Silica‐coated vesicles have been produced by the deposition of silica onto unilamellar vesicles from aqueous solution for the first time. The quaternary ammonium surface of the surfactant vesicles is receptive to silica and facilitates deposition of up to 5–10 nm of it. The “petrified” vesicles are stable to dehydration and can be visualized by conventional TEM (see Figure) without additional staining agents.
We report the case of a cystic fibrosis patient colonized with a smooth-morphotype form of Mycobacterium abscessus who developed acute respiratory failure with the emergence of an isogenic rough (R) variant while he was recovering from peritonitis-induced shock. This report emphasizes the role of R forms in severe M. abscessus infections. (Fig. 1). CASE REPORTIn December 2003, the patient was admitted to the emergency unit of Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France, with a colic perforation and diffuse peritonitis secondary to a stercolith. Septic shock with severe hypoxemia occurred on day 1, requiring mechanical ventilation, inotropic adrenaline support, and treatment with combined antibiotics (ceftazidime, vancomycin, tobramycin, and ornidazole), hydrocortisone hemisuccinate, and drotrecogin alpha. Laboratory parameters showed lymphopenia (absolute lymphocyte count, 1,060/mm 3 ) and raised serum transaminase levels (alanine aminotransferase level, 80 IU/liter, three times the upper limit of the normal range). The patient's clinical status slowly improved. Bronchial aspiration performed on day 6 yielded A. fumigatus and a rough (R) variant of M. abscessus (M. abscessus CF01-R). Positive A. fumigatus antigenemia results led to the initiation of antifungal therapy on day 9.Unexpectedly, septic shock recurred on day 11. Severe respiratory failure was present (ratio of the partial pressure of oxygen in arterial blood to the fraction of inspired oxygen [PaO 2 /FiO 2 index], 190), associated with patchy alveolar consolidation (Fig. 2). A surgical lung biopsy (right thoracotomy) was performed on day 12: the biopsy specimen culture was positive for an R-morphotype isolate of M. abscessus as the sole pathogen, with concordant histology showing a granulomatous epithelioid reaction with giant cells in areas of peribronchovascular fibrosis and multiple microabscesses. Antibiotic therapy was shifted empirically to imipenem-cilastin, amikacin, and clarithromycin on day 13. Bronchial aspiration performed on day 13 yielded results similar to those from the lung biopsy, thus confirming the diagnosis of M. abscessus respiratory infection (7). Antibiotic susceptibility testing performed on several isolated strains (Institut Pasteur, Centre National de Références, Paris, France) showed the strains to be susceptible to the prescribed regimen. Bronchoalveolar lavage on day 32 still yielded an R-morphotype isolate of M. abscessus. Nebulized amikacin was added to the systemic anti-M. abscessus therapy on day 56. The patient became apyrexial on day 77, and mechanical ventilation was stopped on day 83. The patient was discharged on day 128 (April 2004) under a regimen of clarithromycin monotherapy, which was maintained until April 2005. Sputum samples remained repeatedly positive for M. abscessus (R form) throughout treatment (Fig. 1) (24) and multilocus sequence typing (data not shown) confirmed the clonal nature of the isolates of different morphotypes (Fig. 3). These results established the persistence ...
Aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillus bronchitis in CF subjects. We hypothesized that A. fumigatus isolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection of A. fumigatus. MICs of A. fumigatus isolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method. A. fumigatus was isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. Reduced A. fumigatus susceptibility to itraconazole (MIC, >2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, >0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, >2 mg/liter). Mutations in the cyp51A gene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistant A. fumigatus isolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistant A. fumigatus isolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.
Pain is a potential complication of cystic fibrosis (CF), but its consequences in daily life and other issues of pain management are not yet clearly understood. We undertook a comparative study of children and adults with CF to assess the prevalence of pain symptoms, their characteristics and treatment, their impact on daily quality of life, and the occurrence of procedural pain. The study included 73 children (1-18 years) and 110 adults (18-52 years); 59% of the children and 89% of the adults reported at least one episode of pain during the previous month. Pain was significantly more intense and lasted significantly longer among adults, but its rate and recurrence did not differ significantly between the two populations and were not related to the severity of CF. The most prevalent locations were the abdomen for children, and the back, head, and chest for adults. Although pain significantly limited physical activity, only 15% of patients reported that it caused absenteeism, and 27% reported that it negatively affected their family life. The mean pain intensity rates on a visual analog scale for the episode that had caused the greatest pain during the past month were 4.9 (2) (mean [SD]) for children and 6 (2) for adults; however, only 40% and 50%, respectively, of those with pain reported the use of analgesic treatment, mainly paracetamol (acetaminophen). At least one episode of procedural pain during the previous month was reported by 85% of children and 78% of adults. Our study demonstrates the high incidence of undertreated pain in CF patients throughout their lives.
Clinical condition of CF patients with MSSA only or MRSA only appeared similar, whereas MRSA/PA patients had more severe respiratory function than MSSA/PA patients. In CF patients, MRSA might be more deleterious than MSSA only when associated with PA.
Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous ΔF508+/+CF patients versus non‐CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non‐CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0·001). The number of T lymphocytes was higher at the CF distal level (P = 0·035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0·033) in the CF surface epithelium, which overexpressed ICAM‐1 but not VCAM‐1 and E‐selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.
Background: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. Methods: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. Conclusions: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.Cystic fibrosis (CF, MIM 219700) is one of the most frequent life shortening autosomal recessive diseases, characterised in its classical form by chronic pulmonary obstruction and infections, pancreatic insufficiency, male infertility and elevated sweat chloride concentrations.
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