Risk for gastric lymphoma in persons with CagA+ and CagA- Helicobacter pylori infection

Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.     

Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases

The vacuolating cytotoxin and the cytotoxin-associated protein, encoded by vacA and cagA, respectively, are important virulence determinants of Helicobacter pylori. Sixty-five H. pylori strains were isolated from dyspeptic patients (19 with peptic ulcer disease, 43 with chronic gastritis, and 3 with gastric cancer) and studied for differences in the vacA and cagA genes and their relationship to VacA and CagA expression, cytotoxin activity, and the clinical outcome of infection. By PCR, fifty-four (83.1%) of 65 strains had the vacA signal sequence genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the vacA middle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%) strains, respectively. The combinations s1-m2 (31 [47.7%]) and s1-m1 (23 [35.4%]) occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the combination s2-m1 was found. All 19 patients with peptic ulcers harbored type s1 strains, in contrast to 32 (74.4%) of 43 patients with gastritis (P = 0.02). The vacA genotype s1 was associated with the presence of cagA (P < 0.0001), VacA expression (P < 0.0001), and cytotoxin activity (P = 0.003). The cagA gene was detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of 19 ulcer patients and 29 (67.4%) of 43 patients with gastritis (P = 0.17). The vacA genotypes of German H. pylori isolates are identical to those previously reported. H. pylori strains of vacA type s1 are associated with the occurrence of peptic ulceration and the presence of cagA, cytotoxin activity, and VacA expression.     

Infantile Helicobacter pylori associated with thickened gastric folds

This report extends our investigation of double base lesions produced by irradiation of DNA model compounds. Studies of d(CpGpTpA) X-irradiated in oxygenated aqueous solution show that two of the five principal products are oligomers having adjacent bases damaged. In these oligomers guanine is hydroxylated at the 8-position and an adjacent pyrimidine is degraded to a formamido remnant.     

Helicobacter pylori risk associated with sibship size and family history of gastric diseases in Japanese adults

BACKGROUND: Data on whether long-acting somatostatin analogue octreotide causes or prevents pancreatic injury following endoscopic retrograde cholangiopancreatography (ERCP) are controversial. AIM: This multicentre, prospective trial studied the effect of octreotide on pancreatic injury in a large unselected group of patients after ERCP and endoscopic sphincterotomy. METHODS: The study was carried out in a prospective random manner on 2102 patients in 11 endoscopic centres. Patients in the study received 0.1 mg octreotide acetate and those in the control group received isotonic sodium chloride, subcutaneously before and 45 min after ERCP. Pancreatic injury was assessed by clinical symptoms such as pain, fever and abdominal tenderness. Serum amylase and blood sugar were determined prior to, and 6 and 24 h after the endoscopic procedure. RESULTS: Data from 599 patients in the study group and 600 in the control group were included in the final evaluation. When all the patients were considered, octreotide did not induce pancreatic injury as assessed by clinical symptoms, and diminished the increase of serum amylase levels following ERCP. However, when subgroups of patients were studied, the frequency of increased amylase levels decreased significantly in patients with chronic obstructive pancreatitis and in patients who underwent endoscopic sphincterotomy (P < 0.01). The peak serum glucose level was higher in the treated group when compared to the controls. CONCLUSION: The prophylactic use of long-acting somatostatin does not alter the frequency of post-ERCP pancreatic injury, but it may diminish the rate of increased serum amylase levels in patients with chronic obstructive pancreatitis and also in those with an endoscopic sphincterotomy.     

Serum pepsinogen response to therapy for Helicobacter pylori associated gastro-duodenal disease

We investigated the effect of H. pylori therapy on serum concentrations of pepsinogens on 87 patients of gastro-duodenal disease. In addition, we intended to see whether serum pepsinogen can serve as markers of response to H. pylori eradication. In 48 successfully eradicated cases, there was a significant decrease in gastritis score, and was a significant fall in serum pepsinogen II (PG II) level, and was a significant increase in pepsinogen I/II ratio (PG I/II ratio). In contrast, no change in gastritis score, PG II, and PG I/II ratio were observed in 39 unsuccessfully eradicated patients. No change in serum pepsinogen I (PG I) level was observed in both groups. In provisional successfully eradicated cases in PG II of decrease greater than 30% in after treatment, there was a sensitivity of 83.3% and a specificity of 89.7%. For the PG I/II ratio of increased greater than 30% in after treatment, the sensitivity was 95.8%, and the specificity was 94.9%. These findings suggest that PG II, PG I/II ratio can be useful for clinical evaluation of eradication therapy.     

Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death

OBJECTIVES: This study examined the relations of echocardiographically determined left ventricular (LV) mass and hypertrophy to the risk of sudden death. BACKGROUND: Echocardiographic LV hypertrophy is associated with increased risk for all-cause mortality and cardiovascular disease morbidity and mortality. However, little is known about the association of echocardiographic LV hypertrophy with sudden death. METHODS: We examined the relations of LV mass and hypertrophy to the incidence of sudden death in 3,661 subjects enrolled in the Framingham Heart Study who were > or =40 years of age. The baseline examination was performed from 1979 to 1983 and LV hypertrophy was defined as LV mass (adjusted for height) > 143 g/m in men and > 102 g/m in women. During up to 14 years of follow-up there were 60 sudden deaths. Cox models examined the relations of LV mass and LV hypertrophy to sudden death risk after adjusting for known risk factors. RESULTS: The prevalence of LV hypertrophy was 21.5%. The risk factor-adjusted hazard ratio (HR) for sudden death was 1.45 (95% confidence interval [CI] 1.10 to 1.92, p=0.008) for each 50-g/m increment in LV mass. For LV hypertrophy, the risk factor-adjusted HR for sudden death was 2.16 (95% CI 1.22 to 3.81, p=0.008). After excluding the first 4 years of follow-up, both increased LV mass and LV hypertrophy conferred long-term risk of sudden death (HR 1.53, 95% CI 1.01 to 2.28, p=0.047 and HR 3.28, 95% CI 1.58 to 6.83, p=0.002, respectively). CONCLUSIONS: Increased LV mass and hypertrophy are associated with increased risk for sudden death after accounting for known risk factors.     

Immune evasion by Helicobacter pylori: gastric spiral bacteria lack surface immunoglobulin deposition and reactivity with homologous antibodies

We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. In two affected members of the pedigree with histochemical (ragged-red and cytocrome c oxidase - negative fibers) and ultrastructural abnormalities of muscle mitochondria, in vivo muscle phosphorus MR spectroscopy disclosed a slow rate of phosphocreatine resynthesis after exercise. Brain phosphorus MR spectroscopy revealed a defect of the energy metabolism in the two patients and in a third asymptomatic member, as shown by a significantly low phosphocreatine, increased ADP and decreased phosphorylation potential. Molecular analysis of muscle mitochondrial DNA failed to reveal any known mutation, including multiple deletions of the mtDNA which have been associated with some autosomal dominant mitochondrial diseases. The multisystem clinical involvement, the presence of ragged-red fibers and the alterations revealed by in vivo brain and muscle 31P-MRS suggest that this limb-girdle syndrome represents an unusual phenotype of mitochondrial cytopathy.     

Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence

A case report of lethal distant myonecrosis with gas gangrene is presented. Cultures from blood and suppuration of our patient revealed Clostridium septicum. At obduction the patient appeared to have a necrotic metastasis of a known ovarian carcinoma in the cecum wall. Predisposing conditions for this type of infection are hematologic malignancies, colon carcinoma, neutropenia, diabetes mellitus, and disruption of the bowel mucosa. Clostridium septicum is highly associated with the presence of a malignancy, either known or occult at the time infection occurs. Occult tumors are mostly situated in the cecal area of the bowel. Clinical symptoms of the syndrome and therapeutic options are discussed.     

Helicobacter pylori and non-Helicobacter pylori bacterial flora in gastric mucosal and tumour specimens of patients with primary gastric lymphoma

There is an association between Helicobacter pylori (H. pylori) and gastric mucosa-associated lymphoid tissue (MALT) and MALT lymphoma. Histologically, mainly non-specific stains are used to detect H. pylori, such as haematoxylin-eosin (HE) or modified Giemsa (MG). In this study, both a MG and a specific immunohistochemical stain (IMM) for H. pylori (Dako B471) were performed on sequential slides of resected material containing tumour and non-tumorous gastric mucosa from patients with primary gastric lymphoma (n = 52). Special attention was paid to the presence of non-H. pylori bacterial flora diagnosed by a positive MG (according to form and localization) and a subsequently negative IMM. On all slides, bacterial density was scored semiquantitatively (grades 0, 1, 2, 3). In total, 32 (61.5%) patients were H. pylori positive using IMM and 34 (65.4%) were non-H. pylori positive using MG. In 24 out of the 34 patients, the non-H. pylori flora consisted mainly of cocci in combination with rods in 15 patients, mostly in minor quantities; in another 10 patients, high numbers of both cocci and different types of rods were present. Most non-H. pylori bacteria were localized superficially, although in 22 patients minor quantities of non-H. pylori were also seen in the glandular lumina. After all of the patients had been analysed, no differences in the density of H. pylori and of non-H. pylori flora were found. Only when comparing patients who had a small-cell lymphoma with those who had a large-cell lymphoma was a significantly higher density of H. pylori found in the corpus mucosa of large-cell lymphomas and a higher prevalence of non-H. pylori was found in tumours, in antrum or corpus, of patients with large-cell lymphomas. In conclusion, with joint evaluation using MG and a H. pylori-specific immunohistochemical stains, the proportion of H. pylori-positive gastric lymphoma patients was lower than in most previous studies but other bacteria were found in a relatively high proportion. The role of the non-H. pylori intragastric bacterial flora identified in this study has to be further elucidated in the aetiopathogenesis of primary gastric lymphoma.     

Frequency of vacA genotypes and cytotoxin activity in Helicobacter pylori associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma

The vacA genotypes s1,m1 and s1,m2 were detected in 44 and 30% of Helicobacter pylori isolates, respectively, from patients with gastric mucosa-associated lymphoid tissue lymphoma, compared to 26 and 56% of isolates, respectively, from individuals with gastritis. The vacA s1 genotype was significantly associated with, but not predictive of, the presence of vacuolating cytotoxin activity.     

Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins

The consequences of Helicobacter pylori attachment to human gastric cells were examined by transmission electron microscopy and immunofluorescence microscopy. H. pylori attachment resulted in (i) effacement of microvilli at the site of attachment, (ii) cytoskeletal rearrangement directly beneath the bacterium, and (iii) cup/pedestal formation at the site of attachment. Double-immunofluorescence studies revealed that the cytoskeletal components actin, alpha-actinin, and talin are involved in the process. Immunoblot analysis showed that binding of H. pylori to AGS cells induced tyrosine phosphorylation of two host cell proteins of 145 and 105 kDa. These results indicate that attachment of H. pylori to gastric epithelial cells resembles that of enteropathogenic Escherichia coli. Coccoid H. pylori, which are thought to be terminally differentiated bacterial forms, are capable of binding and inducing cellular changes of the same sort as spiral H. pylori, including tyrosine phosphorylation of host proteins.     

Helicobacter pylori infection in a randomly selected population, healthy volunteers, and patients with gastric ulcer and gastric adenocarcinoma. A seroprevalence study in Taiwan

To investigate the association of Helicobacter pylori and gastric ulcer and adenocarcinoma, IgG antibodies against H. pylori were examined in 823 randomly selected subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and 148 with gastric adenocarcinomas in Taiwan, where the prevalence of gastric adenocarcinoma is high. The seropositivity of this population in Taiwan was 54.4%. Gastric ulcer patients had a higher seropositivity (83.8%) than healthy volunteers (62.0%) and gastric adenocarcinoma patients (62.2%) (P < 0.001). Gender difference, blood type, and habit of smoking were not associated with the seroprevalence in any study groups. Gastric ulcer coexistent with duodenal ulcer had a higher seropositivity (94.7%) (P < 0.05). The seropositivity of H. pylori in gastric adenocarcinoma patients was higher than in healthy volunteers only in younger age and was not associated with histologic type, invasion, and location of major tumors. The results reemphasize the association of H. pylori infection with gastric ulcer but not with gastric adenocarcinoma in Taiwan.     

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.     

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy for Helicobacter pylori infection

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection with Helicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication of H. pylori, and the tumor had regressed. Six months later, H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy, H. pylori has been eradicated. The lymphoma has been in remission for 14 months.     

Influence of Helicobacter pylori on gastric secretion. Study on variously associated gastric body, fundus and antrum chronic gastritis

Among the various themes related to Helicobacter pylori (HP) which is still a subject of discussion, there is the possible influence of this bacterium on gastric secretory physiology. In the present study, an evaluation has been carried out of stimulated gastrinemia, stimulated acid secretion and total peptic activity in gastric juice in the course of a paradigmatic condition, as autonomous chronic gastritis, in order to reveal possible modifications induced by the HP infection. In cases of HP positive chronic superficial antral gastritis associated either with normal body-fundic mucosa or with superficial gastritis, there is a significant increase of stimulated gastrinemia in comparison to HP negative groups and controls. In the course of body-fundic atrophic and preatrophic chronic gastritis associated either with antral superficial chronic gastritis or with antral atrophic gastritis, there are no statistically significant differences between HP positive and HP negative subjects. As regards acid and pepsin secretion no significant differences emerge in any group between HP positive and HP negative subjects. In the HP positive subjects with antral superficial gastritis and higher gastrin values the study of acid and pepsin secretion has yielded no significant variations. From the results of this study it emerges how gastric secretory parameters vary exclusively according to the histologic state of gastric mucosa. Therefore, the lesion action of HP may mainly be attributed to a direct action, rather than to substantial gastric secretory changes.     

A new intragastric delivery system for the treatment of Helicobacter pylori associated gastric ulcer: in vitro evaluation

The large and heterogeneous group of patients with "unexplained somatic symptoms," with or without coexisting psychiatric, "functional," or "organic" illnesses, provides continuing difficulty for clinicians. The construct of somatization artificially separates bodily and psychological symptoms that patients experience as a unified whole. Concurrent chronic illnesses make it difficult to exclude "general medical conditions." The diagnosis requires that the patient seek medical care. Conflict between patients' experiences of illness and physicians' diagnostic categories, and fear of blaming the patient, complicate naming and characterizing the illness. We recommend an approach to clinical care that involves exploring the patient's life context, finding mutually meaningful language to arrive at a name for the illness, normalizing the patient's bodily experience of distress, using a chronic disease model that attends to functioning, and addressing the physician's need for certainty and efficacy. Health systems can help coordinate care and avoid iatrogenic harm by appropriately controlling access to medical services.     

Serum progesterone levels in patients with gastric adenocarcinoma before and after gastrectomy

We experienced a case of a hepatic subcapsular hematoma after extracorporeal shock wave lithotripsy (ESWL) for a right renal stone. To our knowledge this presentation is the second case in the Japanese literature. A 63-year-old female with a right renal stone received 2,800 shots of 14.0 kilo-volts shockwave with Sonolith 3,000. Preoperative examination of the blood disclosed no abnormalities in the coagulating system except slight reduction of platelet count and slight impairment of liver function. Postoperative routine ultrasound echograms revealed a hepatic subcapsular hematoma although she had no symptom. The size of the hematoma measured 11.0 x 5.0 cm in computed tomograms (CT). She was carefully observed without any treatments because the hematoma did not increase in size. CT scans 6 months after the ESWL treatment demonstrated neither hematoma nor masses in the liver. As a complication of ESWL for urolithiasis a hepatic subcapsular hematoma is very rare. We herein presented the case and discussed the complications of ESWL briefly in the literature.     

Circadian gastric acidity in Helicobacter pylori positive ulcer patients with and without gastric metaplasia in the duodenum

BACKGROUND: The presence of gastric metaplasia allows helicobacter pylori to colonise the duodenum and this condition is thought to be acquired as a response to acid hypersecretion. This functional disorder, however, is present only in a subgroup of duodenal ulcer patients and, in addition, surface gastric metaplasia has been frequently found in the proximal duodenum of normal subjects and patients with non-ulcer dyspepsia, who cannot be certainly considered as acid hypersecretors. AIMS: To clarify the role of acid in inducing gastric type epithelium in the duodenum. This study aimed at assessing whether the pattern of circadian gastric acidity differs between H pylori positive duodenal ulcer patients with and without duodenal gastric metaplasia. PATIENTS: Seventy one patients with duodenal ulcer confirmed by endoscopy and who were found to be positive for H pylori infection by histology on antrum biopsy specimens were enrolled into this study. METHODS: Gastric type epithelium in the duodenum was found in 49 of 71 ulcer patients (69%). Continuous 24 hour gastric pH metry was performed in 50 healthy subjects and in the two subgroups of duodenal ulcer patients with and without gastric metaplasia in the duodenum. Gastric acidity was calculated for 24 hours (1700-1659), night (2000-0759) and day-time (0800-1959). RESULTS: Ulcer patients without gastric metaplasia showed a significantly higher gastric acidity (p < 0.001) than controls for every time interval considered, while the ulcer subgroup with gastric metaplasia was more acid than healthy subjects (p < 0.001) during the whole 24 hour period and the daytime. There was no difference between the two subgroups of duodenal ulcer patients with and without gastric metaplasia during the various time segments analysed. CONCLUSION: The findings confirm that the circadian gastric acidity of duodenal ulcer patients is higher than that of controls. As there is no difference in gastric pH between duodenal ulcer patients with and without gastric metaplasia, gastric hyperacidity is not specific to patients with duodenal gastric metaplasia. It is probable that this histological change is a non-specific response to mucosal injury resulting from various factors and not exclusively to acid.