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Biomedical subjects

G Delle Fave

Publications and source records attributed to G Delle Fave.

At least 19 recordsLinked to original sources
PubMed2006

Rhabdomyolysis due to severe hypokaliemia in a Crohn's disease patient after budesonide treatment.

Patients with Crohn's disease may experience several non-digestive complications, including muscle disorders. Rabdomyolysis has rarely been reported in patients with inflammatory bowel disease, however a number of factors may cause muscular damage in this setting. We report the case of a young woman with Crohn's disease who developed a severe, symptomatic skeletal muscle damage associated with severe hypokaliemia. Reversal of the potassium levels to normal ranges led to clinical resolution. The possible causes that might have lead to hypokalemia development and subsequent rhabdomyolysis are discussed with special emphasis for the potential causative role of medical treatment, especially budesonide for which similar side effects have been previously reported. Physicians should be aware that hypokalemia is possible in the setting of Crohn's disease and muscle damage can present as a complication.

Adult↗
PubMed2006

Corpus-predominant gastritis as a risk factor for false-negative 13C-urea breath test results.

BACKGROUND: Urea breath test sensitivity seems affected by increased intragastric acidity during therapy with antisecretory drugs. Intragastric pH is increased in patients with corpus gastritis with/without atrophy. AIM: To test the hypothesis that urea breath test results may also be affected by this gastritis phenotype. METHODS: 123 untreated patients underwent gastroscopy plus biopsies and intragastric pH measurement. The study included 82 endoscopically proven Helicobacter pylori-positive patients who were offered urea breath test with an acidic meal. Histological findings, urea breath test results and intragastric pH were compared in 66 of the subjects. RESULTS: 21 of 66 (31.8%) patients had a false-negative urea breath test. In these patients corpus-predominant gastritis (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001) were more frequent than in patients with true-positive urea breath test. Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P = 0.001). In a multivariate analysis, the only risk factor for a false-negative urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95% CI: 1.1-27). There was a negative correlation between the intragastric pH and the delta over baseline values (r = -0.378; P = 0.0023). CONCLUSIONS: Our results support the hypothesis that the pattern of gastritis can affect the sensitivity of urea breath test, and suggest that patients with corpus-predominant gastritis have a high risk of false-negative urea breath test results.

Adult↗
PubMed2006

Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination?

In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-alpha and somatostatin analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon-alpha and somatostatin analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.

Antineoplastic Agents↗
PubMed2006

Unawareness of gastrointestinal symptomatology in adult coeliac patients with unexplained iron-deficiency anaemia presentation.

BACKGROUND: Most adults with coeliac disease have a subclinical form of the disease and iron-deficiency anaemia may be the sole presenting symptom. AIM: To evaluate demographic, clinical and biochemical characteristics of adult coeliac disease patients presenting with iron-deficiency anaemia. PATIENTS: A total of 108 iron-deficiency anaemia patients in whom coeliac disease has been diagnosed were studied. As a control group 108 non-coeliac iron-deficiency anaemia patients, comparable for sex and age, were studied. RESULTS: Of the 108 coeliac disease patients, 95 (88%) were female (mean age 34 years, range 19-72) and 13 (12%) were male (mean age 33 years, range 15-65). The median duration of iron-deficiency anaemia before diagnosis was 66 months in coeliac disease patients and 14 months in the iron-deficiency anaemia control group (P = 0.0001). The occurrence of at least one gastrointestinal symptom, not spontaneously reported, was observed in 92 (85%) patients with coeliac disease and in 67 (62%) patients in the control group (P = 0.001). The concomitant presence of diarrhoea, abdominal pain and abdominal bloating was detected in 14% patients with coeliac disease with respect to 3% in the control group (P = 0.005). CONCLUSIONS: The vast majority of coeliac disease patients with iron-deficiency anaemia presentation were unaware of the gastrointestinal symptoms and this relationship is useful for diet compliance.

Abdomen↗
PubMed2006

Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells.

This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.

Cells, Cultured↗
PubMed2006

Vasoactive intestinal peptide receptor subtypes and signalling pathways involved in relaxation of human stomach.

Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with receptors coupled to cAMP- or cGMP-signalling pathways. Their relative contribution to human gastric relaxation is unknown. This study aimed at investigating, in terms of biological activity, receptor expression and related signalling pathways, the action of VIP separately on the human fundus and the antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53 +/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse transcriptase-polymerase chain reaction analysis showed the sole expression of VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant in the antrum. Functional regional differences in receptor-related signalling pathways were found. Activation of the cAMP-pathway by forskolin or its inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs) inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP-pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583) or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher expression of endothelial nitric oxide synthase was found. In conclusion, regional differences in VIP action on human stomach are related to distinct myogenic properties of SMC of the antrum and the fundus.

Adult↗
PubMed2006

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.

The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up- and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially promising candidates for new diagnostic and treatment strategies. The analysis of liver metastases revealed a previously unknown high level of similarity with the primary lesions.

Adult↗
PubMed2005

Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma.

BACKGROUND: Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. PATIENTS AND METHODS: 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). RESULTS: Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. CONCLUSIONS: Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.

Adult↗
PubMed2005

Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection.

BACKGROUND: Long-term outcome of atrophic body gastritis has not yet been defined. AIM: To investigate at long-term follow-up the behaviour of atrophy and intestinal metaplasia and the occurrence of neoplastic lesions in atrophic body gastritis patients. METHODS: Overall 106 atrophic body gastritis patients with > or = 4-year follow-up were studied; 38 were Helicobacter pylori-positive at histology + serology and cured of infection (group A), 36 were positive at serology and not treated (group B) and 32 were H. pylori-negative (group C). Patients underwent gastroscopy with antral (n = 3) and body (n = 3) biopsies for histology according to the Sydney System. RESULTS: At 6.7-year follow-up body atrophy and intestinal metaplasia remained unchanged in all 106 patients irrespective of H. pylori status. Antral atrophy was significantly increased at follow-up only in group C, whereas antral intestinal metaplasia was unchanged in all three groups. During follow-up eight (8%) patients developed neoplastic lesions (one adenocarcinoma, one adenoma with low-grade dysplasia and six low-grade dysplasia without endoscopic lesions). Antral atrophic gastritis was present at baseline in all but one (88%) of the eight patients with neoplastic lesions, but only in 15 (15%) of the 98 patients without (P < 0.0001, RR = 26.7). CONCLUSIONS: Atrophy and intestinal metaplasia persist at 6.7-year follow-up and atrophic body gastritis patients with panatrophic gastritis are at increased risk of developing neoplastic lesions.

Adult↗
PubMed2005

Occurrence and risk factors for benign epithelial gastric polyps in atrophic body gastritis on diagnosis and follow-up.

BACKGROUND: Benign epithelial gastric polyps have been reported to be more common in atrophic body gastritis. The role of Helicobacter pylori infection in the induction of gastric atrophy is well-known. The development of hyperplastic polyps may be in relation to H. pylori infection. AIM: To investigate occurrence of benign epithelial gastric polyps in atrophic body gastritis patients at diagnosis and follow-up, and the role of H. pylori and other risk factors for the development of benign epithelial gastric polyps. METHODS: A total of 259 consecutive atrophic body gastritis patients included in a follow-up programme, of whom 202 were followed up for median period of 4 years (range: 2-11). At baseline and follow-up gastroscopies, the presence of benign epithelial gastric polyps was evaluated. Biopsies for histology were obtained from all detected benign epithelial gastric polyps. RESULTS: Frequency of benign epithelial gastric polyps in atrophic body gastritis patients were 4.6% at baseline and 5.9% at follow-up. About 91.7% were hyperplastic polyps. H. pylori infection was detected in 79.2% atrophic body gastritis patients with benign epithelial gastric polyps, and in 70.8% without benign epithelial gastric polyps. Smoking was more frequent among patients with benign epithelial gastric polyps [42% vs. 20%, OR 2.8 (95% CI: 1.2-6.9)]. CONCLUSIONS: Benign epithelial gastric polyps occur in about 5% of atrophic body gastritis patients, and the vast majority are hyperplastic polyps. Smoking habit, but not H. pylori infection, increases the risk for benign epithelial gastric polyps in atrophic body gastritis patients.

Adolescent↗
PubMed2004

Large hiatal hernia in patients with iron deficiency anaemia: a prospective study on prevalence and treatment.

BACKGROUND: Although large hiatal hernia may cause bleeding from Cameron erosions, its role in iron deficiency anaemia has been debated, and no data are available on the treatment of these patients with proton pump inhibitors. Aims : To determine the prevalence of large hiatal hernia in out-patients with iron deficiency anaemia and the role of proton pump inhibitors in the prevention of recurrence of anaemia. METHODS: Two hundred and twenty-eight out-patients underwent upper/lower endoscopy. Those with large hiatal hernia were given an oesophagogram, discontinued iron supplementation and received proton pump inhibitor treatment with (group 1) or without (group 2) surgery. Anaemia was re-assessed during 1 year of follow-up. RESULTS: Large hiatal hernia was the likely cause of anaemia in 21 patients (9.2%). The median haemoglobin and ferritin values at the diagnosis of anaemia were 7.9 g/dL and 6 micro g/L, respectively. Cameron erosions were found in 33% of patients. Ten and eleven patients were included in groups 1 and 2, respectively. Haemoglobin values were 13.8 g/dL and 13.4 g/dL at 3 months of follow-up, and 13.4 g/dL and 13.8 g/dL at 1 year of follow-up, in groups 1 and 2, respectively. CONCLUSIONS: Large hiatal hernia may cause iron deficiency anaemia, even without Cameron erosions. Surgery in combination with proton pump inhibitor therapy is no better than proton pump inhibitor therapy alone in preventing the recurrence of anaemia.

Adult↗
PubMed2004

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.

BACKGROUND: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. PATIENTS AND METHODS: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. RESULTS: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04). CONCLUSION: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Adult↗
PubMed2004

Somatostatin receptor subtypes: basic pharmacology and tissue distribution.

The heptahelical receptor superfamily constitutes the largest single family of transmembrane-signalling molecules that regulate a wide range of physiological processes. The five somatostatin receptors represent a distinct subgroup of this seven transmembrane receptor superfamily. They range in size from 356 to 391 amino acids with 39-57% protein identity between the subtypes with 100 residues strictly conserved among the somatostatin receptor sequences. A high grade of mRNA homology exists in somatostatin receptor subtypes cloned from different species. Following somatostatin receptor binding and functional activity studies, two alternative models of ligand-binding interaction have been hypothesised. One relies on the presence of a binding pocket within the receptor structure constituted by specific amino acids residues, the other denies the presence of such binding structures and suggests that it is the interaction of agonists with specific extracellular and/or transmembrane domains that determine stable receptor structure conformation. Somatostatin receptors, as, indeed, all G-protein-coupled receptors are able to regulate their responsiveness to agonist exposure. This agonist-specific regulation includes three main events, namely, desensitisation, receptor internalisation and receptor degradation. The cell expression of somatostatin receptor subtypes, at the mRNA level, has been characterised in rodent and in human organs with multiple subtype expression in brain and peripheral tissues.

Animals↗
PubMed2004

Unlabelled somatostatin analogues in treatment of digestive endocrine tumours.

Somatostatin analogues are considered first-line therapy in patients with digestive endocrine tumours. Indeed, several studies have investigated their efficacy in the control of specific symptoms and in the decrease of tumour markers. However, randomised controlled trials are needed in order to better define their role in non functioning tumours and their effect on tumour growth, which have seldom been assessed. Several new drugs have been developed over the last few years such as, for example, new long-acting formulations, universal analogues binding to all five somatostatin receptors subtypes, and cytotoxic analogues, all of which offer a promising therapeutic tool in the near future, even if further studies are needed to determine their efficacy and safety in man.

Digestive System Neoplasms↗
PubMed2004

Optimisation of isolation of richly pure and homogeneous primary human colonic smooth muscle cells.

BACKGROUND: Inherent properties of gastrointestinal smooth muscle can be assessed using isolated cell suspensions. Currently available isolation techniques, based on short 2-h enzymatic digestion, however, present the disadvantage of low cellular yield with brief viability. These features are an important limiting factor especially in studies in humans in which tissue may not be available daily and mixing of samples is not recommended. AIMS: To optimise the isolation procedure of cells from human colon to obtain a richly pure primary smooth muscle cell preparation. METHODS: Slices of circular muscle layer, obtained from surgical specimens of human colon, were incubated overnight in Dulbecco's modified eagle's medium supplemented with antibiotics, foetal bovine serum, an ATP-regenerating system and collagenase. On the following day, digested muscle strips were suspended in HEPES buffer, and spontaneously dissociated smooth muscle cells were harvested and used either immediately or maintained in suspension for up to 72 h. Cell yield, purity, viability, contractile responses, associated intracellular calcium signals and RNA and protein extraction were evaluated and compared to cell suspensions obtained with the current short digestion protocol. RESULTS AND CONCLUSION: The overnight isolation protocol offers the advantage of obtaining a pure, homogeneous, long-life viable cell suspension that maintains a fully differentiated smooth muscle phenotype unchanged for at least 72 h and that allows multiple functional/biochemical studies and efficient RNA extraction from a single human specimen.

Cell Separation↗