Scandinavian journal of urology and nephrology. Supplementum最新文献

From the oncologist's perspective an interesting development has occurred during the last 10 years regarding the treatment of prostate cancer. In patients with localized prostate cancer the combination of neo-adjuvant hormonal therapy and radiotherapy has been associated with improved survival compared to radiotherapy alone. As prostate cancer patients treated with low doses of external beam radiotherapy, e.g. 70 Gy, have a risk of tumour-like cells remaining in the prostate, there has been renewed interest in the use of dose-escalation radiotherapy for treating localized prostate cancer using various techniques. The reported results indicate benefits in terms of metastasis-free survival and also suggest improved overall survival. New chemotherapy drugs, e.g. mitoxantrone and taxans, are presently being tested in hormone-refractory prostate cancer and hopefully will improve outcomes. Fascinating results have been reported with the combination of radioisotopes and chemotherapy. These results will hopefully add new options for the treatment of prostate cancer. The present overview deals with some of these aspects.

A growing number of patients with pelvic organ dysfunction and failing response to standard treatment concepts are referred to special neuro-urology services. New therapeutic options are available, such as unilateral and bilateral sacral nerve stimulation, and the use of different neurotoxins for the overactive bladder. However, a lack of knowledge and understanding in central innervation and modulation of pelvic organ function prevents a striking progress in this clinical area. A concept of efferent innervation of pelvic organs based on experimental animal studies, using the retrograde, transneuronal and self-amplifying tracer Pseudorabiesvirus, is discussed in a clinical context.

Objective: The overactive bladder is a widespread medical condition with significant quality of life and financial impact. Despite this much remains unknown about the epidemiology and pathophysiology of this condition. This review gives an overview of the current knowledge base and the recent terminology changes approved by the international continence society.

Methods: Critical review of the literature regarding aetiology, epidemiology, urodynamic and clinical aspects of detrusor overactivity. Explanation of the recently adopted terminology.

Results: The term "overactive bladder" has replaced the term "unstable bladder", which held no intuitive meaning. "Detrusor overactivity" is the corresponding urodynamic term, replacing "detrusor instability" and "detrusor hyperreflexia". Knowledge regarding the epidemiology of the overactive bladder is limited. The myogenic and neurogenic theories of pathophysiology require further evidence.

Conclusion: Massive research efforts are required into all aspects of this common chronic disease. The adoption of new ICS terminology will aid consistency in research.

The micturition reflex can be initiated by contraction or distension of detrusor smooth muscle cells, or by signals from the urothelium. It has been shown that bladder distension causes release of ATP from the urothelium, and that ATP can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, most probably the activation of afferent fibres during bladder filling involves not only ATP, but a cascade of inhibitory and stimulatory transmitters/mediators. These mechanisms may be targets for future drugs. Both in the normal and functionally disturbed bladder, muscarinic receptor stimulation produces the main part of detrusor contraction, but evidence is accumulating that in disease states, such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, interstitial cystitis, and also in the ageing bladder, a non-cholinergic activation via purinergic receptors may occur. If this component of activation is responsible not only for part of the bladder contractions, but also for the symptoms of the overactive bladder, it should be considered an important target for therapeutic interventions. Drags blocking different P2X receptor subtypes, or counteracting bladder contraction via other mechanisms, e.g. beta3-adrenoceptor stimulation, may be developed for treatment of the overactive bladder.

Objective: The aim of our study of the pig was to investigate the responses of smooth muscle of the bladder and the urethral sphincter to preganglionic parasympathetic stimulation, and to assess the effect on the lower urinary tract of IV administration of alpha,beta-methylene-ATP.

Materials and methods: In seven anaesthetised female pigs, the responses to repeated 20 s pelvic nerve stimulations before and after IV administration of 0.02 mg/kg alpha-beta-methylene-ATP, and the responses to the drug itself, were recorded in the bladder and the urethra separately.

Results: In the urethral high-pressure zone, pre-stimulation pressure was a mean of 61+/-11 cmH2O. During pelvic nerve stimulation, urethral pressure declined by 48+/-9 cmH2O, while the bladder pressure increased to 30+/-18 cmH2O. The rate of pressure changes during the first 3 s of stimulation (initiation of voiding) was larger in the urethra than in the bladder (urethral pressure decrease: 13.0+/-3.1 cmH2O/s, bladder pressure increase: 3.2+/-2.5 cmH2O/s). Administration of alpha,beta-methylene-ATP was followed by a significant but temporary enlargement in the bladder response to pelvic nerve stimulation to 36+/-20 cmH2O, p = 0.028, n = 7, but no change in urethral response.

Conclusions: At least 80% of the urethral pre-stimulation pressure was exerted by the smooth muscle. The synergic activation of the detrusor and the urethral smooth muscle in response to preganglionic parasympathetic nerve stimulation was controlled by the peripheral nerves or by the neuromuscular transmission. Administration of alpha,beta-methylene-ATP increased the bladder response to pelvic nerve stimulation without changing the urethral response.

Filling at physiological rates (natural filling) is the specific stimulus for activation of the micturition reflex. In urodynamic studies this has rarely been taken into consideration. In the vast majority of clinical urodynamic studies 50 ml/min has been the preferred filling rate. A comparative study in 17 healthy volunteers of cystometry at 50 and 100 ml/min (CMG) and ambulatory monitoring (AM) during natural filling has been performed by other authors (3). It was found that CMG increases volume threshold for micturition, impairs detrusor contractility and has lower sensitivity for detecting spontaneous phasic detrusor activity. These results are discussed in the present article. The nearest explanation is at the cellular level. Filling rates above physiological range (> 15 HD (Hour-Diuresis units)) are a mechanical trauma to receptors, nerve endings, cells and cell junctions, which are temporarily functionally disturbed.

Experimental and clinical studies have shown that the cerebellum participates in the regulation of various visceral responses, including micturition. It is not yet clear through which parts of the central nervous system such cerebellar influences are mediated. However, a series of investigations have shown that the cerebellum is directly or indirectly connected to various centres that appear to be involved in autonomic control. These include parts of the cerebral cortex, the hypothalamus, the periaquaductal grey, nuclei in and around the pontine micturition centre, the dorsal vagal nucleus and nucleus of the solitary tract, and the medullary reticular formation. This article examines some of the circuits that may be involved in cerebellar modulation of visceral reflexes, especially the micturition reflex.