Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

BACKGROUND: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. METHODS: Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. RESULTS: Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. CONCLUSIONS: Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.

Antimicrobial susceptibility testing of 230 Helicobacter pylori strains: importance of medium, inoculum, and incubation time.

No standardized method of susceptibility testing for Helicobacter pylori is currently available, so before a large agar dilution study comprising 230 H. pylori strains belonging to more than 80 genetically different groups was initiated, we performed a relatively small preliminary study to determine the influences of medium, inoculum density, and incubation time. Seven media were investigated and were primarily evaluated on the basis of their abilities to support growth both semiquantitatively and qualitatively; Iso-Sensitest agar supplemented with 10% horse blood was found to be well suited for the purpose; this was closely followed by Mueller-Hinton agar with 10% horse blood, Mueller-Hinton with 10% sheep blood, and finally, 7% lysed horse blood agar. Investigations of two inoculum densities and two incubation times resulted in recommendations for the use of 10(9) CFU/ml (10[6] CFU/spot) as the inoculum and 72 h as the incubation time. A modest inoculum effect was noted for amoxicillin and metronidazole. By the methodology derived from our preliminary study, the susceptibilities of 230 H. pylori strains to six antibiotics were subsequently determined. The results were generally in accord with those of others, and apart from metronidazole, the MIC of which for approximately 25% of the strains tested was >8 microg/ml, resistance was low in Denmark. The situation might, however, quickly change when and if the number of indications for antibiotic therapy for H. pylori infections increase. Consequently, susceptibility testing of all H. pylori strains is recommended in order to survey the development of resistance, and in our hands the described methodology was relatively easy to perform and the results were easy to read.

Diagnosing bacteremia at a Danish hospital using one early large blood volume for culture.

The objective of the study was to evaluate the yield of a blood culture based on inoculating 40 ml of blood drawn from 1 venipuncture. During a 3-year period (1990-1992) 1351 (19.3%) of 6994 blood culture sets were positive. The increased yield of true bacteremic events using 40 ml instead of 30 ml of blood per blood culture was estimated to be 4.2%. Contaminants were isolated in 5% of the blood culture sets, with coagulase negative staphylococci being the most frequently isolated contaminants (3.2%, 1.3% of the culture bottles). In most of cases, contaminants were only isolated in 1 or 2 of the 4 bottles of the set. Furthermore, a positive correlation was observed between the number of positive culture bottles and the recovery of a clinically-significant microorganism. Neither the frequency nor the interpretations of positive blood culture events with microorganisms of questionable significance were major obstacles. In conclusion, the spectrum and yield of microorganisms drawing 40 ml of blood from one venipuncture into 4 culture bottles was satisfactory. The method bears obvious advantages from a clinical point of view, since usually only 1 venipuncture is needed before institution of antibiotic treatment.

Evaluation of the E-test for susceptibility testing of the Bacteroides fragilis group. Danish study group.

The susceptibilities of 100 clinical isolates belonging to the Bacteroides fragilis group to 9 antibiotics, i.e. ampicillin, piperacillin, ceftriaxone, cefotaxime, cefoxitin, imipenem, erythromycin, clindamycin, and metronidazole, were tested using a standard agar dilution method and the E-test. Overall, 81% of the E-test MICs were within one log2 dilution step of the agar dilution MICs and 95% were within two log2 dilution steps. The E-test showed significantly lower MIC values than the agar dilution method for ampicillin, cefotaxime, and imipenem, and significantly higher MIC values for piperacillin, ceftriaxone, erythromycin, clindamycin, and metronidazole. However, this only resulted in minor discrepancies that did not change the susceptibility status. The E-test is easy to perform and read, and the MIC values correlated well with the MICs obtained by the agar dilution method when testing susceptibility of the Bacteroides fragilis group.

Microbiological evaluation of jejunal aspirates and faecal samples after oral administration of bifidobacteria and lactic acid bacteria.

A double-blind placebo controlled investigation was carried out to study the effect of peroral colonization. Human volunteers were given mixtures of bifidobacteria and lactic acid bacteria. Measurements were made over a 1 week treatment period and for another week after the end of the treatment. Two different bacteriological preparations were used, one consisted of Enterococcus faecium and Bifidobacterium longum (a total of 6.4 x 10(8) cfu d-1); the other consisted of Lactobacillus acidophilus, Bif. bifidum, Lact. delbrueckii ssp. bulgaricus, and Streptococcus thermophilus (a total of 9 x 10(9) cfu d-1). Together with a placebo preparation, they were given to 24 healthy controls (eight in each group). Microbiological examinations of jejunal aspirates showed that viable counts of most species were below the detection limit. However, the test preparation containing Ent. faecium and Bif. longum significantly reduced the anaerobe: aerobe ratio in faeces by a factor of three during treatment (P = 0.03), and increased it by a factor of 30 during the following week (P < 0.02). This study shows that peroral administration of certain bacterial cultures may affect the distal intestinal microflora.

[Prevention of duodenal ulcer recurrence with penicillin]. / Forebyggelse af recidiv af ulcus duodeni med penicillin.

The aim of this study was to test the hypothesis that infection with Helicobacter pylori is essential for recurrence of duodenal ulcer. We performed a randomized controlled trial of the relapse rate of duodenal ulcer during 12 weeks treatment with penicillin V or placebo in 170 out-patients from five centres. The relapse rate was 9% during treatment with penicillin and 50% with placebo, P < 0.0001. It is concluded that infection with penicillin-sensitive bacteria, i.e. H. pylori, plays an important role for recurrence of duodenal ulcer disease. Penicillin V suppresses this infection but does not eradicate it.

Antibiotic sensitivity of the Bacteroides fragilis group in Denmark. Danish Study Group.

Resistance rates to 9 antibiotics were determined for 370 isolates of the Bacteroides fragilis group submitted during a 5-month period in 1990-91 from 6 laboratories in Denmark. There was no resistance to imipenem (MIC > 8 mg/l) or metronidazole (MIC > 16 mg/l), while resistance to ampicillin was the rule (97% at > 4 mg/l) and to ceftriaxone rather common (19% at > 32 mg/l). Resistance was uncommon to cefoxitin (0.5% at > 32 mg/l), cefotaxime (6% at > 32 mg/l), piperacillin (7% at > 64 mg/l), ampicillin/sulbactam (1% at > 16 mg/l), and clindamycin (3% at > 4 mg/l). Two hundred and thirty-nine strains were Bacteroides fragilis. The 131 other strains were generally more resistant than the Bacteroides fragilis strains. For 5 antibiotics the Bacteroides fragilis had a significantly lower MIC in western than in eastern laboratories. For the group with other strains there was no significant difference.

Prevention of duodenal ulcer recurrence with penicillin. A double-blind, placebo-controlled trial.

Eradication of Helicobacter pylori is associated with a reduced recurrence of duodenal ulcer (DU). The relationship between H. pylori and DU has been interpreted as causal, but the evidence has been criticized for methodologic reasons. To ascertain whether an antibiotic with no effect on epithelial-cell integrity prevents DU recurrence, we conducted a randomized double-blind trial of phenoxymethylpenicillin (PEN), 2.4 twice daily, and placebo (PLA). Patients with an active DU and positive H. pylori culture from antral biopsy specimens were treated with 40 mg omeprazole daily for 4 weeks, but at week 2 they were allocated at random to PEN (85 patients) or PLA (85 patients) for up to 14 weeks. Those without recurrence during this treatment were followed up for another 6 months. Endoscopy and H. pylori culture were performed at the end of the treatment period and at the end of follow-up, and in between if ulcer symptoms recurred. During the treatment period the ulcer relapse rate was 5 of 58 (9%) in the PEN group and 34 of 68 (50%) in the PLA group (P < 0.0001, log-rank test), with 53% and 14%, respectively, of the patients in the two groups being H. pylori-negative. The relapse rate in the PEN group did not differ between H. pylori-negative and H. pylori-positive patients. The recurrence rate in the PEN group remained low for another 5 months but then approached the rate in the PLA group. The prevalence of H. pylori-negative patients at the end of follow-up was 20% in the PEN group and 10% in the PLA group. These data provide strong evidence that DU has a bacterial cause, with H. pylori as the likely agent.

Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in patients with dyspeptic symptoms and normal persons.

Heat-stable antigens from Helicobacter pylori were investigated for the detection of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique. Antibody titers against H. pylori were measured in 167 dyspeptic patients, of whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482 controls (0-98 years). Increased IgG antibody titers were found significantly more often in dyspeptic patients with active chronic gastritis than in patients with normal morphology, as well as in H. pylori-positive patients as compared to H. pylori-negative patients, independent of the endoscopic findings. The heat-stable antigens were compared with acid glycine-extracted antigens and a high degree of concordance was found in the results obtained with the two antigen preparations. The differences in the IgA antibody titers against H. pylori between H. pylori-positive and H. pylori-negative dyspeptic patients were significant and may be useful to confirm a borderline IgG result. No differences were found in IgM antibody titer between H. pylori-positive and -negative patients. The greatest age-dependent increase in IgG and IgA antibody titers was found in children, and if a lower cut-off level is used for children than for adults, as has been proposed, the proportion of people with increased antibody titers against H. pylori would be almost constant from the age of between five and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG antibodies with IgG antibodies against Campylobacter jejuni and total antibodies against cytomegalovirus (CMV) showed a greater similarity between H. pylori and C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat-stabile antigen seems not to be very different from other crude H. pylori antigens like acid glycine-extracted antigens, but purification and characterization of the antigens are needed to improve antibody assays.

[Shigella sonnei. An epidemic in a day-care institution]. / Shigella sonnei. Epidemi i en daginstitution.

Epidemics caused by dysentery bacteria among children and adults in day-institutions are rare in Denmark. The course of an epidemic of this type is reviewed. Thirty children and six adults went on holiday to a deserted farmer's cottage under primitive conditions in the southern Swedish woods. Immediately prior to this holiday, two of the adults had had serious gastrointestinal infections during a hiking trip in South America. Shigella sonnei was subsequently demonstrated in the stools from a total of 11 children but not in the adults. Three cases of intrafamilial infection occurred. Prior to commencement of the school year in late summer 1988, treatment of the asymptomatic bacterial carriers was carried out. Treatment such as this cannot be recommended as a rule and should, therefore, be discussed with the Medical Officer of Health when accumulated cases of Shigella sonnei dysentery occur.

Thromboprophylaxis in patients with hip fractures: a prospective, randomized, comparative study between Org 10172 and dextran 70.

A prospective, randomized, assessor-blind trial has been undertaken to compare the thromboprophylactic effect and safety of the heparinoid Org 10172 (a mixture of low molecular-weight sulfated glycosaminoglycuronides) and dextran 70 in patients operated on for hip fracture. Prestudy biostatistical calculations led to the need for 260 patients. Three hundred eight patients were randomized and 19 were excluded after randomization, the majority because of postponed surgery. Analyses were made on the 289 patients on an intention-to-treat basis, as well as on the 247 patients given correct prophylaxis. Diagnosis of deep vein thrombosis was based on bilateral ascending phlebography on postoperative days 10 through 12. The frequency of deep vein thrombosis on an intention-to-treat basis was 10% in the Org 10172 group and 30% in the dextran 70 group and, on the basis of correct prophylaxis, 12% and 31%, respectively, both differences being significant (p less than 0.001). Two-month mortality rates were equal in the groups. Three fatal pulmonary emboli were seen in the dextran group. Significantly more patients in the dextran group received postoperative transfusions; no other differences in various hemorrhagic parameters were seen. Thus it can be concluded that Org 10172 has a significantly better thromboprophylactic effect than does dextran in patients with hip fractures without significant side effects.

The Helicobacter (Campylobacter) pylori-colonized duodenal mucosa and gastric metaplasia.

Biopsies were obtained from non-ulcerated sites of the duodenum from 100 dyspeptic patients. Helicobacter (Campylobacter) pylori was cultivated from 19 of these biopsies. Active chronic duodenitis (ACD) was found in 17 biopsies and more than 5% gastric metaplasia in 20 biopsies. H. pylori as well as ACD occurred with a significantly increased frequency when more than 5% gastric metaplasia was found in the duodenal biopsies. H. pylori on metaplastic tissue without ACD was, however, seen in two cases. H. pylori was cultivated from 9% and ACD was found in 5% of the biopsies with less than 5% gastric metaplasia. Gastric metaplasia in the duodenum was found significantly more frequently in patients with endoscopic duodenitis or duodenal ulceration than in patients with normal endoscopy. No association between gastric metaplasia in the duodenum and gastric pH or serum antibodies against H. pylori was seen. This study indicates that there is an established, but not exclusive, connection between gastric metaplasia and the colonization of the duodenum by H. pylori, the most important role being played by the antral gastric mucosa rather than the duodenum.

Transport conditions and number of biopsies necessary for culture of Helicobacter pylori.

Stuart's transport medium with a charcoal impregnated swab was tested for transport of biopsies from the gastric antrum for culture of Helicobacter pylori. Biopsies were cultured under microaerophilic conditions either within 2 h or after a delay of 24 h at 4 degrees C. In 65 patients referred for gastroscopy two biopsies were taken. Helicobacter pylori was found in 39 patients. The rate of survival of Helicobacter pylori was found to be as high in Stuart's transport medium after 24 h at 4 degrees C as in the paired biopsy which was cultured immediately after transportation in normal saline. In five (13%) of 39 patients positive for Helicobacter pylori, the organism was cultured from only one of the biopsies. It is therefore recommended that two biopsies be taken for culture.

[The quality of a manual method for the identification of the lumbar vertebrae]. / Undersøgelse af kvaliteten af en manuel metode til bestemmelse af lumbalhvirvler.

In order to identify the spinous processes in the lumbar region, we employ the following rule: that "the line between the iliac crests passes through the spinous process of L4 or the intervertebral space between the 4th and 5th lumbar vertebrae". Three anaesthetists (two junior staff and one consultant) identified a spinous process marked by lead-shot in 33 patients prior to radiological examination. No significant differences were found between the estimates made by the junior staff and the consultant and none of the following factors were of significance for the estimates: height, weight, weight index, sex or age of the patients. When the patients were subdivided according to the radiographic degree of pathological findings in the lumbar spine, only 48% of the estimates were found to be correct while where no or slight changes were present, 71% of the estimates were correct. The differences were significant. It is concluded that 40% of the estimates were incorrect but never by more than one segment. The method may be employed where unreliability of one segment is acceptable.

Functional radiographic examination of the cervical spine in patients with post-traumatic headache.

The segmental extension-flexion motion of the cervical spine and the overall C1-C7 motion were measured on functional X-rays in 19 patients with post-traumatic headache and 19 age- and sex-matched controls. The extension-flexion C1-C7 motion was reduced in patients with post-traumatic headache due to reduced motion in three segments: C2-C3, C5-C6 (p less than 0.05), and C6-C7 (p less than 0.01). In both groups a negative correlation between the C1-C7 motion and age was found, but the regression coefficients were different. Only in the control group could a negative correlation between segmental motion and age be demonstrated. In the patients with post-traumatic headache a statistically significant negative correlation between the log (pain index) and the age-corrected C1-C7 motion was found (p less than 0.04). On the segmental level a negative correlation between the log (pain index) and the age-corrected C1-C2 and C5-C6 motion could be demonstrated (p less than 0.05). Regarding C6-C7 there was a tendency to negative correlation. Furthermore, a negative correlation between the frequency of associated symptoms (dizziness, visual disturbances and ear symptoms) and the age-corrected C5-C6 motion was found. Consequently the decrement of motion primarily affected C2-C3, C5-C6, and C6-C7, whereas the analysis of correlation with pain index indicated C1-C2 and C5-C6 (C6-C7) as the most important segments involved.

The use of fibrinogen uptake test in screening for deep vein thrombosis in patients with hip fracture.

255 hip fracture patients were studied by 125I-fibrinogen uptake test and bilateral phlebography. We found the sensitivity of fibrinogen scanning to be 44% for the non-operated limb and 50% for the calves. The predictive value of a negative result was found to be 92% and 93% respectively. We conclude that the use of fibrinogen uptake test as single diagnosticum is not valid and can only be recommended in combination with phlebography when studying patient where the frequency of DVT is expected to be low.