Tapered intraluminal versus imbricated extraluminal valve: comparison of two continence mechanisms for urinary diversion

One of the major limitations of continent intestinal reservoirs currently in use is failure of the efferent continence mechanisms. Unsatisfactory results have been reported in the literature in up to 40% of cases. While progress has been made toward better continence in urinary diversions, evolution of the actual continence mechanisms has been along two rather distinct paths: those with a valve mechanism placed inside the pouch (either by intussusception or surgical insertion), and those with the valve outside to the pouch (by imbrication of an externally located ileal segment). A canine experimental model was used to investigate a type of intraluminal continence mechanism and to compare it to an extraluminal imbricated ileocecal valve. In eight mongrel dogs a reservoir was made out of ascending and transverse colon with two different valve mechanisms--one intraluminal and one extraluminal--connected via separate stomas to the skin. Radiographic, sonographic, endoscopic and urodynamic studies of the pouch and its outlets were performed. Results showed that, in contrast to the extraluminal valve, continence in the intraluminal valve was volume dependent. The valve closing pressure of the intraluminal continence mechanism increased far beyond the values of the extraluminal valve (50.38 vs. 30.12 cm. H2O) at maximum pouch filling. Leakage of the intraluminal valve was observed at significantly higher pouch volumes than in the extraluminal valve (348 cc vs. 215 cc). In view of these results, the volume dependent intraluminal valve mechanism appears superior to an extraluminal type, especially at higher pouch volumes.     

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m²) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of ‘true’ CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle’s test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1–9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 ± 2.5 nmol/l (mean ± SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.     

Effect produced by acute and chronic administration of the selective 5-HT3 receptor antagonist BRL 46470 on the number of spontaneously active midbrain dopamine cells in the rat

This study examined the effect of acute and chronic administration of the selective 5-HT₃ receptor antagonist BRL 46470A, an analog of granisetron, on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (A9 or SNC) and the ventral tegmental area (A10 or VTA) in the rat. In the A10 area, the acute administration of BRL 46470A decreased the number of spontaneously active DA cells at a dose of 0.1 mg/kg (0.28 μmol/kg) ip, yet increased the number of spontaneously active DA cells at a dose of 0.3 mg/kg (0.84 μmol/kg). The chronic administration (21 days) of BRL 46470A appeared to produce a multiphasic dose-response curve. Thus, the chronic treatment with BRL 46470A increased the number of spontaneously active A10 DA cells at 0.03 (0.084 μmol) and 0.3 mg/kg, but decreased the number of spontaneously active A10 DA cells at a dose of 0.1 mg/kg. In contrast, BRL 46470A did not decrease the number of spontaneously active A9 DA cells after either acute or chronic administration (0.01-0.3 mg/kg). However, BRL 46470A did increase the number of spontaneously active A9 DA cells at acute and chronic doses similar to those that were effective in A10. The iv administration of (+)-apomorphine (APO) not only failed to reverse the decrease produced by chronic administration of BRL 46470A at 0.1 mg/kg, but further decreased the number of spontaneously active A10 DA cells. Similar to the results obtained with granisetron, the pretreatment of naive rats with either 0.01 or 0.1 mg/kg iv of BRL 46470A significantly potentiated (2-fold) the suppressant action of APO on the basal firing rate of A10, but not A9 DA cells. Overall, our results indicate that similar to granisetron, chronic BRL 46470A at 0.1 mg/kg selectively decreases the number of spontaneously active A10 DA cells, via a mechanism not related to depolarization inactivation. Presently, it is not clear what factors may contribute to the multiphasic dose-response curve of BRL 46470A. © 1994 Wiley-Liss, Inc.     

Effect of Bupivacaine and Levobupivacaine on Exocytotic Norepinephrine Release from Rat Atria

Background: The cardiotoxic mechanism of local anesthetics may include interruption of cardiac sympathetic reflexes. The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings.

Methods: Rat atria were prepared for measurements of twitch contractile force and 3[H]-norepinephrine release. After nerve endings were loaded with 3[H]-norepinephrine, the tissue was electrically stimulated in 5-min episodes during 10 10-min sampling periods. After each period, a sample of bath fluid was analyzed for radioactivity and 3[H]-norepinephrine release was expressed as a fraction of tissue counts. Atria were exposed to buffer alone during sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 [mu]l each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received either bupivacaine or levobupivacaine at concentrations (in [mu]M) of 5 (S3-S4), 10 (S5-S6), 30 (S7-S8), and 100 (S9-S10).

Results: Bupivacaine and levobupivacaine decreased stimulation-evoked fractional 3[H]-norepinephrine release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3 [mu]m. The inhibitory effect of both local anesthetics (~70%) approached that of tetrodotoxin. Local anesthetics abolished the twitch contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0 [mu]m (bupivacaine) and 15.7 +/- 3.9 [mu]m (levobupivacaine). In separate experiments, tetrodotoxin inhibited twitch contractile force by only 30%.     

The impact of detubularization on ileal reservoirs

For many years, parts of the large or small bowel have been used for bladder augmentation and substitution. Recent controversy over the advantages and disadvantages of continent urinary diversion using detubularized ileum (the Kock pouch) and tubular ileum (the Camey procedure) focussed on how a highly compliant urinary reservoir should be formed. We compared the compliance of isolated intact ileal segments and ileal pouches constructed after transection of the antimesenteric border. Hydrodynamic data was obtained at four different points in time: acute (immediately after pouch construction), and after two, six and twelve weeks. Over the first six weeks the reservoirs were connected to the bladder for drainage. At six weeks, subtotal cystectomy and separate anastomosis of the tubular ileal loop and the detubularized ileal pouch to the trigone was performed to study the influence of cyclic reservoir distention. Statistical analysis of the pressure-volume curves revealed significantly better compliance of the detubularized ileal pouch as compared to the intact ileal segments. The area under the pressure curve values (AUC) were p less than 0.025, p less than 0.02, p less than 0.005 and p less than 0.02 for the acute experiment, after two weeks, after six weeks, and after 12 weeks respectively. Our findings suggest that transection of the circular intestinal wall is an important step in the creation of a good-compliant urinary reservoir.     

Purification of B16-F1 melanoma autocrine motility factor and its receptor.

Tumor autocrine motility factor (AMF) is a cytokine which stimulates both random and directed cell migration by self-producing cells. AMF has been detected in and purified from serum-free conditioned medium of murine B16-F1 melanoma cells. Under nonreducing conditions AMF migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band of Mr 55,000, whereas under reducing conditions it migrates as a single polypeptide of Mr 64,000. Two-dimensional polyacrylamide gel electrophoresis of the purified AMF resolved two polypeptides with isoelectric points of 6.35 (major) and 6.4 (minor). No carbohydrate side chains were detected in the B16-F1 AMF. Purified AMF stimulated B16-F1 cell migration in a dose-dependent fashion and bound directly in a protein-protein-binding assay to the AMF receptor, a cell surface glycoprotein of Mr 78,000 [glycoprotein (gp) 78]. The involvement of gp78 in AMF-stimulated function was demonstrated by motility assays. These results suggest that AMF is the natural ligand for the gp78-AMF receptor.