The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

Background  

Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported.     

Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

What consideration should be given to Helicobacter pylori in treating nonsteroidal anti-inflammatory drug ulcers?

Although Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) both cause peptic ulcers, they do so by different mechanisms so any interaction is not necessarily harmful. H. pylori has been shown to enhance gastric mucosal prostaglandin synthesis, while NSAIDs suppress it Pragmatically, there is no compelling evidence in favour of H. pylori eradication in all patients who take NSAIDs. As a broad generalisation, in therapeutic studies of NSAID users, those who have no ulcer at trial entry are more prone to ulcer development if they are H. pylori-positive. By contrast, in those who have ulcers at baseline, H. pylori-positive individuals are less likely to develop ulcers, particularly if taking acid-suppressive therapy. Trials of H. pylori eradication therapy tend to replicate this dichotomy. In one study of patients starting NSAIDs for the first time, with no ulcer history and no baseline ulcer, use of bismuth-based eradication therapy was associated with a lower incidence of gastric ulcer at 2 months. Conversely, in a study of patients with endoscopically proven ulcers and/or troublesome dyspepsia, proton pump inhibitor based eradication treatment had no effect on outcome (of acid suppression) over 6 months. H. pylori eradication has been associated with significantly slower healing of gastric ulcers compared with patients who did not undergo eradication. However, the effect of H. pylori eradication on healing of NSAID-associated duodenal ulcers does not appear to be so dramatic, and limited evidence suggests that it may be possible to prevent H. pylori-associated duodenal ulcer by eradicating the infection. An evidence-based approach to treatment would suggest that NSAID users should undergo H. pylori eradication therapy if they have a duodenal ulcer, whether or not they continue NSAIDs. Because COX-2 inhibitors appear not to be ulcerogenic, management of H. pylori in patients taking these drugs can be based upon the same risk assessment as in patients not taking anti-arthritis drugs. H. pylori eradication should not be used universally or in high-risk gastric ulcer patients who require management with acid suppression.     

Educating and Training a Workforce for Nutrition in a Post-2015 World

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals.     

Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.     

Treatment of reflux oesophagitis with trimoprostil

Forty-four patients with symptomatic endoscopically proven mild to moderate reflux oesophagitis were enrolled in a single-centre, double-blind, clinical trial comparing trimoprostil 750 micrograms taken 4 times daily with placebo. Patients treated with trimoprostil but not placebo experienced a significant reduction in the frequency (p less than 0.005) and duration (p less than 0.02) of heartburn. Both groups reported a reduction in the severity of heartburn and resulting sleep disturbance during the trial, but differences between them in these respects at the end of the trial did not reach statistical significance. There was a significant reduction in the severity of oesophagitis seen at endoscopy after treatment with trimoprostil (p less than 0.01) but not placebo. Trimoprostil was well tolerated and appears to be more effective than placebo in the treatment of mild to moderate symptomatic reflux oesophagitis. Although this agent's mode of action was not investigated, we speculate that it may be protective to human squamous oesophageal mucosa.     

Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group

OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design). METHODS: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively. RESULTS: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. CONCLUSION: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.