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R De Giorgio

Publications and source records attributed to R De Giorgio.

At least 37 records · Page 2Linked to original sources
PubMed2002

Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders.

BACKGROUND: Little is known about the clinical and immunological features of coeliac disease patients with neurological disorders. In a large series of adult coeliac disease patients, we investigated the prevalence of neurological disorders and anti-neuronal antibodies, along with the clinical course. METHODS: Neurological symptoms were investigated in 160 consecutive patients (120 F, 40 M) with biopsy-proven coeliac disease. Anti-neuronal antibodies to central/enteric nervous systems were investigated in all neurological patients, 20 unaffected ones and 20 controls. RESULTS: Thirteen (8%) patients had neurological disorders, including epilepsy (n = 3), attention/memory impairment (n = 3), cerebellar ataxia (n = 2), peripheral neuropathy (n = 2), multiple sclerosis (n = 1), Moyamoya disease (n = 1) and Steinert's disease (n = 1). No significant demographic or clinical differences (gastrointestinal or other gluten-related signs) were found between patients with and without neurological involvement. In all but 2 of the 13 cases, the neurological disorder preceded diagnosis ofcoeliac disease. Neurological symptoms improved or disappeared in 7 patients who started a gluten-free diet within 6 months after neurological onset, and in none of 4 patients who began later. Prevalence of central nervous system anti-neuronal antibodies was significantly higher in neurological (61%) than in other patients (5%) (P = 0.0007) or controls (0%) (P = 0.00001). CONCLUSIONS: Coeliac disease can sometimes present in the guise of a neurological disorder, which may greatly improve when a gluten-free diet is started promptly. Therefore, the possible presence of coeliac disease needs to be carefully considered in patients with cerebellar ataxia, epilepsy, attention/memory impairment or peripheral neuropathy.

Adolescent↗
PubMed2002

A role for inflammation in irritable bowel syndrome?

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.

Animals↗
PubMed2001

Review article: the pharmacological treatment of acute colonic pseudo-obstruction.

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.

Acute Disease↗
PubMed2001

Tachykinin-dependent and -independent components of peristalsis in the guinea pig isolated distal colon.

BACKGROUND & AIMS: In the intestine, tachykinins regulate motility by participating in neuromuscular and neuro-neuronal transmission. The aim of this study was to test the hypothesis that colonic propulsion is regulated by an interplay between tachykinergic and cholinergic transmission. METHODS: Propulsion was elicited by intraluminal distention of a thin rubber balloon, which traveled from the oral to the anal end of guinea pig isolated distal colon segments. The overall contribution of endogenous tachykinins to colonic propulsion was examined by blocking NK1, NK2, and NK3 receptors simultaneously. RESULTS: NK2-receptor blockade by MEN 11420 inhibited propulsion, whereas blockade of NK(1) by SR 140333 or of NK3 receptors by SR 142801 had minor effects on motility. Blockade of muscarinic or nicotinic receptors by hyoscine or hexamethonium decelerated peristalsis up to propulsion arrest. In the presence of partial muscarinic receptor blockade, the NK1-receptor antagonist SR 140333 and the NK2-receptor antagonist MEN 11420 markedly inhibited propulsion. Propulsion was also inhibited by the NK3-receptor antagonist SR 142801 in the presence of partial nicotinic receptor blockade. The simultaneous administration of the 3 tachykinin antagonists inhibited propulsion by 50%. CONCLUSIONS: This study demonstrates the existence of an interplay between tachykinergic and cholinergic pathways during peristalsis and the importance of endogenous tachykinins acting at multiple receptor sites in the control of colonic propulsion.

Animals↗
PubMed2001

Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice.

BACKGROUND & AIMS: Chronic abdominal symptoms develop in some patients after acute enteric infection. This study examined mechanisms underlying smooth muscle hypercontractility that persists after acute infection in mice. METHODS: Euthymic and athymic National Institutes of Health (NIH) Swiss mice were infected with Trichinella spiralis and studied 4 weeks postinfection (PI). Isometric tension was assessed in longitudinal muscle. Cytokine and cyclooxygenase (COX)-2 messenger RNA was determined in the muscularis externa by reverse-transcription polymerase chain reaction. COX-2 protein was identified by immunohistochemistry and prostaglandin E(2) was measured by enzymatic immunoassay. Studies were performed in euthymic and athymic NIH Swiss mice 28 days PI and in the presence or absence of treatment with corticosteroid or COX inhibitors. RESULTS: Muscle hypercontractility was evident in euthymic mice but was attenuated in athymic mice or in steroid-treated euthymic mice 28 days PI. Expression of Th2 cytokines interleukins 4, 5, and 13 was increased during the acute infection but not thereafter. COX-2 was localized to muscle and its enzymatic activity remained significantly increased in the muscle on day 28 PI. Selective COX-2 inhibition in vitro reduced the sustained increase in tension generation. CONCLUSIONS: These findings show that COX-2 activation in resident cells of the muscularis externa contributes to the muscle hypercontractility that persists after infection.

Adrenal Cortex Hormones↗
PubMed2001

Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat.

BACKGROUND: In the rat, gastric distension elicits an intensity dependent pseudoaffective bradycardia mediated via capsaicin sensitive afferent and cholinergic efferent vagal pathways. Inflammation alters visceral perception although the mediators responsible have not been identified. In the nematode infected rat, there is a substantial increase in neuronal substance P (SP) content of the gut. AIMS: To examine the effects of inflammation on perception of a noxious visceral stimulus and on SP and neurokinin 1 (NK-1) receptor immunoreactivity (IR) in visceral afferent pathways. METHODS: Immunohistochemistry was performed on sections from the jejunum, dorsal root ganglia (DRG), and spinal cord (T1-L1) using SP and NK-1 rabbit polyclonal antibodies. In the DRG, the number of SP-IR or NK-1-IR neurones per section was visually quantified. The pseudoaffective cardiac reflex response to gastric stimulation was compared in control and Trichinella spiralis infected rats. RESULTS: Intestinal inflammation induced a rightward shift in the intensity dependent bradycardic response to gastric distension. This was associated with a marked increase in SP-IR not only in the gut wall but also in the DRG and dorsal horn of the spine. In contrast, NK-1-IR was not increased in the gut wall. Moreover, inflammation evoked a decrease in NK-1-IR in the dorsal horn. No NK-1-IR was identified in the DRG of either control or infected animals. CONCLUSIONS: Intestinal inflammation modulates the capsaicin sensitive pseudoaffective autonomic response to gastric distension, increases SP-IR in afferent pathways, and downregulates dorsal horn NK-1-IR. As the pseudoaffective response is capsaicin sensitive, the rightward shift of the response is likely the consequence of the decrease in NK-1 receptors in the sensory pathways.

Animals↗
PubMed2000

Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons.

In the rat small intestine, neurotrophin-3 immunoreactivity was identified in ganglion cells and in processes mostly innervating the mucosa and occasionally the muscle layer and vasculature. The vast majority of neurotrophin-3 immunoreactive neurons contained vasoactive intestinal polypeptide (VIP), but not substance P or related tachykinin (SP/TK). Neurotrophin receptors visualized by pan-trk immunoreactivity were found in numerous ganglion cells of both plexuses and in nerve processes in the intestinal wall. Pan-trk submucosal neurons contained VIP (36%) or SP/TK-IR (47%). Pan-trk myenteric neurons contained VIP-IR (57%) or SP/TK (27%). Our data suggest that neurotrophin-3 and neurotrophin receptors may be involved in the maintenance of enteric neuronal circuits, transmission and phenotypic expression.

Animals↗
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↗