Muscarinic receptors in the lower urinary tract

This thesis, comprising of clinical studies, basic research as well as review of data, has aimed to provide further insight into the role and function of muscarinic receptors in the lower urinary tract. In light of increasing evidence of beneficial effects of combinations of pharmacological therapies for lower urinary tract symptoms (LUTS), understanding mechanisms of action and interaction are crucial to maximize its therapeutic potency. The first part of this thesis focusses on the prostate, the second part on interaction of muscarinic and adrenergic signaling and the last part focusing on muscarinic antagonists in clinical practice. As muscarinic receptors are abundantly present in the prostate, and antimuscarinic therapy is increasingly used in male patients with LUTS, direct effects of antimuscarinics on the prostate need to be considered. Thereby we demonstrate that muscarinic receptors cause direct contraction and inhibition of relaxation in the bladder, but the two responses involve different subtypes and, at least for M3 receptors, different signaling pathways. The α1-adrenoceptor antagonist effects of muscarinic antagonist propiverine are explored and demonstrated, although these effects need to be confirmed in patients. In the third part we demonstrate that solifenacin, and perhaps other muscarinic receptor antagonists are similarly suitable for the treatment of OAB symptoms in both genders, irrespective of previous vaginal deliveries. Finally an overview is presented of antimuscarinics at risk for reduced tolerability in special patient populations, e.g. in those with impaired renal or liver function or those with comedications or genetic heterogeneity in drug metabolizing enzymes

Crioablación laparoscópica de las pequeñas masas renales

To review the current status of cryoablation of small renal masses and to preliminary report our experience at the AMC. Material and methods: A bibliographic search was conducted (PubMed/Medline/Embase) and the most important series were analyzed. Our series includes 13 patients with a solitary small renal mass treated by Laparoscopic assisted Cryoblation with fine cryoprobes (1,5 cm diameter). Postoperative follow-up was done by means of CT and/or MRI every three months during the first year and every 6 months during the second year. Results: There are no randomized trials comparing Cryoblation of renal masses

Crioablación laparoscópica de las pequeñas masas renales

To review the current status of cryoablation of small renal masses and to preliminary report our experience at the AMC. Material and methods: A bibliographic search was conducted (PubMed/Medline/Embase) and the most important series were analyzed. Our series includes 13 patients with a solitary small renal mass treated by Laparoscopic assisted Cryoblation with fine cryoprobes (1,5 cm diameter). Postoperative follow-up was done by means of CT and/or MRI every three months during the first year and every 6 months during the second year. Results: There are no randomized trials comparing Cryoblation of renal masses

The performance of 17-gauge cryoprobes in vitro

In cryosurgery it is crucial that the performance of cryoprobes is predictable and constant. In this study we tested the intra- and interneedle variation between 17-gauge cryoprobes in two homogeneous mediums. Also, a multiprobe setup was tested. Cryoprobe performance was defined as the time it takes one cryoprobe to lower the temperature from 0 to -20 degrees C as measured by four thermosensors each at 3 mm distance from the cryoprobe. In agar eight cryoprobes were tested during six freeze cycles, and in gel four cryoprobes during four freeze cycles; each freeze cycle in a different cup of agar or gel. Using more accurate 'bare' thermosensors three cryoprobes were tested in gel during two freeze cycles. A multiprobe configuration with four cryoprobes was tested during two freeze cycles in both agar and gel. Statistical analyses were done using ANOVA for repeated measures. There was no significant intraneedle variation, whereas both in agar and gel there was a significant interneedle variation (

The test-retest reproducibility of the multiple array probe Leiden in men with lower urinary tract symptoms

BackgroundWe aimed to study the test-retest reliability of the Multiple Array Probe Leiden (MAPLe), a multiple electrode probe designed to acquire and discriminate electromyography signals in the pelvic floor muscles, in men with lower urinary tract symptoms (LUTS). MethodsAdult male patients with LUTS with sufficient knowledge of Dutch language, but without complications (e.g., urinary tract infection), or previous urologic cancer and/or urologic surgery were enrolled. In the initial study, next to physical examination and uroflowmetry, all men underwent MAPLe assessment at baseline and after 6 weeks. Second, participants were reinvited for a new assessment using a stricter protocol. A time interval of 2 h (M2) and 1 week (M3) after baseline (M1) allowed the calculation of the intraday agreement (M1 vs. M2), and the interday agreement (M1 vs. M3) for all 13 MAPLe variables. ResultsThe outcomes of the initial study in 21 men suggested a poor test-retest reliability. The second study in 23 men showed a good test-retest reliability with intraclass correlations ranging from 0.61 (0.12-0.86) to 0.91 (0.81-0.96). The agreement was generally higher for the intraday determinations than for the interday determinations. ConclusionsThis study revealed a good test-retest reliability of the MAPLe device in men with LUTS, when using a strict protocol. With a less strict protocol, the test-retest reliability of MAPLe was poor in this sample. To make valid interpretations of this device in a clinical or research setting, a strict protocol is needed