Mohammad S. Rahnama'i

The additional value of ambulatory urodynamic measurements compared with conventional urodynamic measurements

Study Type – Diagnostic (exploratory cohort)

The role of prostanoids in urinary bladder physiology

Five primary prostanoids are synthesized by the cyclooxygenase enzymes, COX-1 and COX-2: the prostaglandins PGE2, PGF2α, PGI2, PGD2 and thromboxane A2. High levels of these signaling molecules have been implicated—in both animal models and human studies—in decreased functional bladder capacity and micturition volume and increased voiding contraction amplitude. Thus, inhibition of prostanoid production or the use of prostanoid receptor antagonists, might be a rational way to treat patients with detrusor muscle overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity. Although some promising results have been reported, the adverse effects of nonselective cyclooxygenase inhibitors are a major concern that restricts their use in the treatment of functional bladder disorders. Further preclinical and clinical studies are needed before cyclooxygenase inhibitors, prostanoid receptor agonists and antagonists become worthwhile therapeutic tools in this setting.

Functional Detrusor Myoplasty for Bladder Acontractility: Long-Term Results

PURPOSE We present the long-term results of a multicenter investigation with latissimus dorsi detrusor myoplasty in patients with bladder acontractility caused by lower motor neuron lesion in whom there is no treatment alternative other than lifelong clean intermittent catheterization. MATERIALS AND METHODS From 2001 to 2008, 24 patients (median age 39 years, range 13 to 63, 16 males, 8 females) requiring complete clean intermittent catheterization 4 to 7 times daily underwent latissimus dorsi detrusor myoplasty at 4 centers worldwide. Before the procedure patients were on clean intermittent catheterization for a median of 55 months (range 17 to 195). Median followup was 46 months (range 8 to 89) and was performed by urodynamics and measurement of post-void residual urine volume. Bladder contractility index was calculated. The t test was used for statistical analysis. RESULTS Of the 24 patients 17 (71%) gained complete spontaneous voiding with a mean post-void residual urine volume of 25 ml (range 0 to 100). Mean bladder contractility index increased from 20.1 ± 7.6 to 176.2 ± 25.4 (p <0.001). In 3 patients (13%) the frequency of clean intermittent catheterization was reduced to 2 to 4 times daily with a mean post-void residual urine volume of 200 ml (range 150 to 250). Mean bladder contractility index was 12.0 ± 7.2 preoperatively and 68.7 ± 28.1 postoperatively (p = 0.12). Recurrent urinary tract infections (defined as the presence of clinical symptoms such as dysuria and fever, and microbiological evidence of germs) ceased in 21 of 23 patients (91%, mean preoperatively 8 per year). Four patients (17%) required clean intermittent catheterization with the same frequency as before the procedure (mean bladder contractility index preoperatively 22.5 ± 10.3 and postoperatively 26.0 ± 12.3, p = 0.83). No chronic pain at the donor site or vesicoureteral reflux was observed in any patient. CONCLUSIONS The results of this multicenter analysis demonstrate that latissimus dorsi detrusor myoplasty is an effective alternative to clean intermittent catheterization in a select group of patients with neurogenic bladder acontractility.

The Relationship Between Prostaglandin E Receptor 1 and Cyclooxygenase I Expression in Guinea Pig Bladder Interstitial Cells: Proposition of a Signal Propagation System

PURPOSE We explored the structural relationship between enzymes producing prostaglandin (cyclooxygenase I) and 1 of the receptor families that respond to prostaglandin (prostaglandin E receptor 1) in the bladder muscle. MATERIALS AND METHODS Nine male guinea pigs were sacrificed by cervical dislocation. Bladders were removed and fixed in 4% paraformaldehyde in phosphate buffered saline. Frozen sections (10 μm) were cut and stained with antibodies to prostaglandin E receptor type 1, cyclooxygenase I and vimentin. RESULTS Prostaglandin E receptors 1 was identified on smooth muscle cells, and vimentin positive surface muscle and intramuscular interstitial cells. Muscle staining was less intense than on interstitial cells and had a punctuate appearance. Prostaglandin E receptor 1 expression on interstitial cells was highly localized. Discrete regions of intense staining were noted on interstitial cell processes. Cyclooxygenase I was also expressed in muscle interstitial cells. Cyclooxygenase I positive interstitial cells were more prevalent in the muscle bundles of the inner muscle than in the outer muscle layers. Cyclooxygenase I staining was noted on discrete regions of the cell or cell processes. Double staining with prostaglandin E receptor 1 and cyclooxygenase I suggested that cell regions expressing the former are different from those expressing the latter. CONCLUSIONS The discovered arrangement of prostaglandin E receptor 1 and cyclooxygenase I may have the potential to facilitate the propagation of signals in the interstitial cell network. Such a signaling system may have a role in coordinating events, as in bladder pathology, facilitating the global coordinated changes associated with bladder wall remodeling.

Scrotal Approach to Both Palpable and Impalpable Undescended Testes: Should It Become Our First Choice?

OBJECTIVES To determine the advantages of scrotal incision in the treatment of undescended testis. Undescended testis is a common pediatric condition and is conventionally managed surgically by orchidopexy. A single scrotal incision orchidopexy has become accepted as a valid approach for patients with palpable undescended testicles. Because this approach also allows easy detection of atrophic testes or testicular remnants, it recently has also emerged as an alternative initial surgical approach to impalpable undescended testicles. METHODS All orchidopexies performed between 2004 and 2008 at our university hospital were prospectively included in this study. A total of 194 scrotal orchidopexies were performed in 154 patients (mean age, 71 months; range, 4-229 months). In all cases a scrotal approach was chosen irrespective of the initial position or presence of an open processus vaginalis. Testicular position was examined at follow-up after a mean period of 10 months (3-22 months). RESULTS Overall, 36 of the 46 impalpable testicles (78%) could be diagnosed and treated accordingly, using only a scrotal incision. Conversion to laparoscopy was needed in 4 cases. A limited number of postoperative complications were seen. In all cases, the testes were palpable and remained in the scrotum on follow-up. CONCLUSIONS Initial single scrotal incision can be recommended for orchidopexy, even in the more difficult cases of impalpable undescended testes. Advantages seem to include shorter operative time, a cosmetically appealing single incision, and possibly less pain. The scrotal incision technique significantly reduces the need for laparoscopy in impalpable testes. Surprisingly, it even allows successful orchidopexy of abdominal testes, provided an open processus is present.

The role of phosphodiesterases in bladder pathophysiology

Nitric oxide and the cyclic nucleotide monophosphates cAMP and cGMP have a role in control of the micturition process and hence, are suggested to be involved in the pathophysiology of storage and voiding disorders. Phosphodiesterase enzymes (PDEs) hydrolyse cAMP and cGMP. Inhibition of PDEs increases cAMP and cGMP levels and relaxes urinary bladder smooth musculature. Although many preclinical studies have been conducted, to date, only PDE1 and PDE5 inhibitors have been tested clinically for the management of storage and voiding disorders. Treatment with PDE1 inhibitors might improve micturition frequency in patients with overactive bladder, whereas inhibition of PDE5 improves lower urinary tract symptoms in men, either with or without BPH and erectile dysfunction (ED). Furthermore, the combination of a PDE5 inhibitor and an α-adrenoceptor antagonist has superior efficacy to monotherapy with either agent. However, the role of PDE5 inhibitors in the treatment of women with detrusor overactivity remains unclear. The clinical application of agents that inhibit other PDEs, including PDE4, also certainly merits scientific attention. PDE inhibitors seem likely to become a valuable alternative treatment for patients with storage and voiding disorders in the future.

Overactive Bladder Syndrome and the Potential Role of Prostaglandins and Phosphodiesterases: An Introduction

In this paper, a general introduction is given, presenting the overactive bladder syndrome (OAB) and its impact on the quality of life and economical burden in patients affected. Moreover, the anatomy, physiology and histology of the lower urinary tract are discussed, followed by a brief overview on the possible role of prostaglandin (PG) and phosphodiesterase type 5 (PDE5) in the urinary bladder. The current literature on the role and distribution of PGE2 and its receptors in the urinary bladder is discussed. In both animal models and in human studies, high levels of signaling molecules such as PG and cGMP have been implicated, in decreased functional bladder capacity and micturition volume, as well as in increased voiding contraction amplitude. As a consequence, inhibition of prostanoid production, the use of prostanoid receptor antagonists, or PDE inhibitors might be a rational way to treat patients with detrusor overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity.

The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015

The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications.

Can we create a valid treatment algorithm for patients with drug resistant overactive bladder (OAB) syndrome or detrusor overactivity (DO)? Results from a think tank (ICI‐RS 2015)

To review and assess the definitions of drug resistance and the evidence supporting treatment for drug resistant overactive bladder/detrusor overactivity (OAB/DO).

Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014.

The use of botulinum toxin A (BoNT/A) is commonplace now in the management of refractory overactive bladder and neurogenic detrusor overactivity (NDO). Despite one formulation now having a license, the full mechanism of action is not fully understood. Furthermore practice varies worldwide in the way the toxin is delivered to the bladder. At the ICI‐RS 2014 Meeting in Bristol, UK a Think Tank session was conducted on the topic of “Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder?” This manuscript reflects the Think Tanks summary and opinion.