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Biomedical subjects

C R Chapple

Publications and source records attributed to C R Chapple.

At least 55 records · Page 3Linked to original sources
PubMed2000

Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial.

OBJECTIVES: To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo. PATIENTS AND METHODS: In all, 208 patients were allocated at random to either TCl or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy. RESULTS: Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one-sided P = 0. 0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one-sided P = 0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two-sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group). CONCLUSION: Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.

Adult↗
PubMed2000

5-Hydroxytryptamine-induced potentiation of cholinergic responses to electrical field stimulation in pig detrusor muscle.

OBJECTIVE: To determine whether detrusor muscle from the pig can be used as a model to study presynaptic 5-hydroxytryptamine (HT)4-receptor-mediated effects on the electrical field stimulated (EFS) cholinergic responses previously identified in the human bladder. Materials and methods Strips of detrusor muscle were mounted in physiological Krebs' solution under 1 g tension and field stimulated (25 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals and allowed to equilibrate. Concentration-response curves to 5-HT (1 nmol/L to 300 micromol/L) were constructed in the presence and absence of the 5-HT4-selective antagonists RS-100235 and GR-113808 (both at 0.3, 1 and 3 nmol/L). All experiments were conducted in the presence of methiothepin and ondansetron (both 1 micromol/L) to block 5-HT1, -HT2 and -HT3 receptors. RESULTS: 5-HT potentiated the cholinergic responses to EFS in pig bladder strips in a concentration-dependent manner, with a maximum mean (SEM) potentiation of 48.3 (7.7)% of the resting tension (n = 25). Both RS-100235 and GR-113808 antagonized the effect of 5-HT with high affinity, yielding apparent pKB values which were consistent with the responses being mediated via the 5-HT4 receptor subtype. CONCLUSION: These data indicate that 5-HT can potentiate EFS responses in isolated pig bladder strips and that the 5-HT4 receptor subtype mediates this response. Therefore, the pig may be used as an effective model to study presynaptic 5-HT4 receptors previously reported in the human bladder.

Action Potentials↗
PubMed2000

Principles of ureteric reconstruction.

The principles of ureteric reconstruction are not different from those of reconstructive urology in the rest of the urinary system. The importance of ensuring good vascular supply, complete excision of pathological lesions, good drainage and a wide spatulated and tension-free anastomosis of mucosa to mucosa remain paramount. Although time of diagnosis is the most single most adverse factor affecting outcome, the majority of ureteric injuries still present postoperatively, and delays in diagnosis are the rule rather than the exception. Successful management requires early and definitive intervention using endoscopic means or percutaneous drainage and stenting where possible. Failing this, a number of open surgical options to foreshorten the course of the ureter should be implemented. Most ureteric injuries below the pelvic brim can be treated easily with a ureteroneocystostomy using a bladder elongation procedure or a Boari flap. Mid and upper ureteric injuries above the pelvic brim, however, can be repaired with a spatulated ureteroureterostomy if the defect is small. In those with extensive ureteral loss, measures such as mobilizing the kidney, transureteroureterostomy, renal autotransplantation and ureteral substitution using small bowel may be required. Artificial ureteral substitutes may be an alternative in selected cases.

Anastomosis, Surgical↗
PubMed2000

Randomised prospective trial of contact laser prostatectomy (CLAP) versus visual laser coagulation of the prostate (VLAP) for the treatment of benign prostatic hyperplasia. 2-year follow-up.

OBJECTIVE: To determine the long-term efficacy and complications of visual laser coagulation/ ablation, VLAP (side-firing fibre) and direct contact laser ablation, CLAP (sapphire-tipped fibre) of the prostate in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with clinical BPH, obstructed at voiding cystometry, were recruited and randomised to undergo either CLAP (21 patients) or VLAP (17 patients). At baseline, 1, 6, 12 and 24 months, patients underwent clinical evaluation, International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual urine volume, and pressure/flow urodynamics. RESULTS: The mean operating time for CLAP was 37.7 min and 24.5 min for VLAP. There was minimal morbidity with only 5 men requiring bladder irrigation after CLAP, 1 of whom had a blood transfusion. No patient required irrigation after VLAP. The mean catheterisation time after CLAP was 4.5 days (range 1-31 days) and 13.2 days (range 7-70 days) after VLAP. IPSS and Qmax improved significantly and maintained at 2 years. After CLAP, the IPSS decreased from 20.9 to 13.5 at 2 years while Qmax rose from 10 to 15.5 ml/s at 2 years. After VLAP, the IPSS decreased from 21.8 to 13.3 at 2 years while Qmax rose from 10 to 15. 9 ml/s. There was no difference between CLAP and VLAP. Pressure/flow urodynamics at 6 months showed reduced bladder outflow obstruction. CONCLUSIONS: CLAP and VLAP offer the same improvement in flow rates and symptoms at 2years. Both procedures lead to minimal morbidity, but the excellent haemostasis that is achieved at VLAP makes it of more use in treating patients at high risk of haemorrhage after surgery.

Aged↗
PubMed2000

Urodynamic assessment of the bashful bladder.

PURPOSE: We prospectively studied the potential contribution of ambulatory urodynamic monitoring in men with urinary symptoms unable to initiate a void on conventional video cystometrography. MATERIALS AND METHODS: A total of 40 consecutive symptomatic men with a median International Prostate Symptom Score of 19 (range 1 to 29) and median age of 51.9 years (range 30 to 75) who were unable to void during video cystometrography underwent ambulatory urodynamic monitoring. Solid-state transducers mounted on silicone coated catheters were inserted urethrally and rectally, and connected to a portable recorder. Subjects voided in private into a specially designed flow meter, which they connected to the recording device. RESULTS: Of the patients 2 (5%) failed to attend ambulatory urodynamic monitoring, despite multiple reminders, and in 1 (2.5%) the trace was uninterpretable. Pressure flow data were available for the remaining 37 patients with mean plus or minus standard deviation 2.72+/-0.1 storage void cycles recorded per patient. All 6 patients (15%) with obstruction were older than 40 years. In 6 cases (15%) obstruction was equivocal and the remainder were unobstructed. Transurethral prostatic resection in 2 and urethrotomy in 1 of 6 patients with obstruction resulted in subjective and objective improvement. CONCLUSIONS: The bashful bladder syndrome was not associated with any specific urodynamic diagnosis. Ambulatory urodynamic monitoring will yield a urodynamic diagnosis in more than 90% of cases after failure to record void data on video cystometrography. A surgically correctable cause of symptoms can be found in about 20% of men older than 40 years. The contribution of ambulatory urodynamic monitoring compared to more conventional evaluation in men younger than 40 years is negligible.

Adult↗
PubMed1999

Regulation of prostatic stromal cell growth and function by transforming growth factor beta (TGFbeta).

BACKGROUND: The majority of the overgrowth in benign prostatic hyperplasia (BPH) specimens is comprised of connective tissue. Factors that control stromal growth in the prostate are poorly understood; however, members of the transforming growth factor beta (TGFbeta) family may be of particular importance in the etiology of BPH. METHODS: Thirty-two low-passage stromal cultures were generated from human prostatectomy specimens. Their stromal origin was confirmed and expression of TGFbetas analyzed by duplex reverse transcription-polymerase chain reaction (RT-PCR). Challenge experiments were designed to study the effects of exogenous TGFbeta1 on stromal cell growth and synthesis of extracellular matrix components. RESULTS: The expression of TGFbetas 1, 2, and 3 was demonstrated in all 32 cell strains. The stromal origin of the cell lines was confirmed. Exogenous TGFbeta1 added to stromal cultures resulted in inhibition of cell growth and increased production of type I collagen. CONCLUSIONS: The prostatic stromal cell strains we have developed are a reliable mod- el for investigating prostatic connective tissue biology. The challenge experiments with TGFbeta1 provide further evidence for the involvement of TGFbetas in prostatic enlargement, as modulators of the extracellular matrix in the absence of growth stimulation.

Amino Acid Sequence↗
PubMed1999

Pharmacodynamics of anticholinergic agents measured by ambulatory urodynamic monitoring: a study of methodology.

The aim of the study was to establish a methodology whereby ambulatory urodynamic monitoring (AUM) may be used in the assessment of the effects of darifenacin on urodynamic measures of detrusor function and symptoms associated with detrusor instability. Six patients (one man and five women) with detrusor instability (DI) on conventional urodynamic monitoring were recruited into this placebo-controlled crossover study. The study was divided into two periods of 7 days of treatment with either darifenacin 5 mg t.d.s. or placebo with the patient crossing over to the alternative treatment after a washout period of 7 days. On the 7th day of each treatment, AUM was carried out. Parameters used to quantify detrusor activity on AUM were the number, amplitude, and duration of detrusor contractions and the total area under the detrusor pressure/time curve. "Events" recorded were urge, leakage episodes, voids, and pain. Six comparable hours of AUM for each treatment period could be analyzed in four patients and 4 hr in one. In three of the five patients, reduction in activity on AUM while on darifenacin was apparent. Symptom data closely matched the changes in detrusor activity measured on AUM. This is the first study reporting the use of AUM in the development of a drug with an effect on detrusor activity. AUM has clear advantages over conventional cystometry, which can only measure surrogate urodynamic parameters at a single time point. The optimal duration of monitoring in this context appears to be 6 hr with prolongation of monitoring time beyond this being unlikely to yield additional useful information. Correlation between symptoms and findings on AUM is good with changes in parameters recorded on AUM relating closely to the improvement in symptoms.

Benzofurans↗
PubMed1999

In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

In vitro investigation of the bladder-vascular selectivity of levcromakalim and YM934 in human tissues.

OBJECTIVE: To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. MATERIALS AND METHODS: Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80% of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. RESULTS: Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. CONCLUSIONS: Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.

Benzoxazines↗
PubMed1999

A pilot study for a randomized controlled trial comparing the efficacy, safety and cost-effectiveness of surgical treatments of the prostate.

OBJECTIVE: To assess the numbers of men in outpatients and subsequently undergoing transurethral resection of the prostate (TURP) who were referred during 1993-94 and 1996-97, thereby assessing the feasibility of a subsequent study of treatment efficacy in men with bladder outlet obstruction secondary to benign prostatic hyperplasia, prospectively randomized to the surgical treatment options, i.e. TURP, laser ablation of the prostate, transurethral needle ablation and T3 thermotherapy, to investigate treatment outcome, cost-efficacy and cost-benefit. PATIENTS AND METHODS: All patients considered and consenting for prostate surgery were reviewed prospectively with a view to inclusion in the proposed trial. The diagnosis was based on two estimates of flow rate from voids of >150 mL and from symptoms assessed using the International Prostate Symptom Score. All patients had TURP explained by a urological surgeon and nursing staff, and subsequently had further consultation with research staff. RESULTS: Patients seen in clinic as new referrals increased by 11% between the periods assessed, although the numbers undergoing TURP decreased by 19%. Of the 383 patients screened, who were on the waiting list for TURP, only 13 elected to enter the trial. Of the 383 men, 267 (67%) ultimately had prostate surgery, with 39 (10%) electing to continue with watchful waiting and 34 (9%) continuing with pharmacotherapy. CONCLUSION: Although more men with benign prostatic disease and lower urinary tract symptoms are being seen in clinics, the reduced proportion of patients continuing to surgical intervention will lead to increasing difficulty in carrying out randomized controlled clinical trials assessing surgical options. With ever more therapeutic options available, patients find it difficult to make decisions in both the clinical situation and when asked to enter a trial. Fully informed decisions by both the surgeon and the patient will only be possible when objective data are available from trials that investigate outcome, cost-efficacy and cost-benefit. This study suggests that when presented with more information and counselling, fewer men decide to undergo prostate surgery for symptomatic BPH.

Adult↗
PubMed1999

A comparison of ambulatory and conventional urodynamic studies in men with borderline outlet obstruction.

OBJECTIVE: To compare detrusor function and outlet behaviour on ambulatory urodynamic monitoring (AUM) with conventional cystometrography in symptomatic men with borderline evidence of bladder outlet obstruction (BOO), as determined by conventional cystometrography, and to assess the usefulness of AUM in reclassifying this population of patients into obstructed and unobstructed groups. PATIENTS AND METHODS: Sixty-nine consecutive men (mean age 59.6 years) with lower urinary tract symptoms (mean International Prostate Symptom Score 19.1) and borderline BOO on a medium-fill conventional urodynamic study (CUS) were examined prospectively with AUM. Detrusor contractility, obstruction grade, maximal voiding detrusor pressure (pdet(max)), detrusor pressure at peak flow (pdet Qmax) and peak flow rate (Qmax) determined by both methods were compared. The incidence of detrusor instability (DI) detected by both modalities was also evaluated. RESULTS: There was considerable disagreement between the investigations during the voiding phase. Detrusor contractility was higher on AUM than on CUS (P= 0.003) and obstruction grade was significantly lower on AUM (P=0.018). There was no difference in pdet(max) nor pdet Qmax. The mean (95% confidence interval) Qmax was higher on AUM, at 12.9 (1.3) mL/s, than on CUS, at 8.9 (0.8) mL/s. On the Abrams-Griffiths nomogram the most significant changes were six men (10%) from equivocal to obstructed, seven (11%) from equivocal to unobstructed and two (3%) from obstructed to unobstructed on CUS and on AUM, respectively. Thus, in 24% of patients there was a potentially clinically significant change resulting from the information generated by AUM. DI was identified on CUS in 26 (41%) men and on AUM in 25 (40%); 35 men (56%) had evidence of DI on either AUM or CUS. CONCLUSION: The significant disagreement between the findings on CUS and AUM suggests that the conditions under which pressure-flow investigations are carried out significantly affect findings in borderline cases. The reclassification of patients by AUM into obstructed and unobstructed groups occurs in 24% and may be clinically relevant. AUM appears to be complementary to CUS in the assessment of men who are borderline for obstruction on conventional testing, but the clinical implications of this have yet to be determined.

Constriction, Pathologic↗
PubMed1999

Contemporary management of urethral trauma and the post-traumatic stricture.

This review discusses the contemporary management of urethral trauma and post-traumatic urethral strictures occurring in both the anterior and posterior urethra. Experience in the full spectrum of urethral reconstructive procedures is important. The initial management of patients relies upon adequate drainage of the bladder and management of any other associated acute life-threatening injuries. The principles of urethral reconstruction in both the anterior and posterior urethra are discussed, with reference to the recent literature on the subject.

Female↗
PubMed1999

Transurethral needle ablation (TUNA). A critical review of radiofrequency thermal therapy in the management of benign prostatic hyperplasia.

Radiofrequency thermal therapy of the prostate is a new minimally invasive treatment for symptomatic benign prostatic hyperplasia (BPH). The procedure is called transurethral needle ablation (TUNA). With TUNA, the inner region of the prostate is selectively ablated with temperatures approaching 90-100 degrees C while the prostatic urothelium is preserved. The objective of this article is to discuss the basics of radiofrequency energy, instrumentation, surgical techniques, and to present an update of the clinical results as it applies to the treatment of BPH.

Animals↗