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Biomedical subjects

G Barbara

Publications and source records attributed to G Barbara.

At least 19 recordsLinked to original sources
PubMed2006

Gastro-oesophageal reflux and interstitial lung disease.

BACKGROUND: Interstitial lung disease is a heterogeneous entity, which encompasses a large number of pulmonary disorders, including idiopathic pulmonary fibrosis. Gastro-oesophageal reflux appears to be more prevalent in idiopathic pulmonary fibrosis than in controls and in patients with secondary pulmonary fibrosis, but its contribution to interstitial lung disease remains unsettled. AIMS: To prospectively evaluate gastro-oesophageal reflux in patients with interstitial lung disease and to define acid reflux patterns in patients with idiopathic and secondary forms of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight patients (15M, median age 66 years, interquartile range 60-71) were studied by history taking, pulmonary function tests, high resolution computed tomography, oesophageal manometry and 24h oesophago-gastric pH monitoring. RESULTS: Sixteen patients (57%) had typical reflux symptoms. All patients completed 24h pH metry and 14 underwent oesophageal manometry. An abnormal oesophageal acid exposure was observed in 19 patients (68%), 13 of which complained of predominant typical reflux symptoms. A diagnosis of idiopathic pulmonary fibrosis was made in 18 patients, while the remaining 10 patients were classified as secondary pulmonary fibrosis. Secondary pulmonary fibrosis patients had more restrictive lung defect, as expressed as Tiffeneau index (p<0.05) and greater acid reflux at nighttime (p<0.05) than idiopathic pulmonary fibrosis patients. CONCLUSIONS: The prevalence of abnormal acid reflux in interstitial lung disease patients is high and, in particular, patients with secondary pulmonary fibrosis show higher oesophageal acid exposure than those with idiopathic form.

Aged↗
PubMed2006

Anti-ganglioside antibodies in coeliac disease with neurological disorders.

BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. RESULTS: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.

Adult↗
PubMed2006

Functional gastrointestinal disorders and mast cells: implications for therapy.

The pathophysiology of functional gastrointestinal disorders is poorly understood. Accepted common mechanisms include psychosocial factors, abnormal gastrointestinal motility and disturbed visceral sensory perception, but the underlying causes remain unclear. Mast cells (MCs) are immunocytes widely distributed throughout the gastrointestinal tract. Several stimuli (e.g. allergens, neuropeptides and stress) lead to MC activation with consequent mediator release (e.g. histamine, tryptase and prostanoids). The MC mediators interact with nerves supplying the gut leading to altered gut physiology and increased sensory perception. The intestinal mucosa of irritable bowel syndrome patients contains on average an increased number of MCs. These cells release an increased amount of mediators in close vicinity to mucosal innervation. The MC activation and their close proximity to nerve fibres is correlated with the severity of perceived abdominal painful sensations. These data provide a strong basis for considering MCs as important participants in visceral hypersensitivity and pain perception in irritable bowel syndrome. Inhibition of MC function may ameliorate irritable bowel symptoms. Novel drugs with an increased potential in the control of MC function (e.g., anti-IgE antibodies, the intracellular protein tyrosine kinase inhibitor Syk) and mediator release (e.g., second generation antihistamines, proteinase-activated receptor antagonists) may be useful pharmacological tools for these common disorders.

Animals↗
PubMed2006

Postinfectious gastroparesis related to autonomic failure: a case report.

BACKGROUND AND AIM: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing and autopsy. HOSPITAL COURSE: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva manoeuvre although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteraemia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. CONCLUSION: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiological and autonomic studies with histological findings.

Adult↗
PubMed2006

HLA and enteric antineuronal antibodies in patients with achalasia.

The aetiopathogenesis of primary achalasia is largely unknown, although an immunogenetic predisposition is suspected. To establish whether a correlation exists among possible aetiological factors, including class II human leucocyte antigen (HLA) alleles and autoantibodies to enteric neurones, and clinical features of patients with achalasia, a total of 60 patients and 200 healthy subjects were typed by high-resolution HLA-DQ and HLA-DR alleles. Circulating antineuronal antibodies were investigated by using indirect immunofluorescence on enteric neurones of rat ileum and colon and immunoblotting assay in a subset of achalasic patients and in all controls. The DQB1*0502 and DQB1*0601 alleles were significantly increased in patients with achalasia compared with controls (P < 0.03, P < 0.001, respectively). Moreover a negative correlation with the DQB1*0201 allele was found (P = 0.016). As a whole, 14 of 60 (23.3%) achalasia patients were carriers of HLA risk alleles, and 10 of 41 (24.4%) presented antineuronal antibodies. No significant correlation among HLA risk alleles, antineuronal antibodies and clinical features was found. In achalasia, no correlation exists among HLA alleles, antineuronal antibodies and clinical features. However, given the association between achalasia and HLA-DQ1, further research is needed to clarify the role of HLA antigens and antineuronal antibodies in this disease.

Age of Onset↗
PubMed2006

Constitutive expression of cyclooxygenase-2 in the neuromuscular compartment of normal human colon.

Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX-1 and COX-2. The initial hypothesis that COX-2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX-2 in normal human colon. Colonic surgical specimens were processed for COX-2, protein HuC/HuD, neurofilament, S-100 protein and CD117/c-kit immunodetection. COX-2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX-2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX-2 immunoreactive. This study provides a detailed mapping of COX-2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology.

Blotting, Western↗
PubMed2005

Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus.

BACKGROUND: Evidence indicates that patients with familial achalasia associated with Allgrove or triple-A syndrome (i.e. alacrima, achalasia and adrenocorticotropin-resistant adrenal insufficiency with neurological impairment) have mutations of the alacrima achalasia adrenal insufficiency syndrome (AAAS) gene. AIM: The present study was aimed at identifying possible AAAS gene mutations in patients with established idiopathic non-familial achalasia. METHODS: Genomic DNA of 41 patients was isolated from peripheral blood cells using standard methods. The 16 exons of the AAAS gene (or ALADIN) were screened for mutations using the denaturing high-performance liquid chromatography method. RESULTS: Four heterozygous nucleotidic variations have been identified in patients with idiopathic achalasia, among which three were exonic conservative polymorphisms [i.e. D138D (GAT-->GAC), L227L (TTG-->CTG) and F285F (TTC-->TTT) in exons 5, 7 and 9, respectively]. The fourth nucleotidic variation was located in intron 13 (IVS14-23delT). All variants have been regarded as polymorphisms resulting in a normal ALADIN protein since they are either conservative or lying outside the consensus splice sites. CONCLUSIONS: Our data do not support a pathogenetic role for common AAAS gene mutations in patients with idiopathic achalasia as seen in Allgrove syndrome. These findings suggest the participation of different mechanisms in the pathogenesis of idiopathic achalasia.

Adult↗
PubMed2004

Pancreatic involvement in systemic sarcoidosis. A case report.

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.

Amylases↗
PubMed2004

Abnormalities of somatic peptide-containing nerves supplying the pelvic floor of women with genitourinary prolapse and stress urinary incontinence.

OBJECTIVES: To test the hypothesis that genital prolapse may be related to peripheral nerve abnormalities, we examined the changes occurring to peptide-containing nerve processes supplying the periurethral muscles in women with stress urinary incontinence associated with prolapse. METHODS: Thirty patients with genital prolapse and 10 age-matched control subjects entered the study. All patients were evaluated by urodynamic investigations. Ten of 30 patients had pure stress urinary incontinence; none of the control subjects was incontinent. During surgery, four biopsy samples were obtained from each woman from the periurethral and perirectal muscles. The muscle sections were processed for immunohistochemistry using specific antibodies to glial (S-100 protein) and general neuronal markers (neuron-specific enolase) and neuropeptides, including neuropeptide Y, vasoactive intestinal polypeptide, and substance P. The evaluation of immunolabeled nerves was based on a semiquantitative analysis that allowed for a four-point ordinate scale score. RESULTS: S-100 and neuron-specific enolase immunoreactive nerve fibers, running either singly or in small bundles, along with a dense network of neural processes containing neuropeptide Y, vasoactive intestinal polypeptide, and substance P, were found throughout the connective tissue and striated muscle of the control specimens. In contrast, in the muscle specimens from those with genitourinary prolapse, both the density and the intensity of neuropeptide Y, vasoactive intestinal polypeptide, and substance P immunoreactive nerves were markedly reduced compared with the control specimens. CONCLUSIONS: The evidence of a reduced peptide-containing nerve supply to the perineal muscles provides a morphologic basis suggesting that neural abnormalities contribute to the pathogenesis of genital prolapse and urinary incontinence.

Aged↗
PubMed2004

New pathophysiological mechanisms in irritable bowel syndrome.

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.

Central Nervous System Diseases↗
PubMed2004

Diagnosis and therapy of irritable bowel syndrome.

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.

Anti-Bacterial Agents↗
PubMed2004

New insights into human enteric neuropathies.

The functioning of enteric neuronal circuitries has been elucidated in the recent past. Evidence is now gathering to explain how dysfunction of the enteric nervous system (ENS) may lead to human gastrointestinal motor disorders. These conditions include achalasia, congenital hypertrophic pyloric stenosis, chronic intestinal pseudo-obstruction, Hirschsprung's disease, chronic idiopathic constipation, and probably irritable bowel syndrome. Degenerative, inflammatory and genetic mechanisms exert a critical role in ENS dysfunction underlying gut dysmotility. The study of the ENS abnormalities in gut dysmotility provides a framework to better understand the mechanisms involved in degeneration and neuronal loss and fosters the development of targeted therapeutic options.

Autonomic Nervous System Diseases↗
PubMed2003

Unsolved problems in the management of patients with gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is a common problem that brings large numbers of patients to physicians every day. It lowers the quality of life of affected individuals and exposes them to potentially dangerous complications. An increasing awareness exists among patients, doctors and authorities about the relevance of this pathological condition. Despite an improved understanding of many aspects of gastro-oesophageal reflux disease, clinical management of several cases is still unsatisfactory. Atypical cases with extra-oesophageal manifestations often defy diagnosis. Even typical symptoms are often misunderstood and considered to be part of the poorly defined area of dyspepsia by both patients and doctors. As a consequence, management remains uncertain for too many cases. If correctly diagnosed, gastro-oesophageal reflux disease can be efficaciously treated with proton pump inhibitors (PPIs). Although standard doses of PPIs can heal mucosal lesions and provide symptom relief in the vast majority of oesophagitis patients, non-oesophagitis symptomatic individuals and those with extra-oesophageal manifestations may fail to respond to similar regimens. Antireflux surgery is a possible alternative to PPI therapy, but it is hampered by complications in a substantial percentage of cases and by sporadic casualties even when performed by experienced surgeons. The high prevalence of gastro-oesophageal reflux disease in the general population and the relatively high management costs should prompt any doctor to seek the best possible therapeutic approach.

Disease Management↗
PubMed2003

Predictors of gastroparesis in out-patients with secondary and idiopathic upper gastrointestinal symptoms.

BACKGROUND: Delayed gastric emptying occurs frequently in patients with upper gastrointestinal symptoms associated with functional or organic diseases. AIMS: To evaluate whether: (i) the prevalence of delayed gastric emptying is influenced by the presence of organic disease; (ii) demographic or clinical factors predict modestly or markedly (gastroparesis) delayed emptying. PATIENTS: A total of 327 consecutive out-patients with upper gastrointestinal symptoms. METHODS: Routine diagnostic work-up and evaluation of demographic factors, gastrointestinal symptom evaluation and scintigraphic gastric emptying of solids were performed. RESULTS: Organic diseases were detected in 227/327 (65%) patients: 33% had delayed emptying and 20% gastroparesis. Female gender (OR: 2.1; 95% C.I.: 1.3-3.4). overweight (0.5; 0.3-0.9), relevant postprandial fullness (1.8; 1.1-3.2) and relevant epigastric bloating (1.8; 1.1-2.9), but not the presence of organic diseases, were associated with delayed emptying. Female gender (3.9; 1.3-11.9) and relevant postprandial fullness (4.1; 1.7-10.2) were associated with gastroparesis. CONCLUSIONS: (i) There is a high prevalence of delayed gastric emptying and gastroparesis in out-patients with upper gastrointestinal symptoms, which is not influenced by the presence of organic disease; (ii) female gender, low body weight, relevant fullness and bloating are associated with delayed emptying; female gender and relevant postprandial fullness predict gastroparesis.

Adult↗
PubMed2003

Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse.

BACKGROUND AND AIMS: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. METHODS: NEP knockout (NEP-/-) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. RESULTS: Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP-/- mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP-/- mice. Infusion of rhNEP to NEP-/- mice significantly reduced MPO activity 24 hours PI. CONCLUSIONS: These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP-/- mice likely play a role in the earlier onset of intestinal inflammation.

Animals↗