Explicaciòn de la docente del tema: Factorización 2 Juego: Tingo Tango para las tablas de multiplicar

Ethical approval was obtained from Camden and Islington Community NHS Trust Research Ethics committee. The study was performed at St Paneras Hospital. The first twelve studies were performed by Dr Adrian Wagg- the author then performed all subsequent studies.

The study used the same basic design throughout the different subgroups. Women undergoing urodynamic testing as part o f the investigation o f lower urinary tract symptoms were recruited. An information sheet was given and a consent form signed (appendix 1). A standardised basic neurological

examination was performed (appendix 1).

A standardised history protocol was filled in, including urgency. Urgency is defined as a sudden compelling desire pass urine, which is difficult to defer. The history was taken by the author, and standardised questions asked. Urgency was described in interview as 'a sudden need to pass urine, with a feeling that you can't hang on'. In our protocol, the symptom was divided into mild, moderate or severe (or absent). These were not defined more closely. This follows the classification used in previous work from this unit. A frequency volume chart was filed in prior to attendance at the clinic, again as part o f the standard clinic protocol in use at the time o f the study.

The definitions used for urodynamics were those o f ICS (Abrams et al 1988 then Abrams et al 2002). -Thus detrusor overactivity was defined as a urodynamic observation characterised by involuntary detrusor contractions during the filling phase which may be spontaneous or provoked. I have used this term throughout without reference to causation. Some o f the published

work suggests that patients with overactive bladders may represent a different subgroup with respect to their susceptibility to local biochemical change. For example, the work o f Sethia and Smith (1977) suggested that subjects with detrusor overactivity may be more susceptible to the effects o f pH than patients with stable bladders. At the beginning o f the study, the vast majority o f women examined had stable bladders, as a large part o f the practice at the time was preoperative assessments for stress incontinence surgery. The first study to be performed was the intracellular and extracellular pH modification study.

Following this part o f the study, the recruitment procedure was changed in order to attempt to recruit more women with detrusor overactivity. Patients with symptoms o f urgency or mixed symptoms on referral letters were selected for research clinics. If there was a history o f neurological disease, they were not selected. It was felt that patients with neurological cause for their bladder overactivity could well, on the basis o f previous literature, represent a separate subgroup and it was unlikely that the requisite numbers would be obtained to make any part o f the study significant for this group. Therefore it was

T e s t so lu tio n via c a th ete r to h ea tin g co il in w a te r b ath at 3 7 C Control so lu tio n h e a te d in w a ter bath

Figure 3.1- Modified urodynamies setup

G a s from cylin d er p ip ed into te s t so lu tio n s Control or te s t so lu tio n via c o n n e c to r to urodynam ic pum p and th e n to filling ca th eter P atient

The basic urodynamic set-up was modified (figure 3.1) to accommodate a water bath to keep the solutions at 37C, and a mechanism for changing the test

solutions. The solutions were kept at 37C in an attempt to reduce the variables from the ‘physiological norm’. The solutions were then pumped by the standard pump via an extended tubing round a coil (8 coils around a 10 cm by 10 cm plastic coil holder) in the water bath, and then via an extension tube to the catheterised subject. The gas was bubbled via sterile catheter tubing into the bottles, and the tubing held in place by a specially designed weighted collar.

This then allowed the catheter to be moved from one solution to the other between fills, without detaching it from the connector tubing and the heating coil. These elements were changed between patients, but not between fills for the same patient. The solutions were left in the water bath for 40 minutes prior to the study, and the designated gas was bubbled during this time. This was 95% O2, 5% CO2 for the normocapnie studies- the extracellular alkalosis study and the normocapnie control in the intracellular acidosis study. In the

hypercapnie test solution for the intracellular acidosis study the gas used was 80% O2, 20% CO2 (see section 3.2). EarUer experiments performed by Dr Adrian Wagg investigated the drop in temperature from bottle to catheter with a temperature probe and found that there was at most a 1.1C drop in temperature over the time o f filling. (A Wagg, personal communication). The solutions were made up in glass bottles, pre ordered from the sterile pharmaceutical department o f Camden and Islington Community NHS Trust. The 8.4% bicarbonate was added at the time o f use by syringe and quill. ( details in section 3.2). pH was measured by a Jenway 3030 pH meter calibrated before each session. The pH measurements were made immediately after the study on residual solution, for reasons o f sterility. This is discussed further in section 5.6.

Standard urodynamic testing was performed. This was as follows- The patient attended with a full bladder. A free flow void was performed, then residual catheterisation performed with a CHIO Nelaton Jaques Catheter and a single lumen transducer catheter (CH6) simultaneously. The rectum was then

catheterised using a standard rectal transducer line. The catheters were secured, and the patient transferred to a commode. The bladder was then filled using 2 or 3 filling solutions in order to modify the intravesical environment. The bladder

was filled at 50 mls/minute to cystometric capacity, then at the end o f the first fill, the filling catheter was detached from the urodynamic filling tube, and the bladder emptied. The fill was then repeated immediately using the next solution, which was connected at the bottle, and had been pre-warmed in the water bath. The filling solutions were used in orders dictated by random allocation from random number tables. The intracellular and extracellular pH modification study pH change used three fills. Other studies used two fills. The patient was blinded to the nature o f the filling solution. During filling, the following sensations were noted- first sensation o f filling (FSF), first desire to void (FDV), urgency and cystometric capacity (CC). The bladder was filled until a maximum o f 500 ml had been infused, unstable detrusor activity prohibited further filling, or discomfort prevented further filling. The void was only performed after the final fill. The solutions were bubbled with the appropriate gas for 20 minutes prior to the test to allow saturation. The voided solution was not checked for osmolality, pH or composition in general.

The urodynamic tests were performed on two machines. Initially, a tailor made machine with software designed by UCL staff was used. This acquired data at 8 Hz on all channels and ran on a 486 PC. This was used until April 1997 and was also used for all other urodynamics at St Paneras Hospital. The subsequent machine used was a Dantec Duet. This acquires data at 50 Hz for each channel and uses a Butterworth 3 order filter. The transducers used for all experiments were Dantec MX860. These have a sensitivity o f 5 microvolts/ mmHg and a zero drift o f <2mmHg in 4 hours (Dantec, communication).