Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time and clinical sequelae. A prospective observational study.

BACKGROUND: In the diagnosis and treatment of biliary disorders, establishing percutaneous transhepatic biliary drainage (PTBD) is an invasive procedure that can potentially lead to infectious complications in both the short and long-term. We therefore prospectively analysed the time course and spectrum of biliary bacteria in patients undergoing PTBD. METHODS: Forty-nine patients (19 F, 30 M; mean age 64 years) with malignant (65%) or benign (35%) biliary disorders were included, 20 of whom had a newly established PTBD (group A), while the remaining 29 had already had their PTBD in situ (group B) for a mean of 8 months. Bacteriological analyses of bile and blood were carried out, and clinical symptoms and laboratory values were obtained. RESULTS: Biliary bacteria were found in 60% of cases during the initial PTBD placement, and 24 h later this rate had already increased to 85%; two or more microorganisms were found in 40% initially and in 70% after a few days. At later PTBD exchanges, bacteriobilia was found in 100%, with all patients harbouring multiple organisms. Whereas the initial spectrum was mixed, Escherichia coli and enterococci (97% each), Klebsiella (73%) and Bacteroides species (37%) later predominated; Candida increased initially from 15% to 80%, but later decreased to 30%. Clinical signs of cholangitis were observed in 30% initially (no sepsis), but decreased to 6% at later exchanges. CONCLUSIONS: Bacteriobilia is initially a frequent, and later a regular, event in PTBD; however, clinically significant complications are rare during the long-term course and limited to the initial, more invasive, phase of PTBD. A knowledge of the bacterial spectrum is important for selecting appropriate antibiotic coverage if complications arise and/or major interventions such as surgery are planned.

Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment.

BACKGROUND: It has been suggested that intrasphincteric injection of botulinum toxin (BTX) may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP) and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection). METHODS: Forty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients). Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX). The symptoms were assessed using a global symptom score (0-10), which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy. RESULTS: After BTX injection, there was a significant reduction in LOSP (before, 38.2+/-11.3 mmHg; 1 week after, 20.5+/-6.9 mmHg; 1 month after, 17.8+/-6.8 mmHg; P < 0.001). The global symptom score and symptom subscores (dysphagia, regurgitation, chest pain) were significantly decreased after 1 week and 1 month. When the beneficial effects following BTX injection were compared (untreated vs. pretreated), neither changes in LOSP nor beneficial effects on the symptom scores significantly differed. After 6 months, 67.7% of all treated patients were still in symptomatic remission (subgroups: previously untreated patients, 61.5%, n = 26; prior dilatation, 71.4%, n = 7; prior myotomy, 71.4%, n = 7; prior BTX, 73.9%, n = 8). CONCLUSIONS: BTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up.

BACKGROUND: Diffuse esophageal spasm is a rare esophageal motility disorder for which there are no satisfactory pharmacologic alternatives for treatment. The aim of this study was to investigate whether botulinum toxin (BTX) injection is an effective short- and long-term treatment for patients with symptoms caused by diffuse esophageal spasm. Whether recurrence of clinical symptoms can be successfully retreated by BTX injection was also studied. METHODS: Nine symptomatic patients (6 women, 3 men; 57-86 years) with manometrically proven diffuse esophageal spasm underwent BTX injection. One hundred IU BTX were diluted in l0 mL of saline solution and injected endoscopically at multiple sites along the esophageal wall beginning in the region of the lower esophageal sphincter and moving proximally in 1- to 1.5-cm intervals, and into endoscopically visible contraction rings. Symptom scores based on an analogue scale for dysphagia, regurgitation, and noncardiac chest pain were assessed before and after therapy, 1 day thereafter, and at 1 and 6 months. RESULTS: Symptoms improved immediately in 7 (78%) patients after 1 injection session. After 4 weeks 8 (89%) patients were in remission with a decrease in total symptom score. The total symptom score decreased from a median 8.0 (interquartile range: 6.75; 9.0) before treatment to 2.0 (1.5; 3.75) after 1 day (p < 0.01) and to 2.0 (interquartile range: 0.75; 3.0) after 1 month (p < 0.01). After 6 months all 8 patients with a response at 1 month still had a symptom score of 3 or less without further treatment. Subsequently 4 patients required reinjection 8, 12, 15, or 24 months after the initial treatment with similarly good results. No serious adverse effects were observed. CONCLUSIONS: BTX injection at several levels of the tubular esophagus is an effective treatment for patients with symptoms caused by diffuse esophageal spasm. Symptom relapse can be effectively treated by repeated BTX injection.

Treatment of achalasia: botulinum toxin injection vs. pneumatic balloon dilation. A prospective study with long-term follow-Up.

BACKGROUND AND STUDY AIMS: In patients with achalasia, intrasphincteric injection of botulinum toxin (BTX) has been suggested as an alternative regimen to balloon dilation and has been shown to be superior to placebo injection. The aim of the present study was to test the effectiveness, the long-term outcome and the cumulative costs of BTX injection in consecutive patients with symptomatic achalasia in comparison with pneumatic balloon dilation. PATIENTS AND METHODS: 37 patients, who presented with symptomatic achalasia between January 1994 and December 1996 were treated with either BTX injection (n = 23) or pneumatic dilation (n = 14). Patients with short-term or long-term symptomatic failures of the initial procedure were treated again, either with the same or with the alternative method, depending on the initial response and on the patient's wish. Symptoms were assessed using a global symptom score (0 - 10) which was evaluated before treatment and 1 week, 1 month and then every 6 months after the treatment. In addition, body weight and recurrence of symptoms were noted and manometry was carried out before and after treatment. The patients were regularly contacted for the long-term follow-up. RESULTS: There were significant improvements in the global symptom scores of all patients treated, in both the BTX injection group (before 8.2 +/- 1.3, after 3.0 +/- 1.6) and the dilation group (before 8.3 +/- 1.1, after 2.3 +/- 1.9). There was also a significant decrease of lower esophageal sphincter pressure after treatment in the BTX group and the dilation group. There were no significant differences with regard to overall treatment failure and long-term outcome between patients who had or had not received previous treatment. No major complications were encountered in either group. An actuarial analysis over 48 months comparing patients receiving BTX injection or balloon dilation demonstrated that after 12 months neither therapy was significantly superior. After 24 months a single pneumatic dilation was superior to a single BTX injection, and after 48 months all patients treated by BTX injection had experienced a symptomatic relapse. In contrast, 35 % of all patients treated by dilation and 45 % of patients treated successfully by dilation were still symptom-free in an intention-to-treat analysis after 48 months. When the overall costs of treatment and further treatment after recurrence were compared, dilation and BTX injection showed a similar cost-effectiveness (costs per symptom-free day) after 48 months. CONCLUSIONS: BTX injection, which can be performed in an outpatient setting, is as safe and cost-effective as balloon dilation in symptomatic achalasia. Taking into account the lower long-term efficacy of BTX injection therapy, however, it is an alternative only in a minority of older or high-risk patients.

Life-threatening gastrointestinal bleeding due to a jejunal lesion of Henoch-Schönlein purpura.

The case of a 56-year-old patient with Henoch-Schönlein purpura (HSP) and fulminant gastrointestinal bleeding is reported. The patient was admitted to hospital because of palpable purpura on both legs, painful joints and diffuse abdominal pain. Suspected HSP was histologically proven and treated with prednisolone. Despite recovery, acute gastrointestinal bleeding, with melena and a drop in hemoglobin concentration from 11.2 to 4.2 g/dl, occurred 30 days after medication was started. Immediate endoscopic examination of the upper gastrointestinal tract showed no signs of bleeding whereas colonoscopy showed fresh blood and blood clots in the terminal ileum and the colon. Since the bleeding source could not be detected endoscopically, mesenteric angiography was performed, demonstrating active bleeding from a jejunal artery. Thereafter the bleeding source was located by intraoperative peroral enteroscopy and treated by resection of a short segment of jejunum.

A new system for rapid large-caliber percutaneous transhepatic drainage in patients with obstructive jaundice: a prospective randomized trial.

UNLABELLED: BACKGROUND AND STUDY, AIMS: Percutaneous access to the biliary tract is an important diagnostic and therapeutic tool in the management of biliary diseases. It is usually chosen when the endoscopic approach via endoscopic retrograde cholangiopancreatography (ERCP) fails, or is not possible. Once established, the percutaneous tract is then used for the treatment of biliary stones and strictures. To establish a percutaneous tract with a caliber large enough for cholangioscopy to be performed, or for a large-bore permanent drainage tube to be inserted, stepwise dilation up to 14 Fr or 16 Fr is usually required. We present here a new method of rapid dilation using specially designed materials, including a stiffenable guide wire and specially adapted bougies. PATIENTS AND METHODS: Consecutive patients undergoing percutaneous drainage for biliary diseases were included in this prospective study, over a 19-month period. After establishment of a 10-Fr transpapillary drain, the patients were randomly assigned to either conventional percutaneous transhepatic biliary drainage (PTBD) or stepwise dilation using the new method, aiming at a need for only one further session, using a specially designed stiffenable metal guide wire of 6.6 Fr and plastic bougies. The details of the procedure (duration, materials used, technical ease), initial and later complications, assessment by the patients, and procedural costs were compared between the two groups. RESULTS: Of the 60 patients included, 29 were randomly assigned to group I (the new method) and 31 to group II (the conventional approach); there were no significant differences between the two groups in terms of clinical data or biliary pathology. The clinical efficacy of PTBD was similar in the two groups, although three patients in group II were switched to the new procedure because of failure of dilation using the conventional approach. The rates of major complications (four of 29 in group I, five of 31 in group II) and patient tolerance were also similar. However, the new procedure led to a significant reduction in the cumulative procedure duration (20.1 minutes vs 30.1 minutes), mean number of sessions (1.1 vs. 1.7), and mean number of hospital days (2.0 vs 5.5), and was therefore also cost-effective, reducing costs from a mean of 5813 to 2581 German marks (DM) per patient. CONCLUSIONS: The new system for rapid establishment of large-caliber PTBD offers significant advantages in terms of saving hospital resources while maintaining clinical efficacy.

[Hemosuccus pancreaticus (bleeding into the pancreatic duct). A rare complication of pancreatitis]. / Haemosuccus pancreaticus. Eine seltene Komplikation der Pankreatitis.

HISTORY AND ADMISSION FINDINGS: A 41-year-old man was admitted because of recurrent tarry stools and dizziness. Chronic pancreatitis induced by alcoholism was known. The main abnormal laboratory finding was anaemia (haemoglobin 4.6 g/dl, erythrocytes 2.28/fl). INVESTIGATIONS, TREATMENT AND COURSE: At endoscopy of the oesophagus, stomach and duodenum, fresh blood was found in the duodenum, a small trickle of blood coming from the papilla of Vater. Endoscopic retrograde cholangiography discovered no abnormality in the biliary system. Selective contrast imaging of the pancreatic duct demonstrated a short prepapillary stenosis and a prestenotic dilatation (up to 15 mm diameter) of the pancreatic duct with a cloudy contrast filling defect. After catheter withdrawal from the pancreatic duct blood spurted from the papilla. Emergency angiography revealed pseudoaneurysmatic dilatation of the gastroduodenal artery in the region of the head of the pancreas. At selective catheterization this artery was successfully occluded with metal coils placed both proximally and distally to the source of bleeding. CONCLUSION: Gastrointestinal bleeding is a rare but potentially life-threatening complication of pancreatitis. When searching for bleeding in the upper gastrointestinal tract, the papilla of Vater should be looked for as a possible source. Bleeding from the pancreas occurs particularly in pancreatitis, pancreatic pseudocyst or pancreatic tumour.

Long-term outcome in patients with advanced hilar bile duct tumors undergoing palliative endoscopic or percutaneous drainage.

OBJECTIVE: Advanced tumors of the hepatic duct bifurcation (Klatskin tumors) present problems to the endoscopist in deciding which procedure to use for palliative treatment of the resulting cholestasis--endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD), or both. There are technical difficulties with all forms of treatment for stenoses in the hilar region and intrahepatic bile ducts, and there are as yet no clear data on which type of drainage is feasible or preferable. SUBJECTS: 59 consecutive patients (30 men, 29 women; mean age 71 years) underwent palliative treatment for malignant hilar bile duct tumors of Bismuth stages II-IV during a three-year period (1992-94). METHOD: A retrospective analysis was carried out, and long-term follow-up data were obtained from telephone interviews with the patients, relatives, or referring physicians. RESULTS: The 59 patients were treated using ERCP (n = 20) or PTBD (n = 39). Three died within 30 days, and six were lost to follow-up. Clinically adequate drainage was achieved in 78% (n = 46) of the total patient group. Patient survival was a median of six months (range 0.5-38), and was slightly longer when the primary drainage procedure was successful (7.5 months). Initial complications occurred in 11% after ERCP and in 33% after PTBD, with a 30-day mortality of 5%. After the initial intervention, five patients who received ERCP treatment had to be switched to PTBD during the longer-term course. Three of these five patients died within 30 days of the PTBD insertion. CONCLUSIONS: Palliative treatment in patients with advanced Klatskin tumors is still suboptimal, even when combined endoscopic and percutaneous techniques are used in the same institution, allowing treatment to be tailored to the individual patient's needs. There is therefore a need for improvements in existing forms of treatment, as well as for the development of new forms of treatment.

Endohyperthermia--experimental evaluation of a new therapeutic approach for treatment of biliary carcinoma.

BACKGROUND AND STUDY AIMS: To improve the prognosis of patients with unresectable, locally advanced bile duct carcinoma, new treatment strategies need to be evaluated. Hyperthermia has been successfully applied as part of multimodal therapy in esophageal and rectal carcinoma. We performed in-vitro and in-vivo experiments with a new intraluminal hyperthermia system in the biliary tract. METHODS: A radiofrequency system (13.56 MHz, Endoradiotherm XERT-200A; Olympus Optical Co., Tokyo, Japan) was used with a special intraluminal microelectrode (diameter 4.5 mm, length 40 mm) covered by a silicone balloon with cooling water and a large counter electrode for focusing the electromagnetic field around the electrode. The heating capacity of the endohyperthermia unit was examined in vitro in a muscle-equivalent phantom (agar 4 %), in isolated livers of pigs and cows, as well as in vivo in anesthetized sheep. Continuous thermometry was done with thermosensors at the applicator surface, and with multichannel thermocouple probes in the environment of the applicator. RESULTS: Endohyperthermia induced a homogeneous heating of the phantom and the isolated liver bile duct preparation to a temperature > or = 40 degrees C in an area at least 10 mm in depth. After placement of the applicator into the common bile duct of anesthetized sheep, endohyperthermia led to a consistent and repeatable heating of the surrounding tissue to 40.5 +/- 0.5 degrees C at 1 cm distance, and 39.9 +/- 0.7 degrees C at 2 cm distance. Blood pressure, heart rate, and systemic temperature did not change in vivo. Histological examination of the bile duct showed superficial mucosal necrosis (depth 100-200 microm), microvascular damage with petechiae, congestion and edema of the bile duct wall and adventitia after hyperthermia treatment in vivo. CONCLUSIONS: The intraluminal endohyperthermia system produces consistent and repeatable heating of the surrounding tissue. Since effective thermal power can reach a depth of up to 2 cm, tumors may also be heated adequately.

Initial experience with a new Yamakawa-type prosthesis for long-term percutaneous transhepatic drainage.

BACKGROUND AND STUDY AIMS: In a previous study evaluating the problems of long-term percutaneous transhepatic biliary drainage (PTBD) using Yamakawa-type prostheses in patients with benign and malignant stenoses, breakage of the tube proved to be a serious problem, occurring in 19.7 % of PTBD exchanges. As a consequence of these results, a new PTBD tube made of Tecothane has been developed. PATIENTS AND METHODS: From September 1997 to September 1998, this new PTBD tube was applied in 64 patients (39 men, 25 women; median age: 70, range 29-89) in the treatment of benign (n = 30) or malignant stenoses (n=31; three stenoses remained indeterminate), and the course was followed. RESULTS: A total of 134 stent exchanges were performed, 52 of these being ahead of schedule (39 %). Not a single case of breakage occurred. However, other PTBD-related problems remained unchanged. Patients accepted the new prosthesis very well; among 19 patients who had experience of both the new one and the conventional one, 11 had preferences-eight for the new one and three for the old one. CONCLUSIONS: This new Tecothane prosthesis has solved the problem of PTBD breakage, which was often accompanied by serious problems. As was to be expected, other PTBD-related problems were not substantially affected. Nevertheless, this new tube represents progress in the percutaneous treatment of biliary stenoses.

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.

The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.

Long-term results of percutaneous transhepatic biliary drainage for benign and malignant bile duct strictures.

BACKGROUND: Long-term percutaneous transhepatic biliary drainage (PTBD) is a valid alternative to surgery in patients with benign or malignant bile duct strictures in whom endoscopic drainage has failed. However, few data are available on the long-term outcome with percutaneous drainage, specially when the application of Yamakawa-type prostheses is considered. METHODS: During 1996, 48 patients who were either treated with primary PTBD insertion followed by PTBD exchanges (n = 15) or who presented only for exchange of an earlier PTBD (n = 33) were included in the study. Thirty-one patients had malignant strictures, and 17 had benign ones. The PTBD catheters were scheduled for exchange every 3 months or earlier if signs and symptoms of obstruction or other problems were present. The data were collected prospectively during each follow-up visit and included both symptoms and the status and function of the PTBD at the time of exchange. RESULTS: Although PTBD was highly effective in relieving jaundice (progression of cholestasis was observed in only 2 cases), 73 of the 157 PTBD exchanges (47%) had to be carried out earlier than scheduled. Premature exchange was needed for clinical reasons, such as fever indicating PTBD dysfunction, in only 19% of these cases. The other reasons were related to the PTBD catheter and consisted of bile leakage alongside the drain (33%), PTBD disconnection or complete dislocation (30%), or occlusion suspected during regular flushing of the drain (15%). In most cases exchanging the drain was sufficient to solve the problem; in cases of complete dislocation, dilation of the same tract (n = 6) or fresh puncture and establishment of a new drainage site (n = 2) were necessary. Reducing the PTBD exchange interval from 3 to 2 months would have decreased the number of premature stent exchanges by 26%. CONCLUSIONS: Although PTBD is an effective method of biliary drainage, there are frequently minor problems-mostly catheter-related-which require premature exchange of the drain in almost half of the cases, and this may affect the patients' quality of life. Improvements in PTBD materials and catheter design are therefore needed. The effectiveness of reducing the intervals between PTBD exchanges should also be examined.

[Polyposis of the gastrointestinal tract as a manifestation of diffuse follicular lymphatic hyperplasia]. / Polypose des Gastrointestinaltraktes als Manifestation der diffusen follikulären lymphatischen Hyperplasie.

HISTORY AND ADMISSION FINDINGS: A 21-year-old previously healthy Turkish man who had been living in Germany for 15 years was admitted because of worsening cramp-like abdominal pain with nausea, vomiting and watery diarrhoea. Palpation elicited diffuse muscular guarding over the entire abdomen and a mass of about 8 cm in the right lower abdomen. INVESTIGATIONS: Abnormal laboratory results were erythrocyte sedimentation rate (55 mm), C-reactive protein (6.2 mg/dl), total bilirubin (2.1 mg/dl), creatine kinase (137 U/l) and thymidine kinase (5.5 U/l). There was a slight leucocytosis (13,700/microliter) and mild anaemia (haemoglobin 13.4 g/dl) with a normal differential count. Listeria ivanovii was repeatedly cultured from stool. Ultrasonography and computed tomography of the abdomen demonstrated a 6 cm mass in the right lower abdomen, splenomegaly (15.5 x 5 cm) and several lymphomas, up to 1.8 cm in diameter. Endoscopy revealed dense, in part grass-like, polyps, 3 to 6 mm deep, in the mucosa from the terminal ileum to the rectum, and to a lesser extent also in the duodenum. Histological examination of the polyps demonstrated diffuse follicular hyperplasia without evidence of malignancy. TREATMENT AND COURSE: On antibiotic treatment with ofloxacin (2 x 400 mg intravenously) the symptoms quickly regressed, but the endoscopic findings remained unchanged. CONCLUSION: Diffuse follicular lymphatic hyperplasia manifested itself in this patient as diffuse gastrointestinal polyposis. Listeria ivanovii cannot be ruled out as a causative factor.

Regulation of gastrin, somatostatin and bombesin release from the isolated rat stomach by exogenous and endogenous gamma-aminobutyric acid.

BACKGROUND/AIMS AND METHODS: gamma-Aminobutyric acid (GABA) is localized in epithelial cells and intrinsic nerve fibers of the gastric mucosa raising the possibility of a regulatory role for this transmitter. Therefore, it was the aim of the present study to examine the effect of exogenous and endogenous GABA on the neuroendocrine functions of the isolated perfused rat stomach. RESULTS: Infusion of GABA (10(-8), 10(-6), 10(-4) M) caused a significant increase in gastrin release by 187 +/- 98, 328 +/- 43 and 493 +/- 84 pg/20 min and a significant decrease in somatostatin secretion by -540 +/- 203, -867 +/- 96 and -893 +/- 195 pg/20 min, respectively. Release of bombesin-like immunoreactivity (BLI) remained unchanged during infusion of GABA at the concentrations employed. The gastrin and somatostatin responses to 10(-4) M GABA were completely inhibited by the GABA(A) antagonist bicuculline (10(-5) M) and the cholinergic blocker atropine(l0(-7) M), whereas the GABAB antagonist CGP 35348 (5 x 10(-5) M) was ineffective. To evaluate the contribution of endogenous GABA in the vagal regulation of gastric neuroendocrine functions, gastrin, somatostatin and BLI responses to electrical stimulation of the vagal nerves were examined in the presence of bicuculline. Vagal stimulation (10 V, 10 Hz, 1 ms) induced a significant inhibition of somatostatin release by - 518 +/- 78 pg/10 min, which was attenuated to -259 +/- 143 pg/10 min (p < 0.05) in the presence of bicuculline. Atropine (10(-7) M) turned vagally induced inhibition of somatostatin release into a stimulation by 928 +/- 266 pg/10 min which was not altered by additionally infused bicuculline. Vagally stimulated gastrin release was reduced from 397 +/- 47 to 217 +/- 72 pg/10 min (p < 0.05) by bicuculline, while atropine had no effect. Vagally induced BLI release was not altered by bicuculline and atropine. Since the effect of bicuculline on vagally induced gastrin release was independent of cholinergic mechanisms, a potential direct effect of GABA on gastrin release was examined in isolated rabbit antral G cells. In this preparation carbachol (10(-4) M) and neuromedin C (10(-9) M) significantly stimulated gastrin release from 2.6 +/- 0.4 to 4.9 +/- 0.3 and 8.5 +/- 0.9% of the total cellular content, respectively, while GABA (10(-10)-10(-3) M) changed neither basal nor carbachol- and neuromedin C-stimulated gastrin release. CONCLUSION: The present data confirm that exogenous GABA stimulates gastrin release and inhibits somatostatin release from the isolated rat stomach via GABA(A) receptors by activating cholinergic neurotransmission. Furthermore, it was shown for the first time that endogenous GABA contributes to the vagal regulation of gastrin and somatostatin release from the rat stomach. Inhibition of somatostatin secretion by endogenous GABA is mediated by cholinergic mechanisms, whereas stimulation of gastrin release is mediated by pathways unrelated to the cholinergic system and bombesin peptides.