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PubMed1997

Unhealed duodenal ulcers despite Helicobacter pylori eradication.

BACKGROUND: Our aims were 1) to study the influence of several factors (age, sex, smoking, previous ulcer disease, ulcer size, chronic gastritis, serum gastrin and pepsinogen I levels, therapy regimen and, especially, eradication of Helicobacter pylori) on duodenal ulcer healing; 2) to evaluate the frequency of duodenal ulcer healing failure despite eradication of H. pylori, to study why this failure occurs, and to verify its evolution without antisecretory therapy; and 3) to confirm whether a week's prescription of omeprazole is sufficient to obtain ulcer healing. METHODS: Three-hundred and eight patients (mean age, 45 +/- 13 years; 71% males) with duodenal ulcer and H. pylori infection were studied prospectively. Biopsy specimens were obtained at initial endoscopy, and serum gastrin and pepsinogen I levels were measured. A repeat endoscopy (with biopsies) was performed 1 month after eradication therapy had been completed, and a 13C-urea breath test was also carried out. Three eradication therapies were used: omeprazole plus amoxycillin for 2 weeks (OA group, n = 61); 'classic' triple therapy (with bismuth; CTT group, n = 65); and 'new' triple therapies for 1 week (NTT group, n = 182): omeprazole plus two of the following antibiotics: clarithromycin, metronidazole, and amoxycillin. When the ulcer did not heal despite successful H. pylori eradication, antacids were prescribed on an as-needed basis, and endoscopy was repeated 1 month later (2nd control endoscopy). If the ulcer was still present, the acid output (basal and pentagastrin-stimulated) was measured, a secretin test was performed, and a final endoscopy (3rd control endoscopy) was carried out after an additional month. The statistical method used was multiple logistic regression. RESULTS: Overall eradication was achieved in 69% (n = 212) of the patients, and ulcer healing in 76% (n = 233): 57% in the OA group, 80% in the CTT group, and 81% in the NTT group (P < 0.01 when comparing the OA group with the others). Ulcer healing was achieved in 90% of H. pylori-eradicated patients and in only 45% of patients with eradication therapy failure (P < 0.001). Similar results were obtained when only patients treated with NTT were considered: ulcer healing in 90% of patients with the organisms eradicated. Eradication of H. pylori (odds ratio (OR), 11.8; 95% confidence interval (CI), 6.3-22) and sex (OR, 2.5; 95% CI, 1.2-5.1) were the only variables that correlated with ulcer healing in the multivariate analysis. The ulcer persisted despite successful eradication of H. pylori in 22 patients. The duodenal ulcer had healed spontaneously in 73% of these patients at the 2nd control endoscopy. Finally, by the 3rd control endoscopy, only three patients still had duodenal ulcer. Therefore, ulcer healing was finally achieved in 98.1% (95-99%) of patients in whom H. pylori was eradicated. Gastrin, pepsinogen I, acid output, and the secretin test had normal values in all patients. CONCLUSIONS: Eradication of H. pylori favours ulcer healing, which is achieved in most patients in whom the organism is eradicated. Just 1 week of omeprazole therapy (that is, the antibiotic administration period in the new triple therapies) is enough to obtain a high ulcer healing rate. Most duodenal ulcers that do not heal initially despite H. pylori eradication will ultimately do so after several weeks without additional therapy.

Amoxicillin↗
PubMed2002

History and prospects for viral disease eradication.

Edward Jenner first articulated the concept of eradication when he first inoculated the vaccinia. Before considering a disease for eradication some factors should be considered, such as the biological characteristics of the infectious agent: does the infectious agent infects only humans? Does it have a non-human reservoir and induce long-life immunity after infection? Is there a tool or intervention that effectively interrupts the chain of transmission from one individual to another? The first disease to be eradicated was smallpox. This extraordinary initiative set the example for any future disease eradication program. The eradication of polio from the Americas was launched in May 1985 and the Region of the Americas was certified polio-free in September 1994. At this same year, the Pan American Health Organization (PAHO) launched an initiative to eradicate measles from the Americas. Only 1,500 cases have been reported during the year 2000, and transmission was interrupted in most countries of the Region. Tremendous progress has been achieved in disease eradication efforts, which resulted in the global eradication of smallpox, the eradication of poliomyelitis from the Americas and its nearly global eradication, and the nearly complete eradication of measles from the Americas. The biotechnology revolution is providing us with many new vaccines and we have to continue the search for those diseases that could eventually be eradicated. Eradication of a disease brings the greatest health benefit, which is the absence of the health threat. It is also the quintessential example of health equity, as all mankind reaps the benefits, bringing eternal cost savings. As Louis Pasteur pointed out, "it is within the power of man to eradicate infection from the earth".

Americas↗
PubMed2000

Symptomatic benefit 1-3 years after H. pylori eradication in ulcer patients: impact of gastroesophageal reflux disease.

OBJECTIVES: Eradication of Helicobacter pylori (H. pylori) infection markedly reduces the recurrence of duodenal and gastric ulcers. However, there is little information regarding its efficacy in resolving dyspeptic symptoms in ulcer patients. The primary aim of this study was to assess the effect of eradicating H. pylori infection on dyspeptic symptoms in ulcer patients. The secondary aim was to identify predictors of symptomatic response to H. pylori eradication. METHODS: A total of 97 dyspeptic patients with active duodenal and/or gastric ulceration associated with H. pylori infection and unrelated to NSAID use had the severity and character of their dyspeptic symptoms measured before and again 1-3 yr after H. pylori eradication therapy. RESULTS: Pretreatment, the median dyspepsia score was 12 (4-16). Posttreatment, 55% of those eradicated of H. pylori had resolution of dyspepsia (score <2) compared with 18% of those not eradicated of the infection (95% CI for difference, 11-62%). Of the ulcer patients 31% had symptoms and/or endoscopic evidence of coexisting gastroesophageal reflux disease (GERD) at initial presentation and this influenced the symptomatic response to eradication of H. pylori. Of the 22 patients with heartburn or acid reflux as the predominant presenting symptom, but no endoscopic esophagitis, only 27% experienced resolution of dyspepsia after H. pylori eradication, compared with 68% of the 59 without those as predominant symptoms (95% CI for difference, 18-63%). Only one of the five patients with coexisting endoscopic esophagitis at initial presentation experienced resolution of dyspepsia after H. pylori eradication. Symptomatic benefit was unrelated to time lapsed since the infection was eradicated. Only three of 50 subjects developed de novo GERD symptoms after eradication of H. pylori, whereas 21 of 36 subjects experienced resolution of GERD symptoms after eradication of the infection. CONCLUSIONS: A substantial proportion of ulcer patients have symptoms and/or signs of coexisting GERD at initial presentation and this reduces the symptomatic benefit from H. pylori eradication. However, we have found no evidence that eradicating H. pylori induces de novo GERD symptoms in ulcer patients.

Adult↗
PubMed1997

Measles eradication: recommendations from a meeting cosponsored by the World Health Organization, the Pan American Health Organization, and CDC.

Recent successes in interrupting indigenous transmission of measles virus in the Americas and in the United Kingdom prompted the World Health Organization (WHO), Pan American Health Organization (PAHO), and CDC to convene a meeting in July, 1996 to consider the feasibility of global measles eradication. Presentations at the meeting included an overview of global measles control and elimination efforts; detailed reviews of successful measles elimination efforts in Latin America, the English-speaking Caribbean, Canada, and the United States; surveillance for clinical disease; laboratory tools for antibody detection and virus identification; and other factors that might influence the feasibility of disease eradication. With this background information, meeting organizers asked participants to address five questions: 1) Is global measles eradication feasible? 2) Is measles eradication feasible with current vaccines? 3) What are the appropriate vaccination strategies for measles eradication? 4) How should surveillance for measles be carried out? 5) What role should outbreak control play in the strategy to eliminate measles? Participants agreed that measles eradication is technically feasible with available vaccines and recommended adoption of the goal of global eradication with a target date during 2005-2010, with the proviso that measles eradication efforts should not interfere with poliomyelitis eradication but should build on the successes of the global Poliomyelitis Eradication Initiative. Although existing vaccines are adequate for eradication, vaccination strategies that rely on administration of a single dose of vaccine are not. In the Americas, sustained interruption of indigenous measles virus transmission has been achieved through a three-tiered vaccination strategy that includes a) "catch-up" vaccination of all persons aged 1-14 years, regardless of disease history or vaccination status; b) "keep-up" vaccination of > or = 90% of children in each successive birth cohort at age 12 months and c) "follow-up" campaigns designed to vaccinate all persons within a specific age range whenever the number of susceptible persons in the preschool-aged population approximates the size of a typical birth cohort (in practice, every 3-5 years). In other regions, different strategies may be optimal. Surveillance, a critical component of any strategy to eliminate or eradicate measles, has two functions: to assess the effectiveness of the measles elimination strategy and to detect circulation of measles virus in a population. Systematic surveillance based on clinical diagnosis should be implemented early in any measles elimination program. In countries attempting to eliminate indigenous measles, all isolated cases of measles and at least one case in each chain of transmission should be confirmed by laboratory tests. Specimens for virus isolation (e.g., urine, nasopharyngeal swabs, or blood) should be collected in conjunction with field investigations. Vaccination campaigns generally have not proved to be effective responses to measles outbreaks. Outbreaks should be treated as opportunities to reinforce surveillance and to identify measures to prevent future outbreaks. The major obstacles to measles eradication are not technical but perceptual, political, and financial. Measles is often mistakenly perceived as a mild illness. This misperception, which is particularly prevalent in industrialized countries, can inhibit the development of public and political support for the allocation of resources required for an effective elimination effort. The disease burden imposed by measles should be documented, particularly in industrialized countries, so that this information can be used to educate parents, medical practitioners, public health workers, and political leaders about the benefits of measles eradication.

Disease Outbreaks↗
PubMed2006

ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates.

Endoplasmic reticulum (ER) stress-induced accumulation of misfolded proteins in the ER stimulates the ER-associated degradation (ERAD) process. ERAD in turn eliminates those misfolded proteins. Upregulation of ubiquitination enzymes is an essential mechanism by which ER stress enhances ERAD. However, ectopic overexpression of ubiquitination enzymes often fails to increase, and sometimes, inhibits ERAD. To further understand how ER stress regulates ERAD, we studied the effects of ER stress on ubiquitin ligase (E3) gp78-mediated ERAD and on the stabilities of gp78 and another ERAD E3 Hrd1. The results showed that ER stress-inducing agent tunicamycin significantly enhanced ERAD in cells that either express endogenous or overexpress gp78. Importantly, ER stress could increase ERAD even when new protein synthesis was inhibited by cycloheximide. Surprisingly, tunicamycin treatment stabilized gp78, an established ERAD E3 and an ERAD substrate as well, for up to 8h. By contrast, ER stress had little effects on the stability of another E3 Hrd1 except that it reduced the total ubiquitination level of Hrd1. Our data suggest that ER stress differentially regulates the stabilities of ERAD E3s and their substrates, which may represent a novel mechanism by which ER stress increases ERAD.

Animals↗