A hematologist's view of unexplained iron deficiency anemia in males: impact of Helicobacter pylori eradication

BACKGROUND AND OBJECTIVES: Helicobacter pylori infection with, or without coexisting autoimmune gastritis has been implicated in several recent studies as an important cause of IDA in patients with unexplained iron deficiency anemia (IDA). However, the role of H. pylori in the causation of IDA is still unsettled as the vast majority of reported patients were premenopausal women in whom menstrual blood loss was likely the dominant factor determining IDA. DESIGN AND METHODS: Prospective study of 44 consecutive male IDA patients referred for hematologic evaluation. Following standard endoscopic studies, all patients were screened for non-bleeding GI conditions including celiac disease, autoimmune gastritis and H. pylori gastritis. All subject with H. pylori infection were offered triple therapy for H. pylori eradication. RESULTS: Only 15 patients had a likely source of blood loss identified. The 29 males with "unexplained" IDA were distinguished by their younger age (36+/-20 vs. 57+/-17 years p<0.001), poor initial response to oral iron treatment, and high prevalence of H. pylori infection (25 of 29 vs. 5 of 15 p<0.0001) with (10) or without (15) coexistent autoimmune gastritis. Three had celiac disease. Following H. pylori eradication, all patients achieved normal hemoglobin levels with follow-up periods ranging from 4 to 69 months (38+/-15 months mean+/-1SD). This was accompanied by a significant decrease in H. pylori IgG antibodies and serum gastrin. Sixteen patients discontinued iron treatment, maintaining normal hemoglobin and ferritin and may be considered cured. Remarkably, 4 of the 16 achieved normal hemoglobin without ever having received oral iron after H. pylori eradication. INTERPRETATION AND CONCLUSIONS: The favorable long-term clinical results of H. pylori eradication offer strong evidence for a cause-and-effect relation between H. pylori and IDA. Recognition of the respective roles of H. pylori and autoimmune gastritis in the pathogenesis of iron deficiency may have a strong impact on the clinical management of unexplained and refractory iron deficiency anemia.     

Effect of curing Helicobacter pylori infection on intragastric acidity during treatment with ranitidine in patients with duodenal ulcer.

BACKGROUND: In patients with duodenal ulcer cure of Helicobacter pylori infection resulted in a pronounced decrease in intragastric pH during treatment with omeprazole. AIM: To test the hypothesis that treatment of H pylori adversely affects the pH response to ranitidine. PATIENTS: Eighteen patients with duodenal ulcer who were infected with H pylori were studied. METHODS: Twenty four hour pH recordings were performed during treatment with ranitidine (300 mg) at night before and four to six weeks after cure of H pylori infection. Presence of H pylori was assessed by a rapid urease test, culture, histology, and a 13C urea breath test. Also, the fasting gastrin concentrations were measured before and after treatment for H pylori infection. RESULTS: Cure of H pylori infection resulted in a considerable improvement in both antral and corpus gastritis and a decrease in fasting gastrin concentrations. As a result of the cure the night time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v 5.4; p = 0.007), whereas the acidity during the daytime was not affected. CONCLUSIONS: In patients with duodenal ulcer the intragastric pH during treatment with ranitidine depends on H pylori. However, the loss of effectiveness in altering pH seems to be less pronounced than previously found with omeprazole.     

Impact of Helicobacter pylori eradication on the anti-secretory efficacy of lansoprazole in gastroesophageal reflux disease patients

BACKGROUND: Helicobacter pylori eradication was recommended for the prevention of atrophic gastritis in gastroesophageal reflux disease (GERD) patients on long-term omeprazole treatment. It has been also shown that the treatment with proton pump inhibitors produces lower intragastric pH after H. pylori eradication in subjects with peptic ulcer and healthy individuals. The aim of the present study was to test the hypothesis of whether the efficacy of lansoprazole is reduced after the eradication of H. pylori in GERD patients with peptic esophagitis. METHODS: Eight-hour intragastric pH recordings were performed before and after an 8-day course of lansoprazole (30 mg once daily) in 10 H. pylori-positive male patients with reflux esophagitis and were repeated after the H. pylori eradication. Intragastric acidity was measured by using an antimony electrode placed 10 cm below the cardia. RESULTS: Baseline median preprandial, post-prandial, total intragastric pH and the percentage of time with pH < 3 were not different before and after H. pylori eradication without lansoprazole treatment. During lansoprazole treatment, median post-prandial intragastric pH was lower (4 vs 2.7; P < 0.05) and the percentage of time with pH < 3 was longer (3.4%vs 41.8%; P < 0.05) after H. pylori eradication. Median total intragastric pH tended to be lower after eradication but no difference was found in preprandial median pH. CONCLUSIONS: In patients with reflux esophagitis treated with lansoprazole, intragastric pH increased significantly when H. pylori was present, especially in the post-prandial period, whereas baseline pH remained unchanged after H. pylori eradication.     

Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.     

Intragastric acidity as a predictor of the success of Helicobacter pylori eradication: a study in peptic ulcer patients with omeprazole and amoxicillin.

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p < 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.     

Gastropathic sideropenia

There has been an increasing awareness recently of subtle, non-bleeding gastrointestinal conditions that may result in abnormal iron absorption leading to iron-deficiency anaemia (IDA) in the absence of gastrointestinal symptoms. Thus, the importance of coeliac disease as a possible cause of IDA refractory to oral iron treatment, without other manifestations of malabsorption syndrome, is increasingly being recognized. In addition, Helicobacter pylori has been implicated in several recent studies as a cause of IDA refractory to oral iron treatment, and the anaemia responds favourably to H. pylori eradication. Likewise, achlorhydric gastric atrophy or atrophic body gastritis (ABG), a condition associated with chronic idiopathic iron deficiency, has been shown to be responsible for refractory IDA in over 20% of patients with no evidence of gastrointestinal blood loss. It has also been suggested that H. pylori gastritis may represent an early phase of ABG in which infection may trigger an autoimmune process directed against gastric parietal cells by means of antigenic mimicry. In this review we examine in a critical manner the role of H. pylori gastritis in the causation of IDA, the role of ABG in the pathogenesis of iron malabsorption, the evidence supporting a possible cause-and-effect relationship between H. pylori gastritis and ABG, and the implications of these findings for the diagnostic work-up and management of IDA.     

Effect of Helicobacter pylori infection on 24 hour intragastric acidity in patients with gastritis and duodenal ulcer.

Helicobacter pylori status, gastric histology, and 24 hour acidity were studied in 35 gastritis patients, 21 duodenal ulcer patients, and 14 subjects with normal gastric mucosa. H pylori was identified in 21 of 35 patients with chronic active gastritis and in 19 of 21 duodenal ulcer patients, but in none of those with normal gastric mucosa. Mean scores of activity of gastritis were similar in H pylori positive gastritis and duodenal ulcer patients, but were significantly lower in H pylori negative gastritis patients (2.1 (0.8) and 2.3 (0.9) v 1.4 (0.7); p < 0.01, respectively). Median 24 hour hydrogen ion activity (interquartile range) was 21 (8.9-38.0) mmol/l in normal subjects and 23 (11.2-49.0) mmol/l, 19 (7.1-33.1) mmol/l, 44 (25.1-63.1) mmol/l, and 36 (31.6-39.8) mmol/l respectively in gastritis and duodenal ulcer patients with and without H pylori infection. During all predefined time periods, intragastric acidity was significantly higher in patients with H pylori positive duodenal ulcers compared with gastritis patients and normal subjects. However, there was no significant difference in intragastric acidity between the H pylori positive and negative gastritis patients. These results suggest that most of the subjects with chronic H pylori infection have normal gastric acidity.     

Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori.

An ELISA test determined serologically that eight of 95 apparently healthy men (aged 19-26 years) had an asymptomatic infection with Helicobacter pylori at the time of simultaneous measurement of 24 hour intragastric acidity and 24 hour plasma gastrin concentration. There was no significant difference in the median integrated 24 hour intragastric acidity between the H. pylori positive and H. pylori negative subjects (688 and 842 mmol/h/l; p = 0.271, respectively), whereas the median integrated 24 hour plasma gastrin concentration was significantly higher in the H pylori positive than in the H pylori negative subjects (389 and 198 pmol/h/l; p less than 0.001). Longterm hypergastrinaemia, associated with persistent H pylori infection, could be a cause of the increased parietal cell mass that is considered characteristic of duodenal ulcer patients.     

Influence of H pylori on plasma ghrelin in patients without atrophic gastritis

AIM:To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis.METHODS:Fifty consecutive patients(24 males and 26 females)with either H pylori-positive gastritis(n = 34)or H pylori-negative gastritis(n = 16)with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study.Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid,1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d,followed by an additional 4 wk of 30 mg lansoprazol treatment.H pylori infection was eradicated in 23 of 34(67.6%)patients.H pylori-positive patients were given eradication therapy.Gastric acidity was determined via intragastric pH catethers.Serum ghrelin was measured by radioimmunoassay(RIA).RESULTS:There was no signifficant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups(81.10 ± 162.66 ng/L vs 76.51 ± 122.94 ng/L).In addition,there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy.CONCLUSION:H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.     

Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects

BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO2- in relation to endogenous acid production and infection with Helicobacter pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas both pH and NO2- concentration were similar in the two groups. During inhibition of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2- concentration in gastric aspirates were significantly higher in H. pylori positives than in the controls. Furthermore, during omeprazole treatment the intragastric NO levels were almost absent in H. pylori positives, whereas approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton-pump inhibition in H. pylori-infected individuals abolishes the intragastric chemical reduction of swallowed NO2- in the fasting stomach.     

Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole.

To test the hypothesis that Helicobacter pylori infection is associated with a decreased intragastric acidity during omeprazole therapy, ambulatory 24 hour dual point gastric pH recordings were performed in 18 H pylori positive and 14 H pylori negative subjects. There was a four to six week washout period between the two pH recordings made in each subject after one week courses of placebo or omeprazole, 20 mg daily. During placebo, median 24 hour pH values were not different in the corpus (H pylori positive = 1.5, negative = 1.4; p = 0.9) or antrum (H pylori positive = 1.3, negative = 1.2; p = 0.1). However, during omeprazole treatment, median 24 hour pH values were higher in H pylori positive subjects, both in the corpus (H pylori positive = 5.5, negative = 4.0; p = 0.001) and antrum (H pylori positive = 5.5, negative = 3.5; p = 0.0004). During placebo treatment, the only difference between the two groups was a higher later nocturnal pH in the antrum in the H pylori positive group. During omeprazole treatment, gastric pH was higher both in the corpus and in the antrum in the H pylori positive group for all periods, except for mealtime in the corpus. These data indicate that omeprazole produces a greater decrease in gastric acidity in subjects with H pylori infection than in those who are H pylori negative. It is not, however, known whether there is a causal relationship between H pylori infection and increased omeprazole efficacy.     

TLR4基因多态性与慢性胃炎幽门螺杆菌感染无相关性

目的:研究我国湖北汉族人群TLR4基因 Asp299Gly多态性与慢性浅表性胃炎及幽门螺杆(H pylori)感染的关系．方法:采用病例-对照研究和多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测 115例慢性浅表性胃炎患者115例和正常对照者2644例的TLR4等位基因Asp299Gly基因型分布．结果:慢性浅表性胃炎患者的H pylori阳性率 89．6％,显著高于正常对照组61．7％(P<0．000 1, OR=5．319．95％CI:2．784-10．162)．在H pylori 感染相关性的慢性胃炎组和正常对照组中 TLR4基因Asp299Gly基因型所有个体均为 AA纯合子,未发现的突变型,其基因型、等位基因以及携带者频率总体分布无显著性差异．结论:TLR4基因Asp299Gly基因多态性与H pylori相性慢性胃炎无明显相关性．     

Helicobacter pylori and CagA status,serum gastrin,interleukin-8 and gastric acid secretion in gastric cancer

BACKGROUND: Despite numerous epidemiological studies, the association between Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This study was designed to determine the seropositivity of H. pylori and cytotoxin-associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO) in a large series of GC patients and controls. METHODS: 337 GC patients (118 men and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum-amidated gastrin was determined by specific radioimmunoassay and correlated with gastric luminal pH. RESULTS: The numbers of GC patients and controls involved in the study in various age groups, ranging from 20 to > 70 years, were similar, but overall H. pylori IgG seropositivity in GC patients was significantly higher (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the calculated cut-off value (38.88 pM/L) were found in several-fold larger number in GC patients (48%) than in controls (8.3%) and. similarly, serum IL-8 values over the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH = 4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls, and strong correlation between the serum gastrin and gastric pH was found in GC but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl: 1.61-4.22) for CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have significant influence on GC formation (OR > 1 in logistic regression). CONCLUSIONS: 1. CG patients show significantly higher H. pylori IgG and CagA seropositivity than dyspeptic age- and gender-matched controls, confirming that gastric infection with CagA expressing H. pylori greatly increases the risk of GC. 2. Serum gastrin levels in GC but not in controls are correlated with the rise in intragastric pH, indicating that excessive gastrin release in GC is affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity are significantly increased in the majority of GC patients, and are the only variables in multivariable analysis to have a predominant influence on GC formation, which suggests that both these parameters may be implicated in H. pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce significantly more IL-8 than do non-GC controls, probably reflecting CagA-positive H. pylori-associated gastritis.     

Leptin and ghrelin in relation to Helicobacter pylori status in adult males

CONTEXT: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. OBJECTIVE: We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin. DESIGN, SETTING, AND PATIENTS: We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center. OUTCOMES: We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs. RESULTS: Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P < 0.0001 and r = 0.35; P < 0.0001, respectively) and H. pylori- (r = 0.65; P < 0.0001 and r = 0.41; P < 0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (<80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P < 0.0001). CONCLUSIONS: These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.     

Extragastrointestinal manifestations of Helicobacter pylori infection: Facts or myth? A critical review

Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders. Among these, the best evidence so far is in ITP and unexplained IDA, with high-quality studies showing the improvement of IDA and ITP after H. pylori eradication. The evidence of its association with coronary artery disease is weak and many of the results may be erroneous. The role of H. pylori infection in affecting serum leptin and ghrelin levels has attracted a lot of attention recently and available data to date have been conflicting. There have also been many uncontrolled, small sample studies suggesting an association between H. pylori infection and neurological disorders or chronic urticaria. However, more studies are required to clarify such proposed causal links.     

Nutritional aspects of Helicobacter pylori infection

H. pylori is a gram-negative pathogen, etiologically associated with atrophic and non-atrophic gastritis, peptic ulcer, primary gastric B-cell lymphoma and gastric carcinoma. Several observations demonstrated a correlation between H. pylori and malabsorption of essential nutrients; epidemiological studies have shown an association between H. pylori infection and iron deficiency anemia, while the absorption of some vitamins such as vitamin B12, vitamin A, vitamin C, folic acid and Vitamin E may be affected by the infection. The main mechanism related to malabsorption of this components is the modified intragastric pH (hypo- achlorhydria) due to H. pylori infection. Moreover H. pylori is also able to determine a modification of gastrointestinal hormones by reducing plasma levels of ghrelin and increasing those of leptin and gastrin, thus affecting appetite and promoting the occurrence of dyspeptic symptoms. On the other hand, H. pylori eradication has been shown to improve serum level of iron and vitamin B12, has some effects on Vitamin A and Vitamin E absorption and has a late effects on ghrelin levels. As a consequence of those effects, H. pylori is also associated with childhood malnutrition in developing countries either for the occurrence of malabsorption or for an increased susceptibility to enteric infections caused by hypochlorhydria.     

Comparison of 24-hour gastric pH in normal controls and patients with duodenal ulcer or atrophic gastritis

Twenty-four intragastric acidity was measured by continuous recording using intragastric glass electrodes in 16 normal controls, 18 inactive duodenal ulcer patients and 7 patients with atrophic gastritis. Median pH for the 24 h period, for the 8 AM-8 PM period, and for the 8 PM-8 AM period were significantly lower in duodenal ulcer patients than in controls (1.19 vs 1.78; 1.17 vs 2.05; 1.27 vs 1.64). Median pH for these 3 periods were significantly higher in patients with atrophic gastritis than in controls (3.90; 3.72; 3.81). The median pH for the 24 h period was higher than the lower quartile value of the control group in 33 per cent of duodenal ulcer patients. During the night (24 h-3 h), duodenal ulcer patients had significantly lower median pH (1.03) than controls (1.51). Antisecretory treatment should be directed to decrease this period of unbuffered acidity.     

Lactoferrin sequestration and its contribution to iron-deficiency anemia in Helicobacter pylori-infected gastric mucosa

BACKGROUND AND AIM: It is known that lactoferrin serves as a source of iron for Helicobacter pylori in gastric mucosa. The present study was undertaken to investigate the relationship between lactoferrin and H. pylori infection coexistent with iron-deficiency anemia by determining the lactoferrin levels in gastric biopsy specimens, and by locating the major sites of lactoferrin expression, according to the presence or absence of iron-deficiency anemia. METHODS: One hundred and one adolescents who underwent gastroduodenoscopy were divided into four groups: controls without H. pylori infection (NL; n =43); patients with H. pylori infection (HP; n = 26); patients with iron-deficiency anemia (IDA; n = 6); and patients with H. pylori gastritis and coexisting iron-deficiency anemia (HPIDA; n = 26). The gastric mucosal levels of lactoferrin were measured by immunoassay. Immunohistochemical technique was used to allow identification of the location and quantification of the lactoferrin expression. RESULTS: The mucosal level of lactoferrin was highest (3.93 +/- 2.73 ng/microg protein) in HPIDA, followed by 2.67 +/- 1.79 ng/microg protein in HP, 0.59 +/- 0.57 ng/microg protein in NL and 0.14 +/- 0.10 ng/microg protein in IDA. Their multiple comparisons were statistically significant at the 0.05 level. After the eradication of H. pylori in 12 HPIDA patients who underwent follow-up endoscopy, the mean mucosal level of lactoferrin decreased significantly, while the blood hemoglobin level correspondingly increased. The major sites of lactoferrin expression by immunohistochemistry were in glands and neutrophils within epithelium. Lactoferrin was stained weakly in NL and IDA, and strongly in HP and HPIDA. CONCLUSION: The lactoferrin sequestration in the gastric mucosa of HPIDA was remarkable, and this finding seems to give a clue that leads to the clarification of the mechanism by which H. pylori infection contributes to iron-deficiency anemia.     

Eradication of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis

BACKGROUND: A substantial minority of patients with gastro-oesophageal reflux disease (GERD) are infected with Helicobacter pylori, but there is controversy as to whether these patients should be treated for their infection. We hypothesized that H. pylori eradication increases gastro-oesophageal acid reflux in such patients with time. METHODS: Thirty-five consecutive H. pylori-infected patients (16 M and 19 F) with mild or moderate reflux oesophagitis were enrolled. Twenty-four-hour intra-oesophageal (n = 35) and intragastric (n = 12) pH-metry was recorded before and 15 months after H. pylori eradication. Gastric biopsy specimens from the antrum and corpus were obtained from 10 consecutive patients before and 15 months after H. pylori eradication. RESULTS: Fifteen months after eradication of H. pylori there was a significant decrease in percentage time oesophageal pH < 4 in the recumbent position only (P = 0.04). Despite a marked reduction in the severity of gastritis, there was no significant change in gastric acidity, total intra-oesophageal acid exposure or symptom score. Heartburn improved in 12, worsened in 7. and remained unchanged in 16 patients (P = 0.36) without any significant relationship to individual changes in acid exposure (P = 0.60). CONCLUSIONS: H. pylori eradication does not increase gastric acidity or gastro-oesophageal acid reflux in patients with mild to moderate reflux oesophagitis over the first 15 months.     

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Studies were performed in patients with and without renal failure to investigate the role of bacterial ammonia production in the pathogenesis of the mucosal abnormalities caused by Helicobacter pylori. The high rate of H pylori ammonia production in uraemic patients should accentuate any ammonia induced effects. The median (range) gastric juice ammonium concentration in the H pylori positive patients with renal failure was 19 mmol/l (II-43) compared with 5 mmol/l (1-11) in the H pylori positive patients without renal failure (p < 0.005). In the H pylori negative patients the values were 3 mmol/l (0.5-11) and 0.7 mmol/l (0.1-1.4) respectively in the patients with and without renal failure (p < 0.01). Despite the much higher ammonia production in the H pylori positive uraemic patients, the nature and severity of their gastritis was the same as that in the H pylori positive non-uraemic patients. The median (range) fasting serum gastrin concentration was raised in the uraemic patients compared with the non-uraemic patients but was similar in the uraemic patients with (95 pmol/l (52-333)) or without (114 pmol/l (47-533)) H pylori infection. The median (range) serum pepsinogen I concentration was also high in the uraemic compared with the non-uraemic patients and was significantly higher in uraemic patients with H pylori (352 ng/ml, range 280-653) than in those without H pylori infection (165 ng/ml, range 86-337) (p < 0.01). These findings indicate that the gastritis and hypergastrinaemia associated with H pylori infection are not the result of mucosal damage induced by the organism's ammonia production.