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V Stanghellini

Publications and source records attributed to V Stanghellini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations.

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 frequencies > or =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

Aged↗
PubMed2000

Review article: the continuing dilemma of dyspepsia.

Dyspepsia drains a substantial proportion of healthcare resources in industrialized countries and an appropriate management strategy is needed. An aetiological role for Helicobacter pylori infection has been demonstrated in a number of pathological conditions associated with dyspepsia, such as peptic ulcer and gastric malignancies, but not in functional dyspepsia. Endoscopy and diagnosis-based treatment, H. pylori testing and eradication therapy, history taking and empirical therapy, are the main tools that are currently available for managing patients with upper gastrointestinal symptoms. Endoscopy identifies malignancies and organic diseases of the proximal gut and therefore provides reassurance to both doctors and patients. It should be recommended in older patients with suspicious symptoms and it has proven to be more cost-effective than empirical H2-receptor antagonists in patients with ulcer-like symptoms. Empirical eradication in all dyspeptics without suspicious symptoms is a cost-effective approach that cures the majority of peptic ulcers. Nevertheless, it does not control symptoms in the majority of patients, it may exacerbate gastro-oesophageal reflux disease, and it encourages antibiotic resistance. The realities of current clinical practice require empirical therapy in most, if not all, the dyspeptics seen by general practitioners. A detailed history taking can help to diagnose gastro-oesophageal reflux disease and to identify suspicious symptoms. Furthermore, identification of dyspepsia subgroups may provide guidance for empirical therapy. Nevertheless, even analysis of individual symptoms does not provide a sufficient diagnostic yield to differentiate functional from organic dyspepsia and appropriate investigations are needed in patients with poor response to short-term therapy or frequent relapses.

Dyspepsia↗
PubMed2000

Role of antibiotic therapy on long-term germ excretion in faeces and digestive symptoms after Salmonella infection.

BACKGROUND: 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. AIM: To investigate the role of antibiotic therapy on long-term germ faecal excretion and digestive symptoms after Salmonella infection. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adult↗
PubMed2000

Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patient's symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

Adult↗
PubMed2000

Assessment of gastric emptying using a low fat meal: establishment of international control values.

OBJECTIVE: The diagnosis of gastroparesis implies delayed gastric emptying. The diagnostic gold standard is scintigraphy, but techniques and measured endpoints vary widely among institutions. In this study, a simplified scintigraphic measurement of gastric emptying was compared to conventional gastric scintigraphic techniques and normal gastric emptying values defined in healthy subjects. METHODS: In 123 volunteers (aged 19-73 yr, 60 women and 63 men) from 11 centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low fat meal (egg substitute) and percent intragastric residual contents 60, 120, and 240 min after completion of the meal. In 42 subjects, additional measurements were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc-labeled liver meal was compared with that of the 99Tc-labeled low fat meal. RESULTS: Median values (95th percentile) for percent gastric retention at 60, 120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power exponential model yielded similar emptying curves and estimated T50 when using images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric emptying was initially more rapid in men but was comparable in men and women at 4 h; it was faster in older subjects (p < 0.05) but was independent of body mass index. CONCLUSIONS: This multicenter study provides gastric emptying values in healthy subjects based on data obtained using a large sample size and consistent meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed emptying, a value comparable to those provided by more intensive scanning approaches. Gastric emptying of a low fat meal is initially faster in men but is comparable in women at 4 h; it is also faster in older individuals but is independent of body mass.

Adult↗
PubMed1999

Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct.

In functional experiments, we have investigated the effect exerted by neurotransmitters released from capsaicin-sensitive primary afferent nerve terminals in the isolated guinea-pig common bile duct. In resting preparations, capsaicin (0.1 microM) produced a quick contraction (45.1+/-4% of KCl 80mM) which was abolished by either atropine (1 microM) or tetrodotoxin (0.5 microM). The tachykinin receptor-selective antagonists GR 82334 (NK1 receptor-selective; 3 microM), MEN 11420 (NK2 receptor-selective; 1 microM) and SR 142801 (NK3 receptor-selective; 0.1 microM) administered separately failed to reduce the capsaicin-evoked contraction, whereas any combination of the three antagonists was effective: GR 82334 plus MEN 11420, 36+/-7% reduction; GR 82334 plus SR 142801, 48+/-4% reduction; MEN 11420 plus SR 142801, 55+/-3% reduction; GR 82334 plus MEN 11420 plus SR 142801, 57+/-5% reduction. Neither the CGRP1 receptor antagonist h-CGRP (8-37) (1.5 microM) nor the P2X purinoceptor antagonist PPADS (50 microM) affected the contractile response to capsaicin. The effect of capsaicin (0.1 microM) was abolished by pretreatment with capsaicin itself (10 microM for 15 min). Human calcitonin gene-related peptide (h-CGRP; 0.1 microM) mimicked the effect of capsaicin on resting preparations (contractile response =28% of KCl 80 mM). In preparations precontracted with a submaximal concentration of KCl (24 mM), and in the presence of atropine (1 microM), GR 82334 (3 microM) and MEN 11420 (3 microM), capsaicin (1 microM) produced a tetrodotoxin-insensitive long-lasting relaxation (45+/-3% reduction of tone, at 4min from administration), which was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM). h-CGRP (10-50 nM) produced a similar sustained relaxation of precontracted preparations (59+/-4% reduction of tone). h-CGRP (8-37) (1.5 microM) almost completely reversed the relaxations produced by both capsaicin and h-CGRP. Application of electrical field stimulation (EFS: trains of stimuli of 10Hz; 0.25ms pulse width; supramaximal voltage; for 60s) to precontracted preparations produced a sustained, tetrodotoxin (1 microM)-sensitive relaxation (32+/-4% reduction of tone). L-NOARG (100 microM) greatly reduced (69+/-5% inhibition) the EFS-elicited relaxation. A complete reversal of the relaxant response to EFS into a contraction was obtained by administering L-NOARG to preparations in which a functional blockade of capsaicin-sensitive primary afferent neurons had been achieved by incubating the tissue with capsaicin (10 microM) for 15 min. At immunohistochemistry, tachykinin- and CGRP-immunoreactivities (TK-IR/CGRP-IR) were detected in varicose nerve fibers throughout the common bile duct, while TK-IR cell bodies were observed in the terminal portion (ampulla) only. In vivo pretreatment with capsaicin (50 mg/kg; 6-7 days before) decreased the number of CGRP-IR nerves, whereas the TK-IR neural network was apparently unchanged. In conclusion, our data provide functional evidence for the presence of capsaicin-sensitive primary afferent nerve endings in the guinea-pig terminal biliary tract, whose stimulation by capsaicin or EFS produces the release of tachykinins and CGRP. In addition, morphological evidence is provided that the bulk of TK-IR material in the biliary tract is contained in intrinsic neuronal elements, while CGRP in this tissue is of extrinsic origin only. Tachykinins, probably released in small amounts by capsaicin, act by activating receptors of the NK1, NK2 and NK3 type, most probably located on intrinsic cholinergic neurons, which in turn release ACh to produce the final excitatory motor response. The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters. CGRP produces either indirect excitatory or direct inhibitory responses by stimulation of CGRP2 and CGRP1 receptors, respectively.

Animals↗
PubMed1999

Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index.

BACKGROUND: There is not at present a suitable disease-specific health-related quality of life instrument for uninvestigated dyspepsia and functional (non-ulcer) dyspepsia. AIM: To develop a new multi-dimensional disease-specific instrument. METHODS: The Nepean Dyspepsia Index (NDI) was designed to measure impairment of a subject's ability to engage in relevant aspects of their life and also their enjoyment of these aspects; in addition, the individual importance of each aspect is assessed. A 42-item quality of life measure was developed and tested, both in out-patients presenting to general practice with upper gastrointestinal complaints (n = 113) and in a randomly chosen population-based sample (n = 347). RESULTS: Adequate face and content validity was documented by an expert panel. Factor analysis identified four clinically relevant subscales: interference with activities of daily living, work, enjoyment of life and emotional well-being; lack of knowledge and control over the illness; disturbance to eating or drinking; and disturbance to sleep because of dyspepsia. These scales had high internal consistency. Both symptoms and the quality of life scores discriminated dyspepsia from health. CONCLUSION: The Nepean Dyspepsia Index is a reliable and valid disease-specific index for dyspepsia, measuring symptoms and health-related quality of life.

Adult↗
PubMed1999

Three-month prevalence rates of gastrointestinal symptoms and the influence of demographic factors: results from the Domestic/International Gastroenterology Surveillance Study (DIGEST).

BACKGROUND: This paper reports the 3-month prevalence rates of gastrointestinal (GI) symptoms from the Domestic/International Gastroenterology Surveillance Study (DIGEST), and their relationship with demographic factors; namely age, gender and body mass index (BMI). METHODS: Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with randomly selected members of the general population aged 18 years and over (50.6% female; mean age 44 years). The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms, or no GI symptoms. Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom: gastro-oesophageal reflux (GORD)-like symptoms, ulcer-like symptoms or dysmotility-like symptoms. Symptoms were classified as relevant if they were of at least moderate severity and/or occurred at least once a week. RESULTS: A mean of 46.4% of subjects reported experiencing one or more of the 14 GI symptoms, with 28.1% experiencing upper GI symptoms classified as relevant. Significant differences between the prevalences of relevant symptoms were evident between sampling sites. The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7%. For ulcer-like symptoms, prevalence was 4.1%, and for dysmotility-like symptoms 15.5%. Significant differences were observed in the prevalence rates of symptom groups between countries. Women were significantly more likely than men to experience relevant symptoms, with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms. The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age; ulcer-like symptoms showed no significant relationship with age; and dysmotility-like symptoms decreased significantly with age. The prevalence of relevant symptoms increased with increasing BMI. CONCLUSIONS: In conclusion, the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms, and their association with biological factors.

Adult↗
PubMed1999

Risk indicators of organic diseases in uninvestigated dyspepsia: a one-week survey in 246 Italian endoscopy units.

OBJECTIVE: To evaluate the predictive value of demographic and clinical features and of the results of an office-based test for Helicobacter pylori antibodies, in the presence of organic dyspepsia. DESIGN: Over a 1-week period, 2206 consecutive patients first referred for endoscopy in 246 Italian centres were included. METHODS: Demographic and clinical features, endoscopy findings, and histological diagnosis of H. pylori infection were recorded for all patients. IgG antibodies to H. pylori were determined in 2128 cases by a rapid, immunochromatographic method (Flex Sure HP, S.K.D., San Jose, CA). RESULTS: Endoscopic abnormalities were found in 939 patients (42.6%). Histologically assessed H. pylori infection was predictive for duodenal ulcer (odds ratio (OR), 6.79; 95% confidence interval (CI), 4.4-10.5). Being male (OR, 1.97; 95% CI, 1.7-2.3), older than 40 years (OR, 1.81; 95% CI, 1.5-2.2), a smoker (OR, 1.88; 95% CI, 1.6-2.3), and presenting nocturnal awakening (OR, 1.62; 95% CI, 1.3-2.0) were independently associated with secondary dyspepsia. Epigastric (OR, 1.50; 95% CI, 1.2-1.9) and retrosternal pain (OR, 1.39; 95% CI, 1.1 -1.8) severe enough to affect the usual activities were predictive of organic diseases. The results of the Flex Sure HP test correlated poorly with histological findings. CONCLUSIONS: Male gender, older age, cigarette smoking, a family history of peptic ulcer, symptoms severe enough to induce awakening, epigastric/retrosternal pain severe enough to influence the usual activities are all independently (although weakly) associated with organic dyspepsia. H. pylori infection is strongly associated with duodenal ulcer, but the rapid test we used was not sensitive enough to achieve clinical utility.

Adult↗
PubMed1999

Predominant symptoms identify different subgroups in functional dyspepsia.

OBJECTIVE: Dyspepsia is a common syndrome that often defies diagnosis. Whether the unexplained (or "functional") dyspepsia represents a homogeneous syndrome or includes different subgroups with specific clinical features has not been clarified. The aim of this study was to investigate the relationship between symptom severity, demographic features, and gastric dysmotility in a large series of patients with functional dyspepsia. METHODS: Severity of individual digestive symptoms, demographic features, and scintigraphic gastric emptying of solids were evaluated in 483 patients with chronic unexplained dyspepsia. RESULTS: Two main subgroups were identified. The first was characterized by predominant epigastric pain, male gender (61%), and normal gastric emptying. The second subgroup was characterized by predominant nonpainful symptoms, female gender (60%), a high frequency of associated irritable bowel syndrome (30%), and delayed gastric emptying (42%). A third group included approximately one-third of patients who did not present with any predominant symptom, and was characterized by a high frequency of delayed gastric emptying (30%), overlapping irritable bowel syndrome (28%), and gastroesophageal reflux disease (41%). CONCLUSIONS: Different subgroups exist among patients with functional dyspepsia seen in a referral center. They can be identified by the predominant symptom and are characterized by different demographic, clinical, and pathophysiological features.

Adult↗
PubMed1999

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia.

OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean +/- SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 +/- 0.1) and the gastric component (2 +/- 0.6) of the LES as compared to those in controls (15 +/- 5 and 12 +/- 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 +/- 1) were significantly reduced in comparison to those of controls (10 +/- 2) (p < 0.05). CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Adult↗
PubMed1999

How should Helicobacter pylori negative patients be managed?

Dyspepsia is a digestive syndrome distinct from (although frequently overlapping with) gastro-oesophageal reflux disease (GORD) and irritable bowel syndrome (IBS), which is characterised by various combinations of painful and non-painful symptoms arising from the epigastrium. Dyspepsia can be secondary to a variety of diseases, but in most instances it is idiopathic. Helicobacter pylori infection is responsible for the majority of peptic ulcers and of other diseases potentially associated with dyspepsia. Nevertheless, a causal role for H pylori infection in symptom occurrence has not been established. Experimental data indicate that H pylori eradication does not improve symptoms in the majority of dyspeptic patients. It has been proposed recently that H pylori negative patients should be managed according to their clinical presentation. Some reports suggest that taking into consideration the most relevant or "predominant" symptom may help to identify distinct subgroups among dyspeptic patients with different underlying pathophysiological abnormalities and different responses to treatment. Well designed and conducted prospective studies are needed to verify whether treatment of H pylori negative dyspeptic patients based on the predominant symptom actually is a cost effective approach.

Dyspepsia↗
PubMed1999

Functional gastroduodenal disorders.

While widely used in research, the 1991 Rome criteria for the gastroduodenal disorders, especially symptom subgroups in dyspepsia, remain contentious. After a comprehensive literature search, a consensus-based approach was applied, supplemented by input from international experts who reviewed the report. Three functional gastroduodenal disorders are defined. Functional dyspepsia is persistent or recurrent pain or discomfort centered in the upper abdomen; evidence of organic disease likely to explain the symptoms is absent, including at upper endoscopy. Discomfort refers to a subjective, negative feeling that may be characterized by or associated with a number of non-painful symptoms including upper abdominal fullness, early satiety, bloating, or nausea. A dyspepsia subgroup classification is proposed for research purposes, based on the predominant (most bothersome) symptom: (a) ulcer-like dyspepsia when pain (from mild to severe) is the predominant symptom, and (b) dysmotility-like dyspepsia when discomfort (not pain) is the predominant symptom. This classification is supported by recent evidence suggesting that predominant symptoms, but not symptom clusters, identify subgroups with distinct underlying pathophysiological disturbances and responses to treatment. Aerophagia is an unusual complaint characterized by air swallowing that is objectively observed and troublesome repetitive belching. Functional vomiting refers to frequent episodes of recurrent vomiting that is not self-induced nor medication induced, and occurs in the absence of eating disorders, major psychiatric diseases, abnormalities in the gut or central nervous system, or metabolic diseases that can explain the symptom. The current classification requires careful validation but the criteria should be of value in future research.

Aerophagy↗
PubMed1999

Relationship between upper gastrointestinal symptoms and lifestyle, psychosocial factors and comorbidity in the general population: results from the Domestic/International Gastroenterology Surveillance Study (DIGEST).

BACKGROUND: The Domestic/International Gastroenterology Surveillance Study (DIGEST) investigated the prevalence and economic/quality-of-life impact of upper gastrointestinal (GI) symptoms over 3 months among the general population of seven international sites (n = 5581). METHODS: Respondents were classified as having relevant or non-relevant symptoms, and were further classified as having gastro-oesophageal reflux disease (GORD)-, ulcer-, or dysmotility-like symptoms, based on their most bothersome symptom. Associations were investigated between the prevalence of relevant upper GI symptoms and these subtypes, and the following potential risk factors: psychosocial variables (income, educational level, marital status, having children, occupation, any significant life event during previous year); lifestyle variables (tobacco use, levels of alcohol and caffeine consumption); comorbidity variables (illnesses or symptoms experienced in the previous 3 months, concurrent conditions diagnosed by a doctor, prescriptions and over-the-counter (OTC) medications taken in the previous 3 months for health problems other than upper GI symptoms). RESULTS AND CONCLUSIONS: The most notable risk factors for the occurrence of upper GI symptoms, including symptoms indicative of GORD, were found to be various indicators of psychological stress (particularly recent life events) and psychiatric disease. A wide range of other non-psychiatric illnesses and their treatments was also clearly associated with the occurrence of upper GI symptoms, consistent with these symptoms occurring in many organic illnesses or as adverse effects of their treatments. Smoking was also found to be associated with GORD-like symptoms.

Adult↗