K. Seppälä

Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after eradication of Helicobacter pylori.

Titres of antibody to Helicobacter pylori are known to fall with eradication of bacteria. To find out what degree of fall would reliably indicate eradication, 144 patients with Helicobacter pylori infection were given antimicrobial therapy for 2 weeks and then followed up at 6 weeks, 6 months, and 12 months with serological tests, bacterial cultures, and histological studies of gastric specimens. 6 weeks after treatment IgG titres had fallen by 20-30% irrespective of the success of bacterial eradication. In the 121 bacteria-negative patients the decrease continued. 6 and 12 months after treatment the titre was 50% or less of pretreatment value in 97% of these patients. In the 23 patients who remained infected, the initial drop of IgG titres, if any, was followed by unchanged or slightly rising titres. IgA and IgM titres, initially raised in 64% and 4% of the patients, respectively, showed similar trends. The high sensitivity (97%) of the IgG antibody tests and a consistent fall within 6 months after eradication of H pylori infection made IgG the most useful immunoglobulin class for follow-up of antimicrobial therapy in individual patients. IgA antibodies were valuable in the 2% patients who had raised titres in this immunoglobulin class only. The few patients (5.5%) who had raised IgM titres also had high IgG titres. Serological tests thus are a cheap and reliable means of monitoring success of eradication of H pylori.

Long-term treatment of ulcerative colitis with ciprofloxacin: A prospective, double-blind, placebo-controlled study

BACKGROUND & AIMS Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.

Cumulative 10-Year Risk of Symptomatic Duodenal and Gastric Ulcer in Patients with or without Chronic Gastritis: A Clinical Follow-up Study of 454 Outpatients

The cumulative rate of symptomatic peptic ulcer (PU) was examined in a 10-year clinical follow-up study of 454 consecutive outpatients who had undergone diagnostic gastroscopy, from whom routine biopsy specimens were taken from the antral and corpus mucosa, and who were found to be ulcer-free before and at the time of this initial gastroscopy. During the follow-up period 34 (11%) of 321 patients who showed gastritis in the biopsy specimens at the initial gastroscopy had contracted symptomatic PU (18, 5, 7, and 4 cases of duodenal, pyloric, antral, and angular or corpus ulcer, respectively), which was verified by endoscopy. Only 1 (0.8%) of 133 patients with normal antral and corpus mucosa had contracted PU. It was calculated that the 10-year cumulative probability of PU was 10.6% (95% confidence interval (CI95), 7.2-14.0%) in the patients with gastritis, whereas this probability was only 0.8% (0-2.2%) in the patients who had normal antral and corpus mucosa in the initial specimens. The cumulative probability of PU was found to be highest, 27.3% (1.0-53.6%), in middle-aged men (41-60 years of age) who had chronic antral gastritis or chronic pangastritis (gastritis in both antrum and corpus). It is concluded that chronic gastritis precedes the appearance of PU and that the cumulative 10-year risk of PU is very low when both antral and corpus mucosa are normal but may be high if chronic gastritis is present.

A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid

BACKGROUND/AIMS Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. RESULTS There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. CONCLUSIONS These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.

Triple Therapy of Helicobacter pylori Infection in Peptic Ulcer: A 12-Month Follow-up Study of 93 Patients

This study was undertaken to evaluate the success of triple therapy in peptic ulcer patients and ulcer relapses. One hundred and one consecutive Helicobacter pylori-positive peptic ulcer patients were assigned to an open trial with 2 weeks of treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. At the 6-week follow-up only 1 duodenal ulcer was unhealed of 57 active ulcers, and H. pylori was found to be eradicated in 84% of the 100 subjects. The sensitivity to metronidazole was determined from 71 pretreatment strains of H. pylori. Eradication of H. pylori succeeded in 89% of the patients with metronidazole-susceptible strains and in 61% of patients with metronidazole-resistant strains (p < 0.03). All 16 patients in whom the treatment failed to eradicate the organism had metronidazole-resistant strains after treatment. The ulcer relapse rate was low. At the 12-month follow-up of 93 patients only 1 of the 84 H. pylori-negative patients (including 4 patients after new successful therapy) had relapsing ulcers (2 asymptomatic episodes), and 1 had H. pylori reinfection, whereas 3 of the 9 bacteria-positive patients relapsed (p = 0.002); at the 2-year control 2 more patients had ulcer relapses. The eradication of H. pylori infection clearly prevents relapses of peptide ulcer, but the success of triple therapy depends on the frequency of pretreatment metronidazole-resistant H. pylori strains.

Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients.

Background: Treatment with a proton pump inhibitor (PPI) and antimicrobials cures Helicobacter pylori infection in about 90% of patients. This is a retrospective overview of our studies aiming to cure the infection in all compliant patients with failed initial therapy. Methods: We retreated 120 (19% of 644) H. pylori-infected patients whose initial therapy had failed. The retreatments included (i) triple therapy (TT): colloidal bismuth subcitrate, metronidazole, amoxicillin (or tetracycline); (ii) quadruple therapy (QT): TT and a PPI; or (iii) high doses of both a PPI and clarithromycin combined with a further 1-3 individually selected antimicrobials. The eradication results were determined after 6-12 months. Results: The 1st retreatment was successful in 70 of 120 patients. The 2nd retreatment cured 25 of the remaining 42 patients, the 3rd 13 of 17, and the 4th the last 4 patients. The cumulative eradication rate (ITT) was 93% (95% CI: 88.9%-97.9%; 8 patients withdrew after a failed 1st retreatment) and the rate was 100% in the remaining 112 patients who accepted several retreatments. The 1st retreatment with TT cured 23% (95% CI: 12%-34%) of 57 patients and QT 85% (95% CI: 74%-96%) of 41 patients who had initially undergone a failed metronidazole-based treatment. All retreatments were well tolerated. Conclusions: In this study, high doses of a PPI and clarithromycin combined with 1-3 antimicrobials according to susceptibility data proved to be the best drug combination in the cure of H. pylori infection after failed primary treatment. Giving imidazole- and bismuth-based QT (without clarithromycin) as the first-line treatment of H. pylori infection ensures that the number of failures remains low.BACKGROUND Treatment with a proton pump inhibitor (PPI) and antimicrobials cures Helicobacter pylori infection in about 90% of patients. This is a retrospective overview of our studies aiming to cure the infection in all compliant patients with failed initial therapy. METHODS We retreated 120 (19% of 644) H. pylori-infected patients whose initial therapy had failed. The retreatments included (i) triple therapy (TT): colloidal bismuth subcitrate, metronidazole, amoxicillin (or tetracycline); (ii) quadruple therapy (QT): TT and a PPI; or (iii) high doses of both a PPI and clarithromycin combined with a further 1-3 individually selected antimicrobials. The eradication results were determined after 6-12 months. RESULTS The 1st retreatment was successful in 70 of 120 patients. The 2nd retreatment cured 25 of the remaining 42 patients, the 3rd 13 of 17, and the 4th the last 4 patients. The cumulative eradication rate (ITT) was 93% (95% CI: 88.9%-97.9%; 8 patients withdrew after a failed 1st retreatment) and the rate was 100% in the remaining 112 patients who accepted several retreatments. The 1st retreatment with TT cured 23% (95% CI: 12%-34%) of 57 patients and QT 85% (95% CI: 74%-96%) of 41 patients who had initially undergone a failed metronidazole-based treatment. All retreatments were well tolerated. CONCLUSIONS In this study, high doses of a PPI and clarithromycin combined with 1-3 antimicrobials according to susceptibility data proved to be the best drug combination in the cure of H. pylori infection after failed primary treatment. Giving imidazole- and bismuth-based QT (without clarithromycin) as the first-line treatment of H. pylori infection ensures that the number of failures remains low.

Gastric Inflammation and Neutrophil-Activating and Cytotoxin-Producing Helicobacter pylori Strains

BACKGROUND Some Helicobacter pylori strains activate human neutrophils without opsonins and/or produce vacuolating cytotoxin. METHODS Human gastric isolates of H. pylori were studied for their ability to nonopsonized induce an oxidative burst in human neutrophils as measured by chemiluminescence and for the production of vacuolating cytotoxin. In all, 80 strains were examined, and the type and grade of inflammation in the gastric biopsy specimens from the antrum and corpus of these patients were assessed in accordance with the Sydney system. RESULTS CL+ (rapid, strong response in chemiluminescence) strains (p < 0.0001) and Tox+ (cytotoxin-producing) strains (p < 0.0001) were associated with higher acute inflammation scores in gastric ulcer patients. CL+ (p = 0.0002) and Tox+ (p < 0.0001) strains were also associated with higher chronic inflammation scores in gastric ulcer patients. CONCLUSIONS CL+ and Tox+ strains seem to cause more severe inflammation in the gastric mucosa during H. pylori infection.

Campylobacter pylori is associated with chronic gastritis but not with active peptic ulcer disease

Campylobacter pylori is supposed to be involved in the pathogenesis of gastroduodenal peptic ulcer diseases and chronic gastritis. In order to study whether the Campylobacter pylori in the stomach of peptic ulcer patients is related to ulcer itself or to a co‐existing chronic gastritis, we examined the frequency of the bacteria in Giemsa stained histological sections of biopsy specimens from a series of patients with active peptic ulcer and from series of non‐ulcer control subjects. We found no difference in the frequency of Campylobacter‐ positive cases between ulcer patients and non‐ulcer controls when the comparison was done within the same category of chronic gastritis; e.g., within the category of chronic superficial gastritis 74% and 78% of cases showed the bacteria in antral biopsies from ulcer patients and from non‐ulcer controls, respectively. In both ulcer patients and control subjects, in similar way in both antral and body mucosa, the Campylobacter pylori was strongly associated with chronic superficial gastritis but was more weakly associated with chronic atrophic gastritis, and the bacteria were only occasionally seen in normal mucosa. We conclude that Campylobacter pylori is associated with chronic gastritis in peptic ulcer patients but is not related to active ulcer.

Hemorrhagic gastropathy in epidemic nephropathy

A patient with epidemic nephropathy (NE) and with gastrointestinal symptoms and hemorrhagic gastropathy prompted us to study further 10 consecutive patients with NE. Gastroscopy was carried out within 1 to 4 weeks after the beginning of the symptoms, and in every case a hemorrhagic gastropathy was observed. Hemorrhagic lesions were more marked, the shorter the elapsed time interval from the beginning of symptoms. Hemorrhagic changes were always more prominent in the proximal than in the distal part of the stomach. In 7 of 10 patients lesions were also observed in the duodenum. Colonoscopy was done in one patient and it showed similar spotty hemorrhages, suggesting that hemorrhagic lesions were not limited to the gastroduodenal mucosa only. Histological studies disclosed that the hemorrhagic lesions were associated with edema in the lamina propria, but without inflammatory changes. Follow-up gastroscopy in three patients 3 to 8 weeks later showed disappearance of hemorrhagic lesions in every patient. Thus, these results show for the first time that hemorrhagic gastropathy is a common finding in NE, and it may explain the abdominal symptoms and gastrointestinal bleeding in some of these patients. However, the mechanism of the hemorrhagic lesions needs further exploration.

Association of CagA-positive infection with Helicobacter pylori antibodies of IgA class.

cagA gene, the best known virulence factor of Helicobacter pylori, codes for an immunodominant CagA protein. In this study, CagA antibodies of the IgG class were measured by immunoblot or enzyme immunoassay in subjects with positive H. pylori serology, and the presence of CagA antibodies was compared with that of H. pylori antibodies of IgA and IgG classes. Serum samples were available for a total of 1481 subjects, including gastroscopied patients with biopsy-verified H. pylori infection, smoking men with a normal or low serum pepsinogen I level indicating atrophic corpus gastritis, and subjects who later developed gastric cancer and their matched controls. CagA antibodies were significantly more prevalent among individuals with elevated H. pylori antibody titres of the IgA class than in those with IgG antibodies only, with the exception of a small subgroup of individuals who later developed gastric cancer. CagA-positive H. pylori strains seem to induce an immune response with a markedly higher frequency of IgA than what is found in inflammation caused by CagA-negative strains. The presence of serum IgA antibodies to H. pylori seems to indicate a higher risk for CagA-positive H. pylori infection and possibly more severe late sequelae of the disease.