26 research outputs found
The role of inflammatory mediators in the overactive and bladder pain syndromes
No full textThe Overactive Bladder (OAB) and Bladder Pain Syndrome (BPS) are debilitating disorders for which the pathophysiological mechanisms are poorly understood. Injury or dysfunction of the protective urothelial barrier layer, specifically the proteoglycan composition and number, has been proposed as the primary pathological characteristic of BPS. For OAB, the myogenic theory with dysfunction of the muscarinic receptors is the most reiterated hypothesis. For both over activity of the inflammatory response has been posited to play a major role in these diseases. We hypothesise that BPS and OAB are peripheral sensory disorders, with an increase in inflammatory mediators, such as cytokines and chemokines, which are capable of activating, either directly or indirectly, sensory nerve activity causing the disease. The aim of the PhD is to identify potential new therapeutic targets for the treatment of BPS and OAB. We used medium throughput quantitative gene expression analysis of 96 inflammation associated mediators to measure gene expression levels in BPS and OAB bladder biopsies and compared them to control samples. Then we created a novel animal model of disease by specific proteoglycan deglycosylation of the bladder mucosal barrier, using the bacterial enzymes Chondroitinase ABC and Heparanase III. These enzymes specifically remove the glycosaminoglycan side chains from the urothelial proteoglycan molecules. We tested role of the identified mediators in this animal model. In addition, in order to determine on which patients peripheral treatment strategies may work, we assessed the effect of local anaesthetics on patients with bladder pain. Gene expression analysis did not reveal a difference in inflammatory genes in the OAB versus control biopsies. However, several genes were upregulated in BPS versus control samples, from which two genes, FGF7 and CLL21 were correlated with patient clinical phenotypes for ICS/PI symptom and problem indices respectively. In order to determine which patients are likely to respond to treatment, we sought to characterise the bladder pain in BPS patients. Using urodynamics and local anaesthetics, we differentiated patients with peripherally mediated pain and patients with central sensitisation of their pain. Finally to determine the role of these mediators in bladder pain, we created an animal model of disease, which specifically replicates the human pathology: namely disruption in the barrier proteoglycan molecules. CCL21 led to an increase in painrelated behaviour, while FGF7 attenuated this behaviour, as measured by cystometry, spinal c-fos expression and mechanical withdrawal threshold examination. In conclusion, we have identified CCL21 and FGF7 as potential targets for the treatment of BPS. Manipulation of these ligands or their receptors may prove to be valuable previously unexploited targets for the treatment of BPS
Neuromodulation for Pelvic and Urogenital Pain
No full textChronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes
Implications of underactive bladder syndrome for nocturia:Do we need urodynamic assessment?
No full textNocturia is a common urological symptom defined by the International Continence Society (ICS) as “the number of times urine is passed during the main sleep period. Having woken to pass urine for the first time, each urination must be followed by sleep or the intention to sleep. This should be quantified using a bladder diary” [ [1] ]. The prevalence of nocturia is high in both genders and increases with age. Nocturia or nocturnal polyuria can be caused by wide-ranging nonurological factors, such as cardiovascular disease, obstructive sleep apnoea, polypharmacy, or learnt behaviour. These mainly contribute to an increase in the rate of urine production. Alongside these, factors impairing the reservoir function of the bladder need to be considered. Underactive bladder (UAB) is characterized by a slow urinary stream, hesitancy, and straining to void, with or without a feeling of incomplete bladder emptying, sometimes with storage symptoms [ [2] ]. UAB has a varied phenotype, and for many patients with UAB the storage symptoms can be prominent and problematic. Urgency and increased daytime frequency are present in a large proportion of patients, meaning that overactive bladder syndrome (OAB) commonly coexists with UAB.<br/
Manipulating the extracellular matrix: an animal model of the bladder pain syndrome
No full textBladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.</p
Scoliosis : density-equalizing mapping and scientometric analysis
No full textBackground: Publications related to scoliosis have increased enormously. A differentiation between publications of major and minor importance has become difficult even for experts. Scientometric data on developments and tendencies in scoliosis research has not been available to date. The aim of the current study was to evaluate the scientific efforts of scoliosis research both quantitatively and qualitatively.
Methods: Large-scale data analysis, density-equalizing algorithms and scientometric methods were used to evaluate both the quantity and quality of research achievements of scientists studying scoliosis. Density-equalizing algorithms were applied to data retrieved from ISI-Web.
Results: From 1904 to 2007, 8,186 items pertaining to scoliosis were published and included in the database. The studies were published in 76 countries: the USA, the U.K. and Canada being the most productive centers. The Washington University (St. Louis, Missouri) was identified as the most prolific institution during that period, and orthopedics represented by far the most productive medical discipline. "BRADFORD, DS" is the most productive author (146 items), and "DANSEREAU, J" is the author with the highest scientific impact (h-index of 27).
Conclusion: Our results suggest that currently established measures of research output (i.e. impact factor, h-index) should be evaluated critically because phenomena, such as self-citation and co-authorship, distort the results and limit the value of the conclusions that may be drawn from these measures. Qualitative statements are just tractable by the comparison of the parameters with respect to multiple linkages. In order to obtain more objective evaluation tools, new measurements need to be developed
Present status and advances in bladder pain syndrome: central sensitisation and the urinary microbiome
No full textKey content Bladder pain syndrome (BPS) presents as a spectrum of urological symptoms with poorly understood pathophysiology. Bladder mucosal injury secondary to low grade sub-clinical infection is a possible trigger, leading to nociceptive upregulation and, subsequently, central sensitisation. Brain abnormalities associated with BPS suggest that neuropathological brain alterations exist, which may contribute to the perceived pain. Central sensitisation plays a role in the disease pathophysiology via an augmentation in the responsiveness of the central pain signalling neurons. The urinary microbiome is implicated as a trigger for the development and maintenance of BPS. Future directions to improve treatment strategies include stratification of patients with BPS into subtypes such as peripheral or central disease and investigation of the urinary microbiome and bladder barrier replacement. Learning objectives To update clinicians’ knowledge of current research into the urinary microbiome and pain sensitisation in BPS pathophysiology. To understand the biodiversity and abundance of urinary microbes and the role of peripheral and central pain sensitisation, which will help identify future management techniques for BPS. Ethical issues What are the consequences of long-term antibiotics use for BPS management on bacterial resistance
