Adjuvant-induced joint inflammation causes very rapid transcription of beta-preprotachykinin and alpha-CGRP genes in innervating sensory ganglia.

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical inflammatory arthritis. We examined the very early changes in response to adjuvant injection in a rat model of unilateral tibio-tarsal joint inflammation and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and hyperalgesia were apparent, and marked increases in beta-preprotachykinin-A (beta-PPT-A) and alpha-calcitonin gene-related peptide (CGRP)-encoding mRNAs were observed in small-diameter L5 DRG neurones innervating the affected joint. This response was augmented by recruitment of additional small-diameter DRG neurones expressing beta-PPT-A and CGRP transcripts. The increased mRNA was paralleled by initial increases in L5 DRG content of the protein products, substance P and calcitonin gene-related peptide. Within 15 min of adjuvant injection there were increases in electrical activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in beta-PPT-A and CGRP mRNA expression in DRG neurones. Increased expression of heteronuclear (intron E) beta-PPT-A RNA suggests that increases in beta-PPT-A mRNA levels were, at least in part, due to transcription. Pre-treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAS: This and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.

Analysis of the risk factors associated with endoscopic sphincterotomy techniques: preliminary results of a prospective study, with emphasis on the reduced risk of acute pancreatitis with low-dose anticoagulation treatment.

BACKGROUND AND STUDY AIMS: The aim of the present study was to analyze the risk factors associated with complications of endoscopic sphincterotomy (ES). PATIENTS AND METHODS: In all consecutive endoscopic sphincterotomies carried out between September 1994 and December 1996, the possible risk factors (12 patient-related factors and 12 procedure-related ones), as well as the concomitant medical treatment, indications, techniques, and success of endoscopic sphincterotomy were evaluated prospectively. Risk factors were analyzed on an exploratory basis using univariate methods. "Potential risk factors" (univariate, P<0.1) underwent multivariate analysis to determine independent "risk factors" (multivariate, P<0.05). In addition, the complication rate was calculated according to the number of potential risk factors present. RESULTS: A total of 438 patients who underwent ES were analyzed. Complications occurred in 7.5% (n = 33; acute pancreatitis 4.3%, hemorrhage 2.3 %, cholangitis 0.9%, technical 0.2%). Statistical analysis of the complications identified three independent risk factors (coagulopathy, patient age (< or =60 years, pancreas divisum), and one protective factor (pancreatic duct obstruction). The frequency of acute pancreatitis was increased by two independent risk factors (pancreas divisum, ES frequency <40 procedures/year) and was reduced if low-dose anticoagulation (unfractionated heparin or low molecular weight heparin) was administered (0.9%, one of 115 vs. 5.8%, 18 of 313; P<0.05). The effect of anticoagulation was not confounded by the presence or absence of other potential risk factors for acute pancreatitis. Neither the risk nor the severity of hemorrhage were increased by low-dose anticoagulation. Due to the low number of events, only potential risk factors for hemorrhage were identified (coagulopathy, intensive-care treatment). The overall complication rate and the incidence of pancreatitis and hemorrhage increased significantly depending on the number of simultaneous potential risk factors present (P<0.0001). CONCLUSIONS: Patients at risk for complications after endoscopic sphincterotomy can be identified by risk factor analysis. These data suggest the hypothesis that low-dose anticoagulation prior to endoscopic sphincterotomy reduces the risk of acute pancreatitis after sphincterotomy.

Safety and efficacy of pancreatic sphincterotomy in chronic pancreatitis.

BACKGROUND: Endoscopic pancreatic sphincterotomy (EPS) is being performed with increasing frequency as a prerequisite to interventional measures in the pancreatic duct. The aim of this study was to evaluate EPS with regard to technique, success, complications, and mortality in patients with chronic pancreatitis. METHODS: Between January 1989 and September 1996, the results of all consecutive EPSs in patients with chronic pancreatitis were documented in a standardized form. Patients were followed by clinical investigation and blood sample analysis at 4, 24, and 48 hours after EPS. Complications were classified according to commonly accepted criteria. RESULTS: EPS was performed in 118 patients with chronic pancreatitis (men 75%, women 25%, 48+/-10 years). Ninety-four patients (80%) underwent guidewire-assisted EPS, and 24 patients (20%) underwent needle-knife EPS. Seventy-seven EPS procedures (65%) were primarily successful (guidewire EPS: 60 of 94, 64%; needle-knife EPS: 17 of 24, 71%). Additional endoscopic cutting techniques (needle-knife papillotomy, biliary endoscopic sphincterotomy) were required in 41 patients (35%). In total, EPS was successful in 116 patients (98%). The complication rate was 4.2% (4 cases of moderate pancreatitis, 1 severe bleeding, no deaths). All complications were managed nonoperatively. CONCLUSIONS: In patients with chronic pancreatitis, EPS with a standard sphincterotome or with a needle-knife offers an effective and reliable approach to the pancreatic duct system. Additional cutting techniques may be necessary in approximately one third of cases before an EPS can be successfully performed. The complication rate of EPS in patients with chronic pancreatitis appears to be lower than the complication rate of biliary sphincterotomy for other indications.