Symptoms and gastric functions in dyspepsia--goodbye to gastroparesis or to inadequate studies?
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Biomedical subjects
Publications and source records attributed to V Stanghellini.
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BACKGROUND AND STUDY AIMS: 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). PATIENTS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.
BACKGROUND: Helicobacter pylori eradication is recommended currently only in peptic ulcer patients. The accumulating evidence of a possible pathogenetic role of the germ in other pathological conditions, such as mucosa-associated lymphoid tissue lymphomas and (possibly) also functional dyspepsia and gastric cancer, creates increasing pressure in favor of an expansion of such indication. However, at present, cultural and practical considerations should discourage widespread screening and eradication programs. METHODS: The basis for our study is a critical review of the literature. RESULTS: The lack of a sound pathophysiological basis linking H. pylori infection to both dyspeptic symptom perception and gastric cancer risk sharply contrasts with the numerical and clinical relevance of these pathological conditions. Screening tests are not sufficiently cheap, easy, and reliable to be applicable on a large scale. Also, eradication therapies may provide suboptimal therapeutic effects and excessive side effects if applied by physicians who are not prepared culturally. CONCLUSIONS: Improvement of pathophysiological, diagnostic, and therapeutic knowledge must be achieved before eradication programs can be proposed on a large scale.
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Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation, ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.
BACKGROUND & AIMS: Although gastric dysmotility and dyspeptic symptoms are often associated, their relationship remains unclear. The aim of this study was to evaluate the relationship between gastric emptying abnormalities and clinical features in functional dyspepsia. METHODS: In 343 patients with functional dyspepsia, the gastric emptying of solids was measured by a radioisotopic technique and four dyspeptic symptoms (epigastric pain and burning, postprandial fullness, nausea, and vomiting) were measured as absent, mild, relevant, and severe, according to their influence on patients' usual activities. RESULTS: Delayed gastric emptying was detected in 33.5% of dyspeptics. Delayed gastric emptying was particularly frequent in patients characterized by female sex, low body weight, presence of relevant and severe postprandial fullness, nausea, vomiting, and absence of relevant and severe epigastric pain. Logistic regression showed that delayed gastric emptying was invariably associated with female sex and postprandial fullness (odds ratio, 2.34; 95% confidence interval, 1.45-3.75) and vomiting (odds ratio, 4.04; 95% confidence interval, 1.30-12.54) when coded as severe and only postprandial fullness (odds ratio, 3.78; 95% confidence interval, 1.78-8.01) when coded as relevant and severe. CONCLUSIONS: Female sex, relevant and severe postprandial fullness, and severe vomiting are independently associated with delayed gastric emptying of solids in patients with functional dyspepsia seen in a referral center.
OBJECTIVE: To evaluate the effect of weight loss induced by dietetic treatment, with or without an intragastric balloon, on gastric emptying of obese subjects. SUBJECTS: 20 morbidly obese subjects (21-54 years, 45.3-58.0 kg/m2) and 20 healthy controls (21-56 years, 20.3-24.8 kg/m2). DESIGN: Parallel study of a 4 month, low calorie dietetic treatment with or without a 500 ml intragastric balloon. RESULTS: In basal conditions, obese subjects had accelerated gastric emptying as compared to healthy controls. At the end of the dietetic treatment period, a significant decrease of body weight was obtained. Patients also showed a slowing of gastric emptying. Both the weight loss and the slowing of gastric emptying occurred irrespective of the presence or absence of the intragastric balloon. CONCLUSION: The present findings are compatible with the hypothesis that gastric emptying, food intake and body weight are integrated parameters in subjects with morbid obesity.
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.
BACKGROUND & AIMS: Nitric oxide, a putative cellular messenger synthesized from L-arginine, is a powerful modulator of gastric motility and secretions. The aim of this study was to investigate whether (1) guinea pig gastric chief cells express NO synthase, (2) NO modulates the pepsinogen secretion and guanosine 3',5'-cyclic monophosphate (cGMP) generation induced by calcium (Ca2+)-mediated agents, and (3) NO donors and cGMP analogues stimulate pepsinogen release. METHODS: Chief cells were prepared by sequential digestion with collagenase and Ca2+ chelation. NO generation was measured by determining the NO coproduct citrulline. RESULTS: NO synthase immunoreactivities were constitutively expressed in approximately 70% chief cells. Carbachol (10 mumol/L) caused a 4- 6-fold increase in pepsinogen release, citrulline generation, intracellular Ca2+ concentration ([Ca2+]i) and cGMP concentration. These effects were concentration dependently inhibited by NG-monomethyl-L-arginine (L-NMMA). As gastrin, cholecystokinin, thapsigargin, and Ca2+ ionophore increased NO generation, [Ca2+]i seemed to regulate NO synthase activity. [Ca2+]i chelator and calmodulin antagonist inhibited the carbachol-induced pepsinogen secretion and NO generation. Preincubating the cells with L-NMMA had no effect on carbachol-stimulated inositol triphosphate generation or [Ca2+]i or Ca(2+)-dependent adenosine triphosphatase levels. Nitrovasodilator agents and 8-bromo-cGMP stimulated pepsinogen release. CONCLUSIONS: Gastric chief cells express a Ca2+/calmodulin-dependent NO synthase. NO modulates the stimulatory effect of Ca(2+)-mediated agonists on pepsinogen release.
OBJECTIVE: To assess the effects of chronic oral administration of standard doses of lansoprazole on the luteinizing hormone pulsatile pattern and on follicle stimulating hormone (FSH) and testosterone levels in young men. DESIGN AND METHODS: Eleven healthy volunteers were studied on three separate occasions, before and after two 3-week periods of treatment with lansoprazole (30 mg every morning) or a placebo, according to a randomized, double-blind, double-dummy, cross-over design. On each study day, blood samples were taken every 15 min for 8 h. The pulsatile pattern of luteinizing hormone, mean concentrations of FSH and total testosterone plasma levels were determined for each patient using specific radioimmunoassays. RESULTS: Lansoprazole did not significantly affect mean plasma levels, the pulsatile pattern of luteinizing hormone, or mean plasma concentrations of FSH and testosterone compared with the placebo. CONCLUSIONS: This study indicates that chronic oral administration of standard doses of lansoprazole does not affect the concentrations of gonadal hypothalamic pituitary or sex steroid hormones.
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The aims of our study were 3-fold: (1) to determine the effect of an acute cold pressor test on vagally stimulated gastric acid secretion, (2) to evaluate whether adrenergic blockers are able to prevent the stress-induced alterations of vagally stimulated gastric acid secretion, and (3) to assess the effect of stress and adrenergic blockers on serum levels of vagally stimulated pancreatic polypeptide and gastrin. Twenty-eight studies were carried out on 7 healthy subjects, each one of them being evaluated on four separate occasions. Active (4 degrees C) or control (37 degrees C) cold pressor tests were applied in random order after an interval of 15 min following completion of a vagal stimulation represented by modified sham feeding. Each stressful stimulus was preceded by an intravenous bolus plus an infusion of either adrenergic blockers (propranolol and phentolamine) or placebo. Modified sham feeding significantly stimulated gastric acid secretion and circulating hormonal levels, compared to basal values. Cold pressor test significantly stimulated gastric acid secretion 30 min after the beginning of the stressful stimulus. This stress-induced secretory response was completely prevented by infusions of adrenergic blockers. No effect was induced by stressful stimuli or by adrenergic blockers on human pancreatic polypeptide and gastrin circulating levels. The present study demonstrates that the cold pressor test induces a late increase of vagally stimulated gastric acid secretion suggesting a possible role mediated by adrenergic neural pathways.
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 aim of this study was to determine the optimal dosage regimen of cisapride for the treatment of idiopathic gastroparesis. We studied 17 patients with documented idiopathic gastroparesis in a three-way, cross-over, double-blind study with three 4-day treatment periods separated by at least 3 days without treatment. In each period, the patients were preloaded with cisapride (10 mg tid) for three days. On the fourth day (the test day) they took either 10 mg or 20 mg before breakfast and placebo before lunch (1 x 10 mg), (1 x 20 mg), or 10 mg before breakfast and 10 mg before lunch (2 x 10 mg). The medications were taken 30 min before meals. Gastric emptying of solids (99mTc-sulphur colloid) was measured at lunch time under basal conditions and during each treatment period. Plasma concentrations of cisapride were determined before the breakfast dose, before the lunch dose, and at 1, 2, 3, 4 and 5 h after. The greatest acceleration in gastric emptying occurred with the 2 x 10 mg regimen. Although the single morning dose of 20 mg also significantly accelerated gastric emptying (P = 0.05), the reduction was not as substantial. Plasma concentrations of cisapride were significantly higher after 2 x 10 mg than after 1 x 20 mg or 1 x 10 mg. There was a significant relation between cisapride plasma concentrations and changes in gastric emptying. Peak concentrations of cisapride greater than 60 ng.ml-1 were invariably associated with acceleration of gastric emptying. We conclude that cisapride 10 mg tid before meals is the optimal dose for the treatment of idiopathic gastroparesis.
The present study evaluated the effect of a one-day high-dose combined therapy on Helicobacter pylori infection. Thirty-two consecutive patients (suffering from either peptic ulcer or nonulcer dyspepsia) with Helicobacter pylori infection received omeprazole (40 mg) + bismuth subcitrate (240 mg x 4) + amoxicillin suspension (2000 mg x 4) + metronidazole (500 mg x 4), for only one day. Endoscopy, histology, culture, and susceptibility studies were done at entry and 30 and 90 days after the treatment day. Successful eradication was obtained in 23/32 (72%) patients and gastritis had resolved in 95% of these. Side effects were induced by the treatment in 6/32 (19%) patients, but these were all self-limiting, short-lasting, and did not require any specific treatment. Development of bacterial resistance to metronidazole occurred in 6/9 (67%) non-eradicated patients. These data suggest that one-day treatment with high doses of amoxicillin, metronidazole, bismuth, and omeprazole represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection.