR Circuits
Authors: Soliman Ahmed M. , Saad Ramy A.
Published: September 2010

Two new configurations for realizing ideal floating frequency‐dependent negative resistor elements (FDNR) are introduced. The proposed circuits are symmetrical and are realizable by four CCII or ICCII or a combination of both. Each configuration is realizable by eight different circuits. Simulation results are included to support the theory.
Preparation and Characterization of a Novel Skin Substitute
Authors: Castagnoli Carlotta , Fumagalli Mara , Alotto Daniela , Cambieri Irene , Casarin Stefania , Ostorero Alessia , Casimiri Raffaella , Germano Patrizia , Pezzuto Carla , Stella Maurizio
Published: September 2010

Autologous epidermal cell cultures (CEA) represent a possibility to treat extensive burn lesions, since they allow a significative surface expansion which cannot be achieved with other surgical techniques based on autologous grafting. Moreover currently available CEA preparations are difficult to handle and their take rate is unpredictable. This study aimed at producing and evaluating a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis (AAGD) and CEA to overcome these difficulties. A procedure that maintained an intact basement membrane was developed, so as to promote adhesion and growth of CEA on AAGD. Keratinocytes were seeded onto AAGD and cultured up to 21 days. Viability tests and immunohistochemical analysis with specific markers were carried out at 7, 14, and 21 days, to evaluate keratinocyte adhesion, growth, and maturation. Our results support the hypothesis that this newly formed skin substitute could allow its permanent engraftment in clinical application.
Basal Cell Carcinoma in a Child
Authors: Kuvat Samet Vasfi , Gücin Zuhal , Keklik Barış , Özyalvaçlı Gülzade , Başaran Karaca
Published: September 2010

Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a3×4 cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family.
PALB2/FANCN: Recombining Cancer and Fanconi Anemia
Authors: Tischkowitz Marc , Xia Bing
Published: September 2010

Partner and localizer of BRCA2 (PALB2) was originally identified as a BRCA2-interacting protein that is crucial for key BRCA2 genome caretaker functions. It subsequently became clear that PALB2 was another Fanconi anemia (FA) gene (FANCN), and that monoallelic PALB2 mutations are associated with increased risk of breast and pancreatic cancer. Mutations in PALB2 have been identified in breast cancer families worldwide, and recent studies have shown that PALB2 also interacts with BRCA1. Here, we summarize the molecular functions and clinical phenotypes of this key DNA repair pathway component and discuss how its discovery has advanced our knowledge of both FA and adult cancer predisposition. Cancer Res; 70(19); 7353–9. ©2010 AACR.
Epidermal Growth Factor Receptor Expression Identifies Functionally and Molecularly Distinct Tumor-Initiating Cells in Human Glioblastoma Multiforme and Is Required for Gliomagenesis
Authors: Mazzoleni Stefania , Politi Letterio S. , Pala Mauro , Cominelli Manuela , Franzin Alberto , Sergi Sergi Lucia , Falini Andrea , De Palma Michele , Bulfone Alessandro , Poliani Pietro L. , Galli Rossella
Published: September 2010

Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFRpos and EGFRneg TIC subpopulations within the same tumor might affect clinical response to treatment. Cancer Res; 70(19); 7500–13. ©2010 AACR.
Sequential Cytarabine and α-Particle Immunotherapy with Bismuth-213–Lintuzumab (HuM195) for Acute Myeloid Leukemia
Authors: Rosenblat Todd L. , McDevitt Michael R. , Mulford Deborah A. , Pandit-Taskar Neeta , Divgi Chaitanya R. , Panageas Katherine S. , Heaney Mark L. , Chanel Suzanne , Morgenstern Alfred , Sgouros George , Larson Steven M. , Scheinberg David A. , Jurcic Joseph G.
Published: September 2010

Purpose: Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the potency of the antibody without the nonspecific cytotoxicity associated with β-emitters, the α-particle–emitting radionuclide bismuth-213 (213Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of 213Bi-lintuzumab, the first targeted α-emitter, after partially cytoreductive chemotherapy.

Experimental Design: Thirty-one patients with newly diagnosed (n = 13) or relapsed/refractory (n = 18) AML (median age, 67 years; range, 37-80) were treated with cytarabine (200 mg/m2/d) for 5 days followed by 213Bi-lintuzumab (18.5-46.25 MBq/kg).

Results: The MTD of 213Bi-lintuzumab was 37 MB/kg; myelosuppression lasting >35 days was dose limiting. Extramedullary toxicities were primarily limited to grade ≤2 events, including infusion-related reactions. Transient grade 3/4 liver function abnormalities were seen in five patients (16%). Treatment-related deaths occurred in 2 of 21 (10%) patients who received the MTD. Significant reductions in marrow blasts were seen at all dose levels. The median response duration was 6 months (range, 2-12). Biodistribution and pharmacokinetic studies suggested that saturation of available CD33 sites by 213Bi-lintuzumab was achieved after partial cytoreduction with cytarabine.

Conclusions: Sequential administration of cytarabine and 213Bi-lintuzumab is tolerable and can produce remissions in patients with AML. Clin Cancer Res; 16(21); 5303–11. ©2010 AACR.
Involvement of Human Herpesvirus-6 Variant B in Classic Hodgkin's Lymphoma via DR7 Oncoprotein
Authors: Lacroix Aurélie , Collot-Teixeira Sophie , Mardivirin Laurent , Jaccard Arnaud , Petit Barbara , Piguet Christophe , Sturtz Franck , Preux Pierre-Marie , Bordessoule Dominique , Ranger-Rogez Sylvie
Published: September 2010

Purpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation.

Experimental Design: HHV-6 DR7B protein was produced in a Semliki Forest virus system. Polyclonal antibodies were then generated and used for immunochemical HHV-6 localization in HL biopsies. Binding between DR7B and p53 was studied using a double-hybrid system. Transactivation of NFκB was observed after transient transfection using reporter gene assays. We looked for Id2 factor expression after stable transfection of the BJAB cell line by reverse transcription-PCR and Western blot analysis.

Results: HHV-6 was more common in nodular sclerosis subtype HL, and DR7B oncoprotein was detected in RS cells for 73.7% of EBV-negative patients. Colocalization of EBV and HHV-6 was observed in RS cells of doubly infected patients. DR7B protein bound to human p53 protein. p105-p50/p65 mRNA expression and activation of the NFκB complex were increased when DR7B was expressed. Stable expression of DR7B exhibited a strong and uniform expression of Id2. A slightly higher percentage of remission was observed in patients with RS cells testing positive for DR7B than in those testing negative.

Conclusions: Collectively, these data provide evidence for the implication of a novel agent, HHV-6, in cases of nodular sclerosis HL. Clin Cancer Res; 16(19); 4711–21. ©2010 AACR.
Poly(ADP-Ribose) Polymerase Inhibition: “Targeted” Therapy for Triple-Negative Breast Cancer
Authors: Anders Carey K. , Winer Eric P. , Ford James M. , Dent Rebecca , Silver Daniel P. , Sledge George W. , Carey Lisa A.
Published: September 2010

In contrast to endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)–positive breast cancer, novel agents capable of treating advanced triple-negative breast cancer (TNBC) are lacking. Poly(ADP-ribose) polymerase (PARP) inhibitors are emerging as one of the most promising “targeted” therapeutics to treat TNBC, with the intended “target” being DNA repair. PARPs are a family of enzymes involved in multiple cellular processes, including DNA repair. TNBC shares multiple clinico-pathologic features with BRCA-mutated breast cancers, which harbor dysfunctional DNA repair mechanisms. Investigators hypothesized that PARP inhibition, in conjunction with the loss of DNA repair via BRCA-dependent mechanisms, would result in synthetic lethality and augmented cell death. This hypothesis has borne out in both preclinical models and in clinical trials testing PARP inhibitors in both BRCA-deficient and triple-negative breast cancer. The focus of this review includes an overview of the preclinical rationale for evaluating PARP inhibitors in TNBC, the presumed mechanism of action of this novel therapeutic class, promising results from several influential clinical trials of PARP inhibition in advanced breast cancer (both TNBC and BRCA deficient), proposed mechanisms of acquired resistance to PARP inhibitors, and, finally, concludes with current challenges and future directions for the development of PARP inhibitors in the treatment of breast cancer. Clin Cancer Res; 16(19); 4702–10. ©2010 AACR.
Cisplatin-Induced Downregulation of OCTN2 Affects Carnitine Wasting
Authors: Lancaster Cynthia S. , Hu Chaoxin , Franke Ryan M. , Filipski Kelly K. , Orwick Shelley J. , Chen Zhaoyuan , Zuo Zhili , Loos Walter J. , Sparreboom Alex
Published: September 2010

Purpose: Carnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function.

Experimental Design: Excretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration. The transport of carnitine was assessed in cells that were transfected with OCT1 or OCT2. The effect of cisplatin treatment on gene expression was analyzed using a mouse GeneChip array and validated using quantitative reverse transcriptase-PCR.

Results: In wild-type mice, urinary carnitine excretion at baseline was ∼3-fold higher than in mice lacking the basolateral cisplatin transporters Oct1 and Oct2 [Oct1/2(−/−) mice], indicating that carnitine itself undergoes basolateral uptake into the kidney. Transport of carnitine by OCT2, but not OCT1, was confirmed in transfected cells. We also found that cisplatin caused an increase in the urinary excretion of carnitine and acetylcarnitine in wild-type mice but not in Oct1/2(−/−) mice, suggesting that tubular transport of cisplatin is a prerequisite for this phenomenon. Cisplatin did not directly inhibit the transport of carnitine by Octn2 but downregulated multiple target genes of the transcription factor peroxisome proliferator activated receptor α, including Slc22a5, in the kidney of wild-type mice that were absent in Oct1/2(−/−) mice.

Conclusion: Our study shows a pivotal role of Oct1 and Oct2 in cisplatin-related disturbances in carnitine homeostasis. We postulate that this phenomenon is triggered by deactivation of peroxisome proliferator activated receptor α and leads to deregulation of carnitine-shuttle genes. Clin Cancer Res; 16(19); 4789–99. ©2010 AACR.
The Use of One-Bead One-Compound Combinatorial Library Technology to Discover High-Affinity αvβ3 Integrin and Cancer Targeting Arginine-Glycine-Aspartic Acid Ligands with a Built-in Handle
Authors: Xiao Wenwu , Wang Yan , Lau Edmond Y. , Luo Juntao , Yao Nianhuan , Shi Changying , Meza Leah , Tseng Harry , Maeda Yoshiko , Kumaresan Pappanaicken , Liu Ruiwu , Lightstone Felice C. , Takada Yoshikazu , Lam Kit S.
Published: September 2010

The αvβ3 integrin, expressed on the surface of various normal and cancer cells, is involved in numerous physiologic processes such as angiogenesis, apoptosis, and bone resorption. Because this integrin plays a key role in angiogenesis and metastasis of human tumors, αvβ3 integrin ligands are of great interest to advances in targeted therapy and cancer imaging. In this report, one-bead one-compound (OBOC) combinatorial libraries containing the arginine-glycine-aspartic acid (RGD) motif were designed and screened against K562 myeloid leukemia cells that had been transfected with the human αvβ3 integrin gene. Cyclic peptide LXW7 was identified as a leading ligand with a built-in handle that binds specifically to αvβ3 and showed comparable binding affinity (IC50 = 0.68 ± 0.08 μmol/L) to some of the well-known RGD “head-to-tail” cyclic pentapeptide ligands reported in the literature. The biotinylated form of LXW7 ligand showed similar binding strength as LXW7 against αvβ3 integrin, whereas biotinylated RGD cyclopentapeptide ligands revealed a 2- to 8-fold weaker binding affinity than their free forms. LXW7 was able to bind to both U-87MG glioblastoma and A375M melanoma cell lines, both of which express high levels of αvβ3 integrin. In vivo and ex vivo optical imaging studies with the biotinylated ligand/streptavidin-Cy5.5 complex in nude mice bearing U-87MG or A375M xenografts revealed preferential uptake of biotinylated LXW7 in tumor. When compared with biotinylated RGD cyclopentapeptide ligands, biotinylated LXW7 showed higher tumor uptake but lower liver uptake. Mol Cancer Ther; 9(10); 2714–23. ©2010 AACR.
Antitumor Effect of Temsirolimus against Oral Squamous Cell Carcinoma Associated with Bone Destruction
Authors: Okui Tatsuo , Shimo Tsuyoshi , Fukazawa Takuya , Kurio Naito , Hassan Nur Mohammad Monsur , Honami Tatsuki , Takaoka Munenori , Naomoto Yoshio , Sasaki Akira
Published: September 2010

The mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous cell carcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR inhibitor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, we investigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral squamous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. Significantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. Reverse transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor activator for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 cells. Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral hypercalcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma. Mol Cancer Ther; 9(11); 2960–9. ©2010 AACR.
Genetic Variations in the Sonic Hedgehog Pathway Affect Clinical Outcomes in Non–Muscle-Invasive Bladder Cancer
Authors: Chen Meng , Hildebrandt Michelle A.T. , Clague Jessica , Kamat Ashish M. , Picornell Antoni , Chang Joshua , Zhang Xiaofan , Izzo Julie , Yang Hushan , Lin Jie , Gu Jian , Chanock Stephen , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Garcia-Closas Montserrat , Grossman H. Barton , Dinney Colin P. , Malats Núria , Wu Xifeng
Published: September 2010

Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non–muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P ≤ 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P ≤ 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 × 10−3 (SHH rs1233560) and 1.3 × 10−3 (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guérin (BCG; P ≤ 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 × 10−4 and 9 × 10−4, respectively). The wild-type genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P ≤ 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients. Cancer Prev Res; 3(10); 1235–45. ©2010 AACR.
Association between C-Peptide Concentration and Prostate Cancer Incidence in the CLUE II Cohort Study
Authors: Lai Gabriel Y. , Helzlsouer Kathy J. , Clipp Sandra L. , Rifai Nader , Platz Elizabeth A.
Published: September 2010

Diabetes, characterized by perturbations in insulin production and signaling, is inversely associated with prostate cancer risk irrespective of stage. Obesity, a diabetes risk factor, is inversely associated with localized disease but positively associated with advanced disease. To understand the complex association between hyperinsulinemia and prostate cancer, we evaluated the association of plasma C-peptide, an insulin secretion marker, with prostate cancer risk in a case-control study nested in a prospective community cohort. Prostate cancer cases (n = 264) and matched controls (n = 264) were identified in the CLUE II cohort between 1989 (baseline) and 2002. C-peptide concentration was measured in baseline plasma by ELISA. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression, adjusting for being overweight or obese and family history. Median C-peptide concentration was lower in cases (1,180 pmol/L) than in controls (1,365 pmol/L; P = 0.03). Men in the highest (versus lowest) fourth of C-peptide had a lower risk for prostate cancer (OR, 0.65; 95% CI, 0.37-1.14; P-trend = 0.08), primarily localized disease (OR, 0.44; 95% CI, 0.19-1.03; P-trend = 0.04). Associations were similar to overall, when excluding cases diagnosed during the first 5 years of follow-up, men with diabetes, or men who had not had a prostate-specific antigen test. C-peptide concentration was inversely associated with subsequent diagnosis of prostate cancer, primarily localized disease, similar to the association for obesity. However, we cannot rule out detection bias that might result if men with higher C-peptide have lower prostate-specific antigen irrespective of whether prostate cancer is present or not. Cancer Prev Res; 3(10); 1334–41. ©2010 AACR.
Effect of Varicocele Grade and Age on Seminal Parameters
Authors: Vivas-Acevedo Giovanny , Lozano Jesús Ricardo , Camejo María Isabel
Published: September 2010

Aim: To evaluate the effect of presence, grade and anatomical side of varicocele on semen parameters and to identify age-related modifications in semen quality in men with varicocele. Methods: A prospective clinical study was performed in 363 men with varicocele and 155 normozoospermic men without varicocele. We determined the presence, grade and anatomical localization of varicocele: left (grades I–III), right or bilateral. Additionally, evaluation of semen was done and the hypoosmotic swelling test (HOST) percentage determined. Results: The percentage of spermatozoa with normal morphology, motility, vitality, and HOST was reduced in patients with varicocele. Comparison of semen parameters between the different degrees of left varicocele (I, II or III) shows that the percentage of normal sperm morphology is reduced in men with varicocele grade III, while other parameters are not affected. The percentage of patient normozoospermic was 50 and 24% in men with left varicocele grades I and III, respectively. A negative correlation between increase of age in men and sperm motility was observed only in the varicocele group. Conclusions: This study suggests that both the varicocele grade and an increase of age in men with varicocele could determine the extent of alteration to semen quality.
Titration of Dosage for the Protective Effect of Zoledronic Acid on Bone Loss in Patients Submitted to Androgen Deprivation Therapy due to Prostate Cancer: A Prospective Open-Label Study
Authors: Rodrigues Paulo , Meler Alex , Hering Flavio
Published: September 2010

Background: Bisphosphonates were incorporated as agents for the long-term effect of androgen deprivation therapy (ADT) but no comparative study was established for the optimal schedule for bone preservation. Methods: Ninety-five consecutive prostate cancer patients submitted to radical retropubic prostatectomy were recruited. At rising PSA they were prospectively enrolled in nonrandomized fashion and grouped to receive no treatment (21 – control group), and monthly (17), bi-monthly (15), tri-monthly (19) or semestral (15) 4 mg zoledronic acid infusions. The patients were followed to a minimum of 30 months after receiving ADT by LHRH agonists. Bone mineral density (BMD) was measured every 6 months in all 5 studied groups in order to compare the effect of each regimen to nontreatment. Tukey-Kramer and Scheffe’s tests were used. Results: The control group showed an impressive BMD loss throughout the study period. The 4 groups treated with zoledronic acid infusions showed increased BMD in the lumbar area on periodical densitometry and no statistical differences could be established among the 4 studied schedules. Different individual patterns of decreasing (control) or increasing (treated) BMD could be seen along the study as measured by bone densitometry. Conclusions: Zoledronic acid treatment promoted effective osseous protection against the natural demineralization process in patients with prostate cancer recurrence submitted to ADT.
Single-Port Extraperitoneal Transvesical Adenomectomy: Initial Operative Experience
Authors: Oktay Bulent , Vuruskan Hakan , Koc Gokhan , Danisoglu Mahmut Esad , Kordan Yakup
Published: September 2010

Background: Laparoscopic extraperitoneal adenomectomy is occasionally performed for symptomatic large-volume benign prostatic hyperplasia. Two different multichannel ports were used during operations. We describe the technique of single-port extraperitoneal transvesical adenomectomy and present the initial operative experience. Methods: Three patients in whom an open adenomectomy was indicated underwent single-port extraperitoneal transvesical adenomectomy. Following preparation of the extraperitoneal space via an umbilical incision, a multichannel port was inserted. A transverse cystotomy adjacent to the prostatovesical junction, incision of mucosa overlying the adenoma, subcapsular plane development, prostatic adenomectomy and cystotomy repair were performed as the standard steps of the laparoscopic procedure. Results: All cases were completed without conversion to standard laparoscopy. Mean operative time was 105 min. Mean blood loss was 190 ml. Hospital stay was 4 days and catheter duration was 6 days for all patients. No intraoperative or postoperative complication occurred. Conclusions: Single-port extraperitoneal transvesical adenomectomy for large benign prostate hyperplasia is feasible with excellent cosmetic results and minimal morbidity.
Developing a System for Regulating Expression of Human Hepatocyte Growth Factor Using Tetracycline in NRK52E Cells
Authors: Ren Shu-Ting , Yu Lin-Hua , Zhang Jian , Han Shui-Ping , Xu Chang-Fu
Published: September 2010

Introduction: Hepatocyte growth factor (HGF) is a target of gene therapy for renal fibrosis. The aim of this study was to establish a human HGF gene expression system that is regulated by tetracycline (Tet) in normal rat kidney tubular epithelial cells (NRK52E cells). Materials and Methods: The plasmids pTet-on, pBI-L-HGF and pTK-Hyg were transfected sequentially into NRK52E cells using Lipofectamine 2000. The expression of HGF gene was measured, and the activity of expressed HGF was detected. Results: A clone of pBI-L-HGF/NRK52E cells showing strong reaction to doxycycline (Dox) was selected using a luciferase reporter assay system. The expression of both HGF mRNA and protein was significantly higher (both p < 0.01) in the Dox group than that in the control group. Furthermore, the bioactivity of expressed HGF was confirmed in the assay. Conclusions: A Tet-regulated human HGF gene expression system in NRK52E cells has been established. This cell line may prove useful for gene therapy against renal fibrosis.
Prostatic Biopsy Undergrading: The Feasibility of Secondary Laparoscopic Pelvic Lymphadenectomy
Authors: Hellawell Giles , Ramírez-Backhaus Miguel , Rabenalt Robert , Do Minh , Dietel Anja , Stolzenburg Jens-Uwe
Published: September 2010

Objectives: Prostate biopsy grade is a key factor when deciding whether to perform pelvic lymph node dissection (PLND) at laparoscopic radical prostatectomy. In common with many laparoscopic radical prostatectomy centers, we perform PLND in patients found to have intermediate and high-risk prostate cancer based upon preoperative PSA, prostate biopsy and imaging. We assessed the feasibility of performing a secondary laparoscopic PLND 6 weeks postoperatively in the presence of postoperative upgrading in patients who did not have PLND. Methods: A prospective study recording the pathological results and operative outcomes prospectively over a 10-month period during which 24 patients underwent a secondary PLND. All patients had a preoperative PSA level <10 ng/ml and biopsy Gleason score of ≤6 (3 + 3) and the prostatectomy specimen was subsequently found to have a Gleason score of ≧7 (4 + 3) or increased stage. Results: During the 10-month period, 377 prostatectomies were carried out in our department in which 54 (18.3%) had an upgrading in the prostatectomy specimen. 24 patients (mean age 60 and mean PSA 6.7 ng/ml) agreed to a secondary PLND. No lymph nodes metastases were observed. One patient who was sexually potent following a nerve-sparing prostatectomy was impotent after the secondary PLND. Conclusions: Upgrading of prostate Gleason score is seen in up to a third of cases in many large published series that is reflected in our experience. A laparoscopic secondary lymphadenectomy is feasible with low morbidity and yields valuable pathological clinical staging for subsequent surveillance and therapy for these high-risk patients.
Downregulation of Nucleostemin Causes G1 Cell Cycle Arrest via a p53-Independent Pathway in Prostate Cancer PC-3 Cells
Authors: Liu Ranlu , Zhang Zhihong , Xu Yong
Published: September 2010

Aims: To screen the genes and possible signal transduction pathways with which nucleostemin (NS) interacts and explore the mechanism of NS in prostate cancer. Methods: NS-specific short-hairpin RNA expression plasmid was used to downregulate the NS level in PC-3 cells and the changes of cell cycle were studied. After that, oligonucleotide DNA microarray was used to screen the genome changes in PC-3 cells and quantitative real-time PCR was used to further confirm the differentially expressed genes. Results: Detection of cell cycle showed a decrease of S stage and an increase of G1 stage after downregulation of NS. 219 differentially expressed genes were found and these genes were involved in cell cycle, cell proliferation, signal transduction, cell apoptosis and cell differentiation, and so on. Genes related to cell cycle were discussed emphatically. INK4 family genes (P15, P16, P18) were upregulated while cyclin D1 HDAC1 were downregulated. These genes were tightly related to CDK4/6-cyclin D and pRb-E2F1 complexes. Conclusion: NS is an important G1/S checkpoint regulator and it could regulate cell cycles via a p53-independent pathway in prostate cancer.
The Endothelial Nitric Oxide Synthase Gene Is Associated with Coronary Artery Disease: A Meta-Analysis
Authors: Li Junyan , Wu Xinxing , Li Xingwang , Feng Guoyin , He Lin , Shi Yongyong
Published: September 2010

Introduction: Previous case-control studies have suggested that the endothelial nitric oxide synthase (eNOS) gene polymorphisms (G894T, 4b/a, T-786C) are associated with coronary artery disease (CAD). However, other studies do not confirm these relationships. The objective was to assess these relationships using meta-analysis. Methods: Databases, including Pubmed and Embase, were searched to access the relevant genetic association studies up to July 2009. Results: The meta-analysis included 56 studies, consisting of 23 studies for G894T, 19 for 4b/a and 14 for T-786C. For the allelic analysis of the G894T variant, all studies showed a positively significant association (OR = 0.83, p = 0.004). For the genotypic analysis, the combined studies of the T allele showed significance (OR = 1.57, p = 0.003). For the allelic analysis of the T-786C variant, all studies showed an obviously significant association (OR = 0.79, p = 0.0007), reflected in both non-Asian and Asian studies. For the genotype analysis, combined studies of the C allele showed significance (OR = 0.72, p = 0.0001). Moreover, non-Asian studies showed significant results. For the analysis of the 4b/a variant, none of the studies showed significant results. No publication bias was found in the meta-analysis. Conclusion: The synthesis of available evidence supports the fact that eNOS G894T andT-786C are associated with CAD.
Intrauterine Device-Associated Actinomycosis of the Ovary and Urinary Bladder: A Case Report
Authors: Bottai Andrea , Li Marzi Vincenzo , Alessandrini Marco , Villari Donata , Nesi Gabriella , Nicita Giulio
Published: September 2010

Actinomycosis of the urinary bladder is rare, mostly subsequent to abdomino-pelvic infection, and usually affects women with long-term use of an intrauterine device. We describe a case of vesical actinomycosis mimicking a papillary bladder tumour in a 56-year-old woman with primary manifestation of the disease in the genital tract, subjected to two transurethral resections after relapse of a polypoid mass in the bladder. Urological procedures are necessary to differentiate actinomycosis from bladder cancer and the diagnosis is often made histologically.
Relationship between Prostate-Specific Antigen and Body Mass Index according to Age: Lower Prostate-Specific Antigen in Middle-Aged Overweight and Obese Korean Men
Authors: Yang Won Jae , Cheon Sang Hyeon , Kim Young Sig , Kim Dong Jun , Seong Do Hwan , Song Yun Seob , Cho Soung Yong , Cho In Rae , Kim Sun Il , Kim Se Joong , Kim Chun Il , Choi Young Deuk , Hong Sung Joon , Im Hyoungjune , Cho Jin Seon
Published: September 2010

Objective: To analyze the relationship between serum prostate-specific antigen (PSA) and body mass index (BMI) according to age in a population of ostensibly healthy Korean men. Patients and Methods: Between 2002 and 2006, data from 13,025 men who visited health promotion centers were evaluated. All men underwent anthropometric measurements and serum PSA determination. The relationship between serum PSA and BMI according to age was analyzed. Results: The median age was 50.0 years and the median serum PSA level was 0.69 ng/ml. There was no relationship between serum PSA and BMI in the group whose BMI was <23 kg/m2. The serum PSA showed a significant inverse relationship in those with BMI of ≧23 kg/m2. However, this finding was only true among 40- to 59-year-old middle aged men and no such relationship between serum PSA and BMI was seen in the older groups (60–79 years of age). Conclusion: Our study revealed serum PSA had a significant inverse relationship with BMI in overweight and obese men aged between 40 and 59 years; however, there was no relationship between serum PSA and BMI in men whose age was older than 60 years.
Preoperative, Postoperative and One-Year Follow-Up of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Volume Overload of Aortic Regurgitation: Comparison with Pressure Overload of Aortic Stenosis
Authors: Song Bong Gun , Park Yong Hwan , Kang Gu Hyun , Chun Woo Jung , Oh Ju Hyeon , Choi Jin-Oh , Lee Sang-Chol , Park Seung Woo , Oh Jae K. , Sung Ki Ick , Park PyoWon , Jeon Eun-Seok
Published: September 2010

Objectives: Limited data are available regarding the impact of pressure or volume overload on the clinical or echocardiographic parameters and the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with chronic severe aortic valve diseases. We aimed to investigate and compare the relationships between these parameters in such patients. Methods: One hundred twenty-four consecutive patients who underwent aortic valve replacement for chronic severe aortic valve diseases were enrolled. Plasma NT- proBNP was measured and echocardiographic parameters were recorded before surgery, before discharge and 12 months after surgery. Results: NT-proBNP levels were significantly higher in patients with aortic regurgitation (AR) (n = 63) than in those with aortic stenosis (n = 61) (1,836.0 ± 376.1 vs. 508.4 ± 74.5 pg/ml, p = 0.001). There was a significant relationship between NT-proBNP levels and left ventricular mass index (LVMI) in AR (r = 0.436, p = 0.002) and a weaker, but significant, relationship between NT-proBNP levels and LVMI in aortic stenosis patients (r = 0.290, p = 0.046). In the AR group, preoperative NT-proBNP levels positively correlated with LVMI regression during the 12 months after surgery (r = 0.488, p = 0.001). Conclusion: NT-proBNP levels may reflect LVMI changes that are caused by volume overload rather than pressure overload in chronic aortic valve diseases. Higher preoperative NT-proBNP levels may predict left ventricular reverse remodeling early after surgery for chronic severe AR.
Investigative Clinical Study on Prostate Cancer Part II: On the Role of the Pretreatment Total PSA to Free Testosterone Ratio as a Marker Assessing Prostate Cancer Prognostic Groups after Radical Retropubic Prostatectomy
Authors: Porcaro Antonio B. , Monaco Carmelo , Romano Mario , Petrozziello Aldo , Rubilotta Emanuele , Lacola Vincenzo , Sava Teodoro , Ghimenton Claudio , Caruso Beatrice , Antoniolli Stefano Zecchini , Migliorini Filippo , Comunale Luigi
Published: September 2010

Objectives: To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. Patients and Methods: 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. Results: The average age was 65.80 (range 51.21–77.26) years, mean PSA was 8.88 (range 1.22–44.27) µg/l, mean FT was 35.32 (range 13.70–69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04–1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≧0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Conclusions: Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS.
Does Current Oral Antiplatelet Agent or Subtherapeutic Anticoagulation Use Have an Effect on Tissue-Plasminogen-Activator-Mediated Recanalization Rate in Patients with Acute Ischemic Stroke?
Authors: Ibrahim Mohamed M. , Sebastian Joseph , Hussain Muhammad , Al-Hussain Fawaz , Uchino Ken , Molina Carlos , Khan Khurshid , Demchuk Andrew M. , Alexandrov Andrei V. , Saqqur Maher ,   for the CLOTBUST Investigators
Published: September 2010

Objective: Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. Methods: We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤2) using χ2 test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Results: Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60%). There was no difference in the rate of symptomatic intracranial hemorrhages in patients on AP agents as compared to those not on AP (9/180, 5% vs. 9/95, 9.5%) (p = 0.13). A good long-term outcome (mRS ≤2) was achieved in 85/160 (53%) of the patients naïve to AP and in 33/84 (39%) of the patients on AP (p = 0.035). In multiple regression, AP use was not a predictor of either recanalization rate (p = 0.057) or good outcome (p = 0.27). Conclusions: No correlation was found between AP use and recanalization rate and good outcome in patients with acute stroke who received IV rt-PA treatment. Prior AP use should not defer patients from receiving IV rt-PA treatment in an acute stroke setting.
Prevalence of Twiddler’s Syndrome as a Cause of Deep Brain Stimulation Hardware Failure
Authors: Burdick Adam P. , Okun Michael S. , Haq Ihtsham U. , Ward Herbert E. , Bova Frank , Jacobson Charles E. , Bowers Dawn , Zeilman Pam , Foote Kelly D.
Published: September 2010

We reviewed our deep brain stimulation patient database to describe hardware complications which resulted from implantable pulse generator mobility, a phenomenon referred to as twiddler’s syndrome. A prospectively collected database of adverse events for all patients operated on at the University of Florida was queried searching for hardware malfunctions. Of 362 total leads implanted in 226 patients since 2002, there were 17 hardware malfunctions. Three of them were due to twiddler’s syndrome, representing 1.3% of patients (3 of 226 patients) and 1.4% of leads (5 of 362 leads). The subjects had characteristic presentations including re-emergence of symptoms, pain along the path of the hardware, abnormal impedances/current drain and radiographic signs of twisting/fracture. In all cases securing the implantable pulse generator within the chest pocket resolved the issue. Twiddler’s syndrome in the population of movement disorder patients treated with deep brain stimulation is an uncommon but important adverse event. It possesses a characteristic presentation and with appropriate diagnostic evaluation it is treatable and future occurrences are preventable.
Predicting Acute Affective Symptoms after Deep Brain Stimulation Surgery in Parkinson’s Disease
Authors: Schneider Frank , Reske Martina , Finkelmeyer Andreas , Wojtecki Lars , Timmermann Lars , Brosig Timo , Backes Volker , Amir-Manavi Atoosa , Sturm Volker , Habel Ute , Schnitzler Alfons
Published: September 2010

The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson’s disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.
Sevelamer Carbonate Reduces Inflammation and Endotoxemia in an Animal Model of Uremia
Authors: Hauser Aline B. , Azevedo Iuly R.F. , Gonçalves Simone , Stinghen Andréa , Aita Carlos , Pecoits-Filho Roberto
Published: September 2010

Background: Renal failure is associated with activation of inflammatory response, but the mechanisms behind this observation and potential anti-inflammatory strategies are yet to be defined. Endotoxin (ET) translocation from the intestinal lumen can potentially trigger systemic inflammatory response, and ET binding represents a potential anti-inflammatory strategy in renal failure. The aim of this study was to evaluate the ET-binding capacity of sevelamer carbonate in an animal model of renal failure. Material and Methods: Rats were 5/6 nephrectomized to induce uremia (U) and sham-operated rats were allocated to receive normal chow (controls) or a diet with 3% sevelamer carbonate added (+SC) for 60 days. Tumor necrosis factor-α (TNF-α) and ET were measured in plasma on days 7, 30 and 60 in all animals. Results: Renal failure induced an inflammatory response, since TNF-α levels were undetectable in all control animals in contrast to the uremic group (3.18 ± 0.62, 2.58 ± 0.54 and 1.86 ± 0.47 pg/ml, respectively, on days 7, 30 and 60; p < 0.05 at all time points). Similarly, uremic rats presented an increase in ET levels (0.038 ± 0.007 EU/ml) when compared to sham-operated animals (0.008 ± 0.006 EU/ml; p < 0.05). During the study, TNF-α levels in U + SC rats were significantly lower compared with U-control animals (p < 0.05). Similarly, ET levels in U + SC rats were lower when compared with U-control rats (p < 0.005). Conclusion: In conclusion, induction of renal failure triggered inflammation and induced endotoxemia in this experimental model of chronic kidney disease, which were reduced by sevelamer treatment. This data suggests that sevelamer carbonate induces an anti-inflammatory effect in parallel to a reduction in ET.