Tristan Keys

Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia.

PURPOSE We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction. MATERIALS AND METHODS Adult male Sprague-Dawley® rats were divided into control, arterial endothelial injury and arterial endothelial injury with tadalafil treatment groups. The arterial injury and arterial injury-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group received a regular diet. At 8 weeks urodynamic investigation was performed. Bladder tissue was harvested for pharmacological studies, and histological examination of the iliac arteries and bladders was performed. RESULTS Iliac arteries from arterial injury and arterial injury-tadalafil rats showed neointimal formation and luminal occlusion. In the arterial injury group the micturition interval was significantly shorter (mean ± SEM 5.4 ± 0.5 vs 11.1 ± 1.1 minutes), and bladder capacity and voided volume were less than in controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly less after arterial injury than in controls. The arterial injury group showed a significantly increased percent of collagen compared with controls (mean 37.4% ± 1.8% vs 21.5% ± 1.8%). In the arterial injury-tadalafil group intimal formation and luminal occlusion were not prevented. However, there were significant improvements in all functional and morphological parameters compared with the arterial injury group. CONCLUSIONS Arterial occlusive disease may lead to chronic bladder ischemia and bladder hyperactivity. Chronic treatment with tadalafil protects bladder function and morphology, resulting in decreased bladder hyperactivity. If valid for humans, the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia related bladder dysfunction.

Synthetic Mesh in the Surgical Repair of Pelvic Organ Prolapse: Current Status and Future Directions

In light of the recent Food and Drug Administration public health notification regarding complications associated with transvaginally placed mesh for pelvic organ prolapse (POP) repair, we review recent literature to evaluate current outcomes and complication data, analyze the clinical need for mesh on the basis of genetic and biochemical etiologies of POP, and investigate trends of mesh use via an American Urological Association member survey. Mesh-based techniques show better anatomic results than traditional repair of anterior POP, but subjective outcomes are equivalent. Further research and Level I evidence are required before mesh-based repair of POP can be standardized. Adequate surgical training and patient selection should decrease complication rates.

Correlation of Gene Expression with Bladder Capacity in Interstitial Cystitis/Bladder Pain Syndrome

PURPOSE Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. MATERIALS AND METHODS Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. RESULTS A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. CONCLUSIONS Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology.

Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model.

BACKGROUND Postoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model. MATERIAL AND METHODS Laparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 μg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel. RESULTS Treatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation. CONCLUSIONS Keratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.

Re: Post-Implantation Alterations of Polypropylene in the Human: G. Sternschuss, D. R. Ostergard and H. Patel J Urol 2012; 188: 27–32

To the Editor: We believe this article is biased and contains multiple statements that are poorly supported by quality science. No specific criteria for selection of references are listed. Of the 21 references 12 are more than 15 years old. The authors rely heavily on a study by Clavé et al, wherein all samples were from patients with polypropylene (PP) mesh erosion. However, they leave out series where mesh was removed for noninfective reasons, whose investigators concluded, “No graft degradation had occurred in PP [mesh] material. Autologous and cadaveric fascia had the most demonstrable graft degradation.” There are several experimental studies in small and large animals showing that the inflammatory response to large pore polypropylene mesh is short lived and is needed for healing. Furthermore, Clavé et al could perform chemical analysis in only 32 of 84 explants, which is too small a sample for an appropriately powered study. Examples of statements with partial truth include results from the article by Clavé et al taken out of context. The authors emphasize the oxidative process that the mesh undergoes during manufacture and then after implantation (in the subsection entitled “Degradation”). Clavé et al make several statements that their analysis is unable to confirm the oxidative damage of implanted mesh leading to degradation, including, “Several hypotheses concerning the degradation of the PP are described below. None of these, particularly direct oxidation, could be confirmed in this study . . . . The [Fourier transform infrared] analysis neither confirmed nor excluded oxidation of the PP in the in vivo environment.” The argument regarding toxicity is interesting since, if one searches PubMed using the key words polypropylene mesh, vaginal use and toxicity, the only name that comes up is the senior author, as he has used these words liberally in many of his editorials and review articles. This argument is similar to the argument of intact genetic material in the cadaveric fascia and animal derived biodegradable meshes without a single reported case in the urological literature. The authors also cite a study by Frostling et al, which has nothing to do with implanted devices, but actually deals with the aerosolized byproducts of polypropylene production. The animals in that study with measurable toxic substance were directly exposed to aerosolized PP byproducts 6 hours daily 5 days a week for 2 or 3 weeks, which altered glutathione activity in the liver/lungs/brain. There were variable changes in microsomal monooxygenation activity in the different organs. The authors provide no justification for extrapolating these results, obtained under industrial conditions, to implanted mesh toxicity. Furthermore, we could not substantiate the statement regarding mesh degradation at 25C, as the study by Frostling et al relates to degradation at industrial temperature. The authors try to use the ophthalmological literature to support the degradation argument. However, Clavé et al note that ultraviolet radiation leading to deterioration is not

Urological Complications of the Renal Graft

Urological complications represent the most common surgical problems encountered after renal allograft transplantation. These can be categorized into occurring in the early versus the late postoperative period. In either scenario, major open reconstructive procedures have historically been the mainstay for tending to these complications. Fortunately, improvements in technology over time have provided minimally invasive techniques and opportunities for management yielding good outcomes. Nevertheless, the treatment paradigm for addressing urological complications must be tailored to the individual case. This chapter reviews the major urological complications after renal transplantation, reporting on treatment options available.

Do we need new patient reported measures to evaluate lower urinary tract dysfunction

For correspondence: Dr. Tristan R. Keys, Department of Urology, Wake Forest Baptist Health, Medical Center Blvd, Winston Salem, NC 27157, USA. E-mail: tkeys@wakehealth.edu With our current knowledge, lower urinary tract symptoms (LUTS) are thought to be caused by a dysfunction of one or more urological organs such as prostate or bladder. As such, the evaluation of these patients has largely been driven by clinical measures. Recently, there has been a major shift in the understanding and evaluation of lower urinary tract dysfunction (LUTD). More emphasis is given to the patient’s self-report of their symptom severity, and the subsequent impact on their quality of life (QoL). Accurate assessment of the patient’s perspective of their own symptoms becomes paramount, and as such the means by which this is measured must itself be precise.

Transcriptome analysis of bladder biopsy from interstitial cystitis/bladder pain syndrome patients.

Interstitial cystitis and bladder pain syndrome (IC/BPS) are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, the disease etiology is not well understood and providing diagnosis and treatment can be challenging. In our study, published recently in the Journal of Urology (Colaco et al., 2014), we describe the use of microarrays as a tool to characterize IC/BPS and to determine if there are clinical factors that correlate with gene expression. This data-in-brief article describes the methodology for that study, including data analysis, in further detail. Deposited data can be found in the Gene Expression Omnibus (GEO) database: GSE57560.