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We hypothesized that in adults with cystic fibrosis, the acquisition of a new strain of Pseudomonas aeruginosa may be associated with a pulmonary exacerbation. Eighty-four patients who were chronically infected with P. aeruginosa were prospectively followed from eight centers over a 26-month period. Patients had sputum cultures performed every 3 months while clinically stable and at the time of an exacerbation. Forty patients (48%) had an exacerbation requiring intravenous antibiotics during the study period, and in 36 of these patients, their P. aeruginosa isolates were genetically typeable by pulsed-field gel electrophoresis. In 34 of the 36 patients (94%), P. aeruginosa recovered during clinical stability and at exacerbation were of the same genotype. In only two patients (6%; 95% confidence interval, 0-18%) was a new P. aeruginosa clone cultured during an exacerbation that had not been cultured during clinical stability. There were no significant differences in antibiotic susceptibilities, measured as mean minimal inhibitory concentrations, for isolates retrieved during clinically stable periods compared with isolates retrieved during exacerbations. We conclude that for the majority of adult patients with cystic fibrosis a new pulmonary exacerbation is not caused by the acquisition of a new strain of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Abstract Introduction Vertebral artery dissection has become increasingly recognized as an important cause of stroke. It usually presents with posterior headache or neck pain followed within hours or days by signs of posterior circulation stroke. To the best of our knowledge, the clinical presentation of a Brown-Séquard syndrome with a vertebral artery dissection has been reported only once before. Case presentation An otherwise healthy 35-year-old man presented with acute left-sided weakness. He had experienced left-sided posterior neck pain after a 4-hour flight 4 weeks previously. Physical examination was consistent with a left Brown-Séquard syndrome. Magnetic resonance angiography showed evidence of left vertebral artery dissection. He improved after therapy with anticoagulants. Conclusion We report a case of an unusual presentation of a relatively uncommon condition. This diagnosis should be considered early in relatively young patients with stroke-like symptoms or unexplained neck pain, because missing a dissection can result in adverse outcomes.

Background: Endoscopic procedures performed after-hours often require therapeutic interventions that are technically demanding for the endoscopist. The aim of this position paper is to provide guidance on the minimum standard of equipment that should be available on a mobile endoscopy cart for provision of a safe and effective after-hours emergency endoscopy service. The guidance is based on consensus among academic and community gastroenterologists in Canada., Methods: A modified Delphi process was used to establish consensus among 9 participants. A list of statements was prepared by an expert panel of endoscopists. The statements were divided into three broad sections for what should be on an after-hours endoscopy cart including medications, nonendoscopic tools and therapeutic/diagnostic equipment. Consensus for being on the endoscopy cart was achieved when 75% or more of voting members indicated 'agree'., Results: For nonendoscopic tools, there was agreement for having sterile saline, sterile water, endoscope lubricant, various syringes, bite blocks (paediatric and adult size), a water pump with foot peddle, formalin jars for biopsy specimens, digital photo and printing capability and an overtube. For medications, there was agreement for having hyoscine butylbromide and epinephrine on the cart. For therapeutic/diagnostic tools, there was agreement for having biopsy forceps (standard and jumbo), polypectomy snares, sclerotherapy needles and agent (for a variceal bleed), band ligation kit, multipolar electrocautery probes, heater probe catheter, endoscopic clips, hemostatic powder and retrieval devices., Interpretation: This position paper provides guidance on the minimum standard of items that should be on an after-hours endoscopy cart. Standardization of equipment may help improve safety and quality of after-hours endoscopic procedures., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Background: The incorporation of abstracts from scientific meetings into systematic reviews and practice guidelines may reduce publication bias and delays in implementing therapeutic interventions., Methods: All abstracts of Phase III randomized controlled trials in inflammatory bowel disease accepted at Digestive Disease Week (1998-2003) were identified. MedLine, PubMed (1997-current), EMBASE, and Google Scholar were searched for subsequent full publications. Characteristics of methodology and outcomes of the abstracts and articles were analyzed., Results: The 5-year cumulative publication rate of the 82 eligible abstracts was 78%. Abstracts that presented negative results were less likely to be published than those with positive findings, particularly after the first 2 years (hazard ratio 6.45; 95% confidence interval [CI]: 2.22-18.7) with 5-year cumulative publication rates of (50% versus 91%, respectively, P < 0.001). The median time to publication was longer for negative than positive abstracts (58 versus 26 months, P < 0.001). Abstracts selected for oral presentation were more likely to be published than poster presentations (89% versus 69%; P = 0.03). A change in primary outcome results was observed in 28% (n = 18) of abstracts compared to that in the final publication, and 6% (n = 4) had a statistically significant change resulting in a change of study conclusions., Conclusions: Our findings suggest that the use of abstract data would enable detection and mitigation of publication bias. Improving the uniformity and quality of abstract reporting of randomized clinical trials at scientific meetings may facilitate their incorporation in practice guidelines and systematic reviews.

Background: Patients with ulcerative colitis (UC) are at high risk of colonic dysplasia. Therefore, surveillance colonoscopy to detect early dysplasia has been endorsed by many professional organizations., Objectives: To determine whether gastroenterologists at Hamilton Health Sciences (Hamilton, Ontario) adhere to recommendations for UC surveillance issued by the Canadian Association of Gastroenterology and to retrospectively assess the incidence and type of dysplasia found and the subsequent outcome of patients with dysplasia (ie, colorectal cancer [CRC], colectomy, dysplasia recurrence)., Methods: A retrospective chart review of all patients with UC undergoing colonoscopy screening at Hamilton Health Sciences from January 1980 to January 2005, was performed. Patients were classified by the extent of colonic disease: limited left-sided colitis (LSC), pancolitis and any disease extent with concurrent primary sclerosing cholangitis., Results: A total of 141 patients fulfilled eligibility criteria. They underwent 921 endoscopies, including 453 for surveillance, which were performed by 20 endoscopists. Overall, screening was performed on 90% of patients, and surveillance at the appropriate time in 74%. There was a statistically significant increase in the mean number of biopsies per colonoscopy after the guidelines were published (P<0.01 for all categories). Colonic dysplasia was detected in 24 of 141 patients (17.0%), with 17 of 24 (70.8%) found at surveillance. Two patients (8.3%) had CRC successfully treated. The average age of patients with dysplasia was 56.1 years, with a mean disease duration of 10.9 years in LSC versus 11.8 years in pancolitis (P not significant). Colectomy was not recommended for any patient with flat dysplasia. No patients progressed to high-grade dysplasia or CRC. Patients with pancolitis had a higher incidence of neoplasia (21% [18 of 86]) than patients with LSC (12% [6 of 49]; P=0.24). Forty-one patients (29.5%) had at least one hyperplastic or inflammatory polyp., Conclusions: For the majority of patients who underwent surveillance colonoscopies, their procedures were performed within the recommended time intervals, and biopsy compliance has improved. Dysplasia tended to arise after approximately 10 years of disease duration and in middle age, with flat dysplasia being rare. Interventions resulted in no dysplasia progressing to CRC, implying successful prevention.

Background and Aim: Current guidelines for upper gastrointestinal endoscopy (UGIE) advise at least 6-8 h fasting for solids and 4-h fasting for liquids. We aimed to determine whether a 6-h fast for solids and one-hour fast for water prior to UGIE gives good endoscopic vision and less patient discomfort., Methods: 128 patients referred for UGIE were given a standard meal 6 h before endoscopy, and then randomized to either nil by mouth for 6 h (group A, n = 65) or allowed to drink water for up to one hour prior to endoscopy (group B, n = 63). Before endoscopy patients were requested to indicate discomfort due to fasting on a visual analog scale. Fluid in the gastric fundus was aspirated, when present, for volume and pH measurements, and endoscopic vision was graded., Results: 53 patients in group A and 43 patients in group B completed the study. Discomfort was significantly lower in group B than group A (P < 0.0001). Endoscopic vision was good in all 53 patients in group A and 40 in group B, and average in 3 patients in group B. Fluid in the gastric fundus was noted in 11 patients in group A and 16 in group B, but there were no significant differences in volume or pH between groups. There were no complications attributable to endoscopy in either group., Conclusions: A 6-h fast for solids and a 1-h fast for water prior to UGIE gives good endoscopic vision, and causes minimum patient discomfort.

The present authors hypothesised that bronchoscopy with protected specimen brush may sample biofilm-forming bacteria adherent to the airway wall, whereas traditional sputum collection may not. Pseudomonas aeruginosa obtained from sputum, bronchoalveolar lavage and protected brush, taken from the right upper lung bronchus of 12 adult patients with cystic fibrosis, were compared. Retrieved bacteria were genotyped, and grown in planktonic cultures and as biofilms, and susceptibilities to individual antibiotics and to antibiotic combinations were determined. Bacterial cultures obtained using bronchoscopy did not yield any new strains of bacteria that were not also found in sputum. A total of 10 patients (83%) had a single strain of P. aeruginosa found using sputum, bronchoalveolar lavage and protected brush techniques, and two patients (17%) had two strains recovered in sputum, but only one strain was recovered using bronchoscopic techniques. Susceptibility to single antibiotics and to antibiotic combinations were not different between planktonically or biofilm-grown bacteria derived from sputum, as compared to those obtained by bronchoalveolar lavage and protected brush. In conclusion, sputum collection provides as much information as bronchoscopy for characterising the genotype and antibiotic susceptibility of chronic Pseudomonas aeruginosa infection in patients with stable cystic fibrosis.

Adenoviruses (Ads) have shown great utility as vectors for the delivery of genes to mammalian cells, partly because of their ability to infect a wide range of different cell types independent of the replicative state of the cell. However, Ads do not transduce mature muscle efficiently because of low levels of the natural viral primary receptor, the coxsackie virus and adenovirus receptor, on the surface of adult muscle cells. In this study, we have addressed whether incorporation of polylysine [p(K)] or arginine-glycine-aspartic acid (RGD) placed in the H-I loop of the adenoviral fiber protein can improve helper-dependent Ad vector (hdAd) transduction of mature muscle cells. We show that incorporation of the p(K) motif into the fiber of early region 1 (E1)-deleted Ad results in enhanced transduction of undifferentiated and differentiated C2C12 cells relative to a virus, containing a wild-type fiber (12- and 21-fold enhancement, respectively). Incorporation of the RGD motif resulted in only a 60-70% increase in transduction efficiency in these cells. The two fiber modifications were then incorporated into helper viruses for use in the Cre-lox system for generating hdAd, and the resulting retargeted Ad vectors, which encoded the beta-galactosidase reporter gene (beta-Gal), demonstrated enhanced transduction of C2C12 cells in culture. Although hdAdpK also showed enhanced infection of mature mouse muscle in vivo, hdAdRGD did not. All hdAd vectors elicited only minor anti-Ad immune responses, compared with an E1-deleted control vector, but each vector elicited strong anti-beta-Gal immunoreactivity. Our results demonstrate that hdAd with modified cell tropism can be generated efficiently and, in the case of polylysine-modified hdAd, can lead to improved transduction of adult muscle cells in vivo.

Smac/DIABLO is a mitochondrial protein that is proteolytically processed and released during apoptosis along with cytochrome c and other proapoptotic factors. Once in the cytosol, Smac protein binds to inhibitors of apoptosis (IAP) proteins and disrupts the ability of the IAPs to inhibit caspases 3, 7, and 9. The requirement for mitochondrial processing and release has complicated efforts to delineate the effect of Smac overexpression and IAP inhibition on cell death processes. In this report, we document a novel expression system using ubiquitin fusions to express mature, biologically active Smac in the cytosol of transfected cells. Processing of the ubiquitin-Smac fusions is rapid and complete and generates mature Smac protein initiating correctly with the Ala-Val-Pro-Ile tetrapeptide sequence that is required for proper function. The biological activity of this exogenous protein was demonstrated by its interaction with X-linked IAP, one of the most potent of the IAPs. The presence of mature Smac was not sufficient to trigger apoptosis of healthy cells. However, cells with excess Smac protein were greatly sensitized to apoptotic triggers such as etoposide exposure. Cancer cells typically display deregulated apoptotic pathways, including Bcl2 overexpression, thereby suppressing the release of cytochrome c and Smac. The ability to circumvent the requirement for mitochondrial processing and release is critical to developing Smac as a possible gene therapy payload in cancer chemosensitization.

Epitope mapping studies and the determination of the structure to 1.8 A resolution have been carried out for the antigen-binding fragment MR1 in complex with peptide antigen. MR1 is specific for the novel fusion junction of the mutant epidermal growth factor receptor EGFRvIII and has been reported to have a high degree of specificity for the mutant EGFRvIII over the wild-type EGF receptor. The structure of the complex shows that the peptide antigen residue side-chains found by epitope mapping studies to be critical for recognition are accommodated in pockets on the surface of the Fv. However, the most distinctive portion of the peptide antigen, the novel fusion glycine residue, makes no contact to the Fv and does not contribute directly to the epitope. The specificity of MR1 lies in the ability of this glycine residue to assume the restricted conformation needed to form a type II' beta-hairpin turn more easily, and demonstrates that a peptide antigen can be used to generate a conformational epitope., (Copyright 2001 Academic Press.)