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Background Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled. Methods Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors. Key Results Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect. Conclusions & Inferences Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.

To evaluate the changes occurring in the somatic innervation throughout the levator ani muscle in women with genitourinary prolapse and stress urinary incontinence (SUI).Thirty-four patients with genital prolapse entered the study and ten subjects with non-malignant pathologies acted as a control group. All patients were evaluated by urodynamic investigation and an electromyographic study of pelvic floor muscles to define the type of urinary incontinence. Biopsy samples were obtained from both groups of patients: the site of muscle biopsies were left and right part of perirectal pubococcygeus muscle. The evaluation of immunoreactivity was semiquantitative and based on staining intensity and distribution.In all cases, S-100 protein and NSE immunoreactivities were found in nerve fascicles running throughout the striated muscle. NPY and VIP positivities were more intense and diffuse, whereas SP immunoreactivity was quite scanty. The different patterns of NPY and VIP expression changed in relation to degree of genital prolapse and to the presence of SUI.Our immunohistochemical study shows the presence in the pelvic floor of neurons that are able to synthesize neuropeptides. The lower immunoreactivity score of same neuropeptides (VIP, NPY) observed among patients with third degree genital prolapse and with SUI could be related to biochemical damage of the neurons with subsequent lower production of chemical messengers.

Background Unlike chronic idiopathic intestinal pseudo-obstruction (CIIP), severe digestive syndromes that are not characterized by episodes resembling mechanical obstruction remain poorly characterized. The present study compared clinical features, small bowel motility, and quality of life (QoL) in patients with CIIP or severe functional gastrointestinal disorders (SFGID), compared to irritable bowel syndrome (IBS). Methods We enrolled 215 consecutive patients: 70 CIIP, 110 malnourished SFGID [body mass index (BMI) 17.8±1.8kgm -2] and 35 non-malnourished SFGID (BMI 22.8±3.6kgm -2). Key Results Abnormal motor patterns that fulfilled diagnostic criteria for small bowel dysmotility were virtually absent in IBS patients, but were recorded in69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 SFGID patients without malnutrition (65.7%) (P

BACKGROUND: Acute administration of the antitumoral drug cisplatin can induce nausea/emesis and diarrhea. The long-term effects of cisplatin on gastrointestinal motility, particularly after repeated administration, are not well known. Because cisplatin is highly neurotoxic, myenteric neurons can be affected. Our aim was to study the prolonged effects of repeated cisplatin administration in a rat model, focusing on gastrointestinal motor function and myenteric neurons. METHODS: Rats received saline or cisplatin (1 or 3 mg kg(-1), i.p.) once weekly for 5 weeks. One week after treatment, both upper gastrointestinal transit and colonic activity were evaluated, and tissue samples from ileum, colon and rectum were processed for histological analysis. Intestinal transit was measured invasively (charcoal method). Colonic activity was determined electromyographically. The gut wall structure was evaluated in sections using conventional histology and immunohistochemistry. Whole-mount preparations from the distal colon were labeled for different markers, including nitric oxide synthase (NOS) and calcitonin-gene related peptide (CGRP) to determine relative proportions of myenteric neurons vs the total neuronal population labeled with HuC/D. KEY RESULTS: One week after repeated cisplatin exposure, the upper gastrointestinal transit rate and colonic activity were dose-dependently reduced. The number of NSE- or HuC/D-immunoreactive myenteric neurons per ganglion was decreased; the proportion of CGRP-immunoreactive neurons was decreased, whereas that of NOS-immunoreactive cells was increased. CONCLUSIONS & INFERENCES: Chronic cisplatin may induce an enteric neuropathy characterized by changes in myenteric neurons associated with marked gastrointestinal motor dysfunction.

Acute infectious gastroenteritis is the strongest known risk factor for the development of irritable bowel syndrome (IBS), one of the most common functional gastrointestinal disorders. The knowledge about the incidence and prevalence of post-infectious IBS (PI-IBS) in the general population is still limited. Risk factors have been identified in the development of PI-IBS. These include the virulence of the pathogen, younger age, female sex, the long duration of the initial illness and the presence of psychological disturbances. Histopathologic data demonstrate a low-grade mucosal inflammation in a subset of patients with IBS. Furthermore, a change in intestinal microflora could also be involved although confirmatory studies are required. The use of probiotics or non absorbable antibiotics during the acute infective episode could play a preventive role. Nonetheless, the discovery that an infective episode may trigger the development of IBS has not substantially changed the clinical management of this subset of patients compared to the classical (non infective) form of IBS. Future studies aimed at identifying specific therapies are waited.

Zollinger-Ellison syndrome (ZES) is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumor of the pancreas (gastrinoma). ZES is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of ZES is certain when the plasma gastrin is1000 pg/mL and the basal acid output is15 mEq/h in patients with an intact stomach,5 mEq/h in gastrectomised patients, or when the hypergastrinemia is associated with a pH2. Treatment is based on the control of gastric acid hypersecretion and of the malignant tumor and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered at high dosages without drug-related adverse effects. All sporadic, localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like cells, and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy and/or interferon are indicated only in patients with malignant progressive disease. Embolisation and chemoembolisation are effective in controlling clinical symptoms; however, they do not seem to improve survival.

BACKGROUND AND STUDY AIMS Methods of lubrication are rarely considered to be a matter for study in gastrointestinal endoscopy. We evaluated a new technique, i. e. the release of seed oil in discrete amounts from the tip of the scope during colonoscopy. PATIENTS AND METHODS 346 consecutive patients prospectively underwent colonoscopy with a standard lubricating method (using water-soluble jelly; group A) or with the standard method plus seed oil (corn oil) instillations through the biopsy channel (group B). The following variables were evaluated in the two groups: the success rate for total intubation, and the time required to reach the cecum; the time needed to examine the colon at withdrawal; the detection rates for colorectal diseases; the level of pain and degree of difficulty associated with the examination. Patients in whom total colonoscopy was not achieved were asked to undergo a further examination in which the other lubricating technique was used. RESULTS Successful intubation to the cecum was significantly more frequent ( P < 0.005) in the oil lubrication group (group B, 159/168) than in the control group (group A, 145/170), and less time was needed ( P < 0.001). No significant differences were found with regard to time for examination at withdrawal and detection rates for colorectal diseases. Level of pain and degree of difficulty during colonoscopy were significantly lower in the oil group ( P < 0.001). In the cross-over examinations done in patients in whom total colonoscopy was not achieved, no statistical difference was found between the two groups. We observed no side effects for patients or damage to the instrument. CONCLUSIONS The proposed technique could be a simple, safe, and inexpensive method for easier and less painful colonoscopy; moreover, it might facilitate difficult examinations. Further studies are needed to confirm our data and to ensure that the use of this technique is not liable to damage the scope.

We report a case of serum pancreatic hyperenzymemia as a primary manifestation of sarcoidosis; pancreatic involvement was confirmed by endoscopic ultrasonography which revealed a notable glandular fibrosis of the pancreas. It is important that patients with systemic sarcoidosis who have increased serum levels of amylase and lipase be checked in order to detect the presence of possible pancreatic involvement. Endoscopic ultrasonography represents the technique of choice used to confirm the clinical suspicion of pancreatic inflammation.

Irritable bowel syndrome (IBS) is one of the most common gut functional diseases, affecting 10-20% of people worldwide. Although most patients do not seek medical help, the disease accounts for huge costs for both patients and health-care systems and worsens significantly patients' quality of life. Diagnosis is based on the identification of symptoms according to Manning, Rome I and Rome II criteria and exclusion of alarm indicators. IBS symptoms overlap with those of coeliac disease, lactose intolerance, food allergies and bile salt malabsorption. The treatment of IBS is centred on an excellent doctor-patient relationship along with drugs targeting the predominant symptom, especially during exacerbations. Current pharmacological remedies are unsatisfactory due to the high number of patients complaining of lack of response and/or symptom recurrence. Although useful in some IBS patients, the validity of psychotherapy deserves further investigation. A wide array of potentially useful drugs are currently under consideration in pre-clinical trials. A better understanding of the pathogenetic mechanisms underlying IBS may help to develop more effective drugs for this disease.

Irritable bowel syndrome (IBS) is a functional, multifactorial disease characterized by abdominal pain and erratic bowel habit. Changes in gastrointestinal motor function, enhanced perception of stimuli arising from the gut wall and psychosocial factors are thought to be major contributors for symptom generation. In recent years, several additional factors have been identified and postulated to interact with these classical mechanisms. Reduced ability to expel intestinal gas with consequent gas trapping and bowel distension may contribute to abdominal discomfort/pain and bloating. Abnormal activation of certain brain regions following painful stimulation of the rectum suggests altered processing of afferent signals. An acute gastrointestinal infection is now a recognized aetiological factor for symptom development in a subset of IBS patients (i.e. post-infectious IBS), who are probably unable to down-regulate the initial inflammatory stimulus efficiently. Furthermore, low-grade inflammatory infiltration and activation of mast cells in proximity to nerves in the colonic mucosa may also participate in the frequency and severity of perceived abdominal pain in post-infectious and non-specific IBS. Initial evidence suggests the existence of changes in gut microflora, serotonin metabolism and a genetic contribution in IBS pathophysiology. These novel mechanisms may aid a better understanding of the complex pathophysiology of IBS and to develop new therapies.

Acute colonic pseudo-obstruction (Ogilvie's syndrome) can be defined as a clinical condition with symptoms, signs and radiological appearance of acute large bowel obstruction unrelated to any mechanical cause. Recent reports of the efficacy of cholinesterase inhibitors in relieving acute colonic pseudo-obstruction have fuelled interest in the pharmacological treatment of this condition. The aim of the present review is to outline current perspectives in the pharmacological treatment of patients with acute colonic pseudo-obstruction. The best documented pharmacological treatment of Ogilvie's syndrome is intravenous neostigmine (2-2.5 mg), which leads to quick decompression in a significant proportion of patients after a single infusion. However, the search for new colokinetic agents for the treatment of lower gut motor disorders has made available a number of drugs that may also be therapeutic options for Ogilvie's syndrome. Among these agents, the potential of 5-hydroxytryptamine-4 receptor agonists and motilin receptor agonists is discussed.

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory-motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori-related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role. H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long-term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa. The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori-related dyspepsia and prompt innovative therapeutic approaches.

The role of antibiotic therapy on Salmonella faecal excretion is controversial. Acute Salmonella gastroenteritis induces long-lasting digestive symptoms in up to one-third of subjects. The role of antimicrobial therapy on persistent post-infectious symptoms is unknown.To investigate the role of antibiotic therapy on long-term germ faecal excretion and digestive symptoms after Salmonella infection.1543 subjects [518 aged between 3 and 5 years (35.3%); 950 between 6 and 10 years (64.7%) and 75 adults (4.9%)] involved in a single outbreak of Salmonella enteritis fulfilled the study criteria by repeating stool cultures and answering a symptom questionnaire 3 months post-infection.327 subjects (21.2%) were treated with antibiotics during the acute infection [121 children aged 3-5 years (23.4%), 175 children aged 6-10 years (18.4%) and 31 adults (41.3%)]. Antibiotic treatment did not affect Salmonella excretion at any of the time points studied up to three months post-infection in any age group as compared to age-matched untreated controls. Persistent digestive symptoms were more common among the patients treated with antibiotics (9.5% vs. 2.9%; P=0.003).Antibiotic therapy does not affect Salmonella enteritis excretion. Digestive symptoms after clearance of the infectious agent are significantly higher in patients treated with antibiotics during acute gastroenteritis.

Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days.To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours.A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months).In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed.Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = -0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy.

The morphological pattern and motor correlates of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) innervation in the human isolated gastric fundus was explored. By using the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-diaphorase and specific rabbit polyclonal NO-synthase (NOS) and VIP antisera, NOS- and VIP-containing varicose nerve fibres were identified throughout the muscle layer or wrapping ganglion cell bodies of the myenteric plexus. NOS-immunoreactive (IR) neural cell bodies were more abundant than those positive for VIP-IR. The majority of myenteric neurones containing VIP coexpressed NADPH-diaphorase. Electrical stimulation of fundus strips caused frequency-dependent NANC relaxations. N(G)-nitro-L-arginine (L-NOARG: 300 microM) enhanced the basal tone, abolished relaxations to 0.3 - 3 Hz (5 s) and those to 1 Hz (5 min), markedly reduced ( approximately 50%) those elicited by 10 - 50 Hz, and unmasked or potentiated excitatory cholinergic responses at frequenciesor =1 Hz. L-NOARG-resistant relaxations were virtually abolished by VIP (100 nM) desensitization at all frequencies. Relaxations to graded low mechanical distension (or =1 g) were insensitive to tetrodotoxin (TTX: 1 microM) and L-NOARG (300 microM), while those to higher distensions (2 g) were slightly inhibited by both agents to the same extent ( approximately 25%). In the human gastric fundus, NOS- and VIP immunoreactivities are colocalized in the majority of myenteric neurones. NO and VIP mediate electrically evoked relaxations: low frequency stimulation, irrespective of the duration, caused NO release only, whereas shortlasting stimulation at high frequencies induced NO and VIP release. Relaxations to graded mechanical distension were mostly due to passive viscoelastic properties, with a slight NO-mediated neurogenic component at 2 g distension. The difference between NO and VIP release suggests that in human fundus accommodation is initiated by NO. British Journal of Pharmacology (2000) 129, 12 - 20

Emerging evidence suggests that infection by CagA-positive Helicobacter pylori strains is related to the development of more serious gastroduodenal diseases, thus conferring to the determination of anti-CagA antibodies a relevant clinical significance in serological screenings. The detection of anti-CagA positivity in sera negative for anti-H. pylori antibodies raises the question of whether this apparently nonsense result is merely due to a false positive reaction. To address this issue, we compared three different methods for the detection of anti-CagA antibodies. In all, 272 selected sera from patients with precisely defined H. pylori status (positive or negative concordance of five tests, ie, histology by Giemsa in both antrum and corpus, rapid urease test, culture, [13C]urea breath test, IgG ELISA) were tested for anti-CagA reactivity by three different techniques (western immunoblotting, ELISA, and recombinant immunoblotting assay). In order to assess the sensibility and specificity of each tests, we considered as "true" anti-CagA positive sera those with two out of three positive results. Sera from 70% of H. pylori-positive patients and 10% from H. pylori-negative patients turned out to be "true" positives for anti-CagA antibodies. The three methods showed similar excellent results, in terms of both sensitivity and specificity, always over 93%. It is confirmed that a proportion of patients with a negative conventional serology against H. pylori possess anti-CagA antibodies in their sera. In this paper we demonstrate that it can happen even in patients without any biological signs of actual H. pylori infection. The possibility that this can be due to a false positive laboratory result is very likely ruled out by the accuracy of the three methods used. The clinical management of these patients needs further study on larger series.

A 37-year-old male patient, without any particular symptoms apart from moderate right upper quadrant postprandial pain, was found to have a liver mass identified as a glucagon-producing tumor. Plasma glucagon levels were slightly increased, whereas those of other gut peptides were within the normal range. Despite an extensive pre- and intraoperative diagnostic work-up, a presumed primary glucagonoma remained undetected. This unusual presentation with the absence of any symptoms typical of glucagonoma, as well as the presence of histopathological features characteristic of both benign and malignant forms of glucagonoma, make this case very peculiar. A clinically silent, apparently unrelated adenocarcinoma of the left colon was also found. The concomitant presence of a glucagonoma and a carcinoma of the large intestine has not been previously reported, and its significance remains unclear.

In 153 consecutive patients with cirrhosis we assessed: (1) the prevalence of IgG to Helicobacter pylori and compared it with that found in 1010 blood donors resident in the same area; and (2) the relationships of IgG to Helicobacter pylori with clinical and endoscopic features and with the risk of peptic ulcer. The IgG to Helicobacter pylori prevalence of cirrhotics was significantly higher than in blood donors (76.5% vs 41.8%; P0.0005) and was not associated with sex, cirrhosis etiology, Child class, gammaglobulins and hypertensive gastropathy. In both groups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Among patients with cirrhosis a significantly higher prevalence of Helicobacter pylori was found in patients with previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) and patients with peptic ulcer (P = 0.0004). Multivariate analysis identified increasing age and male sex as risk factors for a positive Helicobacter pylori serology and no independent risk factors for peptic ulcer. The high prevalence of Helicobacter pylori-positive serology found in the present series is related to age and sex and might also be explained by previous hospital admissions and/or upper gastrointestinal endoscopy. Our results do not confirm the role of Helicobacter pylori as risk factor for peptic ulcer in patients with liver cirrhosis.

Endoscopic screening of all dyspeptic patients is not cost-effective, nor is it feasible in many health-care delivery systems. To select the most appropriate candidates, various preendoscopic screening strategies have been proposed, some of which include Helicobacter pylori serology and patient age. We assessed the value of these two criteria in preendoscopic screening of a large series of dyspeptic patients, and compared the results obtained in a referral hospital (university center with an extensive H. pylori research program) with those in nonreferral hospital (participating centers that did not have such a program).Blood samples for determination of anti-H. pylori IgG antibody were collected from patients with uninvestigated dyspepsia undergoing endoscopy at one referral hospital and in 93 nonreferral hospitals throughout Italy. For IgG antibody assay, an in-house enzyme-linked immunosorbent assay (ELISA) technique was used in the referral hospital, while a commercial kit was used in the nonreferral hospitals.A total of 1638 patients were evaluated at the referral hospital (845 men and 793 women, mean age 46.1 years, range 18-89), and 3281 at the nonreferral hospitals (1718 men and 1563 women, mean age 48.8, range 18-96), respectively. If endoscopy had not been performed in patients who were seronegative for H. pylori and younger than 45 years, 19% versus 17.5% of the tests would have been avoided in the referral and nonreferral hospitals, respectively, while six of 304 ulcers (2%) and no cancers would have been missed versus 35 of 557 ulcers (6.3%) and two of 557 cancers (0.3%).A screening strategy based on age and H. pylori serology is a valid means of selecting dyspeptic patients for endoscopy; however, the policy needs further refinement for use in nonreferral hospitals.

It has been showed that peptic ulcer is more frequent in patients with liver cirrhosis, is associated with the severity of cirrhosis, and occurs without upper abdominal pain in up to 70% of patients and with complications in 29%. The aim of this study was to retrospectively assess the characteristics of peptic ulcer in a large series of patients with liver cirrhosis.In this retrospective study the consecutive records of 1,748 endoscopies, performed in patients with liver cirrhosis during a period of 14 years, were reviewed to evaluate the frequency and clinical characteristics of peptic ulcer.The ulcer prevalence was 6.3%, and 77.5% of the ulcers were asymptomatic. Complications from ulcer were present in 29% of all patients and in 32% of those who has the first diagnosis of ulcer during the study. Patients with asymptomatic ulcer had a more decompensated cirrhosis. After healing, 20%-25% of the recurrent ulcers had complications while patients were on standard maintenance treatment.This retrospective study confirms the high frequency of peptic ulcer in patients with liver cirrhosis. It also confirms that the peptic ulcer in these patients is very often asymptomatic and associated with concurrent complications, especially in those with more severe liver disease. The complication rate in recurrent ulcers was 20%-25%. However, due to the retrospective nature of this study, after ulcer healing the endoscopic follow-up was irregular. Regularly repeated endoscopy should be carried out in patients with liver cirrhosis and peptic ulcer to diagnose new and recurrent ulcers and to prevent related complications.

Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome comprises tumors or hyperplasia of different glands, including parathyroid, pituitary, adrenal cortex and the gastroenteropancreatic system. The vast majority of MEN 1 are found in familial clusters, although a few cases are sporadic. Hypercalcemia and/or nephrocalcinosis are the first and most common clinical manifestation in familial MEN 1 syndrome, followed by islet cell tumors (especially those secreting gastrin or insulin) and pituitary dysfunction due to either functioning or non-functioning microadenomas. Genetic studies indicate that familial MEN 1 syndrome is inherited through a dominant gene with incomplete penetrance and variable expression. The diagnosis of MEN 1 syndrome is mainly based on the careful assessment of the clinical history, symptoms physical evaluation along with the assay of serum electrolytes (i.e., calcium, phosphorus, etc.) and hormonal substances (i.e., gastrin, insulin, pancreatic polypeptide, prolactin, adrenocorticotropic hormone, etc.). In addition, several provocative tests have been used to identify endocrine tumors (particularly those of the gastroenteropancreatic system) and imaging techniques play a crucial role for the diagnostic approach in MEN 1 syndrome. Even though in the long term, the prognosis of MEN 1 syndrome is unfavourable. Recently, however, many therapeutic strategies, including both surgical and pharmacological options, have been developed to reduce the size of the neoplasm and control symptoms associated with hormone oversecretion.

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

SUMMARY Background: Pantoprazole is a new substituted benzimidazole which inhibits gastric H+,K+-ATPase. Methods: In this double-blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary–Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks. Results: The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4 % in the pantoprazole and omeprazole groups, respectively (P > 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P > 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events. Conclusion: Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.

In the present study we evaluated the efficacy and tolerability of two different therapeutic schedules in eradicating Helicobacter pylori. Forty-six consecutive patients (suffering from either peptic ulcer or non-ulcer dyspepsia) with helicobacter pylori infection were randomly allocated to one of the following two groups: group 1 (n = 23) 2 weeks of treatment with bismuth subcitrate tablets (120 mgx4) + amoxycillin capsules (500 mgx4) + metronidazole tablets (250 mgx4); group 2 (n = 23) 2 weeks of treatment with amoxycillin capsules (500 mgx4) + metronidazole tablets (250 mgx4). Endoscopy, histology and bacterial culture were performed at entry, and 30 and 90 days after treatment. Two group 1 patients and one group 2 patient did not complete the treatment. Successful eradication was obtained in 20/21 (95%) patients treated with triple therapy (group 1) and in 17/22 (77%) patients treated with double therapy (group 2) (p = 0.2). Side-effects occurred in 9/21 (43%) patients of group 1 and in 9/22 (41%) patients of group 2 (p = 0.9). These were all self-limiting and required no specific treatment. These data suggest that combined therapy with amoxycillin and metronidazole, with or without bismuth subcitrate, represents a safe and effective therapeutic approach for the treatment of Helicobacter pylori infection. In our series, triple therapy determined a numerically higher eradication rate than double therapy.

The development of effective antisecretory drugs has risen the question of what is the ideal inhibition of gastric acid secretion in the treatment of peptic ulcer. Cimetidine, unlike the more recent H2-blockers and proton pump inhibitors, exerts antisecretory effects that are correlated to the blood levels of the drug. For this reason, therapeutic posologies were initially based on the pharmacokinetic features of the drug, while, more recently, direct measurement of intragastric acidity have assumed great relevance. Despite extensive research, the ideal level of gastric acid inhibition in the treatment of peptic ulcer has not been established. Greater healing rates are achieved by more potent antisecretory drugs and the duration of treatment appears to be also important, particularly to the healing of gastric ulcers. Whether the course of peptic ulcer disease is affected by the potency of the drug employed in the treatment of acute episodes has not been established.

Editor—Agreus and Talley’s recommendations for the use of Helicobacter pylori testing in the management of patients with newly appeared dyspepsia1 differ from published guidelines.2,3 They consider eradication therapy an acceptable alternative to endoscopy for patients with a positive test result when access to this investigation is difficult. This alternative option is probably a fait accompli in primary care. In June 1995 I sent a questionnaire to all 298 general practitioners in north and east Devon asking how they would use H pylori testing for the management of patients with dyspepsia. After a reminder questionnaire, 271 general practitioners (91%) responded. The table shows the results. Only 73 (27%) said they would limit the use of this test to younger patients (under 50 years of age) as recommended by published guidelines at the time.2 Eighty five did not know when to use the test but many of these said how they would manage patients with a positive result. Most general practitioners (73%) would use eradication therapy rather than endoscopy in younger patients with a positive test result. Seventy eight (29%) said they would also attempt eradication therapy in older patients. At the time of the survey patients referred for endoscopy had to be placed on a waiting list. General practitioners might have preferred to prescribe antibiotics for dyspeptic patients with a positive H pylori result, which is likely to cure a possible peptic ulcer, rather than wait too long for the diagnosis to be confirmed by endoscopy. I thank all general practitioners in north and east Devon district for their cooperation and Dr I Morrel for his help in designing the questionnaire.

A multi-center study was carried out to compare the healing rates of ranitidine 300 mg nocte and 150 mg b.i.d. in the short-term treatment of gastric ulcers and to assess the side-effect liability of ranitidine 300 mg given in a single daily dose. Forty-five outpatients suffering from endoscopically and bioptically proven uncomplicated benign gastric ulcer were selected for the study. The patients were treated, for 4 weeks, on the basis of a double-blind randomized design. An endoscopic examination was repeated within 4 days after the end of the treatments. The patients who did not demonstrate complete healing were treated for an additional 4-week period. Clinical controls were performed to evaluate symptoms, antacid consumption, compliance with trial tablet consumption; hematological and biochemical tests were also carried out at the end of the 4 and 8-week periods. No differences were observed between the healing rate induced by 300 mg nocte and 150 mg b.i.d., after 4 weeks of treatment (76% and 79% respectively) and after 8 weeks (100% in both groups). Similar results were obtained as far as symptoms, antacid consumption and compliance are concerned. Neither treatment regimen induced appreciable side-effects.

A case of single, polypoid metastatic malignant melanoma of the gallbladder is described. The differential diagnosis with primary malignant melanoma and undifferentiated carcinoma is discussed.