Efficacy of Treatment of Non-hereditary Angioedema.

Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.

Regulation of intestinal and hepatic apoprotein synthesis after chronic fat and cholesterol feeding.

Although diet influences levels of lipoproteins and their corresponding apoproteins, its effects on the molecular regulation of apoprotein synthesis are relatively unknown. Male Sprague-Dawley rats were fed an atherogenic diet containing cholesterol and propylthiouracil (PTU). Intestinal apo AI and AIV mRNA concentrations were decreased by the atherogenic diet, but apo AI and AIV synthesis was increased in vitro (organ explants) and in vivo (polysome runoff), consistent with regulation at the translational level. In contrast, hepatic apo E mRNA concentration and synthesis were increased after the atherogenic diet, consistent with pretranslational regulation. The response to cholesterol feeding for hepatic apo AI and E showed a third pattern of regulation, in which synthesis increased and mRNA content remained stable or fell, again suggesting translational control, but polysome runoff synthesis was unchanged. The apparent importance of translational regulation in the intestine is consistent with the necessity for the tissue to respond rapidly to changes in intraluminal content.

Helicobacter pylori infection in peptic ulcer disease and gastric malignancy.

Helicobacter pylori infection is the world's most common chronic infection in humans and is the cause of most gastritis cases. This infection is accepted as the etiology of the majority of peptic ulcers. It has been implicated as a significant contributing factor in the development of gastric malignancy--both gastric MALT lymphoma and gastric adenocarcinoma. Both endoscopic and non-endoscopic tests are available for accurate diagnosis of the infection. Several multi-drug regimens are useful for effective eradication of the infection. Strategies have been developed for managing patients with gastric MALT lymphoma. Criteria to identify populations with increased risk for gastric malignancy are being developed. H. pylori induces gastritis; it is also involved in both apoptosis and cellular proliferation. The role of H. pylori infection in the pathogenesis of premalignant lesions, altered gastric acid secretion, and significant clinical presentations is the subject of numerous studies worldwide.

Gallium-67 citrate imaging in Hodgkin's disease: final report of cooperative group.

A large cooperative study of Ga-67 uptake in Hodgkin's disease showed that 88% of untreated patients had a positive uptake in one or more lesions. The percent of individual lesions seen on scan, however, was significantly lower; this indicated that negative findings at any one site do not argue strongly against the possiblilty of a lesion there. After treatment, the number of visualized lesions decreased sharply, but the exact role of Ga-67 in evaluating therapy is still not clear. Of the various histologic types of Hodgkin's disease, there was a high incidence of localization in all except the lymphocyte-predominance type, which showed a slightly lower uptake. No lesions less than 1 cm in diameter were successfully imaged and the size most easily detected was 4 cm in diameter. As expected, the imaging technique was much less successful for abdominal lesions than for those at other sites because of interfering concentration in bowel and liver. Both radiotherpy and chemotherapy tend to reverse the abnormalities seen on scan. The finding of a significant number of unsuspected positive lesions in asymptomatic patients returning for routine followup suggests that this is a distinctly valuable use of Ga-67, allowing early therpy for recurrences.

Review article: natural history and epidemiology of Helicobacter pylori infection.

Helicobacter pylori is a common bacterium infecting about half the world's population. It is causally linked with a diverse spectrum of gastrointestinal clinical disorders including peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. The principal reservoir is the human stomach, and transmission probably occurs by person-to-person passage. Prevalence rates are generally much higher in developing countries compared to developed countries, although there are subgroups within many regions with higher H. pylori prevalence than in the general population. The prevalence of H. pylori varies by geographical location, ethnic background, socioeconomic conditions, and age. Recent studies suggest decreasing prevalence in developed countries or those with rapidly improving socioeconomic conditions. Comparative studies of the two fully sequenced H. pylori genomes are providing understanding of its large genetic diversity and bacterial virulence factors. The discovery of the type IV secretion system in H. pylori and its role in translocation of the CagA protein from the bacterial cell into the host epithelial cell provides insight into how host-bacterial interaction may lead to host disease. Cytokine promoter polymorphisms are determinants important in host gastric acid secretion status. Understanding the changing trends in H. pylori epidemiology, details of its transmission pathways, and the bacterial and host determinants leading to gastroduodenal disease remain the challenges in this area. Global epidemiological studies, advances in technology, and medical interventions have converged to help clarify the mechanisms of interaction between this ubiquitous micro-organism and its host that result in its diverse clinical manifestations.

Review article: urease, gastric ammonium/ammonia, and Helicobacter pylori--the past, the present, and recommendations for future research.

The presence of ammonium in gastric contents was described in 1852; urease activity in the stomach was identified 70 years later. The discovery of gastric urease resulted in intense research activity to discover its origin, function, and relation to the gastric levels of ammonium and urea. Interest in urease waned in the 1960s as most pertinent questions appeared to have been addressed and there was strong evidence that gastric urease was not a property of the stomach but was of microbial origin. Identification of Helicobacter pylori as the source of urease in the stomach in the last decade has resulted in a rebirth of interest in gastric urease and its products. There is little actual evidence to support a role for toxicity of ammonia in relation to H. pylori and the bulk of the evidence suggests that the products of urease activity are not toxic and may even be beneficial. The purpose of this review is to examine the older literature and to examine new findings in the perspective of what is already known and to suggest areas remaining to be examined. We ask, 'What is old, what is new, and what needs to be done?'

Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori is not associated with cagA, vacA or picB genotypes.

Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation induced by H. pylori strains with different virulence genotypes. Bacterial sonicates from 12 strains were used to induce phagocyte up-regulation of adherence molecule CD11b, assessed by fluorescence flow cytometry, and oxidative burst responses, assessed by chemiluminescence. A dose-dependent induction of the expression of CD11b was observed with sonicate from all H. pylori strains on both neutrophils and monocytes. Strains negative for cagA and picB genes had the same inducing activity of upregulation of CD11b as strains positive for these genes. A vacA-S2 type strain had the same activity as vacA-S1 type strains. The induction of toxic oxygen radicals by H. pylori-activated neutrophils gave higher median values for the cagA-positive strains than for the cagA-negative strains. For the monocyte chemiluminescence response, cagA-negative strains gave higher median values compared to cagA-positive strains. We conclude that upregulation of the neutrophil and monocyte adherence molecule CD11b induced by H. pylori sonicates is not associated with the presence of cagA, picB or mosaic pattern of vacA, and that cagA, picB-negative strains and vacA-S2 strains retain their inflammatory capacity.

Serologic detection of Helicobacter pylori infection with cagA-positive strains in duodenal ulcer, gastric cancer, and asymptomatic gastritis.

CagA has been suggested as a marker for more virulent strains of Helicobacter pylori. Studies using purified proteins and an enzyme-linked immunosorbent assay (ELISA) method for serological detection of antibodies against CagA reported considerable discordance between the results of the ELISA and molecular detection of the cagA gene, with a tendency for estimation of the prevalence of cagA-positive H. Pylori to be higher by ELISA than by colony hybridization. It is not clear whether the discordance was either due to simultaneous infections with both cagA-positive and -negative strains or because of false-positive ELISA results. We correlated the presence of cagA-positive H. pylori by Polymerase chain reaction (PCR) with the presence of serum antibodies against the CagA protein from denatured H. pylori lysates. Gastric biopsies and sera were obtained from 75 patients from Korea; 25 each with gastric carcinoma, duodenal ulcer, and simple gastritis. Seventy-four of 75 isolates (98.6%) were cagA-positive by PCR and 70 sera were CagA antibody-positive by Western blotting. The cagA gene is common in H. pylori isolates from Korea regardless of the underlying disease. The presence of cagA is almost always associated with antibody to the CagA protein as determined by Western blotting. Western blotting may be the preferred method for serological detection of infection with cagA-positive H. pylori.

Debating the role of Helicobacter pylori infection.

Discussion continues on the role of Helicobacter pylori. The following debate provides a venue to examine 2 sides of this complicated issue. Dr. Vakil presents evidence that the eradication of H pylori will improve patients' health, while Dr. Go introduces evidence that suggests the presence of H pylori can be beneficial in particular cases. These clinicians also discuss the issue of whether to test and treat for H pylori and the role of H pylori in patients with gastroesophageal reflux disease.

Peptic ulcer disease.

Peptic ulcer disease is a common gastrointestinal disease whose management and treatment has changed dramatically over the last 25 years. Treatment of peptic ulcer disease has evolved from dietary modifications and antacids to gastric acid suppression with H2-receptor antagonists and proton pump inhibitors to eradication of Helicobactor pylori infection. Treatment of patients infected with H pylori using antibiotics has changed the natural history of peptic ulcer disease. As a result of H pylori treatment and other unknown factors ulcer disease is declining and complications from ulcer disease have diminished significantly.

Scope and consequences of peptic ulcer disease. How important is asymptomatic Helicobacter pylori infection?

H pylori infection is so common as to seem ubiquitous in many areas of the world. Transmission is believed to be primarily person to person. The pathogen invariably damages the gastric mucosa, resulting in both structural and functional abnormalities. It causes histologic gastritis and is critical in the pathogenesis of the gastritis-associated diseases, namely, gastric ulcer, duodenal ulcer, gastric adenocarcinoma, and primary gastric lymphoma. Elimination of the infection results in healing of gastritis and cure of peptic ulcer disease.

Recognizing peptic ulcer disease. Keys to clinical and laboratory diagnosis.

An algorithmic approach to evaluation of dyspepsia or abdominal discomfort begins with differentiation between peptic ulcer disease and gastroesophageal reflux disease as well as recognition of alarm signs and symptoms for gastric cancer, which are indications for early endoscopy. In the absence of alarm symptoms, most patients should undergo noninvasive testing for H pylori infection with a serologic, urea breath, or stool antigen test. Factors to consider in selection of appropriate testing include reliability, specificity, sensitivity, cost, and local access and expertise. As a general rule, physicians should choose a test that has the best accuracy for the level of testing expertise available. The basic principle underlying testing for H pylori is that patients should not undergo testing unless the physician is willing to treat on the basis of a positive test result. In patients who receive treatment, confirmation of cure is important for preventing further morbidity and reducing risk of transmission of infection.

Practical advice on eradicating Helicobacter pylori infection.

Peptic ulcer disease associated with H pylori infection is curable. The important factors in selecting therapy are efficacy of eradication, prevention of resistance, avoidance or minimization of adverse effects, patient compliance, and cost. The most effective regimens include a bismuth preparation or antisecretory drug (proton pump inhibitor or H2 receptor antagonist) plus two antibiotics administered for 14 days. Dual-drug therapies are not recommended. Triple-drug regimens are more likely to eradicate H pylori and less likely to generate resistant strains among surviving organisms. In general, cure of the infection should be confirmed 4 weeks after completion of the treatment. Antibiotic resistance is an important consideration in choosing therapy, and patients should be taught the importance of compliance. When treatment fails, antibiotic combinations should not be repeated. Considerations for anti-H pylori treatment in a managed care environment mirror those for good medical practice in general, with special attention to stringent cost-control or outcomes-driven measures.

Molecular pathogenesis of H. pylori disease.

H. pylori infection is a ubiquitous infection in man; it is associated with the development of various gastroduodenal disease manifestations. Numerous investigations are now seeking to elucidate the factors important in the microorganism that directly, or in concert with host and/or environmental factors, affect disease outcome. These studies involve the physiology and genetics of both the host and its pathogen, H. pylori.

Helicobacter pylori: its role in ulcer disease and gastric cancer and how to detect the infection.

H. pylori infection is strongly implicated in the pathogenesis of peptic ulcer disease and gastric cancer. Although the infection may be detected in over half the world's population, only a proportion will develop either ulcer disease or gastric cancer. The prevalence of the infection is very high in both diseases, but other factors combined with chronic infection must lead to specific clinical manifestations of the disease. Long-standing infection results in chronic active gastritis. In a certain subset of the H. pylori-infected population, factors such as dietary, environmental, and/or genetic factors, or specific strains of the bacterium, may result in the expression of one disease or another. There are now many investigations into these various aspects of association of the infection and disease outcome which may lead to elucidation of the actual processes in the development of specific disease in the H. pylori-infected patient. Many different tests are now available for accurate diagnosis of the infection. The non-invasive tests include the serologic tests, which include both the ELISA and the rapid-immunoassay, and the urea breath test. Invasive tests can be performed on the patient at the time of endoscopy when tissue specimens can be taken for the rapid urease test, histology, or culture.

Are there susceptible hosts to Helicobacter pylori infection?

Susceptibility to Helicobacter pylori infection may manifest itself as an increased prevalence of H. pylori infection, as reinfection after eradication, or as different clinical outcomes (gastritis, peptic ulcer disease, primary gastric B-cell lymphoma, or gastric cancer). These outcomes are likely to be a result of interaction between environmental and genetic factors. Genetic factors include both host genetic predisposition to infection as well as genetic differences in H. pylori strains. Twin studies indicate that the correlation coefficient for the relative importance of genetic effects (heritability) on acquisition of H. pylori infection is approximately 0.66. The remaining variance is accounted for by shared rearing environmental factors (20%), and non-shared environmental factors (23%), which contribute to the differences and not the similarities seen between family members. Molecular epidemiological studies of both the whole bacterial genome and of amplified regions between specific repetitive DNA sequences also suggest that there are disease-specific strains of H. pylori. There are, therefore, many different facets of susceptibility to H. pylori infection.

What are the host factors that place an individual at risk for Helicobacter pylori-associated disease?

Helicobacter pylori infection is associated with duodenal and gastric ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma. Although more than half the world's population harbors H. pylori, only a proportion will develop clinically significant disease. The specific clinical outcome of an individual can be examined as the modulation of host factors by H. pylori infection. Host acid-secretory status and sensitivity to gastrin can be modulated by H. pylori infection. Once H. pylori has established itself in the stomach, virtually everyone develops gastritis, and variations in gastritis patterns have been associated with different gastric acid responses to H. pylori infection. The patterns of gastritis are important because they seem to determine disease outcome. Blood group antigens have been implicated in studies of ulcer disease. Receptors to Lewis antigens in gastric mucosa indicate that host mucosal factors influence H. pylori attachment. Conversely, H. pylori strains express Lewis antigen-like molecules, suggesting an autoimmune component for some H. pylori-associated diseases. HLA genotypes may influence the host response to H. pylori infection, and those of H. pylori-infected individuals have been correlated with histological features. The clinical outcome of H. pylori infection is most likely a result of complex interactions among host, bacterial, and environmental factors. The mechanisms by which these diverse factors influence the pathogenesis of different clinical outcomes remain under investigation.