Helicobacter pylori infection and perforated peptic ulcer prevalence of the infection and role of antimicrobial treatment

Although the role of Helicobacter pylori infection on noncomplicated peptic ulcer disease has been definitively established, the precise relationship between the organism and complicated ulcer has hardly been studied. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is of only about 65-70%, which contrasts with the almost 90-100% figure reported in noncomplicated ulcer disease. However, H. pylori infection rates in various studies range markedly from 0% to 100%, suggesting that differences in variables as number and type of diagnostic methods used to diagnose H. pylori infection, or frequency of nonsteroidal anti-inflammatory drug intake, may be responsible for the low prevalence reported in some studies. Recurrent ulcer disease after peptic ulcer perforation mainly occurs in patients with H. pylori infection, which suggests that the microorganism plays an important role in this complication. All patients with perforated peptic ulcer should be treated by simple closure of the perforation and with therapy aimed at healing of the ulcer and eradicating the H. pylori infection, as disappearance of the organism prevents, or at least decreases, ulcer recurrence and ulcer perforation in patients with H. pylori-associated perforated ulcers after simple closure. Therefore, H. pylori eradicating treatment should be started during the immediate postoperative period. The patients with intractable recurrent symptoms of peptic ulcer despite adequate medical treatment, but without H. pylori infection (e.g. a patient using nonsteroidal anti-inflammatory drugs), is probably the only remaining indication for elective definitive surgical treatment of peptic ulcer disease.     

Prostaglandin E in peptic ulcer disease

Prostaglandin E₁ and E₂ inhibit gastric secretion in vivo and in vitro under a variety of conditions. It is not known whether these compounds may play a role in normal gastric secretory physiology or in the pathophysiology of peptic ulcer disease. Six normal adults and six patients with documented duodenal ulcer disease were studied under basal conditions and during gastric secretory stimulation with betazole. Prostaglandin E in plasma and gastric juice was measured by radioimmunoassay. Prostaglandin E was significantly higher in the plasma of normal volunteers both in the basal state and during stimulation. Gastric juice prostaglandin E was also significantly higher in normal volunteers during the basal state but the difference disappeared during stimulation. The relative deficiency of prostaglandin E in the ulcer group may indicate a role for prostaglandins in the pathophysiology of gastric hypersecretion.     

Mitochondrial DNA deletion Δ4977 in peptic ulcer disease

Reactive oxygen species (ROS) play a critical role in peptic ulcer disease (PUD). Due to the high rate of ROS production and limited capacity for DNA repair within mitochondria, mtDNA is susceptible to oxidative damage and mutations. mtDNA deletion Δ4977 is one of the most common deletion events identified in mitochondria. We examined the association of 4977-bp mtDNA deletion with PUD. Genotypes were determined in bioptic samples of 150 PUD patients and 190 controls. The 4977-bp mtDNA deletion was found more frequently among patients with PUD (52%) than among controls (22.63%). The strong association between the mtDNA 4977-bp deletion and PUD was confirmed (OR = 3.7; 95% CI, 2.32–5.91; P = 0.0001). The 4977-bp deletion in mitochondrial DNA may be a risk factor for PUD, or may reflect an increase in oxidative stress that commonly accompanies underlying PUD disease. Larger population-based studies are needed to uncover the possible causal relationship between this deletion and peptic ulcer disease.     

Genetic and evolutionary implications in peptic ulcer disease

The evidence for a genetic component in peptic ulcer disease has been based on twin, family, and blood group studies. A polygenic model for the inheritance of peptic ulcers has been displaced by a genetic heterogeneity model based on several lines of evidence, some of the most powerful being recent work using subclinical markers. One marker in particular, an elevated level of serum pepsinogen I (PG I), a pepsin precursor produced by the gastric mucosa, secreted into the stomach lumen and also appearing in the bloodstream, has been found to be associated with a subgroup of duodenal ulcer patients. Segregation analysis of elevated serum PG I in duodenal ulcer sibships demonstrates familial aggregation consistent with autosomal dominant inheritance. Elevated PG I is also accompanied by gastric hyperacidity and presumably indicates those individuals with an increased mass of chief and parietal cells, and thus an increased capacity for peptic activity, an important element in the pathogenesis of ulcer disease. An evolutionary hypothesis based on selection for peptic activity and acidity is offered to explain several of the epidemiologic and genetic elements of this group of chronic diseases.     

Helicobacter pylori and peptic ulcer disease.

Medical therapy for duodenal or gastric ulcer disease has traditionally involved gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter pylori in most patients with peptic ulcer disease has led to a change in this approach. Therapy designed to eradicate H pylori may facilitate ulcer healing with acid antisecretory agents and, more important, may greatly reduce the incidence of ulcer recurrence, obviating the need for maintenance antisecretory therapy. Regimens designed to eradicate H pylori are difficult to comply with, however, and are associated with adverse effects in some patients. In this article we review the diagnosis and treatment of H pylori infection in patients with peptic ulcer disease and make recommendations regarding the use of conventional ulcer therapies and therapies designed to eradicate H pylori.     

Glutathione system of erythrocyte and plasma in peptic ulcer

A complex study of the blood glutathione system has been carried out for the first time in patients with peptic (gastric and duodenal) ulcer. In erythrocytes and blood plasma of patients with the complicated peptic ulcer and postgastroresection syndromes there was the increase of conjugated dienes (and in the second group the increase in antioxidant activity). Under these conditions the main change was the sharp and identical decrease in glutathione peroxidase activity. In patients with uncomplicated peptic ulcer there was sharp increase in erythrocite and plasma glutathione reductase activity and plasma GSH. In operated but basically healthy patients plasma glutathione peroxidase remained decreased but plasma GSH sharply increased. Evidently complicated peptic ulcer is characterized by decreased functioning of the glutathione system. Activation of this system and the decrease or disappearance of manifestations of oxidative stress are associated with a favorable course of this disease, especially at uncomplicated peptic ulcer. The revealed changes significantly differ from those observed in patients with viral hepatitis, blle excretory diseases and strokes.     

X-ray diagnosis of peptic ulcers of the jejunum

The paper is devoted to a study of the results of clinicoroentgenological and endoscopic investigation of 188 patients aged 23 to 60 who developed jejunal peptic ulcer. It was done to specify the features of an x-ray picture of jejunal peptic ulcers with relation to the cause of ulcer development and optimum methods of x-ray investigation. The predominant localization of peptic ulcer in the jejunal efferent loop and its typical ulcero-cicatricial deformity were established. Jejunal peptic ulcers developing as a result of an insufficient area of resection, are characterized by a relatively benign course of the disease. In case ulcer development was determined by the residual antral stomach mucosa at the duodenal stump or by the Zollinger-Ellison syndrome, considerable pathological changes (gigantic ulcer sizes greater than 2.5 cm and a sharp deformity of the jejunal efferent loop) were noted.     

A review of spontaneous ulcer disease in domestic animals: chickens, cattle, horses, and swine.

The human species is perhaps unique for its high incidence of spontaneous, chronic ulcer of the glandular mucosa of the stomach and duodenum. Nevertheless, spontaneous ulcers, usually of the stomach, commonly occur in many domestic animals. Some of these lesions are chronic and they may occur in either the glandular or squamous-lined regions of the stomach. As with the human disease(s) the pathogenesis in domestic animals is multifactorial, poorly understood, and variable between and within species. Some parallelisms exist in aggressive and defensive factors, but parasitic factors, via gastrinemia, and a histaminic factor via diet may occur in some animal ulcers. Underlying environmental stresses, of debated importance with the human disease but of proven importance in several rat ulcer models, may play a key role in some spontaneous gastric ulcer situations in swine and cattle. This is manifest in crowding and transporting situations. Seasonal, age, and weaning factors also alter the incidence of ulcer in cattle. Psychologic/environmental stress-related factors, as well as drug and physiologic stress factors appear to upset the balance in the horse between resistance and aggressive mucosal factors. Dietary factors which are highly important in ulcer disease in swine and chickens, have not yet been incriminated in spontaneous, equine ulcer disease. More investigation of the pathogenesis of domestic animal ulcers will prove useful for both human and veterinary medicine in terms of a) elucidating pathogenetic mechanisms for all species, b) may provide new animal models for study, and c) may enhance prevention of such lesions in domestic animals for economic and humanitarian reasons.     

The rise of peptic ulcer, 1900-1950

The seeming increase in the incidence of peptic ulcer after 1900 quickly occupied the attention of physicians. Their understanding and treatment of peptic ulcer was shaped not only by new diagnostic tools, but by differences between contesting medical specialties, broad concepts or paradigms current in the larger medical and scientific community, and prevailing social and ideological beliefs. Surgeons and internists, for example, were often at odds over appropriate therapies; each maintained that personal experiences demonstrated the efficacy of their therapies. Nor were etiological theories derived from empirical data. The claim that peptic ulcer resulted from focal infections was simply a reflection of the popularity of germ theory. Other explanations included the role of stress, race, constitutional makeup, psychosomatic factors, and the pressures of modern industrial society. Virtually all were derivative and reflected social and intellectual currents that were common in the larger society of which medicine was but a part. Thus, the history of peptic ulcer during the first half of the 20th century provides an instructive and in many ways a typical case study in the complexities posed by the emergence of modern medicine.     

CXC chemokine CXCL12 tissue expression and circulating levels in peptic ulcer patients with Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8 ± 18.31 pg/mL) were significantly higher than those in GH (36.89 ± 6.78 pg/mL) and control groups (33.77 ± 9.12 pg/mL) (P < 0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori-induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease.     

Lesions Associated with Gastroduodenal Haemorrhage,in Relation to Aspirin Intake

The incidence of aspirin ingestion during the week preceding overt gastroduodenal bleeding was recorded in 582 patients. A positive aspirin history was found in 80% of patients with acute gastric lesions, in 63% of those in whom no lesion was found, in 52% of those with a chronic duodenal ulcer, and in 49% of patients with a chronic gastric ulcer. In a control series of 542 consecutive patients without overt bleeding admitted to the same wards during part of the time of this investigation the aspirin incidence was 32%.The difference in aspirin habits between these two series confirms that aspirin is a factor in precipitating overt haemorrhage in acute and chronic peptic ulcers, and that it is an important cause of bleeding from the stomach or duodenum, or both, in the absence of a chronic peptic ulcer.     

Events at the host-microbial interface of the gastrointestinal tract IV. The pathogenesis of Helicobacter pylori persistence

Long-term interactions between Helicobacter pylori and humans significantly increase the risk for peptic ulcer disease and noncardia gastric adenocarcinoma. The vast majority of infected persons remain persistently colonized unless a targeted antibiotic regimen is employed; thus regulation of inflammation by H. pylori is governed by levels of host-bacteria equilibria that are not found during cellular interactions with acute enteric pathogens. It is important to gain insight into mechanisms that regulate immune evasion by H. pylori not only to develop more effective treatments for disease, but also because such knowledge may serve as a paradigm for the role that other chronic infectious agents play in the genesis of pathological lesions that arise from inflammatory foci.     

炎症相关因子在血管性痴呆发病机制中的作用

血管性痴呆（vascular dementia,VD）是指由各种脑血管病,包括缺血性脑血管病、出血性脑血管病及急性与慢性缺氧性脑血管病引起的脑功能障碍,进而产生认知功能障碍的临床综合征。血管性痴呆是一种慢性进行性疾病,被认为是仅次于阿尔兹海默症,导致痴呆的第2位原因。目前,血管性痴呆的发病机制尚不明确,有可能与炎症、神经元损伤、胆碱能系统功能障碍、脑白质病变及氧化应激等有关。其中,炎症反应在急性与慢性脑缺血继发性脑损伤中起主要作用。抑制炎症能改善血管性痴呆动物模型的症状,显示炎症可能在血管性痴呆发病机制中发挥重要作用。参与炎症反应的相关因子,如细胞因子等可对中枢神经系统造成损伤。同时,炎症相关因子会触发炎症级联反应,加重脑损伤。本文总结了有关炎症相关因子参与导致血管性痴呆的各种病理损害和促进其发生发展的分子机制的最新研究进展,这些都有助于了解炎症相关因子在血管性痴呆发病机制中的作用。     

幽门弯曲菌与慢性胃炎和消化性溃疡关系的系列研究

我院自1986年6月至1989年6月检查了634例病人的胃粘膜,从幽门弯曲菌(CP)的细菌学、致病性、病理学、诊断方法及药物治疗等方面进行了研究,探讨CP与慢性胃炎及消化性溃疡的关系。结果发现CP有两种形态并与空弯菌不同,不产生肠毒素;消化性溃疡的CP检出率为80.9％,慢性胃炎为41.6％,显著高于正常胃粘膜(3.7％);CP与消化性溃疡、慢性胃炎,十二指肠炎特别是活动性炎症有密切关系;CP对胃型上皮或粘液有某种亲和性;观察到上皮细胞破溃处有大量细菌聚集,CP有致细胞病变的能力。用阿的平代替吖啶橙荧光染色,并制成CP感染快速诊断试剂盒。呋喃唑酮促进溃疡愈合,使45～73％病例CP消失,50～70％胃炎好转。但有复发,根除CP有困难。     

Incidence of peptic ulcer disease in Gothenburg, 1985.

OBJECTIVE--To determine the incidence and age distribution of peptic ulcer disease in adults in Gothenburg. DESIGN--Retrospective study of patients with symptoms over one year. SETTING--All gastroenterology and x ray departments. PATIENTS--Any patient found to have an active ulcer crater during 1985. MAIN OUTCOME MEASURES--Sex, age, past history of gastrointestinal ulcers, and smoking habit. RESULTS--In 1985, 1402 peptic ulcers were diagnosed in 1137 adults. Over half (403; 54%) of the ulcers in men and 393 (60%) ulcers in women were in patients aged over 60. All types of ulcer showed increasing incidence with age. The sex ratio of patients aged 40-50 with peptic ulcers was 1:1. Nearly half (109; 48%) of ulcers diagnosed for the first time in men and 129 (57%) of such ulcers in women were in patients aged over 60. Elderly men and women were also more likely to develop haemorrhage. CONCLUSIONS--In Gothenburg there is a surprisingly high incidence of peptic ulcer disease, which increases considerably with age, possibly explained by the availability of modern diagnostic techniques as 1121 (80%) ulcers had been diagnosed by gastroscopy. Compared with earlier studies there was no difference in the incidence between men and women aged 40-50.     

Bidirectional Crosstalk between Stress-Induced Gastric Ulcer and Depression under Chronic Stress

Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD), chronic psychological stress ulcer (CPSU) and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS) group showed an opposite result. Additionally, in order to study the relevance of H₂ receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H₂ receptors.     

Seasonal variation in the incidence of peptic ulcera perforations

A series of 986 cases of peptic ulcer perforation during 1958–1972 admitted to Sassoon Hospitals in Poona has been studied. The meteorological factors and their relationship to the incidence of cases were determined. It has been shown by correlation studies that water vapour pressure plays a dominant role in the incidence of perforated peptic ulcer. Combinations of high vapour pressure with small range of diurnal temperature or diurnal vapour pressure are associated with an increase in the incidence of peptic ulcer perforations.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Homeostasis of the gastric mucosa and blood circulation. 2. Role of ischemia in disruption of the gastric mucosa

To date there is a lot of data of literature indicating that microcirculatory disorders play the main role in the development of gastric mucosal damages induced by stress, ethanol, nonsteroidal antiinflammatory drugs and tobacco smoke. Under stress gastric mucosal blood flow disorders may be caused by the actication of sympathetic nervous system. Ulcer healing is accompanied by the angiogenesis and by the increase of blood flow in the ulcer border and tissues surrounding the ulcer. Therefore now the main studies are concentrated on the search of defence-enhancing agent rather than drugs for antisecretory therapy. Therapeutic strategy suggests the use of some potential vasodilators such as NO donors, prostaglandin analogues, oxygen radical scavengers, endothelin, leukotrienes, platelet-activating factor antagonists and/or their synthesis inhibitors. At present, the therapeutic possibilities seem to be restricted and nothing indicates that stimulation of the defensive factor only, is more effective in the treatment of peptic ulcer than inhibition of aggressive factors. However we suggest that blood flow correction may be very important for the treatment of refractory ulcers or for prophylaxis of stress ulceration and peptic ulcer recurrence.