MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer.

BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.

Anti-malarial chemoprophylaxis following evacuation from Afghanistan.

UK forces deployed to Afghanistan between March and November are prescribed anti-malarial chemoprophylaxis (AMC). In 2007 an audit showed poor pre-injury AMC compliance and a prescription rate of 50% amongst those casualties evacuated to Role 4. We re-audited the post-deployment AMC prescribing practice for casualties from Afghanistan for the 2008 and half of the 2009 malaria season. Using the Role 4 prescribing information and communication system (PICS), a retrospective AMC search for Proguanil, Chloroquine, Doxycycline, Mefloquine and Malarone was performed on these casualties. Only five out of 305 (1.64%) inpatients were prescribed appropriate post-deployment AMC medication. Awareness of the need to prescribe AMC following evacuation remains poor, and may be improved by recording AMC compliance in field medical records and modifying the PICS software.

Field intensive care--weaning and extubation.

Injury following ballistic trauma is the most prevalent indication for providing organ system support within an ICU in the field. Following damage control surgery, postoperative ventilatory support may be required, but multiple factors may influence the indications for and duration of invasive mechanical ventilation. Ballistic trauma and surgery may trigger the systemic inflammatory response syndrome (SIRS) and are important causative factors in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, their pathophysiological effect on the respiratory system is unpredictable and variable. Invasive mechanical ventilation is associated with numerous complications and the return to spontaneous ventilation has many physiological benefits. Following trauma, shorter periods of ICU sedation-amnesia and a protocol for early weaning and extubation, may minimize complications and have a beneficial effect on their psychological recovery. In the presence of stable respiratory function, appropriate analgesia and favourable operational and transfer criteria, we believe that the prompt restoration of spontaneous ventilation and early tracheal extubation should be a clinical objective for casualties within the field ICU.

Sequential therapy vs. standard triple therapies for Helicobacter pylori infection: a meta-analysis.

BACKGROUND: As standard triple therapies of achieve unsatisfactory eradication of Helicobacter pylori, several alternative regimens have been proposed. OBJECTIVES: To systematically evaluate whether sequential treatment eradicates H. pylori infection better than standard triple therapies and compare the risk of adverse events with these two regimens. METHODS: We searched electronic databases up to February 2008 for studies evaluating the efficacy of the 10-day sequential therapy vs. standard triple regimens for eradication of H. pylori. The pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: We identified 11 randomized trials, including eight full-text manuscripts and three abstracts. Pooled analysis demonstrated clear superiority of the sequential therapy over 7-day triple regimen with an RR of 1.23 (95% CI 1.19-1.27), and over 10-day triple regimen with a RR of 1.16 (95% CI 1.10-1.23). Adverse event rates were similar. For sequential therapy vs. 7-day triple therapies, RR = 0.96, 95% CI 0.70-1.31. CONCLUSIONS: Sequential therapy was associated with a higher eradication rate of H. pylori compared with both 7-day triple regimen and 10-day triple regimen.

The early detection and management of neuropathic pain following combat injury.

The mechanism of injury on the modern battlefield results in a pattern of wounding which is associated with both nociceptive and neuropathic pain. Nociceptive pain is managed using the WHO Analgesic Ladder but neuropathic pain requires the use of co-analgesic drugs, e.g. antidepressants and anticonvulsants. This study was designed to determine the incidence of neuropathic pain within military casualties with limb injuries. From May to November 2007, 50 casualties were interviewed and assessed using the Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) over consecutive weeks. During the first week post injury, 30% of casualties had a LANSS pain score > 12, suggesting a neuropathic element to their pain. The early detection (using LANSS) and management of neuropathic pain using robust protocols represent the most effective strategy to address this significant problem.

MiR-875 can regulate the proliferation and apoptosis of non-small cell lung cancer cells via targeting SOCS2.

OBJECTIVE: To investigate the effect of miR-875 on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cancer cell line A549 and the related mechanism. PATIENTS AND METHODS: 30 paired tumor tissue and the adjacent tissue were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) has been performed to detect the expression of miR-875 in NSCLC tissues and adjacent normal tissues. Moreover, suppressor of cytokine signaling 2 (SOCS2) has been predicted as a target of miR-875, and Dual-Luciferase reporter assay has been performed to confirm the targeting relationship; furthermore, the expression of SOCS2 in tumor tissue and the adjacent tissue were compared. Next, human NSCLC cell line A549 cells were cultured and transfected with miR-875 inhibitor with or without SOCS2 siRNA, and the proliferation and apoptosis of the cells were evaluated by Cell Counting Kit (CCK-8) and flow cytometry methods. Finally, the relative protein expression of Wnt and ß-catenin were analyzed by Western blot analysis. RESULTS: MiR-875 was significantly up-regulated in NSCLC tissues compared with the adjacent tissues. SOCS2 was confirmed as a target of miR-875, and the expression of SOCS2 was markedly decreased in NSCLC tissues. Moreover, the knockdown of miR-875 inhibited the proliferation and promoted the apoptosis of A549 cells, while transfection of SOCS2 siRNA can block miR-875 inhibitor-induced anti-proliferative effects. Finally, the transfection of miR-875 inhibitor decreased the expression of Wnt and ß-catenin, and SOCS2 siRNA can reverse the effect. CONCLUSIONS: MiR-875 may regulate the proliferation and apoptosis of NSCLC cells via targeting SOCS2, suggesting that miR-875 has the potential to become a therapeutic target for the treatment in NSCLC.

Pathways through the nose for nasal intubation: a comparison of three endotracheal tubes.

BACKGROUND: In nasotracheal intubation, there are two main pathways in the nostril through which the endotracheal tube may pass. The lower pathway lies along the floor of the nose underneath the inferior turbinate. The upper pathway lies above the inferior turbinate, just below the middle turbinate. The lower pathway may be considered to be the safer route as it is located away from the middle turbinate and cribiform plate. METHODS: We conducted a randomized controlled trial comparing the frequency with which preformed, reinforced, and thermosoftened preformed tubes pass through upper and lower pathways. Ninety-two maxillofacial patients requiring nasotracheal intubation as part of their anaesthetic management were studied. Two patients were excluded from the study at endoscopy because of atypical nasal anatomy. After the induction of general anaesthesia, a standardized traditional nasal intubation was performed with a Macintosh laryngoscope, the operators endeavouring to direct the tube along the floor of the nose. Fibreoptic nasendoscopy was then performed by passing the tip of the fibrescope 2-3 cm into the nasal cavity above and below the tube, to identify the pathway taken. RESULTS: Data were analysed on 30 patients in each group. Five (16.7%) preformed tubes, 17 (56.7%) reinforced tubes, and 6 (20%) thermosoftened preformed tubes passed through the lower pathway. Significantly more reinforced tubes took the preferred pathway (P=0.001). Tubes passing through the upper pathway caused significantly more epistaxis than tubes passing through the lower pathway (P=0.003). CONCLUSIONS: Endotracheal tubes, particularly preformed tubes, frequently take the less favourable pathway during nasotracheal intubation, in spite of specific attempts to avoid this.

Using body weight as a pre-hospital fluid infusion device: the relationship between under-body position and flow rate.

This study was designed to identify the most effective underbody position when using the patient's own body weight as an infusion device. Twenty volunteers had an air-less 500 ml bag of saline located at various under-body positions. Mean pressures and flow rates through a 14G cannula were measured in vitro at room temperature. Locating the fluid bag at the buttock cleft delivered the highest mean flow rate at 135 ml/min. This underbody position may provide flow rates sufficient to achieve the clinical aim of fluid resuscitation in the military pre-hospital environment.

Airway management at floor level: a comparison of tracheal intubation using the Macintosh and Airtraq laryngoscopes.

Practitioners providing pre-hospital care during civilian practice and on military operations may be required to perform airway management and tracheal intubation at floor level. It has been shown that intubation using the Airtraq laryngoscope is easier to learn than standard Macintosh laryngoscopy. We hypothesised that the Airtraq would be easier to use and have shorter intubation times than Macintosh intubation. Sixty volunteers attending a medical conference with no prior Airtraq experience, who were skilled in pre-hospital Macintosh intubation, were recruited. Each was required to intubate an anatomically correct manikin at floor level using a Macintosh and Airtraq laryngoscope. The Airtraq was found to be superior in ease of use (VAS 30 mm, P < 0.001), had a shorter total intubation time (19.4seconds) and a higher intubation success rate (P = 0.012) than the Macintosh laryngoscope (VAS 50 mm, 20.4 seconds). Rotating the tracheal tube 90 degrees anticlockwise during loading into the guiding channel, made the Airtraq intubation easier (VAS 30 mm, P = 0.001) and faster (19.4 seconds, P < 0.001) than with standard orientation of the tube (VAS 40 mm, 25.3 seconds). Airtraq intubation may prove to be easier than Macintosh intubation, when utilised in the clinical pre-hospital setting, though randomised controlled clinical trials are required to confirm this.

Meta-analysis: The utility and safety of heparin in the treatment of active ulcerative colitis.

BACKGROUND: The use of heparin for the treatment of ulcerative colitis has been evaluated in several open and controlled trials, with varying outcomes. AIM: To evaluate the efficacy and safety of heparin as supplemental therapy compared with conventional therapy in patients with ulcerative colitis. METHODS: All randomized trials comparing heparin supplementation to conventional therapy were included from electronic databases. Statistical analysis was performed with review manager 4.2.8 (The Cochrane Collaboration, Oxford, UK). Sub-analysis and sensitivity analysis were also performed. RESULTS: Eight randomized-controlled trials, investigating a total of 454 participants, met the inclusion criteria. The odds ratio (OR) for the efficacy of heparin supplementation vs. conventional therapy was 0.78 (95% CI = 0.50-1.21). Few serious adverse events were observed. The OR for the efficacy of unfractionated heparin and low-molecular-weight heparin vs. conventional therapy was 0.26 (95% CI = 0.07-0.93) and 0.92 (95% CI = 0.57-1.47), respectively. The OR for the efficacy of heparin vs. conventional therapy with placebo was 0.87 (95% CI = 0.53-1.44). CONCLUSIONS: Our meta-analysis suggests that administration of heparin in patients with ulcerative colitis is safe, but no additive benefit over conventional therapy is indicated.

Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy.

BACKGROUND: Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies. AIM: To systematically evaluate whether adding probiotics to anti-H. pylori regimens could improve eradication rates and reduce side effects during anti-H. pylori treatment. METHODS: Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti-H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed. RESULTS: We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5-86.7%) and 74.8% (95% CI = 71.1-78.5%) for patients with or without probiotics by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34-2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0-29.4%) and 38.5% (95% CI = 33.0-44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30-0.66). CONCLUSIONS: Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.

The management of difficult direct laryngoscopy and intubation in a field hospital: an alternative to fibreoptic endoscopy.

Fibreoptic endoscopy and intubation continues to be recommended in guidelines for the management of difficult airways. Since fibrescopes are unavailable within United Kingdom field hospitals, an alternative is needed. The Airtraq optical laryngoscope is a versatile, inexpensive, single-use option, which could readily fill this void. It is easy to use and provides a full view of the glottis when direct laryngoscopy has failed. Its introduction will reinforce existing difficult airway equipment and simplify the management of 'can ventilate - can't intubate' patients.

Assessing airway patency and breathing in NBC category 4R--the RG method.

INTRODUCTION: Confirming airway patency and the presence of breathing has significant limitations when both the casualty and medical personnel are in NBC category 4R. In casualties with limited signs of breathing, IPE may adversely affect the efficiency of clinical assessment, and when the triage sieve is used this could result in the misdiagnosis of death. This manuscript describes and evaluates the Respirator-Glove (RG) method, of assessing airway patency and breathing in NBC category 4R. METHODS: A medical examination glove was fitted over the primary speech module of the S10 NBC respirator of a volunteer casualty dressed in 4R. Two groups were studied; the first used an intact glove the second used a glove minus one finger. Breathing patterns A, B and C, representing normal breathing, hypoventilation and apnoea respectively, were randomly performed by the casualty for 15 seconds. A blinded observer recorded the glove inflation and movement and using these signs determined if breathing was present. RESULTS: All of the randomly performed breathing pattern simulations were correctly identified in both groups, with glove inflation only occurring during exhalation. In the perforated glove group, the large expiratory air leak through the hole limited the development of continuous positive airway pressure and the respirator seal was maintained. In the non-perforated glove group the respirator seal was compromised. No difficulty was encountered attaching the gloves to the respirator speech module. DISCUSSION: As an aid to clinical examination, the Respirator-Glove (RG) method provides a reproducible visual assessment of airway patency and spontaneous ventilation in unconscious 4R casualties. It can be utilised at any point in the evacuation chain, may improve the identification of T1 casualties and could reduce the risk of death being misdiagnosed. The efficiency of clinical assessment in 4R will improve by introducing the RG method into CBRN medical training programmes.