Lesion of septal-hippocampal neurons with 192 IgG-saporin alters function of M1 muscarinic receptors.

Cholinergic neurons projecting from the medial septum to the hippocampus were lesioned with the selective neurotoxin 192 IgG-saporin. Injection of 300 ng of 192 IgG-saporin into the medial septum produced a 60% decrease in choline acetyltransferase activity. M1 muscarinic receptor function was examined by measuring enhancement of evoked release of norepinephrine from rat hippocampal slices by the M1 selective agonist McN-A-343. In hippocampal slices from rats which were lesioned with 192-saporin, the response to McN-A-343 was reduced compared to sham-operated controls. Pirenzepine binding demonstrated no change in M1 receptor number or affinity. However, the curve for displacement of pirenzepine by the muscarinic agonist oxotremorine-M was shifted to the right in hippocampal tissue from lesioned rats. This shift was identical to that produced by addition of the non-hydrolyzable GTP analogue GppNHp, which uncouples the M1 muscarinic receptor/G-protein complex. These results suggest that lesion of septal-hippocampal cholinergic inputs causes uncoupling of the M1 muscarinic receptor, decreasing responsiveness to stimulation. These findings are similar to reports of decreased M1 muscarinic receptor coupling to G-proteins and loss of function in Alzheimer's disease. The 192 IgG-saporin lesion may provide a viable animal model in which to study uncoupling of G-proteins and M1 muscarinic receptors.

[Current results of endoscopic sphincterotomy for lithiasis of the common bile duct]. / Résultats actuels de la sphinctérotomie endoscopique pour lithiase de la voie biliaire principale.

Between January 1989 and June 1990, endoscopic sphincterotomy was performed in 308 consecutive patients with common bile duct stones (mean age: 74 years). Complete clearance of common bile duct was achieved at the first attempt in 65% of cases. This rate was significantly related to the size and the number of biliary stones. The success rate reached 97 percent after repeated endoscopic sessions (127 patients), mechanical lithotripsy (20 patients), extracorporeal or intracorporeal lithotripsy (18 and 11 patients, respectively). During the month following the endoscopic sphincterotomy, 39 patients (13%) developed one or more complications and 11 patients (3.7%) died. The complication rate was related to the time elapsed between biliary opacification and endoscopic sphincterotomy (P = 0.04) and between endoscopic sphincterotomy and total common bile duct clearance (P = 0.0007). No patient younger than 75 years died, but death occurred in 4.5% of the patients older than 75 years. Thirty patients (10%) developed endoscopic sphincterotomy-related complications. Cholangitis and bleeding were the most frequent complications (4 and 2%, respectively). Cholangitis occurred more frequently among the patients older than 75 (P < 0.05) or when transhepatic guided endoscopic sphincterotomy or intracorporeal lithotripsy was used (P < 0.005). Cholangitis led to death in 2 patients, 86 and 87 years old (0.7%). Endoscopic sphincterotomy related complications developed within 48 hours in all but 4 patients (2 patients with pancreatitis and 2 patients with cholecystitis).

Endoscopic sphincterotomy for suspected choledocholithiasis in patients with and without stones.

OBJECTIVE: To characterize a subgroup of patients treated with endoscopic sphincterotomy (ES) for a suspected common bile duct lithiasis (CBDL) that was not confirmed and to compare it with the subgroup with confirmed CBDL. METHODS AND RESULTS: Over 18 months, ES was successful in 245 consecutive patients (age 23-97, mean 75 yr, SE 17 yr) with suspected CBDL; 159 patients had CBDL (group 1), and 86 did not (group 2), as confirmed by CBD exploration. Fifty-nine percent of the patients in group 1 and 76.7% of the patients in group 2 had gallbladder in situ. Both groups were different for age (p < 0.001), prevalence of chronic alcoholism (p < 0.001), gallbladder in situ (p < 0.01), and gallbladder stones (p < 0.05). Patients from group 1 had two or more presenting symptoms suggestive of CBDL more often than patients from group 2 (p < 0.05), and pancreatitis was a more frequent presenting manifestation in group 2 (p < 0.0001). Overall morbidity and mortality were not different between groups, but acute cholecystitis developed in six patients from group 2 and in one patient from group 1 (p < 0.01). In a univariate analysis, only elevated alkaline phosphatase and a dilated common bile duct were positively discriminant for the diagnosis of CBDL; chronic alcoholism was negatively discriminant for the diagnosis of CBDL. In a multivariate analysis, only chronic alcoholism and a dilated bile duct were found to be independently discriminant. CONCLUSION: The risk of ES-related complications in the group without CBDL suggests that the selection of patients should be improved by a better use of preoperative criteria.