Giuseppe Fedeli

Association of Virulent Helicobacter pylori Strains With Ischemic Heart Disease

BACKGROUND Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). METHODS AND RESULTS We assessed the prevalence of infection by Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, in 88 patients with ischemic heart disease (age, 57+/-8 years; 74 men) and in 88 age- and sex-matched controls (age, 57+/-8 years; 74 men) with similar social background. Prevalence of Helicobacter infection was significantly higher in patients than in controls (62% versus 40%; P=.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P<.001) adjusted for age, sex, main cardiovascular risk factors, and social class. Patients with ischemic heart disease also had a higher prevalence of CagA-positive strains (43% versus 17%; P=.0002), with an adjusted odds ratio of 3.8 (95% CI, 1.6 to 9.1; P<.001). Conversely, prevalence of CagA-negative strains was similar in patients and controls (19% versus 23%), with an adjusted odds ratio of 0.8 (95% CI, 0.4 to 1.4). CONCLUSIONS The association between Helicobacter pylori and ischemic heart disease seems to be due to a higher prevalence of more virulent Helicobacter strains in patients. These results support the hypothesis that Helicobacter pylori may influence atherogenesis through low-grade, persistent inflammatory stimulation.

Role of Dental Plaque in the Transmission of helicobacter Pylori Infection

With regard to the role of dental plaque in the transmission of Helicobacter pylori infection, data from the literature vary greatly, owing to differences in sample collection and H. pylori-detecting techniques. Using the polymerase chain reaction (PCR), we have determined the incidence of H. pylori colonization in the dental plaque of 31 consecutive patients who underwent gastroscopy. The patients were divided into two groups on the basis of H. pylori infection, determined by Giemsa stain and the rapid urease test: group A made up of 21 H. pylori-positive patients and group B with 10 H. pylori-negative patients. Our PCR assay of dental plaque samples proved negative in all group A subjects but was positive in only one patient in group B. In our study, we found that H. pylori had a low prevalence (3.2%) in the oral cavity, with no significant relationship between gastric mucosa and dental plaque colonization. More comprehensive studies are needed to determine whether dental plaque is an important reservoir in the epidemiology of H. pylori-induced gastric disease.

Prevention and treatment of low-grade B-cell primary gastric lymphoma by anti-H. pylori therapy.

Mucosa-associated lymphoid tissue (MALT) showing a follicular structure can develop in the gastric mucosa as a response to Helicobacter pylori infection. We emphasize the importance of anti-H. pylori antibiotic therapy in the elimination of acquired MALT. Of the 200 patients studied, acquired MALT was found in 70 of the 151 H. pylori-positive patients, whereas it was present in only five of the 49 H. pylori-negative patients. Thirty-eight H. pylori-positive and MALT-positive patients were treated with antibiotic therapy and reevaluated after 6 months: 21 patients were H. pylori negative/MALT negative, 12 were H. pylori positive/MALT positive, four were H. pylori negative/MALT positive, one was H. pylori positive/MALT negative. In the control group (n = 20), H. pylori and acquired MALT were still present at follow-up. One patient with histological and immunohistochemical evidence of low-grade B-cell gastric MALT lymphoma underwent antibiotic treatment and was reexamined after 8, 12, and 24 weeks: histological examination of biopsy samples showed regression of the MALT lymphoma in tandem with the disappearance of H. pylori colonization. Our data confirm the correlation between H. pylori infection and acquired MALT, as documented by the ability of antibiotic therapy to induce the disappearance of acquired MALT and regression of MALT lymphoma. Considering the potential evolution of MALT into low-grade B-cell MALT lymphoma, H. pylori eradication should play a role in the prevention of this tumor.

Vascular Involvement in Inflammatory Bowel Disease: Pathogenesis and Clinical Aspects

Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a microvascular and also macrovascular involvement. Chronically inflamed intestinal microvessels of IBD patients have demonstrated significant alterations in their physiology and function compared with vessels from healthy and uninvolved IBD intestine. Recently, some studies have revealed that the poor mucosal healing, refractory inflammatory ulcerations and damage in the IBD intestine could depend on microvascular dysfunction, resulting in diminished vasodilatory capacity and tissue hypoperfusion in the IBD gut. Furthermore, several data show that the activation of intestinal endothelium plays a critical role in the pathogenesis and/or in perpetuating and amplifying the inflammatory process in IBD and, consequently, it is now emerging as a potential use of anticoagulant or coagulation-related drugs in treating IBD. IBD is also associated with an increased risk of macrovascular venous and arterial thrombosis. Thrombotic events occur prevalently as deep vein thrombosis and pulmonary embolism. They happen at an earlier age than in non-IBD patients. Prothrombotic risk factors in IBD patients could be distinguished as acquired, such as active inflammation, immobility, surgery, steroid therapy, and use of central venous catheters, and inherited. Furthermore, it has been found that IBD, per se, is an independent risk factor for thrombosis. The prevention of thromboembolic events in IBD patients includes the elimination of removable risk factors and, if thrombosis occurs, a pharmacological therapy similar to that used for thromboembolic events occurring in the general population.

A controlled study comparing cimetidine treatment to an intensive antacid regimen in the therapy of uncomplicated duodenal ulcer.

The authors report the results of a randomized study in which comparison was made between two different kinds of treatment in patients affected by uncomplicated duodenal ulcer endoscopically diagnosed. The first group was treated with 1 g of cimetidine per day, during a period of four weeks (200 mg three times a day and 400 mg at bedtime); the second with a liquid Al−Mg antacid compound, 210 ml/day (30 ml, 1 and 3 hr after meals and 30 ml before bedtime) for four weeks. Fifty-one patients were studied, 27 treated with cimetidine, 24 with antacids. At the end of the four-week period, 21 patients (77.7%) in the cimetidine group and 18 patients (75%) in the antacid group were completely healed. Benign side effects were remarked in both types of treatment, none of which made it necessary to suspend treatment. No significant variation of the basal and peak acid output before and after each kind of treatment was observed, while a slight but significant increase in fasting serum gastrin concentration was noted after treatment in the antacid group.

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience

During infliximab treatment of perianal Crohn’s disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10±2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4±8.8 months (range 3–28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25±5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.

CT findings and clinical activity in Crohn's disease

The aim of this study was to evaluate clinical correlations of CT signs in proven Crohns disease. Fifty patients were studied by means of multidetector CT. Clinical activity was assessed using Crohns disease activity index (CDAI) score and some laboratory parameters. All patients with CDAI>150 had CT study scored as pathological. Seventy-nine percent of patients with CDAI<150 showed abnormalities in CT exam. CT findings correlate with some parameters of disease activity, thus underlining the usefulness of performing CT enteroclysis in Crohns disease patients.

Esophageal involvement in Behçet's syndrome.

Two patients with Behçets syndrome had severe esophageal involvement. Both presented the complete clinical pattern (oral, genital, and eye lesions) of Behçets syndrome. In both, esophageal lesions were associated with other gastrointestinal manifestations, in the first a transient episode of ulcerative ileitis, and in the second patient colitis. In both, the differential diagnosis with inflammatory bowel disease was very difficult. Histology of esophageal lesions was nonspecific; no vasculitis was found. Both patients improved on steroid therapy. Esophageal lesions also improved endoscopically and histologically with steroid therapy. When there is obvious gastrointestinal involvement in Behçets syndrome, the differential diagnosis from inflammatory bowel disease is very difficult.

Increased levels of NF-κB inhibitors (IκBα and IκBγ) in the intestinal mucosa of Crohn's disease patients during infliximab treatment

The treatment with infliximab is employed successfully in Crohns disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFα by peripheral blood mononuclear cells (PBMC) and the levels of NF-κB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFα was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kB subunit Rel-A, and its inhibitors IκBα and IκBγ was performed on intestinal biopsies and PBMC. The TNFα production by LPS stimulated PBMC showed mild changes, while it was increased by PHA–stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IκBα and IκBγ inhibitor levels in intestinal biopsies after treatment. An increase of IκB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-κB activity and exerts its anti-inflammatory effects.

Behavior of pancreatic glucagon, insulin, and HGH in liver cirrhosis, after arginine and i.v. glucose

SummaryThe authors studied the behavior of plasma levels of glucagon, HGH and insulin in a group of cirrhotic patients both in basal conditions and after i.v. arginine and glucose in order to assess their respective importance in the pathogenesis of carbohydrate disorders. After i.v. arginine an increased plasma concentration of pancreatic glucagon was found which reached its highest level at 15 min; i.e. glucose did not suppress the increased plasma glucagon levels. Plasma HGH which is consistently increased is not influenced by i.v. glucose. Plasma insulin was consistently raised during both tests; however, the insulinogenic index after i.v. glucose behaved like that of mild diabetics. The true importance of glucagon in the pathogenesis of carbohydrate intolerance in cirrhotics cannot as yet be determined with certainty; according to the authors, hyperglucagonemia is not the primary factor but only one of the main causes of this intolerance.