From authorship to contributorship. Promoting integrity in research publication.

Shared authorship in nursing research presents practical and ethical dilemmas and does not effectively capture individual research participation and accountability. This study, which defined author contributions and practices in multiauthored nursing research, contributed to a better understanding of contemporary author participation and the inherent challenges faced by nurse scholars in determining authorship credit. A method of "contributorship" is proposed which would delineate individual contributions to the research project while maintaining professional integrity, scientific accountability, and scholarly recognition.

Helicobacter pylori gastritis, peptic ulcer, and gastric cancer: clinical and molecular aspects.

Helicobacter pylori causes specific ultrastructural changes to the gastric mucosa. In developing countries a high percentage of infants acquire this infection, which initially causes a transient drop in stomach acid and thus allows transit of lower bowel pathogens, with consequent diarrhea and malnutrition. When infection occurs at an early age, the acid-producing cells of the stomach are involved in the inflammation, and the lifelong reduced acid output means a duodenal ulcer rarely develops. However, lifelong gastric inflammation leads in due course to atrophy, and in the presence of other factors gastric cancer may develop. People infected with H. pylori on average are of shorter stature than uninfected people. Adherence of H. pylori to the gastric mucosa is a prerequisite for infection, and a new binary model of adherence has been shown recently. Chaperonins of H. pylori induce macrophages to secrete cytokines, which leads to an immunologic cascade and inflammation.

Antimicrobial treatment of Helicobacter pylori infection.

Helicobacter pylori is susceptible to many antimicrobials, but clinically only a few are effective. Two antimicrobials with bismuth or ranitidine or a proton pump inhibitor such as omeprazole are required to achieve a cure rate of >90% and to avoid resistance, which occurs when clarithromycin or metronidazole is the single antimicrobial used. Bismuth plus metronidazole and tetracycline is effective but causes more side effects than does treatment with omeprazole, amoxicillin, and clarithromycin; metronidazole can replace clarithromycin. To ensure a high cure rate, treatment is required for 10 days, but 7-day regimens have sometimes been as successful. A course of ranitidine bismuth citrate for 28 days, given with clarithromycin for the first 14 days, cures 80%-85% of patients, but given with amoxicillin it cures only 74%. In developing countries resistance to metronidazole can reach 95%. An inexpensive regimen is bismuth subsalicylate (two tablets) plus furazolidone (100 mg), four times daily for 4 weeks; however, as this yields a cure rate of only 72%, this regimen is not truly cost-effective.

How Helicobacter pylori acquired its name, and how it overcomes gastric defence mechanisms.

At Royal Perth Hospital, Western Australia in April 1982, spiral bacteria were first cultured from a gastric biopsy specimen. Several important taxonomic features were identified which indicated that these bacteria represented a new genus. In October 1989 the new genus name Helicobacter was published. Helicobacter pylori overcomes gastric defence mechanisms by means of its powerful urease enzyme, by its spiral shape allowing it to penetrate mucus, by adherence to the gastric mucosa and by various mechanisms which enable it to evade the immune response.

Microbiology of Helicobacter pylori.

The new genus name Helicobacter was first published in October 1989. H. pylori is a unipolar, multiflagellate, gently spiral organism found on the human gastric mucosa, but in culture and under unfavorable conditions, coccoidal forms emerge, which may be indicative of a dormant state. The biology and metabolism of H. pylori, together with growth requirements and methods of detection in clinical specimens, are described in this article. Enzymes, hemagglutinins, and antibiotic susceptibilities of H. pylori are delineated.

Influence of soluble haemagglutinins on adherence of Helicobacter pylori to HEp-2 cells.

In a study of six laboratory strains of Helicobacter pylori, two different modes of bacterial adherence to HEp-2 cells were found. Electronmicroscopy revealed that strains known to possess soluble haemagglutinin adhered intimately to the cell surfaces, with cupping of the plasma membrane and coalescence of glycocalyces at sites of attachment. Strains of H. pylori without soluble haemagglutinin also attached, but did not induce membrane cupping or show glycocalyx fusion. Light microscopy did not distinguish between these patterns of adherence. Bacterial attachment was unaffected by pre-treatment of HEp-2 cells with neuraminidase. Exposure of the bacteria to trypsin or to colloidal bismuth subcitrate (CBS) before being added to HEp-2 cells markedly impaired bacterial adherence. This effect of CBS may contribute to the known efficacy of bismuth therapy in patients with H. pylori-related gastritis.

Helicobacter nemestrinae sp. nov., a spiral bacterium found in the stomach of a pigtailed macaque (Macaca nemestrina)

A new microaerophilic, spirally curved, rod-shaped bacterium was isolated from the gastric mucosa of a pigtailed macaque (Macaca nemestrina). The gram-negative cells of this bacterium are oxidase, catalase, and urease positive and strongly resemble Helicobacter pylori (Campylobacter pylori) cells. Like H. pylori, this organism does not metabolize glucose, does not reduce nitrate or produce indole, does not produce H2S from triple sugar iron agar, does not hydrolyze hippurate or esculin, and does not grow in the presence of 1% glycine, 1.5% salt, or 1% bile. Also like H. pylori, it is resistant to nalidixic acid and susceptible to cephalothin. However, unlike H. pylori, the colorless colonies are flat and have irregular edges. This organism has a unique cellular fatty acid composition, forming a new gas-liquid chromatography group, group K, and a distinctive DNA content (24 mol% guanine plus cytosine). It exhibits less than 10% DNA-DNA homology (as determined by the nylon filter blot method at 65 degrees C) with other members of the genus Helicobacter. Although the levels of DNA relatedness between previously described Helicobacter species and the new organism are low (less than 10%) and the difference in guanine-plus-cytosine content is large (24 versus 36 to 41 mol%), the genus Helicobacter is the only genus in which it is logical to include the organism at this time. We propose that our single strain represents a new species, Helicobacter nemestrinae, and we designate strain T81213-NTB (= ATCC 49396) as the type strain.

Soluble and cell-associated haemagglutinins of Helicobacter (Campylobacter) pylori.

Some plate-grown strains of Helicobacter (Campylobacter) pylori that were harvested into phosphate-buffered saline and left for 1 h released soluble haemagglutinins. These caused high-titre agglutination of human and guinea-pig erythrocytes, whereas chicken, sheep and bovine erythrocytes were agglutinated at various titres. Six of 10 strains which had been subcultured repeatedly did not possess soluble haemagglutinins. Slide agglutination of bacterial suspensions demarcated the strains into two groups; Group 1 gave strong agglutination with most types of erythrocyte, Group 2 did not. By microtitration assay, all Group-1 strains but only two Group-2 strains produced a soluble haemagglutinin. Cell-associated haemagglutinins were found by microtitration assay in all strains of H. pylori, but higher titres were found within Group-1 strains. The supernates of broth-grown, shaken cultures also showed the presence of soluble haemagglutinins, with higher titres for recently isolated strains. Pre-treatment of human erythrocytes with neuraminidase from Arthrobacter ureafaciens and Clostridium perfringens abolished haemagglutination by the soluble, but not by the cell-associated haemagglutinin. The soluble haemagglutinin was inhibited by sialoproteins containing predominantly the N-acetylneuraminyl (2-3) galactopyranosyl [NeuAc(2-3)Gal] structure, fetuin, glycophorin and bovine N-acetylneuraminyl-lactose (NeuAc-Lac). Transferrin and human NeuAc-Lac, which contain predominantly the N-acetylneuraminyl (2-6) galactopyranosyl [NeuAc(2-6)Gal] structure were not inhibitory. However, bovine submaxillary mucin (BSM) was strongly inhibitory; it contains several structures with sialic acid linked 2-6 to oligosaccharides. These results suggest that the soluble haemagglutinin recognises a NeuAc(2-3)Gal structure, but has high affinity for another, as yet undetermined, sialic acid-containing structure.

Intracellular vacuolization caused by the urease of Helicobacter pylori.

Tissue culture cells were exposed to supernatants of Helicobacter pylori for 24 h at 37 degrees C in the presence of various quantities of urea. In the normal human stomach the concentration of urea is less than or equal to 4 mmol/l, and in the presence of this low concentration up to 10% of Vero cells showed intracellular vacuolization. In the presence of 7.5 mmol/l urea, 25% of the cells showed vacuolization. With 30 mmol/l urea, the final pH was 7.6, indicating that vacuolization was not due to change of pH. The first report of vacuolization of tissue culture cells by H. pylori was in a system without added urea but with concentrated bacterial supernatant; 30% of H. pylori strains demonstrated a cytotoxic effect. In those experiments fetal calf serum was used; it contains 6 mmol/l urea but was used at a concentration of 10%. A urease inhibitor, acetohydroxamic acid, caused a 75% drop in the number of cells showing vacuolization, and ammonia caused vacuolization. Thus the urea of H. pylori probably causes this vacuolization.

Hydrophobic characterisation of Helicobacter (Campylobacter) pylori.

Cell-surface hydrophobicity of Helicobacter (formerly Campylobacter) pylori was tested by aqueous two-phase partitioning and hydrophobic interaction chromatography. The hydrophobicity of H. pylori greatly exceeded that of Campylobacter fetus subsp. fetus, C. jejuni and Bacillus subtilis. A partition coefficient (PC) of hydrophobicity in the two-phase system was determined for H. pylori. PC was dependent on pH and the PC value was increased by greater than 20-fold at pH 2.5. Lithium cations increased PC, indicating a net negative surface charge. The presence of urea prevented the relative loss of hydrophobicity at raised pH. Exposure of H. pylori to proteolytic enzymes reduced the ability of the bacteria to adhere to human polymorphonuclear neutrophils (PMN). These findings suggest that H. pylori possesses protein-associated hydrophobic factors that are responsible for the non-opsonic adherence to PMN cell membranes.

Microbiological aspects of Helicobacter pylori (Campylobacter pylori).

The human gastric pathogen Campylobacter pylori has recently been reclassified as Helicobacter pylori, and a related spiral bacterium found in the stomach of ferrets has been designated Helicobacter mustelae. The general microbiological features of Helicobacter pylori are delineated here, with details of phenotypic differences between Helicobacter pylori and Helicobacter mustelae; comparisons are made with Wolinella succinogenes and Campylobacter jejuni. The Helicobacter organisms possess an external glycocalyx which can be visualised by electron microscopy, and which may be involved in bacterial adherence. The finding of soluble and cell-associated haemagglutinins of Helicobacter pylori is reported. Detection of Helicobacter pylori in clinical specimens, susceptibility of the organism to antibacterial agents, and other aspects of practical and clinical significance are briefly reviewed.

The 14C-urea breath-test for the detection of gastric Campylobacter pylori infection.

A breath-test has been developed for the detection of gastric infection with Campylobacter pylori. Urea that is labelled with carbon 14 is administered to a fasting patient and the patient's breath is sampled for radioactivity over the following 30 minutes. If C. pylori is present in the patient's stomach, urease activity causes hydrolysis of the urea and the 14C is absorbed as carbon dioxide. This carbon dioxide enters the patient's bicarbonate pool and eventually is excreted in the breath. The results are expressed as a percentage of the administered dose/mmol carbon dioxide x kg body weight. Sixty-three patients who were undergoing endoscopy were studied. The radioactivity in exhaled breath which was sampled within five minutes of 14C-urea administration was attributed to the presence of urease enzyme in mouth organisms and was discounted. The time-radioactivity curves for breath samples from five to 30 minutes after the administration of 14C-urea gave an excellent separation between subjects with negative results of the examination of gastric-biopsy samples and patients with microbiological and histological evidence of infection with C. pylori. The area under the time-radioactivity curve at between five and 30 minutes after the administration of 14C-urea in 24 patients with negative microbiological results was 6.9 +/- 4.4 area units; in 35 of 39 patients with positive microbiological results, this area was greater than 40 area units. Measured against the results of the microbiological examination of gastric-biopsy samples, the sensitivity of breath-testing was 90% and the specificity was 100%. Measured against the results of histological examination for the presence of C. pylori infection, breath-testing had a sensitivity of 94% and a specificity of 93%. A positive breath-test result also correlated well (P = 0.0001) with the serological antibody test-result. The role of non-invasive tests--enzyme-linked immunosorbent assays and 14C-urea breath-testing--in the management of gastritis and peptic ulcer disease is discussed. We consider that the 14C-urea breath-test has an important role in the noninvasive confirmation of gastric infection with C. pylori and in the follow-up of patients after treatment.