Painful bladder syndrome/interstitial cystitis.
ABSTRACT Painful bladder syndrome (PBS) is the term used to refer to a chronic symptom complex of urinary frequency and bladder 'pressure', discomfort or pain in the absence of any other reasonable cause for these symptoms (such as infection). Interstitial cystitis (IC) is the established term used by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consensus workshop for which a research definition was formulated in the late 1980s. Opinion varies regarding not only definition but also the usefulness of diagnostic investigations such as urodynamic assessment and the potassium sensitivity test. There are still controversies concerning the most basic investigation of cystoscopy in PBS/IC. New developments in the study of PBS/IC include the identification of a potential urinary biomarker, antiproliferative factor (APF), which is produced by urothelial cells in IC and thought to inhibit proliferation. In addition, condition-specific validated questionnaires should aid evaluation, and a growing number of randomised controlled trials should enable clinicians to use evidence-based therapeutic options.
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ABSTRACT: Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Gene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix--GeneChip Human Genome U133 Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection p-value < 0.05). The difference between the two groups was significant for over 3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression ratio greater than two. The IC pattern had similarities to patterns from immune system, lymphatic, and autoimmune diseases. The dominant biological processes were the immune and inflammatory responses. Many of the up-regulated genes were expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall is a dominant feature of ulcerative IC. Histopathological data supported these findings. GeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC) will further indicate whether the data presented here will be valuable for the diagnosis of IC.BMC Genomics 04/2009; 10:199. · 4.40 Impact Factor
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ABSTRACT: The urinary bladder has certain unique anatomical features which enable it to form an effective barrier to toxic substances diffusing from the urine into the blood. The barrier function is due to the epithelial surface of the urinary bladder, the urothelium, which has characteristic umbrella cells, joined by tight junctions and covered by impenetrable plaques, as well as an anti-adherent mucin layer. Diseases of the urinary bladder, such as bladder carcinomas and interstitial cystitis, cause acute damage to the bladder wall and cannot be effectively treated by systemic administration of drugs. Such conditions may benefit from intravesical drug delivery (IDD), which involves direct instillation of drug into the bladder via a catheter, to attain high local concentrations of the drug with minimal systemic effects. IDD however has its limitations, since the permeability of the urothelial layer is very low and instilled drug solutions become diluted with urine and get washed out of the bladder during voiding, necessitating repeated infusions of the drug. Permeation enhancers serve to overcome these problems to some extent by using electromotive force to enhance diffusion of the drug into the bladder wall or chemical molecules, such as chitosan, dimethylsulphoxide, to temporarily disrupt the tight packing of the urothelium. Nanotechnology can be integrated with IDD to devise drug-encapsulated nanoparticles that can greatly improve chemical interactions with the urothelium and enhance penetration of drugs into the bladder wall. Nanocarriers such as liposomes, gelatin nanoparticles, polymeric nanoparticles and magnetic particles, have been found to enhance local drug concentrations in the bladder as well as target diseased cells. Intravesical drug carriers can be further improved by using mucoadhesive biomaterials which are strongly adhered to the urothelial cell lining, thus preventing the carrier from being washed away during urine voiding. This increases the residence time of the drug at the target site and enables sustained delivery of the drug over a prolonged time span. Polymeric hydrogels, such as the temperature sensitive PEG-PLGA-PEG polymer, have been used to develop in situ gelling systems to deliver drugs into the bladder cavity. Recent advances and future prospects of biodegradable nanocarriers and in situ gels as drug delivery agents for intravesical drug delivery are reviewed in this paper.Journal of Controlled Release 12/2010; 148(2):147-59. · 7.63 Impact Factor
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ABSTRACT: Background This study explores relationships between chronic inflammation and quality of life, making a case for biopsychosocial modeling of these associations. It builds on research from social and clinical disciplines connecting chronic conditions, and inflammatory conditions specifically, to reduced quality of life.Methods Data from Wave I of the National Social Life, Health, and Aging Project are modeled using ordinal logistic and ordinary least-squares regression techniques. Inflammation is measured using C-reactive protein; quality of life is conceptualized as happiness with life overall as well as intimate relationships specifically.ResultsFor most NSHAP participants, chronic inflammation significantly predicts lower odds of reporting high QoL on both emotional and relational measures. Social structural factors do not confound these associations. Inconsistent results for participants with very high (over 6 mg/L) CRP measurements suggest additional social influences.Conclusions Findings echo strong theoretical justification for investigating relationships between CRP and QoL in greater detail. Further research should explore possible mediation of these associations by sociomedical sequelae of chronic disease as well as social relationship dynamics. Elaboration is also needed on the mechanisms by which social disadvantage may cause chronic inflammation.Health and Quality of Life Outcomes 09/2014; 12(1):141. · 2.27 Impact Factor