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Biomedical subjects

Filippo Cremonini

Publications and source records attributed to Filippo Cremonini.

At least 19 recordsLinked to original sources
PubMed2006

Obesity does not increase effects of synthetic ghrelin on human gastric motor functions.

BACKGROUND & AIMS: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. METHODS: After intravenous bolus synthetic human ghrelin (0.33 mug/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined (99m)Tc-single-photon emission computed tomography and scintigraphy ((111)In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. RESULTS: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 +/- 4 kg/m(2)) and 13 female normal-weight (BMI, 22 +/- 2 kg/m(2)) subjects of similar ages, ghrelin increased GH levels (15.0 +/- 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. CONCLUSIONS: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.

Adolescent↗
PubMed2006

Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori eradication.

BACKGROUND: The standard first-line therapies for Helicobacter pylori eradication are based on clarithromycin and amoxicillin or metronidazole. Recent studies suggested levofloxacin as an alternative option for both first-and second-line H. pylori eradication treatment. AIMS: To compare efficacy and tolerability of two different 7-day standard triple therapies versus 7-day levofloxacin-based triple therapy in first-line treatment for H. pylori infection. METHODS: Three hundred consecutive H. pylori positive patients were randomized to receive: clarithromycin, amoxicillin, esomeprazole (Group A: N = 100); clarithromycin, metronidazole, esomeprazole (Group B: N = 100); or clarithromycin, levofloxacin, esomeprazole (Group C: N = 100). H. pylori status was rechecked by (13)C urea breath test 6 wk after the end of therapy. RESULTS: Sixteen out of 300 patients discontinued treatment because of the occurrence of side effects (Group A, 5; Group B, 7; Group C, 4). The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 75% and 79%; Group B, 72% and 77.4%; and Group C, 87% and 90.6%. The eradication rate achieved with levofloxacin-based triple therapy was significantly higher than that with standard therapies in either ITT (87%vs 75%, p <0.05; 87%vs 72%, p <0.01;) or PP analysis (90.6%vs 79%, p <0.05; 90.6 vs 77.4, p <0.05). No difference was found between standard triple therapies. The incidence of side effects was similar among groups. CONCLUSIONS: A 7-day levofloxacin-based triple therapy can achieve higher H. pylori eradication rates than standard regimens. These data suggest levofloxacin-based regimens can be the most effective in first-line anti-H. pylori therapy, at least in the Italian population.

Adolescent↗
PubMed2005

Idiopathic chronic urticaria and celiac disease.

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Adult↗
PubMed2005

Frontiers in functional dyspepsia.

Functional dyspepsia (FD) refers to unexplained pain or discomfort in the upper abdomen and is commonly seen in gastroenterology practice. The underlying pathophysiologic mechanisms associated with FD are unclear, although traditionally, delayed gastric emptying, visceral hypersensitivity to acid or mechanical distention, and impaired gastric accommodation have been implicated as putative physiologic disturbances. It also remains uncertain whether FD and irritable bowel syndrome are different presentations of the same disorder. Recent data on pathophysiologic mechanisms of FD have focused on postprandial motor disturbances (accelerated gastric emptying, antral-fundic incoordination, and abnormal phasic contractions), alterations of neurohormonal mechanisms in response to a meal, and previous acute infection. Pharmacologic therapies for FD may be guided by these novel mechanisms, as current available therapeutic options are limited. Novel prokinetics and gastric accommodation modulators, visceral analgesics, and agents targeting the neurohormonal response to food ingestion are the next therapeutic frontiers in FD. This review summarizes traditional knowledge and more recent advances in the pathophysiology of FD and potential therapeutic opportunities.

Analgesics↗
PubMed2005

Irritable bowel syndrome: epidemiology, natural history, health care seeking and emerging risk factors.

IBS is a common condition, affecting approximately 3% to 15% of the general population based on various diagnostic criteria. There seem to be differences in disease epidemiology between the eastern and the western world. As data from larger Asian epidemiological studies begin to surface,however, such differences appear to be less marked. The proportion of IBS patients who consult a physician for their symptoms is around 50%. Psychological factors and the presence and duration of abdominal pain are all significant predictors for health care seeking. The natural history of IBS is characterized by frequent fluctuation of symptoms and by an overlap with other functional GI disorders, some of which share a number of risk factors for IBS. Unnecessary abdominal surgery is performed in a high proportion of IBS sufferers. Along with the established role for psychosocial conditions in IBS, other risk factors are emerging. Evidence for postinfectious IBS is mounting, but the clinical usefulness of characterizing such patients remains unclear. Food sensitivities are frequently present in IBS, but more well-conducted trials of avoidance diets and desensitization are needed. Finally,genetic markers in IBS are an increasing focus of attention, but the amount of phenotypic variance explained by genetic variability remains to be established.

Food Hypersensitivity↗
PubMed2005

Effect of gastric volume or emptying on meal-related symptoms after liquid nutrients in obesity: a pharmacologic study.

BACKGROUND & AIMS: Altered postprandial satiation influences food intake in obesity. The aim of this study was to evaluate the contribution of gastric motor functions to intra- and postprandial symptoms in obese, otherwise healthy, people. METHODS: In a randomized, parallel-group, double-blind design, 40 obese (body mass index>30 kg/m2) healthy volunteers (n=10/group) received intravenous saline (placebo), atropine (.02 mg/kg), or erythromycin (1 or 3 mg/kg) to alter gastric volume and emptying after liquid nutrient meals, measured by validated imaging methods. The nutrient drink test assessed the volume ingested at maximum satiation, and intra- and early postprandial symptoms. Relationships between gastric motor functions, meal size, and symptoms were assessed by using multiple regression. Circulating levels of candidate upper-gut hormones involved in satiation were measured. RESULTS: Relative to placebo, atropine retarded gastric emptying and increased gastric volumes; erythromycin accelerated gastric emptying and reduced gastric volumes during fasting. Although similar maximal tolerated volumes were recorded across treatments, intra- and immediate postprandial symptoms were increased by these perturbations, particularly nausea and bloating. Upper-gut hormonal profiles generally reflected changes in gastric emptying. Regression analysis showed that fasting predrug gastric volume was a significant predictor of intra- and postprandial bloating. Change in gastric volume postdrug or postmeal did not contribute additionally to predicting intra- or postprandial symptoms. There was significant (negative) association between gastric emptying and fullness score, and significant (positive) association with hunger score 30 minutes postprandially. CONCLUSIONS: In obese individuals, fasting gastric volumes and gastric emptying, but not postprandial gastric volumes, were associated with intra- and postprandial symptoms. Understanding the determinants of gastric volume may provide insights on mechanisms controlling satiation.

Adolescent↗
PubMed2005

Treatments targeting putative mechanisms in irritable bowel syndrome.

The pathophysiology of irritable bowel syndrome (IBS) is heterogeneous; it is possible for several mechanisms to be disturbed in the same patient. Isolating a single target for pharmacological manipulation is also difficult because of the complexity and overlap of the neural circuitry in the enteric and central nervous system. This review summarizes the rationale and efficacy of current and future therapies for IBS, on the basis of putative pathophysiological models. The modulation of gastrointestinal sensorimotor function, intestinal gas handling, the gastrocolonic reflex, neurohormonal stress responses, central processing of afferent information, and microbial flora are the current frontiers for experimental therapeutics for IBS. Patients presumed to have POSTINFECTIOUS IBS have also been targeted as a distinct group. In the very near future, it is unlikely that a single drug will come to the fore as a suitable and successful treatment for everyone with IBS, but new data on potential therapeutic targets lend hope for the improved long-term management of IBS. Disease modification rather than just symptom-based treatments must remain the goal.

Enteric Nervous System↗
PubMed2005

Effect of somatostatin analog on postprandial satiation in obesity.

OBJECTIVE: Altered satiation may impact postprandial symptoms and potentially change food intake in obesity. Our aim was to compare effects of octreotide and placebo on postprandial symptoms, satiation, and gastric volumes in obesity. RESEARCH METHODS AND PROCEDURES: In a randomized, parallel-group, double-blind, placebo-controlled study, 26 obese but otherwise healthy participants received 100 mug of octreotide or placebo subcutaneously 30 minutes before each study. Studies were performed on 2 separate days and included validated non-invasive techniques: (99m)Tc-single photon emission computed tomography imaging to measure fasting stomach volume and gastric volume changes after 90 mL of water and 240 mL of Ensure and a standardized nutrient drink test to measure the maximum tolerated volume and postprandial symptoms. RESULTS: Relative to placebo, octreotide increased gastric volume after 90 mL of water; however, fasting and gastric volume change post-Ensure and maximum tolerated volume of Ensure were not different. Octreotide decreased sensations of fullness (p = 0.035) and bloating (p = 0.05) and tended to reduce aggregate symptoms (p = 0.07) after the fully satiating meal. DISCUSSION: In obese individuals, somatostatin analog significantly reduced postprandial sensations after a satiating meal without altering maximum tolerated meal volume or postnutrient gastric volume, suggesting an effect on upper gut sensation. The role of somatostatin as a permissive factor in the development of obesity by reducing postprandial sensations deserves further study.

Adult↗
PubMed2005

Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study.

BACKGROUND: Cholecystokinin (CCK) is involved in gastrointestinal motor response to meals. The potential role of CCK receptor antagonists in functional gastrointestinal disorders is unclear. AIMS: To evaluate the effects of dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT) and symptoms in patients with constipation-predominant IBS (C-IBS); and to explore the influence of CCK-1 receptor polymorphisms on gut transit and the pharmacodynamic response to therapy. METHODS: A total of 36 patients with C-IBS and normal to slow baseline colonic transit (CT) were randomized (double-blind, parallel design) to 7 days of dexloxiglumide 200 mg or placebo t.i.d. Daily bowel habits diaries and weekly relief of IBS symptoms were recorded. At the end of treatment, GIT and CT were measured. Peripheral blood DNA was examined for polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK gene promoter, and one related to CCK-2. The distributions of allelic variants and association with gastric emptying in response to dexloxiglumide and placebo were assessed. RESULTS: Dexloxiglumide was associated with accelerated gastric emptying t(1/2) (p= 0.004), and slower ascending colon emptying t(1/2) (p < 0.01), with no significant effect on overall CT or satisfactory relief of IBS. There was an association between CCK 779T > C polymorphism and slower rate of gastric emptying (p= 0.04). CONCLUSIONS: Dexloxiglumide accelerates gastric emptying and delays proximal but not overall CT in patients with C-IBS. Dexloxiglumide does not accelerate transit in C-IBS. The role of CCK-1 gene polymorphisms in delaying gastric emptying and in determining response to therapy deserves further study.

Adult↗
PubMed2005

Diagnostic and therapeutic use of proton pump inhibitors in non-cardiac chest pain: a metaanalysis.

OBJECTIVES: To assess (i) the efficacy of short-term proton pump inhibitors (PPIs) in non-cardiac chest pain (NCCP) and (ii) the performance of an empirical short-term treatment with PPI (PPI test) to establish a diagnosis of abnormal acid reflux in NCCP. METHODS: Metaanalysis of English language studies identified by searching MEDLINE (1966-May 2004), EMBASE (1980-May 2004), Cochrane Controlled Trials Register, and abstract books from major gastroenterology meetings (1993-2004). For the metaanalysis of PPI efficacy in NCCP, we selected randomized controlled trials (parallel group and crossover designs) comparing PPI therapy with placebo. For the metaanalysis of PPI test performance, we selected uncontrolled studies comparing the test with a standard reference. RESULTS: Eight studies were included in the PPI efficacy analysis. The pooled risk ratio for continued chest pain after PPI therapy was 0.54 (95% CI 0.41-0.71). The overall number needed to treat was 3 (95% CI 2-4). The pooled sensitivity, specificity, and diagnostic odds ratio for the PPI test versus 24-h pH monitoring and endoscopy were 80%, 74%, and 13.83 (95% CI 5.48-34.91), respectively. All studies were small and there was evidence of publication bias or other small study effects. CONCLUSION: PPI therapy reduces symptoms in NCCP and may be useful as a diagnostic test in identifying abnormal esophageal acid reflux.

Anti-Ulcer Agents↗
PubMed2004

Treatment of Functional Dyspepsia.

Functional dyspepsia is a common chronic condition. It can have a major impact on quality of life and remains a large burden on healthcare resources. Its underlying mechanisms are not fully understood and therapies are mainly empirical. In this review, we summarize the best evidence on available therapeutic interventions in functional dyspepsia. Helicobacter pylori eradication, for those infected, is likely a safe and cost-effective strategy but benefits only a minority. Antisecretory agents such as proton-pump inhibitors and histamine-2 receptor antagonists have shown some benefit and are recommended as the first-line option in the absence of H. pylori infection. There is a lack of strong evidence of benefit from prokinetic agents, and cisapride, the most studied agent, is largely unavailable. Antidepressants need to be adequately tested in functional dyspepsia, but both psychotherapy and hypnotherapy interventions have shown promising results. Herbal therapies need further study in these patients. 5-Hydroxytryptamine3 (5-HT(3)) and 5-HT(4) receptor antagonists, and cholecystokinin type A and neurokinin receptor antagonists remain promising emerging therapies.

Journal Article↗
PubMed2004

The relationship between chronic H. pylori infection, CagA seropositivity and stroke: meta-analysis.

AIMS: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori (H. pylori) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. METHODS: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. RESULTS: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24-1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49-3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12-2.45), and than controls (odds ratio 1.61; 95% CI 1.13-2.32). CONCLUSIONS: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.

Age Distribution↗
PubMed2004

Functional dyspepsia: drugs for new (and old) therapeutic targets.

The therapeutic management of functional dyspepsia remains a major challenge for the gastroenterologist. Current therapies available are based on putative underlying pathophysiologic mechanisms, including gastric acid sensitivity, slow gastric emptying and Helicobacter pylori infection, but only a small proportion of patients achieve symptomatic benefit from these therapeutic approaches. Relatively novel mechanistic concepts under testing include impaired gastric accomodation, visceral hypersensitivity, and central nervous system dysfunction. Serotonergic modulators (e.g. the 5-HT4 agonist tegaserod, the 5-HT3 antagonist alosetron and the 5-HT1P agonist sumatriptan), CCK-1 antagonists (e.g. dexloxiglumide), opioid agonists (e.g. asimadoline), N-methyl-D-aspartate (NMDA) receptor antagonists (e.g dextromethorphan), neurokinin antagonists (e.g. talnetant), capsaicin-like agents and antidepressants are among the agents currently under investigation. It seems unlikely, however, that targeting a single mechanism with an individual drug will result in complete symptom remission in most cases.

Dyspepsia↗
PubMed2004

CagA-positive cytotoxic H. pylori strains as a link between plaque instability and atherosclerotic stroke.

AIMS: Previous studies suggested an association between infection by cytotoxic CagA-positive Helicobacter pylori strains and atherosclerotic stroke. It has been hypothesized that CagA strains could increase the risk for stroke by affecting carotid plaque irregularity. Our aims were: (1) to confirm the association between CagA strains and atherosclerotic stroke, and (2) to assess the association between CagA strains and carotid plaque irregularity. METHODS AND RESULTS: We enrolled 105 consecutive patients affected by atherosclerotic stroke and 130 sex, age, social background-matched controls without relevant vascular diseases. Risk factors for atherosclerotic stroke, H. pylori infection and CagA status were evaluated in all subjects. The presence of plaque instability was evaluated by colour Doppler ultrasound. The prevalence of CagA-positive strains was significantly higher in patients than in controls (adjusted OR 2.99, 95% CI 1.52-5.88, P=0.002). The CagA seropositivity was the only factor independently associated with carotid plaque irregularity (adjusted OR 8.42, 95% CI 1.58-44.64, P=0.004). CONCLUSION: The evidence of significant associations between CagA-positive H. pylori strains and the presence of carotid plaque instability support their possible involvement in the pathophysiology of atherosclerotic stroke.

Aged↗
PubMed2004

Direct visualization of intestinal villi by high-resolution magnifying upper endoscopy: a validation study.

BACKGROUND: New generation videoendoscopes potentially may visualize duodenal villi. This study compared endoscopic findings with this type of instrument to the histopathologic evaluation of duodenal villi. METHODS: A total of 191 patients underwent upper endoscopy for the purpose of obtaining duodenal biopsy specimens. The findings were assessed independently by 3 experienced observers by using a commercially available, high-resolution, high-magnifying (x2) videoendoscope. The duodenal villous profile was determined by endoscopic magnification and by endoscopic magnification after filling the duodenum with water. With both endoscopic magnification and endoscopic magnification after filling the duodenum with water, villous patterns were scored as the following: definitely present, partially present, or definitely absent. Villous patterns also were histopathologically scored as the following: normal, partial villous pattern, or total villous atrophy. RESULTS: Interobserver variability was excellent (kappa = 0.93). The concordance between either endoscopic magnification or endoscopic magnification after filling the duodenum with water and histology was 100% for presence/absence of villi. The sensitivity, the specificity, and the positive and negative predictive values of endoscopic magnification for detection of any villous abnormality were 95%, 99%, 95%, and 99%, respectively; the respective values of endoscopic magnification after filling the duodenum with water were 95%, 98%, 92%, and 99%. CONCLUSIONS: High-resolution magnifying upper endoscopy can reliably predict the presence or the absence of duodenal villi.

Adolescent↗
PubMed2004

Independent influences of body mass and gastric volumes on satiation in humans.

BACKGROUND & AIMS: We assessed the association of body mass and gastric volumes (fasting and postprandial) with satiation and postprandial symptoms. METHODS: Healthy obese and nonobese subjects underwent measurement of caloric intake at maximum satiation; postprandial symptoms were measured with visual analogue scales 30 minutes after a meal. Gastric volume during fasting and after 300 mL of Ensure was measured with technetium-99m single-photon emission computed tomography imaging. We used multiple regression analysis to assess the associations among variables. RESULTS: Among 134 participants (81 women and 53 men), the median age was 26 years (range, 12-58 years), and the median body mass index was 24 kg/m(2) (range, 17-48 kg/m(2)). Increased body mass index, but not height, was associated with delayed satiation (P < 0.003, adjusted for sex). Overweight and obese subjects ingested, on average, 225 +/- 57 more kilocalories (945 +/- 239 kJ) at maximum satiation compared with normal weight individuals. Increased fasting gastric volume was not associated with body mass index or height, but it was significantly associated with delayed satiation (P = 0.001, adjusted for body mass index and sex). An increase of 50 mL in the fasting gastric volume was associated with 114 +/- 32 kcal (479 +/- 134 kJ) more ingested at maximum satiation. Increased body mass index was associated with lower fullness scores 30 minutes after a meal (P = 0.0012, adjusted for sex and volume of Ensure ingested). In contrast, scores of postprandial bloating and pain were higher with increased body mass index (both P < 0.05, adjusted for sex and volume of Ensure ingested). CONCLUSIONS: Greater body mass index and fasting gastric volume are associated with reduced satiation. Increased body mass index or height was not associated with greater gastric volumes.

Adolescent↗
PubMed2004

Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia.

BACKGROUND & AIMS: The aim was to assess relative contributions of gastric volumes (GV) and gastric emptying (GE) to meal size and postprandial symptoms in patients with functional dyspepsia. METHODS: Patients with chronic upper gastrointestinal symptoms were prospectively evaluated. GV during fasting and after 300 mL Ensure was measured with 99m Tc-single-photon emission computed tomography imaging and solid GE (99m Tc-egg) by scintigraphy. Maximum tolerated volume (MTV) and symptoms were measured after Ensure challenge. RESULTS: Of 57 adult patients evaluated, 39 (23 women, 16 men) met Rome II criteria for functional dyspepsia and had no other diagnosis to account for dyspepsia. The most frequent symptoms were abdominal pain (90%), pain predominantly after meals (76%), nausea (85%), and early fullness after meals (79%). Relative to established laboratory normal values, MTV was abnormal in 82%, aggregate symptom score >209 in 72%, GE (at 1 hour) accelerated in 41%, GE (at 4 hours) delayed in 41%, and postmeal GV reduced in 52%. Lower body mass was associated with lower MTV and higher postchallenge symptoms. Lower fasting (not postprandial) GV and faster GE were independent predictors of lower MTV, explaining 18% of the variance after adjusting for body weight (32% of variance). GE was an independent predictor of postchallenge symptoms (10% of variance) after adjusting for volume ingested (10%), age (20%), and weight (10%). CONCLUSIONS: In adults with functional dyspepsia seen in a tertiary referral practice, decreased meal size and postmeal symptoms are associated with low fasting GV and faster GE. These data provide physiologic targets for ameliorating symptoms of functional dyspepsia.

Adolescent↗