Lucio Cuoco

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.

Celiac Disease Associated With Autoimmune Myocarditis

Background—Both celiac disease (CD) and myocarditis can be associated with systemic autoimmune disorders; however, the coexistence of the 2 entities has never been investigated, although its identification may have a clinical impact. Methods and Results—We screened the serum of 187 consecutive patients with myocarditis (118 males and 69 females, mean age 41.7±14.3 years) for the presence of cardiac autoantibodies, anti–tissue transglutaminase (IgA-tTG), and anti-endomysial antibodies (AEAs). IgA-tTG–positive and AEA-positive patients underwent duodenal endoscopy and biopsy and HLA analysis. Thirteen of the 187 patients were positive for IgA-tTG, and 9 (4.4%) of them were positive for AEA. These 9 patients had iron-deficient anemia and exhibited duodenal endoscopic and histological evidence of CD. CD was observed in 1 (0.3%) of 306 normal controls (P <0.003). In CD patients, myocarditis was associated with heart failure in 5 patients and with ventricular arrhythmias (Lown class III-IVa) in 4 patients. From histological examination, a lymphocytic infiltrate was determined to be present in 8 patients, and giant cell myocarditis was found in 1 patient; circulating cardiac autoantibodies were positive and myocardial viral genomes were negative in all patients. HLA of the patients with CD and myocarditis was DQ2-DR3 in 8 patients and DQ2-DR5(11)/DR7 in 1 patient. The 5 patients with myocarditis and heart failure received immunosuppression and a gluten-free diet, which elicited recovery of cardiac volumes and function. The 4 patients with arrhythmia, after being put on a gluten-free diet alone, showed improvement in the arrhythmia (Lown class I). Conclusions—A common autoimmune process toward antigenic components of the myocardium and small bowel can be found in >4% of the patients with myocarditis. In these patients, immunosuppression and a gluten-free diet can be effective therapeutic options.

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.

Immunohistochemical Analysis of ZO-1 in the Duodenal Mucosa of Patients with Untreated and Treated Celiac Disease

Background/Aim: ZO-1 is a good marker for tight junction integrity which may be damaged in many intestinal diseases. ZO-1 can also accumulate in the cellular nucleus in addition to sites of cell-cell contact, suggesting a potential role in cellular proliferation and differentiation. We evaluated the expression and distribution of ZO-1 in patients with celiac disease before and after a gluten-free diet. Methods: The ZO-1 expression was evaluated semiquantitatively by means of immunohistochemical analysis in duodenal bioptic specimens of 10 consecutive patients with celiac disease before and after a gluten-free diet and in 10 controls. Furthermore, the nuclear staining was analyzed quantitatively, evaluating 3,000 cells for each count, and it was expressed as a percentage of labeled nuclei over the total of analyzed cells. Results: The intestinal mucosa of untreated celiac disease patients shows a globally lower ZO-1 labeling than that of controls. The expression of ZO-1 in the treated celiac mucosa did not differ significantly from normal intestinal mucosa of healthy subjects. At the crypt level of untreated celiac mucosa, a low intensity of nuclear labeling (1.75 ± 0.32%) was found, while in both treated celiac disease patients and in normal subjects we observed a statistically significant higher percentage of strongly labeled nuclei (53.72 ± 6.30% and 56.79 ± 5.45%, respectively; p = 0.0002). Conclusions: Our data show a global underexpression of ZO-1 in the duodenal mucosa of active celiac disease patients. Gluten withdrawal allows a normalization of the ZO-1 expression in treated celiac disease patients. Furthermore, the particular pattern of ZO-1 resembles the cellular distribution in undifferentiated cells and may be the result of immaturity of the enterocytes in untreated celiac sprue.

Helicobacter pylori eradication using one-week low-dose lansoprazole plus amoxycillin and either clarithromycin or azithromycin.

Aim: To evaluate and compare two 1‐week low‐dose triple therapies based on lansoprazole, amoxycillin and a macrolide in eradicating Helicobacter pylori.

Gastric Mucosa-Associated Lymphoid Tissue in Autoimmune Thyroid Diseases

BACKGROUND There is increasing evidence for a link between Helicobacter pylori infection and the development of lymphoid follicles in the gastric mucosa. It is not known whether other factors may also play a role. The aim of this study was to investigate the role played by the host with peculiar immunogenic disorders, in the presence or absence of a known antigenic stimulus such as H. pylori. For this, we studied patients with autoimmune thyroid diseases. METHODS Thirty patients with autoimmune thyroid diseases and 30 dyspeptic patients without a history of thyroid disorders (as control group) underwent upper endoscopy. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. RESULTS Organized mucosa-associated lymphoid tissue was found in 73.3% of the patients and in 33.3% of control group. Lymphoid follicles were found in 87.5% of the H. pylori-positive patients and in 57.1% of the H. pylori-negative patients (P = NS). In the control group these follicles were present in 50% of H. pylori-positive subjects and in 14.3% of those who were H. pylori-negative. CONCLUSIONS lYMPHOID follicles in the gastric mucosa are common in autoimmune thyroid diseases. Besides H. pylori infection, other factors (environmental, unknown infectious agents) or mechanisms related to the underlying disease may play a causal role.

Low-dose omeprazole plus clarithromycin and either tinidazole or amoxycillin for Helicobacter pylori infection

BACKGROUND: The aim of our study was to compare two 1‐week, low‐dose triple therapies for Helicobacter pylori eradication. METHODS: One hundred consecutive patients, suffering from dyspeptic symptoms with H. pylori infection, were randomly allocated to 7 days of treatment with omeprazole 20 mg o.m. plus clarithromycin 250 mg b.d. and either tinidazole 500 mg b.d. (group A: n = 50, 19 with peptic ulcer) or amoxycillin 1000 mg b.d. (group B: n = 50, 20 with peptic ulcer). H. pylori‐status was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment. RESULTS: Three patients did not complete the treatment. H. pylori eradication was obtained in 35 patients from group A (73%) (95% CI, 55‐82%) and in 40 patients from group B (82%) (95% CI, 66‐90%). On intention‐to‐treat analysis, the rates of eradication were similar. Side‐effects occurred in seven patients from group A (14.58%) and in four patients from group B (8.33%), but none discontinued therapy because of side‐effects. CONCLUSION: Both triple 1‐week, low‐dose omeprazole therapies gave good eradication rates with infrequent side‐effects.

Interaction between Helicobacter pylori infection and untreated coeliac disease on gastric histological pattern

Objective. Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease. Material and methods. We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value <0.05 was considered significant. Results. Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups. Conclusions. In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.

Small intestinal bacterial overgrowth and symptoms of irritable bowel syndrome

association was first reported by Reifenstein t al. in 1939 (3). Only seven cases of acute pancreatitis presenting as an initial manifestation of SLE have been described in the literature (4). The exact pathogenic mechanisms are not known, but microthrombi, vasculitis, intimal thickening, and drug toxicity are felt to play a role (5). Steroids are considered as one of the possible causes of this complication (6, 7) and have been noted to exacerbate (8), ameliorate (9), or have no effect on the course of pancreatitis. However, Saabet al. (5) in their review of 10 cases did not find any association of steroids as an etiology of pancreatitis. It was also suggested that pancreatitis occurs in the setting of inactive SLE, and that steroid therapy should not be withheld if treatment of SLE pancreatitis is warranted. Intravenous corticosteroids have been suggested as the treatment of choice in the management of acute pancreatitis when it is an initial manifestation of SLE (4), though our patient did not respond and continued to worsen on it.

Relationship between gastric localization of hepatitis C virus and mucosa-associated lymphoid tissue in Helicobacter pylori infection.

Background: Hepatitis C virus (HCV) has been localized in several extra-hepatic sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localization of HCV and its possible relationship with the chronic inflammatory response to Helicobacter pylori infection. Methods: Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutively enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inflammatory infiltrates (classified as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobulin heavy-chain (IgH) gene rearrangements of mucosal B cells. Results: In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach ( P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was significantly associated with marked or moderate inflammatory infiltrates. Oligoclonal IgH gene rearrangements were detected in three group A patients who harboured both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to find HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals. Conclusions: HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inflammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells.