Ultrastructure of the trigone and its functional implications.

OBJECTIVE: To investigate the ultrastructure of the trigonal muscle (= superficial trigone), relate it to normal function, and identify any changes it may undergo in voiding dysfunction. MATERIALS AND METHODS: 20 men (median age 67 years) with low-stage prostatic carcinoma, 10 with and 10 without bladder outlet obstruction, were selected by urodynamic evaluation. Trigonal biopsy was performed at radical prostatectomy, and processed for electron-microscopic study by standard procedures. Biopsies were evaluated independently by 2 examiners without prior knowledge of urodynamic data. RESULTS: Three obstructed and 1 unobstructed bladder had impaired detrusor contractility, and 1 obstructed bladder had detrusor overactivity. Compared to the previously investigated detrusor, the trigonal muscle had smaller compact bundles and fascicles with less collagen and more elastic tissue. Muscle cells had no or rare intermediate junctions that mediate mechanical coupling in normal detrusor, but predominant close cell appositions that mediate electrical coupling. Smooth muscle in most biopsies had widespread or focal features characteristic of the aged detrusor. None, however, had the features previously associated with obstructed detrusor, or detrusor with impaired contractility. CONCLUSIONS: The trigonal muscle does not undergo structural changes as previously described in the detrusor in association with voiding dysfunction. Its contraction depends on electrical coupling of its muscle cells, and has a supportive role in normal micturition, mooring the terminal ureters to the bladder base, to allow efflux and guard against reflux of urine. Activation of volume and tension sensory neuroterminals may contribute to some storage and voiding micturition reflexes, and may be related to normal and abnormal perception of urge.

Effect of radical prostatectomy on sensory threshold and pressure transmission.

PURPOSE: The mechanisms involved in post-radical prostatectomy incontinence remain unclear despite previous anatomical and functional studies. In addition, the factors responsible for the restoration of continence are not well studied. To improve our understanding of the alterations in continence mechanisms, we prospectively investigated the temporal changes in urodynamic parameters after radical prostatectomy. MATERIALS AND METHODS: Cystometry, urethral pressure profilometry and posterior urethral sensory threshold measurements were performed in patients undergoing radical prostatectomy. Preoperative pressure transmission was determined by the maximal urethral pressure divided by the maximal abdominal pressure during cough maneuvers at a bladder volume of 200 ml. Postoperative sensory threshold, pressure transmission (% of pressure transmission), maximal urethral closure pressure and functional sphincter length were measured 6 weeks and 6 months after prostatectomy. These parameters were compared between continent and incontinent patients. RESULTS: Preoperative and postoperative urodynamic studies were completed in 34 patients. The continence rate after 6 weeks was 18% (6 patients) and improved to 82% (28) after 6 months. Preoperatively sensory threshold was 16 +/- 11 mA. After 6 weeks and 6 months, respectively, sensory threshold was significantly higher in incontinent (84 +/- 11 mA., 70 +/- 8 mA.) compared to continent (65 +/- 8 mA., 41 +/- 12 mA.) patients. Preoperative proximal urethral sensory threshold was not correlated with degree of postoperative incontinence determined by pad tests. Pressure transmission was not different in continent and incontinent patients postoperatively. After 6 weeks and 6 months, respectively, pressure transmission was 77% and 91% in continent, and 37% and 58% in incontinent patients (p = 0.04, p = 0.03). Maximal urethral closure pressure was significantly higher in continent patients (35 +/- 6 cm. H2O) compared to incontinent patients (11 +/- 9 cm. H2O). Sphincter length decreased from 50 mm. preoperatively to 24 mm. after 6 weeks and 25 mm. after 6 months. There was no difference in sphincter length between continent and incontinent patients. CONCLUSIONS: Posterior urethral sensitivity and pressure transmission are impaired immediately after prostatectomy. An improvement in these parameters after 6 months is associated with the restoration of continence. These observations suggest that urinary continence after radical prostatectomy depends on the integrity of posterior urethral sensation and the efficiency of pressure transmission.

Effect of a cholecystokinin antagonist on meal-stimulated insulin and pancreatic polypeptide release in humans.

A cholecystokinin (CCK) receptor antagonist, loxiglumide, was used to investigate the potential regulating role of CCK in the entero-insular axis in humans. Ingestion of a mixed liquid meal stimulated plasma CCK, insulin, and pancreatic polypeptide (PP) release in the control experiment. With iv loxiglumide (22 mumol/kg.h), mean plasma insulin and glucose levels did not differ between placebo and loxiglumide treatment. The area under the plasma concentration for PP was reduced to 6,060 +/- 1,706 (P less than 0.05) compared to that during placebo treatment (12,266 +/- 4,748). Administration of loxiglumide failed to change insulin secretion in response to perfusion of the same meal or perfusion of a 10-amino acid solution into the duodenum. However, PP secretion in response to the intraduodenal meal or amino acid mixture was abolished after loxiglumide (P less than 0.05). Intravenous administration of the 10-amino acid mixture stimulated insulin from a mean basal level of 7 +/- 3 microU/mL to a peak level of 16 +/- 4 microU/mL. Infusion of a CCK octapeptide (CCK-8) at 8.6 pmol/kg.h, which produced a plasma concentration of 3.3 pmol/L, which is within the postprandial range, augmented amino acid-stimulated insulin and PP output (P less than 0.05). When CCK-8 was infused with loxiglumide, the insulin and PP responses were similar to the values found with loxiglumide alone. We conclude that CCK receptor blockade with iv loxiglumide does not affect postprandial insulin secretion. CCK is, therefore, not a major incretin. However, it is involved in the postprandial PP response, especially during the intestinal phase stimulation. These data suggest that CCK has a role in the human enteroinsular axis.

Sensitivity of the parietal cell to pentagastrin in health and duodenal ulcer disease: a reappraisal.

In view of the conflicting results on whether pentagastrin sensitivity is genuinely increased in duodenal ulcer (DU) patients, the pentagastrin-gastric acid relationship was restudied in 17 normal subjects and 15 DU patients. In a reproducibility study performed on nine healthy subjects the mean pentagastrin responses obtained on 2 different study days, using a step technique (range, 0.025-6.4 micrograms kg-1h-1), were congruent at each of the five measuring points. Analysis of variance revealed no significant overall differences. However, ED50 values showed a large within- and between-subject variation and failed to correlate significantly, this because a plateau response was not regularly obtained with the top dose. Consequently, ED50 values in normal subjects and DU patients showed a large scatter and were not significantly different, although the potency ratio calculated from the linear parts of the respective dose-response curves was significantly different (2.6; 95% confidence limits, 1.8-3.9). This study thus supplies further evidence that the parietal cell of DU patients has a higher sensitivity to pentagastrin and demonstrates that the reliability of individual ED50 estimations obtained in pentagastrin dose-response studied should not be overrated.

Gallstone ileus after endoscopic sphincterotomy.

An attack of gallstone ileus observed in a 60-year-old female patient is reported. In this patient who previously had been cholecystectomized, instant extraction of giant residual gallstones was unsuccessful despite a large endoscopic sphincterotomy. Three days later, she developed colicky abdominal pain and vomiting. At laparotomy nine days after the endoscopic procedure an impacted gallstone measuring 3.5 cm in diameter was removed from the the jejunum, some 50 cm below the ligament of Treitz. This observation demonstrates an unusual complication of endoscopic sphincterotomy and clearly outlines that very large stones can, after an initial delay, pass into the duodenum despite an apparently "unsuccessful" sphincterotomy.

Clinical experience with impromidine, a highly specific H2-receptor agonist.

The gastric secretory response to impromidine (SKF 92676), a potent selective histamine H2 agonist, has been studied in 40 patients with peptic ulcer disease or ulcer-like dyspepsia. Peak acid output following the intravenous infusion of impromidine, 10 micrograms kg-1h-1, or pentagastrin, 6 micrograms kg-1h-1, was not significantly different. This was also the case when the two drugs were administered subcutaneously at the same dose. Impromidine was well tolerated with only minor effects on the cardiovascular system both in 10 younger patients and in 20 subjects over the age of 55 years with mild to moderate cardiovascular disease. Impromidine can be considered an important tool for further investigation of the role of histamine at the H2-receptor site in man.