Association of Atrial Fibrillation with Insomnia in the Elderly Population.

Introduction/objectives: Insomnia is a common sleep disorders that affects most individuals in the United States, and worldwide. Insomnia is linked with an increased risk of atrial fibrillation (AF) in adults, although the strengths of association were weak, especially in the elderly population. AF is estimated to affect approximately 3 to 6 million people in the United States.

Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma.

Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination.

Association of Risk Factors and Comorbidities With Chronic Pain in the Elderly Population.

Introduction/objective: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors.

Comorbidities and Risk Factors Associated With Insomnia in the Elderly Population.

Introduction/objectives: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.

MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.

Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAP) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAP patients show response to pemetrexed (ORR 43%).

Current practices in nutrition management and disease incidence of common marmosets (Callithrix jacchus).

Background: A survey was developed to characterize disease incidence, common pathology lesions, environmental characteristics, and nutrition programs within captive research marmoset colonies.

Methods: Seventeen research facilities completed the electronic survey.

Results: Nutritional management programs varied amongst research institutions housing marmosets; eight primary base diets were reported.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers.

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells.

Phase 1b Trial to Evaluate Tissue Response to a Second Dose of Intravesical Recombinant Adenoviral Interferon α2b Formulated in Syn3 for Failures of Bacillus Calmette-Guerin (BCG) Therapy in Nonmuscle Invasive Bladder Cancer.

Background: A phase 1b trial was conducted to evaluate the duration of interferon-alpha (IFNα) production after intravesical administration of recombinant adenovirus-mediated interferon α2b (Ad-IFN) formulated with the excipient Syn3. The primary aim was to determine whether a second instillation 3 days after initial treatment produced prolonged urinary IFN production.

Methods: The study enrolled seven patients who experienced recurrent non-muscle invasive bladder cancer after bacillus Calmette-Guerin therapy.

Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.

Purpose: A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months.

Detection of bladder cancer using proteomic profiling of urine sediments.

We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium.

Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer.

Expression of low molecular weight (LMW) isoforms of cyclin E is a strong predictor of poor outcome in patients with breast cancer. The purpose of this study was to examine the expression of full-length and LMW cyclin E in bladder cancer cell lines and patient tumors. We used western blotting, immunoprecipitation and kinase assays to examine the expression and activity of key cell cycle-regulatory proteins in various human bladder cell lines, both tumorigenic and non-tumorigenic.

Perioperative and long-term operative outcomes after surgery for trigeminal neuralgia: microvascular decompression vs percutaneous balloon ablation.

Objectives: Numerous medical and surgical therapies have been utilized to treat the symptoms of trigeminal neuralgia (TN). This retrospective study compares patients undergoing either microvascular decompression or balloon ablation of the trigeminal ganglion and determines which produces the best long-term outcomes.

Methods: A 10-year retrospective chart review was performed on patients who underwent microvascular decompression (MVD) or percutaneous balloon ablation (BA) surgery for TN.

Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers.

Phosphorylation of Thr18 and Ser20 of p53 in Ad-p53-induced apoptosis.

The p53 protein plays a critical role in inducing cell cycle arrest or apoptosis. Because p53 is inactivated in human gliomas, restoring p53 function is a major focus of glioma therapy. The most clinically tested strategy for replacing p53 has been adenoviral-mediated p53 gene therapy (Ad-p53).

Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo.

Purpose: RB94, a truncated form of RB110, has enhanced tumor suppressor potency and activity against all tumor types tested to date including bladder carcinoma. However, efficient, systemic delivery of the gene encoding RB94 specifically to tumors, is an obstacle to clinical application as an anticancer therapeutic. We have developed a systemically given, nanosized liposome DNA delivery system that specifically targets primary and metastatic disease.

Intraventricular schwannoma in a 15-year-old adolescent: a case report.

Introduction: Schwannomas are benign tumors that originate from the myelin-forming Schwann cells of peripheral nerves or at the Obersteiner-Redlich zone of the vestibular division of the eighth cranial nerve. Intraventricular schwannomas are rare, particularly among children.

Discussion: This case report illustrates a right occipital horn schwannoma in a 15-year-old adolescent boy who was successfully treated with surgical resection and discusses the possible origins of the tumor in this unique location.

Forerunner genes contiguous to RB1 contribute to the development of in situ neoplasia.

We used human bladder cancer as a model system and the whole-organ histologic and genetic mapping strategy to identify clonal genetic hits associated with growth advantage, tracking the evolution of bladder cancer from intraurothelial precursor lesions. Six putative chromosomal regions critical for clonal expansion of intraurothelial neoplasia and development of bladder cancer were identified by using this approach. Focusing on one of the regions, which includes the model tumor suppressor RB1, we performed allelotyping of single-nucleotide polymorphic sites and identified a 1.

A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses.

Purpose: This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-beta gene transfer using an adenoviral vector (Ad.IFN-beta) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE).

Experimental Design: Ad.

Management of scalp toxic epidermal necrolysis and cranial osteomyelitis with serratus anterior myocutaneous pedicle flap: a case report.

The aim of this report is to describe the management of scalp toxic epidermal necrolysis (TEN) and cranial osteomyelitis complicating malignant glioma therapy. A 21-year-old man developed TEN while being radiated and receiving antineoplastic and anticonvulsant therapies for a malignant intracranial glioma. The strategy used to manage the above situation included withdrawal of the medications causing TEN, meticulous dermatological wound care, resection of residual glioma, debridement of scalp and bone, and reconstruction of the scalp and calvarial defect with a myocutaneous vascularized free flap.

Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro-angiogenic effect of vascular endothelial growth factor in superficial bladder cancer.

Purpose: Intravesical adenovirus mediated interferon-alpha gene transfer has a potent therapeutic effect against superficial human bladder carcinoma xenografts growing in the bladder of athymic nude mice. We determined whether the inhibition of angiogenesis might contribute to the antitumor effect.

Materials And Methods: We treated several human urothelial carcinoma cells with adenovirus mediated interferon-alpha 2b and monitored its effects on the production of angiogenic factors using real-time reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemical analysis and a gel shift based transcription factor array.

Carotid artery pseudoaneurysm resulting from an injury to the neck by a fouled baseball.

Objective: Blunt carotid artery injury resulting in either dissection or pseudoaneurysm is a rare entity that can result in significant morbidity and mortality if undiagnosed. Although unavoidable in certain traumatic situations such as motor vehicle collisions, direct neck trauma in sports may be preventable with the use of proper protective equipment.

Clinical Presentation: The following report documents a case of extracranial carotid artery dissection resulting from a foul ball striking the upper, lateral neck of an umpire.

Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits angiogenesis in human bladder cancer cells.

In a recent study, we showed that the proteasome inhibitor bortezomib sensitizes human bladder cancer cells to IFN-induced cell death. Here, we characterized the molecular mechanisms underlying the antitumoral effects of the combination in more detail. Bortezomib synergized with IFN-alpha to promote apoptosis via a tumor necrosis factor-related apoptosis-inducing ligand-associated mechanism but did not inhibit production of proangiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8) in human UM-UC-5 cells.

Characterization of a panel of cell lines derived from urothelial neoplasms: genetic alterations, growth in vivo and the relationship of adenoviral mediated gene transfer to coxsackie adenovirus receptor expression.

Purpose: Cell lines have become an essential component for the investigation of cancer. We have developed a panel of cell lines derived from human urothelial cancers and we describe some of their important characteristics.

Materials And Methods: Ten human urothelial cancer cell lines were characterized by their growth in athymic nude mice, CAR expression and their susceptibility to adenoviral mediated transfer of the green fluorescence protein gene.

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia.

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia.