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Roberto Corinaldesi

Publications and source records attributed to Roberto Corinaldesi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Abdominal Pain↗
PubMed2004

Inflammatory neuropathies of the enteric nervous system.

Inflammatory neuropathy of the enteric nervous system is emerging as an important topic in the field of neurogastroenterology. Enteric ganglionitis can be either primary or secondary to a wide array of diseases (i.e., paraneoplastic, infectious, and neurological disorders) and is characterized by a dense infiltrate of inflammatory/immune cells mainly confined to the neural microenvironment. The clinical picture reflects the involved segment of the gastrointestinal tract (achalasia, gastroparesis, pseudo-obstruction, and megacolon). In these settings, symptoms may develop either acutely (frequently after a flulike episode in otherwise previously healthy individuals) or more slowly (e.g., in paraneoplastic syndromes). The inflammatory/immune response in enteric ganglionitis leads to neuronal dysfunction and degeneration over time and sometimes results in a complete loss of enteric neurons. The diagnosis of enteric ganglionitis is supported by detection of circulating antineuronal antibodies against select molecular targets, including Hu and Yo proteins, neurotransmitter receptors, and ion channels. Potential mechanisms involved in neuronal dysfunction include viral antigen expression in the enteric neural environment, molecular mimicry (onconeural antigens), and the role exerted by cellular and humoral autoimmunity. A short course of steroid or other immunosuppressive therapy has been shown to be helpful in the treatment of these conditions. This feature reinforces the concept of a cause/effect relationship of the immune-mediated insult damaging the enteric innervation. An increased awareness of the clinical features and the immunologic and neurodegenerative mechanisms of these forms of peripheral neuropathy is important to correctly diagnose this problem during the early stages of the disease process and to provide appropriate immunosuppressive therapies.

Enteric Nervous System↗
PubMed2004

Prokinetics in the treatment of acute intestinal pseudo-obstruction.

Acute colonic pseudo-obstruction (Ogilvie's syndrome) is characterized by an acute obstruction of the large bowel that is unrelated to mechanical causes. The evidence that cholinesterase inhibitors are effective in relieving acute colonic pseudo-obstruction raised interest in the pharmacological management of this condition. This review analyzes the pharmacological treatment of patients with Ogilvie's syndrome. Intravenous neostigmine is the best pharmacological treatment, leading to rapid colonic decompression. New colokinetic agents, including 5-HT(4) receptor agonists and motilides, may represent other useful therapeutic options for Ogilvie's syndrome.

Animals↗
PubMed2004

Immune-manipulation of the inflammatory response in acute pancreatitis. What can be expected?

Severe acute pancreatitis still has a high mortality rate and multiple organ failure is considered to be a severe complication of the disease. Activated polymorphonuclear leukocytes have an important role in the development of multiple organ failure which may result from acute pancreatitis and they are an important pathogenetic factor in the severity of this disease. Therefore, a logical therapeutic approach is to limit the organ damage by selective suppression of inflammatory mediators involved in the systemic inflammatory response syndrome and protect against systemic complication. In this paper, we review the recent literature data on the possible manipulation of the immune response in acute pancreatitis.

Acute Disease↗
PubMed2003

Anti-HuD-induced neuronal apoptosis underlying paraneoplastic gut dysmotility.

BACKGROUND & AIMS: The role of autoimmunity underlying paraneoplastic gut dysmotility remains unsettled. Because anti-Hu antibodies may impair enteric neuronal function, we tested whether anti-HuD-positive sera from patients with paraneoplastic gut dysmotility or commercial anti-HuD antibodies activated the apoptotic cascade in a neuroblastoma cell line and cultured myenteric neurons. METHODS: Anti-HuD antibodies from patients with severe paraneoplastic gut dysmotility were characterized by immunofluorescence and immunoblot. SH-Sy5Y neuroblasts and cultured myenteric neurons were exposed to sera containing anti-HuD antibodies or 2 commercial anti-HuD antibodies. Cells were processed for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) technique to evaluate apoptosis. Immunofluorescence was used to identify activated caspase-3 and apaf-1, along with microtubule-associated protein 2. RESULTS: In SH-Sy5Y cells, the percentage of TUNEL-positive nuclei observed after exposure to anti-HuD-positive sera (32% +/- 7%) or anti-HuD antibodies (23% +/- 2%) was significantly greater than that of control sera or fetal calf serum (P < 0.001). The time-course analysis showed a significantly greater number of apoptotic neuroblastoma cells evoked by the 2 commercial anti-HuD antibodies at 24, 48, and 72 hours versus controls. The number of TUNEL-positive myenteric neurons exposed to anti-HuD antibodies (60% +/- 14%) was significantly greater than that of fetal calf serum (7% +/- 2%; P < 0.001). Apaf-1 and caspase-3 immunolabeling showed intense cytoplasmic staining in a significantly greater proportion of cells exposed to anti-HuD-positive sera or to commercial anti-HuD antibodies compared with controls. CONCLUSIONS: Anti-HuD antibodies evoked neuronal apoptosis that may contribute to enteric nervous system impairment underlying paraneoplastic gut dysmotility. Apaf-1 activation suggests participation of a mitochondria-dependent apoptotic pathway.

Apoptosis↗
PubMed2003

Early activation of peripheral lymphocytes in human acute pancreatitis.

BACKGROUND: The CD69 antigen is an indicator of early lymphocyte activation. GOALS: To evaluate the early activation of peripheral lymphocytes T, B, and NK in patients with acute pancreatitis in comparison with patients with acute abdomen of nonpancreatic origin. STUDY: Thirty patients with acute pancreatitis were studied; 20 of them had the mild form of the disease and 10 had the severe form. Thirty patients with nonpancreatic acute abdomen were used as controls. All patients were enrolled within 48 hours of the onset of pain. In all patients, leukocytes and total lymphocyte and lymphocyte subset counts (CD4+, CD8+, CD56+, CD19+, CD4+CD69+, CD8+CD69+, CD56+CD69+, CD19+CD69+) were determined upon hospital admission. RESULTS: The percentage of total lymphocytes was significantly lower in acute pancreatitis patients than in those with nonpancreatic acute abdomen (P = 0.014); patients with severe pancreatitis had a percentage of total lymphocytes significantly lower when compared with patients with mild pancreatitis (P < 0.001). The CD19+CD69+ count was significantly lower in patients with severe pancreatitis (24.6 +/- 14.6%) than in patients with mild pancreatitis (46.7 +/- 16.5%; = 0.006). The counts of the other lymphocyte subsets were not statistically different between patients with acute pancreatitis and those with nonpancreatic acute abdomen, as well as between patients with mild and severe acute pancreatitis. CONCLUSIONS: Patients with severe pancreatitis show impaired early activation of peripheral CD19+ cells.

Abdomen, Acute↗
PubMed2003

Mutations of the CFTR gene in pancreatic disease.

INTRODUCTION: An association has been found between CFTR gene mutations and chronic pancreatitis; however, there is a lack of information about the frequency of CFTR gene mutations in acute pancreatitis and in pancreatic cancer. AIM: To prospectively evaluate the prevalence of CFTR gene mutations in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. METHODOLOGY: Ninety-eight consecutive patients were studied and divided into 3 groups: 34 patients with acute pancreatitis, 46 patients with chronic pancreatitis, and 18 patients with pancreatic cancer. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism. RESULTS: Among the 98 patients studied, 12 (12.2%) had CFTR gene mutations: 2 of the 34 patients (5.9%) with acute pancreatitis, 9 of the 46 (19.6%) with chronic pancreatitis, and 1 of the 18 (5.6%) with pancreatic cancer. All the mutations were found in heterozygosis (2 DeltaF508, 1 W1282X, and 9 T5 allele). CONCLUSION: Our prospective study adds further information about the frequency of CFTR mutations in patients with a single episode of acute pancreatitis. Furthermore, our results suggest an association of CFTR gene mutations with chronic alcoholic pancreatitis and emphasize the need for a multicenter study, possibly multinational, to conclusively establish the role of CFTR mutations as a genetic susceptibility factor for this disease.

Acute Disease↗
PubMed2003

Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients.

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome 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 Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. 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 (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.

Aged↗
PubMed2003

New developments in the treatment of functional dyspepsia.

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria. The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia. Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.

Dyspepsia↗
PubMed2003

Pancreatic involvement in Salmonella infection.

CONTEXT: Salmonella has been identified as a causative agent of acute pancreatitis. OBJECTIVE: We prospectively evaluated the frequency of acute pancreatitis, pancreatic enzyme elevation and morphological pancreatic abnormalities in patients with Salmonella infection. SUBJECTS: Thirty consecutive patients with salmonellosis (Salmonella enterica serovar Enteritidis: n=25; Salmonella enterica serovar Typhimurium: n=5) and 30 sex- and age-matched healthy subjects were studied. MAIN OUTCOME MEASURES: All subjects underwent serum amylase and lipase determination and ultrasonography. RESULTS: None of the subjects developed acute pancreatitis. Two patients (6.7%) and two controls showed serum amylase activity above the upper reference limit whereas, in five patients (16.7%) and one control subject (3.3%), the serum lipase activity appeared above the upper reference limit. Salmonella infection significantly increased serum activity of lipase (P<0.001) while it did not significantly affect serum amylase levels (P=0.204). Serum lipase activity was significantly higher in patients infected by Salmonella enterica serovar Typhimurium than in those infected by Salmonella enterica serovar Enteritidis (P=0.012). Ultrasonography did not show pancreatic abnormalities in any of the subjects. CONCLUSIONS: Our data demonstrated an elevation of serum lipase activity in gastroenteritis due to Salmonella infection, but this elevation does not seem to have clinical significance. The elevation of serum lipase seems to be particularly related to infection from Salmonella enterica serovar Typhimurium.

Acute Disease↗
PubMed2002

Dyspeptic symptoms in primary care. An observational study in general practice.

BACKGROUND AND AIMS: Dyspepsia frequently causes patients to consult a general practitioner, but is generally investigated in referral centres. This study describes features of dyspepsia and its relationship with demographic, clinical and socio-economic factors in patients seen by general practitioners in Italy. PATIENTS AND METHODS: In Italy, 10 000 general practitioners were asked to recruit up to 10 consecutive dyspeptic patients during a 1-month period. Painful and non-painful dyspeptic symptoms, retrosternal pain/burning and visible abdominal distension were graded 0-3 by a validated questionnaire. Demographics and clinical features were also recorded. RESULTS: During the test period, 43 446 patients were included (55% were men; 50% were over 45 years old; 49% were smokers; 45% had experienced symptoms for > or = 1 month; 28% had a history of peptic ulcer). Dyspepsia accounted for 8.3% (range 3-11%) of the consultations of a subset of participating doctors. Epigastric pain and fullness were reported in 84% and 79% of patients, respectively. Dyspeptic symptoms were moderate-severe (graded > or = 2) in 69% of patients. Predominant epigastric pain and predominant discomfort were reported in 21% and 25% of the cases, respectively. Male gender, smoking, nocturnal awakening, overlapping reflux symptoms and a history of peptic ulcer were more frequent in patients with predominant pain, while female gender and overlapping abdominal distension were more common in patients with predominant discomfort. Age, educational level and working status were not related to any symptom pattern. Young patients presenting for the first time with uncomplicated dyspepsia accounted for 10% of the dyspepsia workload. CONCLUSIONS: Dyspepsia accounts for a relevant workload for general practitioners. A considerable overlap exists among digestive symptoms. The proportion of patients that can be empirically treated according to current guidelines may be lower than expected.

Adolescent↗
PubMed2002

Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases.

Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.

Adult↗
PubMed2002

Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) and dyspepsia often overlap. Delayed gastric emptying has been reported in IBS patients, although conflicting results exist. Whether overlapping dyspepsia correlates with gastric emptying abnormalities in IBS patients has not been clarified. This study aimed to evaluate gastric emptying of solids and its relationship with dyspeptic symptoms in IBS patients. METHODS: A total of 146 IBS outpatients seen in a referral center were evaluated for dyspeptic symptoms using a validated questionnaire. Gastric emptying of solids was evaluated scintigraphically in all patients and in 50 healthy controls. RESULTS: Overlapping dyspepsia was diagnosed in 96 (66%) IBS patients. On average, gastric emptying rates were lower in IBS patients (mean +/- SEM, 33% +/- 1%/h) compared with controls (40% +/- 2%/h; p < 0.01). Specifically, gastric emptying was delayed in IBS patients with overlapping dyspepsia (31% +/- 1%/h; p < 0.01), whereas IBS patients without dyspeptic complaints showed gastric emptying rates (37% +/- 2%/h) that were similar to those of healthy controls (40% +/- 2%/h). Relevant postprandial fullness (OR = 4.7, 95% CI = 1.8-12.5) and relevant nausea (OR = 3.3, 95% CI 1.2-9.3) were independently associated with delayed gastric emptying. CONCLUSIONS: IBS patients without overlapping dyspepsia have normal gastric emptying of solids. A significant association exists in IBS patients between delayed gastric emptying and overlapping relevant postprandial fullness and nausea.

Adult↗
PubMed2002

Carcinoid of the pancreas.

Pancreatic carcinoids are very rare and usually have a poor prognosis. We describe a case of a pancreatic carcinoid with liver micrometastases in a female of 54 years of age in whom the tumor was without pronounced symptoms apart from rare episodes of flushing. The patient had been treated since November 1995 with the somatostatin analogue octreotide 200 micrograms twice daily for the first 2 years, with the long-acting analogue lanreotide 30 mg every 10 days for the following year, and then with octreotide LAR 20 mg every 28 days until the present. The flushing episodes disappeared completely, and the patient was well. Moreover, the dimensions of the tumor and the liver micrometastases remained stable during the observation period. As far as we known, this is the first case of a pancreatic carcinoid treated successfully with somatostatin analogues and having a satisfactory prognosis.

Antineoplastic Agents↗