Peptic ulcer disease Malfertheiner, Peter, Prof; Chan, Francis KL, MD; McColl, Kenneth EL, MD
The Lancet (British edition),
10/2009, Letnik:
374, Številka:
9699
Journal Article
Recenzirano
Summary Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its ...incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori . With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori -negative NSAID-negative ulcer is also examined.
In the West, the incidence of esophageal adenocarcinoma, which is a long-term complication of damage by gastroesophageal reflux, has been rising over recent decades. Two main factors are likely to ...account for this increase. The first is the rising incidence of central obesity which promotes gastroesophageal reflux. The second is the falling incidence of
H. pylori
infection and associated atrophic gastritis which reduces the acidity and peptic activity of gastric juice, the main factors damaging to the esophageal mucosa. The rise in esophageal adenocarcinoma has been mirrored by a fall in gastric cancer consistent with
H. pylori
atrophic gastritis protecting from the former and predisposing to the latter. The incidence of gastric cancer in Japan is still above the level at which a rise in esophageal adenocarcinoma became apparent in the West. Esophageal adenocarcinoma is likely to rise in Japan also as the incidence of gastric cancer falls but the degree of rise will depend on a variety of other environmental and genetic factors.
The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ ...with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.
To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability ...of the approach and to assess potential effects on local and systemic disease activities.
An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10
, 3×10
or 10×10
tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.
There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10
tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.
IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10
tolDC but no systemic clinical or immunomodulatory effects were detectable.
NCT01352858.
Vitamin C is actively secreted in human gastric juice. Proton pump inhibitor therapy lowers the concentration of vitamin C in gastric juice and the proportion of the vitamin in its active antioxidant ...form i.e., ascorbic acid. This has secondary effects on intragastric nitrite chemistry, resulting in a rise in gastric juice nitrite levels. There is also some evidence that proton pump inhibitors may reduce the bioavailability of ingested vitamin C. The effect of proton pump inhibitors on vitamin C and nitrite chemistry is more marked in Helicobacter pylori-infected subjects. Proton pump inhibitors also reduce the absorption of vitamin B(12) probably by inhibiting intragastric proteolysis and, thus, its release from food required prior to binding to R-proteins and gastric intrinsic factor. Under certain circumstances, the treatment may lower serum vitamin B(12) levels. Proton pump inhibitor therapy reduces the absorption of non-heme iron and this effect has been employed in the management of hemochromatosis. It may also retard clinical response to iron supplementation.
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