Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms.
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Adolescent↗
Biomedical subjects
Francesco Di Mario
Publications and source records attributed to Francesco Di Mario.
Early epigastric pain after PPI administration: exacerbation of Helicobacter pylori corpus gastritis?
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Abdominal Pain↗
The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs.
BACKGROUND AND AIMS: Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk. METHODS: The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage. RESULTS: 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36). CONCLUSIONS: The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.
Aged↗
Rabeprazole in a one-week eradication therapy of Helicobacter pylori: comparison of different dosages.
AIM: Many data regarding omeprazole-, lanzoprazole- and pantoprazole-based triple therapy for Helicobacter pylori (H. pylori) eradication have been reported, but there is few data present regarding rabeprazole (R). We report the efficacy and tolerability of rabeprazole in different dosages in association with clarithromycin (C)and tinidazole (T) in H. pylori eradication. DESIGN AND METHODS: Ninety-four H. pylori-positive patients with dyspeptic symptoms were enrolled and randomly allocated to eradication therapy in two different one-week regimens. In regimen A, 47 patients received R 20 mg b.i.d, C 500 mg b.i.d and T 500 mg b.i.d, while in regimen B, 47 patients received R 10 mg b.i.d, C 500 mg b.i.d and T 500 mg b.i.d. Eradication of H. pylori was evaluated by a 13C urea breath test (UBT) two months after the end of the therapy. RESULTS: Four patients (two in each regimen) did not complete treatment. The H. pylori eradication rate was 91.4% in group A compared to 89.3% in group B (P-value not significant). Minor side-effects were reported in 4.2% of group A and 6.4% of group B patients. CONCLUSION: Rabeprazole showed good efficacy and tolerability in one-week H. pylori therapy at 20 mg b.i.d and 10 mg b.i.d, suggesting the use of the lower dosage.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Helicobacter pylori infection in children and adults: a single pathogen but a different pathology.
BACKGROUND: The aims of this retrospective study were to ascertain in large series of children and adults: the relationship of the infecting strain to gastric mucosal lesions; and the relationship of the infecting strain to its duodenal localization. MATERIALS AND METHODS: We studied 307 and 604 consecutive children and adults. In gastric mucosal samples H. pylori was cultured, genotyped and histologically assessed, while inflammation, activity and intestinal metaplasia were graded. In a subset of 171 patients H. pylori ureaseA (ureA) and cagA genes were amplified (PCR) using mucosal biopsies from the duodenum. RESULTS: H. pylori infection was diagnosed in 40 children and 308 adults. cagA was identified in 50% and 65.5% of infected children and adults. Antral activity was associated with the density of infecting bacteria (p <.001) and with cagA (p <.01). Intestinal metaplasia was correlated with cagA (p <.001). The ureA gene was found in 56 duodenal samples from 82 H. pylori positive patients. Duodenal H. pylori ureA was significantly more frequent in patients with duodenal diseases than in those without (p <.01), cagA positive strains being mainly involved in the infection of this anatomical area (p <.01). CONCLUSIONS: A severe H. pylori-associated gastritis is more prevalent when the density of infecting bacteria is high and when cagA positive strains cause the infection. The most virulent cagA positive H. pylori colonizes not only the gastric, but also the duodenal mucosa, which can be directly damaged by the bacteria itself or by its products.
Adolescent↗
Association of HLA-DRB1*0401 allele with chronic pancreatitis.
INTRODUCTION: Chronic pancreatitis (CP) is characterized by irreversible morphologic and functional alterations of the pancreas, clinically presenting with upper abdominal pain as well as exocrine and endocrine insufficiencies. According to a more recent hypothesis, the pathogenesis may involve genetic and immunologic factors. AIM: To investigate the major histocompatibility complex (MHC) genes as a genetic background of chronic pancreatitis. METHODOLOGY: Allelic polymorphisms were investigated in the genes of the MHC region (HLA B, DRB, DQB) with PCR-based methodologies (PCR-SSP) in 56 patients with CP (44 males and 12 females) and 183 normal controls (78 males and 105 females) of the same ethnic group. All patients and controls gave their informed consent. RESULTS: Among HLA-DRB1 genes, DRB1*04 was significantly higher in CP patients than in controls (26.78% versus 8.1%; pc < 0.003; OR = 4.1; CI = 1.85-9.06). DRB1*04 allele specificities in the DRB1*04-positive patients demonstrated significantly higher frequencies of DRB1*0401 allele (14.3% versus 1.1%; p = 0.00017; OR = 15.08; CI = 3.1-73.36). Neither HLA-B nor HLA-DQB1 associations with the disease were found. CONCLUSIONS: This study supports a role of HLA-DRB1*0401 as a susceptibility factor for patients with CP. HLA DRB1*0401 contains the 70QKRAA74 amino acid sequence, which is also expressed by several human pathogens, including Epstein-Barr virus. T cells may be triggered in the pancreatic tissue upon exposure to foreign peptides similar enough to cross-react and to break immunologic tolerance.
Adult↗
NSAID and aspirin use by the elderly in general practice: effect on gastrointestinal symptoms and therapies.
BACKGROUND: The relationship between NSAID use and gastrointestinal (GI) symptoms and their treatment in elderly patients is not well defined. OBJECTIVES: To identify the prevalence of specific drug use in elderly outpatients and to identify the relationship between NSAID use and GI disturbances and treatments in elderly subjects treated by their general practitioner (GP). SETTING AND PARTICIPANTS: The study was carried out by 63 GPs in north-eastern Italy; 3154 elderly subjects were included in the study over a 2-week period. DESIGN: By using a structured interview, subjects' medical histories and current medication were identified. In particular, the presence and use pattern (i.e. occasional, 'acute' or 'chronic') of NSAIDs and/or aspirin (acetylsalicylic acid) were recorded. In all subjects, the presence of upper GI symptoms, i.e. abdominal pain, reflux symptoms and indigestion syndrome, were noted. RESULTS: The prevalence of drug use was 96.4% (males 96%, females 96.7%). The most prescribed drugs were ACE inhibitors (38%), diuretics (26.7%), NSAIDs and regular-dose aspirin (24.7%), GI drugs (20.6%), and anxiolytics/hypnotics (20.3%). Of 779 subjects who had taken NSAIDs or regular-dose aspirin, 32.9% were 'chronic' users, 24.9% were 'acute' users and 42.1% occasional users. A significantly higher prevalence of upper GI symptoms was observed in elderly NSAID and low-dose aspirin users compared with non-users (24.9% vs 28% vs 16.6% respectively, p < 0.0001). GI symptoms were reported by 27.6% of 'chronic' NSAID users, 22.9% of 'acute' users and 24.7% of occasional users. A significantly higher prescription rate for any GI drug was found in NSAID users than in low-dose aspirin users and non-users (24.0% vs 19.6% vs 19.4% respectively, p = 0.007). This difference was mainly because of a higher number of upper GI drugs taken by NSAID users than by low-dose aspirin users and non-users (18.1% vs 16% vs 13.7% respectively, p = 0.004). Multivariate analysis demonstrated that female gender (odds ratio [OR] = 1.32, 95% CI = 1.16-1.44), low-dose aspirin (OR = 1.88, 95% CI = 1.33-2.65), NSAIDs and/or regular-dose aspirin (OR = 1.48, 95% CI = 1.19-1.83) and multiple therapies, i.e. taking more than four drugs per day (OR = 1.42, 95% CI = 1.14-1.77) were risk factors for GI symptoms in elderly outpatients. CONCLUSION: NSAIDs and/or aspirin use was very high in this elderly outpatient population. The use of these drugs was significantly associated with a greater number of upper GI symptoms and prescriptions for GI drugs. Educational and clinical strategies need to be implemented in order to reduce the GI impact of NSAID and aspirin use in elderly people.
Activities of Daily Living↗
The race from chronic pancreatitis to pancreatic cancer.
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Animals↗
Macrohematuria caused by a fall in prothrombin activity as a clinical presentation of celiac disease.
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Adult↗
Hypercalcemia due to ectopic secretion of parathyroid related protein from pancreatic carcinoma: a case report.
This case is a report of a male, 52 year old, heavy smoker, with a history of about 10 years of alcohol abuse (he quitted in 1993), gastric resection for ulcer (Billroth II 1970), hypoparathyroidism and macroamylasemia, died for undiagnosed pancreatic carcinoma revealed at necroscopy. The only clinical evidence of carcinoma were pulmonary metastasis and paraneoplastic syndrome characterized from hyponatriemia due to inappropriate secretion of antidiuretic hormone and elevation of seric calcium caused by parathyroid hormone related protein. In patients without endocrine abnormalities, such unusual paraneoplastic syndrome could cause hypercalcemia, but in our patient, the increased calcemia did not reach abnormal levels due to the previous hypoparathyroidism. At present time, there are no clinical reports of parathyroid related protein secretion by pancreatic carcinoma and therefore, it could speculate that this modification together with ectopic secretion of antidiuretic hormone, represent a peculiar evidence of otherwise unknown and undetectable pancreatic carcinoma.
Adenocarcinoma↗
Progressive familial intrahepatic cholestasis.
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive childhood cholestasis of hepatocellular origin. PFIC 1, also known as Byler disease, was first described in Amish kindred. It is characterized by cholestasis often arising in the neonatal period and it leads to death due to liver failure. PFIC 1, like Benign Recurrent Intrahepatic Cholestasis (BRIC) which is the benign form of the same disease, recognizes mutations in the ATP8B1 gene. PFIC 2 disease is clinically similar to PFIC 1 but it has a different gene mutation causing a defect in the Bile Salt Export Pump (BSEP), exclusively expressed in the liver and involved in the canalicular secretion of bile acids. PFIC 3 usually appears later in life and it has a higher risk of portal hypertension, gastrointestinal bleeding and liver failure. This particular form of disease (the only one with high serum values of g-glutamil transpeptidase), is associated to a genetic defect in the class III multidrug resistance protein (MDR). External biliary diversion and ursodeoxycholic acid therapy, should be considered as the initial therapy in these patients, even if liver transplantation still seems to be the only solution for most patients.
Cholestasis, Intrahepatic↗
Lactoferrin: mechanism of action, clinical significance and therapeutic relevance.
Lactoferrin is an iron binding protein involved in a large spectrum of biological actions including antimicrobial actions. Lactoferrin plays a central role in ferrokinetics: it binds free iron with great affinity limiting the amount of ions available for microorganism's metabolism. Its role in the host defence mechanisms consists in bacteriostatic and bactericidal effects; moreover it inhibits the proliferation of other microbes such as fungi and viruses. Lactoferrin is also involved in the modulation of immune system and recent studies indicate that lactoferrin directly modulates both production and function of neutrophils and monocytes.
Lactoferrin↗
The Effect of Omeprazole on Serum Concentrations of Theophylline, Pepsinogens A and C, and Gastrin in Elderly Duodenal Ulcer Patients.
With the aim of verifying the effect of omeprazole treatment on theophyline serum concentration in elderly peptic ulcer patients, we studied 10 male subjects aged >65 years (mean age = 75.2, range = 67--86) with chronic obstructive bronchopneumonia and endoscopically diagnosed duodenal ulcer in acute phase. All subjects were treated with a slow-release formulation of theophylline 200 mg b.i.d. plus omeprazole 20 mg daily for 4 weeks. In all subjects serum concentrations of azote, creatinine, theophylline were determined at the beginning and after 1 and 4 weeks; at the beginning and end of the study, pepsinogen group A (PGA), pepsinogen group C(PGC) and gastrin were measured. Statistical analysis was performed with the Student's t-test for paired data. The results showed no statistically significant differences after 1 and 4 weeks of omeprazole treatment in serum concentrations of theophylline (T(0) = 7.4, T(1 week) = 7.5, T(4 weeks) = 6.0, p = ns), azote (T(0) = 45.2, T(1 week) = 30.5, T(4 weeks) = 36.1, p = ns), creatinine (T(0) = 1.27, T(1 week) = 1.02, T(4 weeks) = 1.16, p = ns), PGA (T(0) = 99.5, T(4 weeks) = 126.2, p = ns), and PGC (T(0) = 10.6, T(4 weeks) = 12.1, p = ns); however serum gastrin increased from T(0) = 70.2 plus minus 13.2 to T(4 weeks) = 130.3 plus minus 18.3 (p < 0.0001). It was concluded that (1) serum concentration of theophylline is not affected by the concomitant omeprazole treatment lasting 1 month in elderly patients suffering from chronic obstructive bronchopneumonia and peptic ulcer, (2) modifications of dosages of theophylline and/or omeprazole are not necessary in the elderly with normal renal function, (3) the increase in fasting serum gastrin after 4 weeks of treatment may indicate that omeprazole 20 mg daily is efficacious in inhibiting gastric acid secretion in the elderly people.
Journal Article↗
Once-Daily Bedtime Dose of Roxatidine and Ranitidine in Acute Duodenal Ulcer: A Combined Assessment of Acid Inhibitory Activity and Healing Rate.
This study was carried out in order to compare the antisecretory effect of a single bedtime dose of roxatidine 150 mg and ranitidine 300 mg and to assess the relationship between the degree and the duration of acid suppression and the healing rates obtained in duodenal ulcer patients treated with the above regimens. Sixty-three patients with endoscopically proven ulcer underwent 24-h gastric pH-metry on day 0, day 1, and day 28 of treatment with both roxatidine and ranitidine. Ulcer healing was checked endoscopically after 4 weeks of therapy. RESULTS: Eight patients did not complete the study, leaving 55 patients eligible for final analysis, 28 in the roxatidine group and 27 in the ranitidine group. Duodenal ulcers were healed in 24--28 (85%) patients of the former and in 22--27 (81%) patients of the latter group (p minus sign NS). Gastric pH was significantly higher (p < 0.001) than basal values on days 1 and 28 with both H2-antagonists. The 24-h pH levels did not differ between day 1 and day 28 with both roxatidine and ranitidine. There was also do difference between the two active treatments. The pattern of gastric acidity significantly differed (p < 0.01) between responder (n = 46) and nonresponder (n = 9) patients to both H2-blockers, and this difference was mainly sustained by nocturnal pH. CONCLUSIONS: A bedtime close of roxatidine 150 mg and ranitidine 300 mg was able to heal more than 80% of duodenal ulcers within 4 weeks of treatment. The lack of tolerance to H2-blockers in duodenal ulcer patients contributes to this good result. The antisecretory effect of H2-antagonists is reduced in nonresponder patients with respect to responder patients and this is mainly due to an impaired control of nocturnal acidity.
Journal Article↗
Use of lactoferrin for Helicobacter pylori eradication. Preliminary results.
BACKGROUND: One-week triple therapy is the most frequently recommended treatment of Helicobacter pylori infection. The associated eradication rate is satisfactory; nevertheless, it is advisable to look for more effective therapies. Our aim was to test the efficacy of a standard triple therapy plus bovine lactoferrin for the eradication of H. pylori infection. STUDY: This open, randomized, single-center study was designed to include 150 consecutive H. pylori-positive patients with dyspeptic symptoms and gastritis who received triple therapy with rabeprazole, clarithromycin, and tinidazole plus lactoferrin for 7 days (group A), rabeprazole, clarithromycin, and tinidazole for 7 days (group B), or rabeprazole, clarithromycin, and tinidazole for 10 days (group C). H. pylori status was assessed 8 weeks after the end of treatment by means of the 13C-urea breath test or H. pylori stool antigen test. RESULTS: The 7-day treatment including lactoferrin (group A) was successful in 100% (24/24) of the patients. The eradication rates in groups B and C were 76.9% (20/26 patients; 95% CI, 61%-93%) and 70.8% (17/24 patients; 95% CI, 53%-89%), respectively. A significant difference was found between group A and group B (P = 0.023) and group A and group C (P = 0.022). No differences were found between group B and group C (P = 1.00). CONCLUSION: These results suggest that lactoferrin could be a new, effective agent when added to antimicrobial therapy for the eradication of H. pylori. This treatment schedule could be proposed for larger trials of H. pylori eradication therapy, focusing on the excellent preliminary cure rate, good compliance to the treatment schedule, and relatively low price of lactoferrin for full treatment.
Drug Therapy, Combination↗
Long-term clinical outcome of elderly patients with reflux esophagitis: a six-month to three-year follow-up study.
Although the prevalence of reflux esophagitis is known to increase with age, data on the long-term outcome of esophagitis in elderly patients are scarce. We sought to evaluate the clinical outcome of elderly patients with esophagitis 6 months to 3 years after diagnosis and to identify specific prognostic indicators of a poor outcome. This was a long-term (6 months to 3 years) follow-up study. Patients older than 65 years of age diagnosed as having reflux esophagitis healed after acute treatment (2 to 4 months) were included in the study. Clinical examinations and upper gastrointestinal endoscopy were performed every 6 months for the first year and annually thereafter. After healing, no therapy was prescribed; in the event of symptom recurrence, a maintenance therapy consisting either of H2 blockers or proton pump inhibitors (PPI) was prescribed. At baseline and during follow-up, the following clinical parameters were recorded: gender, age, the presence of symptoms (heartburn, acid regurgitation, epigastric/chest pain), type and dose of the maintenance therapy, nonsteroidal antiinflammatory drug use; gastric Helicobacter pylori infection, diagnosis of hiatal hernia, and/or Barrett's esophagus. The chi-square test, the Kaplan-Meier test, and Cox's proportional hazards regression analysis were used for statistical analyses. Included in the final analysis were 138 patients (M/F, 81/57; mean age, 79.7 years; range, 66-97). The numbers of patients in need of maintenance therapy were 47 of 69 (68.1%) after 6 months, 29 of 58 (50%) after 12 months, 17 of 39 (43.6%) after 24 months, and 12 of 26 (46.1%) after 36 months of follow-up. A significantly higher esophagitis relapse rate was found in patients not treated compared with subjects who were in maintenance therapy: 59% versus 8.5% (P <.0001) at 6 months, 65.5% versus 20.7% at 12 months (P <.002), 63.6% versus 11.7% at 24 months (P =.003), and 57.1% versus 8.3% at 36 months (P =.02). No significant difference in relapse rate was found in patients treated with H2 blockers versus PPIs (21.7% versus 10%). The Cox model demonstrated that no maintenance treatment (P =.00001), the presence of typical symptoms (P =.00001), the presence of hiatal hernia (P =.03), and a high severity grade of esophagitis at baseline (P =.009) were risk factors for relapse of esophagitis. In elderly subjects, esophagitis relapse occurs in a high percentage of cases, particularly in patients not treated with antisecretory drugs. The presence of typical symptoms, hiatal hernia, and a severe grade of esophagitis are risk factors for relapse. The most effective measure for minimizing the occurrence of relapse is a maintenance therapy with antisecretory drugs.
2-Pyridinylmethylsulfinylbenzimidazoles↗