Bile acids and pH values in total feces and in fecal water from habitually omnivorous and vegetarian subjects.

Twenty habitually omnivorous subjects and 19 habitually lactoovovegetarian subjects aged 59-65 y collected feces during 4 consecutive days. The concentrations of bile acids in total feces did not differ between the omnivores and vegetarians, but the bile acid concentrations in fecal water were significantly lower in the vegetarians. The concentration of the colorectal cancer-predicting bile acid deoxycholic acid in fecal water was explained by the intake of saturated fat and the daily fecal wet weight (r2 = 0.50). Fecal pH did not differ between the omnivores and vegetarians. This variable was significantly (P < 0.05) explained by the intake of calcium (r2 = 0.30); 24-h fecal wet weight and defecation frequency were significantly higher in the vegetarians. In conclusion, our vegetarian subjects had a lower concentration of deoxycholic acid in fecal water, higher fecal wet weight, and higher defecation frequency than the omnivorous subjects.

Effects of a calcium binder on the solubility of bile acids and fatty acids in the large intestine of the rat.

Kidney stone patients with hypercalciuria type I are treated with an oral calcium binder. Lower intakes of calcium (Ca) in the range of 0-1500 mg/day have been associated with an increased incidence of colorectal cancer. The aim of this study is to analyze the effects of feeding ethylene diamine tetraacetic acid sodium salt (EDTA), a strong, non-absorbable binder of Ca, on the solubility of bile acids (BA) and long chain fatty acids (LCFA) in the large intestine of the rat. We have shown that the concentrations of soluble BA and LCFA in the large intestine contents remained constant while the concentration of total BA and LCFA decreased. Therefore, lowering the amount of Ca available for binding BA or LCFA is unlikely to increase the risk of colorectal cancer by that method.

Plasma deoxycholic acid is related to deoxycholic acid in faecal water.

Bile acids are considered as a risk factor for colorectal carcinogenesis. They were analysed in samples of faecal water and plasma of fasting heparine blood from 23 urolithiasis patients. Linear regression showed that the highest percentage of variance (52%) was explained by the model: plasma deoxycholic acid (micromol/l) = -3.11 + 0.96(+/-0.25*) 10log deoxycholic acid in faecal water (micromol/l) + 0.35(+/-0.15*) pH of faecal water -0.41(+/-0.19#) defacation frequency (number of stools/day); *P < 0.05, #P = 0.055. In future studies, analysing blood levels of unconjugated deoxycholic acid may substitute faecal measurements.

Improving neuromodulation technique for refractory voiding dysfunctions: two-stage implant.

OBJECTIVES: Neuromodulation is a new technique that uses electrical stimulation of the sacral nerves for patients with refractory urinary urge/frequency or urge-incontinence, and some forms of urinary retention. The limiting factor for receiving an implant is often a failure of the percutaneous nerve evaluation (PNE) test. Present publications mention only about a 50% success score for PNE of all patients, although the micturition diaries and urodynamic parameters are similar. We wanted to investigate whether PNE results improved by using a permanent electrode as a PNE test. This would show that improvement of the PNE technique is feasible. METHODS: In 10 patients where the original PNE had failed to improve the micturition diary parameters more than 50%, a permanent electrode was implanted by operation. It was connected to an external stimulator. In those cases where the patients improved according to their micturition diary by more than 50% during a period of 4 days, the external stimulator was replaced by a permanent subcutaneous neurostimulator. RESULTS: Eight of the 10 patients had a good to very good result (60% to 90% improvement) during the testing period and received their implant 5 to 14 days after the first stage. CONCLUSIONS: The good results of the two-stage implant technique we used indicate that the development of better PNE electrodes may lead to an improvement of the testing technique and better selection between nonresponders and technical failures.

Combined hormono/chemotherapy as primary treatment for metastatic prostate cancer: a randomized, multicenter study of orchiectomy alone versus orchiectomy plus estramustine phosphate. The Dutch Estracyt Study Group.

OBJECTIVES: Based on the theory that hormone-resistant cells are present in all metastatic patients, early administration of chemotherapy appears to be logical and its use is supported by experimental studies. Therefore, trials with combined hormonal and cytotoxic treatment as primary therapy should be conducted. In the present trial, the efficacy and tolerance of estramustine phosphate (EMP) as a chemotherapeutic agent in addition to hormonal treatment (orchiectomy) was studied in patients with metastatic and nonmetastatic prostate cancer not previously treated. EMP was chosen because it produces few serious adverse reactions and no cumulative toxicity. METHODS: Four hundred nineteen patients were included in a 1.5-year period starting in January 1989. Patients with locally advanced prostate cancer or with bone metastases were randomized to orchiectomy (O) or orchiectomy followed by EMP (O + E), given until progression. RESULTS: Analysis of the total group showed no significant difference in time to progression between the treatment groups. Because the course of the disease is different in patients with either T4 tumor only or with lymph node metastases only (M0) as compared with patients with bone metastases (M1) and because the number of progressions in the M0 patients was low, corresponding analyses were performed for these subgroups as well. In the M1 patients, there was a tendency for a longer time to progression in the O + E group than in the O group, but there was no indication of a difference between the groups with regard to survival. In the M0 patients, there was no indication of any difference in results between the treatments. Multivariate analysis of prognostic factors showed pain, alkaline phosphatase, metastasis status, and tumor stage to be significant factors. There was a relation between age and drug treatment in that a significant beneficial effect of EMP in terms of prolonged progression-free interval as well as survival was evident in younger patients (aged less than 73 years) with metastatic disease. Tumor stage was also of importance for the drug effect; T0 to T3 patients who received EMP survived longer than those who were treated with orchiectomy only. The most common adverse reaction was nausea in the O + E group, which led to discontinuation of the drug in 7 patients. Cardiovascular problems are not uncommon in this age group, and there was a higher incidence of cardiovascular events, predominantly cardiac failure, in the O + E group, leading to treatment interruption in 16 patients. CONCLUSIONS: Our results indicate that future studies of hormono/chemotherapy should focus on younger patients with bone metastases.

Persistence or reappearance of nonmotile sperm after vasectomy: does it have clinical consequences?

OBJECTIVE: To determine the percentage of patients with nonmotile sperm 12 weeks after vasectomy, to estimate the time needed for eventual azoospermia in these patients, and to record the percentage of patients with recurrence of nonmotile sperm after initial azoospermia after vasectomy. DESIGN: A review of the semen analysis of vasectomies performed in a 2-year period. Semen analysis in a group of volunteers from 4 months until 24 months after vasectomy. SETTING: Vasectomies performed in an outpatient department of the University Hospital of Maastricht. PATIENT(S): Men referred by the general practitioner for a vasectomy. INTERVENTION(S): Vasectomy. MAIN OUTCOME MEASURE(S): Amount and motility of sperm in postvasectomy semen samples. RESULT(S): Nonmotile sperm was found in 33% of the patients 12 weeks after vasectomy. The mean time to azoospermia was 6.36 months. Nonmotile sperm after initial azoospermia was found in 5 of 65 patients. CONCLUSION(S): Azoospermia as a criterion for sterility leads to unnecessary prolonged semen analysis in a large percentage of the vasectomized patients. Reappearance of nonmotile sperm was found in an unexpectedly high percentage.

PIP: A study was conducted to determine the percentage of patients with nonmotile sperm 12 weeks after vasectomy, to estimate the time needed for eventual azoospermia in the men, and to record the percentage of patients with recurrence of nonmotile sperm after initial azoospermia following vasectomy. A review of semen analyses was conducted in 413 patients who underwent vasectomy between April 1, 1993, and July 31, 1995, in an outpatient department of the University Hospital of Maastricht. 395 patients delivered a sperm sample 12 weeks after vasectomy. Nonmotile sperm was found in 33% of patients 12 weeks after vasectomy, the mean time to azoospermia was 6.36 months, and nonmotile sperm after initial azoospermia was found in 5 of 65 patients. The authors conclude that azoospermia as a criterion for sterility leads to unnecessary prolonged semen analysis in a large percentage of vasectomized patients. The reappearance of nonmotile sperm was found in an unexpectedly high percentage.

Ambulatory urodynamics: extramural testing of the lower and upper urinary tract by Holter monitoring of cystometrogram, uroflowmetry, and renal pelvic pressures.

This article elucidates the clinical applicability and state of the art of ambulatory urodynamics. Ambulatory urodynamics have evolved into practical investigations like EAC, HFM, and EAC combined with renal pelvimetry. EAC has been shown to be the method of preference if detrusor overactivity is involved. Conventional filling cystometry has proved to be an unreliable way to exclude detrusor instability. De novo instability after suspension surgery often indicates that an existing detrusor overactivity was not identified preoperatively. EAC including flowmetry has shown considerable variance in obstructive and contractility parameters in males with LUTS indicative for BPH. This raises doubt whether the clinical flow analysis is the suitable "gold standard" as advocated by the ICS. For a real break through of EAC, less complex automatic analysis is necessary. HFM is a newer method within the range of ambulatory urodynamic tests. It has not yet been completely evaluated. But, because the technique is analogous to the office flowmetry, noninvasive and very well accepted by the patients, it is expected to be widely used. This expectation is strengthened by the fact that HFM seems to show individual therapeutic efficacy of drugs, such as alpha-blockers. As a research tool to evaluate efficacy, it is far more powerful than conventional methods because of the reduction of within-patient standard deviation to about 10%. Finally, EAC combined with pelvimetry offers a promising method for the clinical evaluation of a combined dysfunction of upper and lower urinary tract.

Neuronal circuitry of the lower urinary tract; central and peripheral neuronal control of the micturition cycle.

A new presentation technique is introduce to describe the neuronal circuitry involved in the control of the uropoëtic system and its control mechanisms during the micturition cycle. This method is based on the preparation of flow charts and is applied to the discussion of four qualitative models which are derived from the literature. Opinions concerning the reflex arcs and supraspinal connections said to be involved in micturition and continence are different and sometimes contradictory. Little is known about supraspinal (inter)connections and their function in micturition control is still fragmentary. The control mechanisms which terminate voiding are not totally clear. Moreover, the role of the pelvic floor musculature in the control of the lower urinary tract is probably underestimated. The flow charts presented in this paper contribute to the future design of a single complete qualitative model representing the general central and peripheral nervous connections and control mechanisms. Such a model would provide an approach for future research in neuromodulation and neurostimulation of the uropoëtic system and a reduced version could be used for quantitative modelling, e.g. in neural network simulations.

Treatment of anastomotic strictures and urinary incontinence after radical prostatectomy with urolume wallstent and AMS 800 artificial sphincter.

Anastomotic strictures and urinary incontinence are severe complications after a radical prostatectomy. We report on two patients suffering from both complications. We treated the anastomotic stricture with a Urolume Wallstent and inserted an AMS 800 artificial sphincter prosthesis 4 to 6 months later for treating urinary incontinence. Finally, the patients were fully continent with no evidence of recurrent strictures.

The neuronal control of the lower urinary tract: A model of architecture and control mechanisms.

The human micturition cycle is controlled by central and peripheral nervous structures and connections. In literature, no complete or generally accepted model describes the principles of micturition control. In this paper, the integration of (neuro-)anatomy, (neuro-)physiology and control theory is used to describe and model the neuronal control of the lower urinary tract. Neuroanatomy supplies the most basic information necessary for the modellation of the peripheral pathways and central connections involved in the control of the uropoetic system. It is found that not all the nervous structures and connections have been identified as such yet. The linking up between several nervous structures (e.g., the presence of central and peripheral relay stations) is not completely clear. A s a consequence, each model to describe the micturition cycle from the perspective of control theory is yet of limited physiological value as it cannot exceed a rather general level of modellation. Adding functional considerations (neurophysiology and control theory) to the neuroanatomical skeleton completes the model. Some control mechanisms active during the micturition cycle can still not be revealed in detail. Crucial questions on the neuronal innervation of the human uropoetic system and the control mechanisms active during the micturition cycle remain, like how the supraspinal trigger mechanisms for micturition are organised, or how the voluntary cessation of voiding is realised. A simplified version of the model discussed in this paper can already be used for mathematical modelling, e.g., neural network simulations.

A non-invasive method for bladder electromyography in humans.

No convincing correlation of bladder EMG in humans to simultaneously measured intravesical pressure has been reported in the literature. In most studies on bladder EMG the electrodes contact the bladder wall itself. This causes problems in the discrimination between very small extracellular signals, reflecting actual membrane potential changes of bladder muscle cells, and large electro-mechanical artefact caused by electrode movement as the tissue contracts. Aim of this study is to investigate whether bladder EMG can be performed non-invasively with Ag-AgCl surface electrodes that are placed on the abdominal skin of healthy volunteers. Bipolar electrode signals are obtained in a diagonal, vertical and horizontal direction of the abdominal electrodes. A conventional urodynamic investigation is performed according to International Continence Society standards simultaneously with bladder EMG. This new method shows that voiding is accompanied by a slow voltage change in bipolar electrode signals. The contribution of abdominal and other striated muscle activity to the bipolar electrode signals can clearly be distinguished from the slow voltage changes related to voiding. Free flowmetry shows that the electrical activity picked up by the abdominal electrodes is related to bladder emptying. In pressure/flow studies a relation between the electrical activity and the detrusor pressure is found. The present results suggest that the slow voltage changes found during bladder contraction are caused by summed membrane potential changes of bladder muscle cells, but this concept needs further testing. Also, validation for clinical use remains to be established.

A method for the electromyographic mapping of the detrusor smooth muscle.

Various methods for detrusor EMG in the living mammal have been described in the literature. These methods do insufficiently take into account signal components that are caused by movement between the electrodes and the bladder wall. Reliable detrusor EMG has not been achieved yet. This study investigates the feasibility of a new experimental set-up, in which the electrical activity of the detrusor smooth muscle can be examined. In six rabbits, after cervical dislocation, laparotomy and after excision of the heart, electrical signals of the detrusor muscle are measured with 240 electrodes. The electrodes are positioned on the serosal surface of the filled and isovolumetric bladder. During the recordings, no bladder contractions are deliberately evoked by any stimulus. Consistent results in all six animals show a repetitive spike pattern on multiple electrodes with a repetition frequency of 1.2 Hz. Spikes are triphasic and have a mean duration of 0.47 s (STD = 0.15 s, n = 40) and a mean amplitude of 0.29 mV (STD = 0.07 mV, n = 40). On adjacent electrodes a time shift between the spikes is found, suggesting the propagation of electrical activity across the detrusor surface. The maximum conduction velocity of an arbitrary spike front in the direction of propagation is approximately 30 mm/s. In two animals slow waves are found on the edge of the highpass filter setting. Extensive control experiments are executed to validate the set-up and to interpret the data obtained by the animal experiments. The bladder is still able to contract thirty minutes post mortem. The heart, as a distant signal source, generates a signal that is present on all electrodes and shows no detectable time shift from one electrode to any other. Motion imposed on the electrodes relative to the bladder wall does not reproduce the slow waves and spikes found in the animal experiments. The control experiments support that the results of the animal experiments show electrical activity originating from the detrusor muscle itself. With the experimental set-up described in this paper, nearly artefact free detrusor EMG can be recorded. An electromyographic map of a considerable detrusor smooth muscle area can be obtained.

[Initial experiences with neuromodulation as treatment for incontinence and micturition disorders in The Netherlands]. / Eerste ervaringen met neuromodulatie als behandeling voor incontinentie en mictiestoornissen in Nederland.

Neuromodulation is a new treatment modality for disturbances of bladder function. By stimulation of a sacral nerve the pelvic floor is activated, thus affecting the reflex arcs which control micturition and continence. Along with 2 case histories the methods of the preoperative percutaneous test stimulation and the implantation of stimulator and electrode are described.

[Variation in the diagnosis and treatment of benign prostatic hyperplasia in urological practice]. / Variatie in diagnostiek en behandeling van benigne prostaathyperplasie in de urologische praktijk.

OBJECTIVE: To analyse practice variation among urologists and its determinants with respect to diagnostics and therapy choice in benign prostatic hyperplasia (BPH). DESIGN: Cross-sectional. SETTING: Stratified sample of 12 urological practices throughout the Netherlands. METHODS: On 670 consecutive, newly referred BPH patients > or = 50 years, data were collected about symptomatology, discomfort and sexual functioning (patient questionnaire), diagnostic procedures and outcomes (medical record), and (considerations for) therapy choice (urologist questionnaire). Characteristics of patients as well as of urologists were integrally studied to explain the variation. RESULTS: With respect to diagnostics, highest variation (interquartile ranges) was found for ultrasonography of the prostate (19-86%), kidneys (19-68%), and bladder (42-91%), and lowest variation for digital rectal examination (97-100%) and blood tests and urinalysis (88-100% and 86-99% respectively). For therapy choice, interquartile ranges were 24-42% (surgery), 32-49% (watchful waiting), 5-29% (alpha-blockers), and 0-17% (5-alpha-reductase-inhibitor). Variation in diagnostics was associated with characteristics of urologists and work setting as well as of patients. For differences in therapy choice, symptomatology, discomfort, sexual activity, peak flow, volume of residual urine, prostate volume, comorbidity, experience of the urologist, and the type of hospital were the most important explanatory variables. CONCLUSION: Variation in both diagnostics and therapy choice is considerable. This variation is associated with characteristics of patients as well as of urologists and work setting.

[Determination of infravesical obstruction in men with benign prostatic hyperplasia using pressure-flow measurement and analysis with the Dx/CLIM software program]. / Stanovenie infravezikálnej obstrukcie u muzov s benígnou hyperpláziou prostaty pomocou tlakovo-prietokových meraní a analýzy Dx/CLIM.

BACKGROUND: Quantification of infravesical obstruction is important in the management of clinical benign prostatic hyperplasia (BPH). OBJECTIVES: The assessment of obstruction degree according to the urethral resistance parameter (URA) and bladder contractility (W) with software Dx/CLIM. METHODS: The study retrospectively analysed a group of 61 patients with BPH in order to assess the degree of obstruction and bladder contractility. Each of the patients underwent pressure/flow studies with Dx/CLIM analysis (URA < 29 cm H2O-unobstructed, Wmax > 12.8 W/m2-normal bladder contractility) and symptom score evaluation (maximum 15 points). In a dose-finding, placebo-controlled study 12 patients received 2 mg of doxazosin (alpha-1 blocker) and 11 patients received placebo during 4 weeks of treatment. RESULTS: 15 patients were unobstructed (25%) out of whom 10 had poor bladder contractility. Obstruction was present in 46 patients (75%) out of whom 18 had impaired contractility. During treatment, the symptom score decreased statistically significantly in both groups (p < 0.05). URA decreased significantly only in the 2 mg group (2 mg group: baseline URA = 53.9, final mean URA = 40.1, p < 0.05; placebo group: baseline URA = 52.9, final mean URA = 56.1). Detrusor contractility was not significantly affected. CONCLUSIONS: Pressure/flow studies with Dx/CLIM analysis are very useful in the selection of BPH patients for treatment modalities and in the assessment of efficacy. Doxazosín decreases urethral resistance effectively. (Tab. 3, Fig. 3, Ref. 12.)

Profile of doxazosin in patients with benign prostatic hyperplasia.

Alpha adrenergic receptors in prostatic smooth muscle play a major role in the development of bladder outlet obstruction in patients with benign prostatic hyperplasia (BPH). As a result, alpha adrenoceptor antagonists have been used increasingly in the treatment of this condition. Doxazosin is a selective alpha 1 antagonist with a long half-life and gradual onset of action, which make it suitable for once-daily treatment. In placebo-controlled trials, doxazosin has been shown to improve maximum and mean urine flow rates, reduce urethral resistance and bladder contractility, and improve obstructive and irritative symptoms. These changes develop within a few weeks of starting treatment and are maintained during long-term treatment over periods of years. Doxazosin is also well tolerated; adverse events are generally mild or moderate and do not interfere with treatment. These features combine to make doxazosin an effective, convenient and well-tolerated treatment for the management of patients with BPH.