Although not as prevalent as Pseudomonas aeruginosa, Pseudomonas cepacia is another opportunistic pathogen which colonizes the lungs of at least some patients with cystic fibrosis. A subgroup of these patients exhibits the "cepacia syndrome", i.e., a rapid clinical deterioration and death within one year. To investigate potential early sites of bacterial attachment, we have measured the specific binding of P. cepacia isolates from cystic fibrosis (CF) sputa to both CF and non-CF mucins purified from respiratory and intestinal secretions, respectively. As shown in microtiter binding assays, clinical isolates from 19/22 patients were found to bind to both mucins, with the highest specific binding exhibited by isolates from eight patients, seven of whom later died with the cepacia syndrome. No differences were observed in the binding capacity of the two (CF versus non-CF) mucins. Binding was specific, saturable, and not influenced by tetramethylurea, a disruptor of hydrophobic associations. Individual sugars were ineffective as hapten inhibitors, as were several lectins. Mucins treated by reduction/alkylation or chloroform/methanol extraction showed enhanced bacterial binding, findings which were attributed to exposure of underlying binding sites. Deglycosylation procedures indicated that mucin receptors for P. cepacia include N-acetylglucosamine and N-acetylgalactosamine, probably linked together as part of core oligosaccharide structures. P. cepacia isolates also bound to buccal epithelial cells, and mucin partially inhibited the binding of those isolates of P. cepacia that also had the ability to bind to mucin. We speculate that specific binding of P. cepacia to secreted mucins may be an early step in the pathogenesis of the cepacia syndrome.
Objective. Cystic fibrosis (CF) has variable clinical presentation. Disease severity is partially associated with the type of mutation. The aim of this study was to report genotype-phenotype analysis of the G85E mutation. Patients. The phenotype of 12 patients (8 were from the same extended family, and 5 of them were siblings from 2 families) carrying at least one copy of the G85E mutation was evaluated and compared with the phenotype of 40 patients carrying the two severe mutations, W1282X and/or ΔF508 (group 1), and with 20 patients carrying the splicing mutation, 3849+10kb C->T, which was found to be associated with milder disease (group 2). Results. A high phenotypic variability was found among the patients carrying the G85E mutation. This high variability was found among patients carrying the same genotype and among siblings. All the studied chromosomes carrying the G85E mutation had the 7T variant in the polythymidine tract at the branch/acceptor site in intron 8. Of the G85E patients, 25% had pancreatic sufficiency and none had meconium ileus, compared with 0% and 32%, respectively, of patients from group 1, and 80% and 0%, respectively, from group 2. Two patients carrying the G85E mutation had sweat chloride levels <60 mmol/L whereas all the others had typically elevated levels >80 mmol/L. Compared with group 2, patients carrying the G85E mutation were diagnosed at an earlier age and had higher sweat chloride levels, with mean values similar to group 1 but significantly more variable. Forced expiratory volume in 1 second (FEV1) was similar in the three groups, with no differences in the slope or in age-adjusted mean values of FEV1. The levels of transcripts lacking exon 9 transcribed from the G85E allele measured in 3 patients were 55%, 49%, and 35% and their FEV1 values were 82%, 83%, and 50% predicated, respectively. Conclusions. The G85E mutation shows variable clinical presentation in all clinical parameters. This variability could be seen among patients carrying on the other chromosome the same CFTR mutation, and also among siblings. This variability is not associated with the level of exon 9 skipping. Thus, the G85E mutation cannot be classified either as a severe or as a mild mutation.
We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn9s disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). The mean height velocity of patients with growth potential increased from 2.4 (2.3) cm per year preoperatively to 8.1 (3.4) cm per year in the first postoperative year (p=0.0001). These results support an early approach to surgery in the management of ileal Crohn9s disease with or without caecal or right colonic involvement, especially when complicated by persistent growth failure. The higher recurrence rates in more diffuse ileocolonic disease emphasise the need for alternative treatment strategies in these children.
Purpose: The purpose of this study was to compare the effectiveness of the Flutter device (Axcan Scandipharm Inc., Birmingham, AL) with that of the PEP Mask (Astra Tech AB, Molndal, Sweden) in the treatment of adults with cystic fibrosis (CF). Methods: Forty-two adults (mean age 29 F 8.4 years) were recruited from the Adult Cystic Fibrosis Program at St. Michael's Hospital and were randomly assigned to airway clearance treatment with either the Flutter device or the PEP Mask. Pulmonary function tests, the Quality of Well-Being Scale (QWB), and the Chronic Respiratory Disease Questionnaire (CRQ) were administered 1 month postrecruitment and every 3 months thereafter for 13 months. Results: Using linear regression, the mean slope or annual rate of change of forced expiratory volume in 1 second (FEV1) percent predicted was 2.0 (F 8.1) for the Flutter group and 4.2 (F 8.0) for the PEP group (p=.4). There were no significant between-group differences in the slopes of the QWB (p=.3) or CRQ (p = 1.0) total scores. The power to detect differences was low (0.137). Conclusions: When comparing the Flutter device and the PEP Mask in the treatment of adults with CF over a 13-month period, there were no significant differences in pulmonary function or health-related quality of life. A much larger sample would be needed to conclude with confidence that there were no between-group differences. Therefore, additional research is needed to further examine the effectiveness of the Flutter device and the PEP Mask.
BACKGROUND--Liquid diets given enterally combined with "bowel rest9 are efficacious in the treatment of active Crohn9s disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS--This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn9s disease in children. PATIENTS AND METHODS--Children and adolescents with active Crohn9s disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS--Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn9s disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn9s Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION--After successful treatment of active Crohn9s disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.
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