Fibrous wound dressings encapsulating essential oils as natural antimicrobial agents.

Preventing infections is one of the main focuses of wound care. The colonisation of wounds by microorganisms can in fact have negative consequences on the healing process, delaying it. Here, we propose the use of essential oils as natural antimicrobial agents for cellulose-based fibrous dressings. We demonstrate the production of composite electrospun fibres that effectively encapsulate three different types of essential oils (cinnamon, lemongrass and peppermint). The fibrous scaffolds are able to inhibit the growth of Escherichia coli, even when small amounts of essential oils were used. At the same time, they are not cytotoxic, as proved by biocompatibility assays on skin cell models. The created dressings are promising as advanced biomedical devices for topical treatments.

Laser-induced disaggregation of TiO2 nanofillers for uniform nanocomposites.

Exploiting the intrinsic photosensitivity of TiO2 nanoparticles, we demonstrated how ultraviolet (UV) pulsed laser irradiation of acrylate polymer nanocomposite solutions can separate the initial clusters of these colloidal semiconductor nanorods into clearly distinct units. From the irradiated solutions, optically clear nanocomposite films are obtained which exhibit enhanced optical properties with respect to the nanocomposites obtained without previous UV treatment.

A thermodynamic and structural study of myelin basic protein in lipid membrane models.

Myelin basic protein (MBP) is a major protein of the myelin membrane in the central nervous system. It is believed to play a relevant role in the structure and function of the myelin sheath and is a candidate autoantigen in demyelinating processes such as multiple sclerosis. MBP has many features typical of soluble proteins but is capable of strongly interacting with lipids, probably via a conformation change. Its structure in the lipid membrane as well as the details of its interaction with the lipid membrane are still to be resolved. In this article we study the interaction of MBP with Langmuir films of anionic and neutral phospholipids, used as experimental models of the lipid membrane. By analyzing the equilibrium surface pressure/area isotherms of these films, we measured the protein partition coefficient between the aqueous solution and the lipid membrane, the mixing ratio between protein and lipid, and the area of the protein molecules inserted in the lipid film. The penetration depth of MBP in the lipid monolayer was evaluated by x-ray reflectivity measurements. The mixing ratio and the MBP molecular area decrease as the surface pressure increases, and at high surface pressure the protein is preferentially located at the lipid/water interface for both anionic and neutral lipids. The morphology of MBP adsorbed on lipid films was studied by atomic force microscopy. MBP forms bean-like structures and induces a lateral compaction of the lipid surface. Scattered MBP particles have also been observed. These particles, which are 2.35-nm high, 4.7-nm wide, and 13.3-nm long, could be formed by protein-lipid complexes. On the basis of their size, they could also be either single MBP molecules or pairs of c-shaped interpenetrating molecules.

Vitamin A and E deficiency and lung disease in infants with cystic fibrosis.

OBJECTIVES: Vitamin A and E deficiency is common in cystic fibrosis (CF). These vitamins have immunomodulating properties and we determined whether decreased serum vitamin A and E levels in young infants are associated with early CF lung disease and lower airway inflammation. METHODS: A post-hoc analysis was undertaken on previous data collected prospectively in 39 newly diagnosed infants identified by a newborn CF screening programme. Assessment of CF genotype, nutrition, pancreatic status, serum retinol and alpha-tocopherol levels was performed at diagnosis. Pulmonary status was determined clinically, by Brasfield chest radiographic scores and analysis of bacterial counts and inflammatory indices in bronchial lavage (BL) fluid. These assessments were repeated 12 months later. RESULTS: At diagnosis, 20 out of 39 (51%) CF infants had low serum retinol (mean (SD) 0.7 (0.3) micromol/L) and 9/38 (24%) had low alpha-tocopherol (mean (SD) 13.4 (8.4) micromol/L) levels. Dietary energy intake was related to serum retinol concentrations at diagnosis (r(2) = 0.27; P = 0.001). At 1 year, serum retinol and alpha-tocopherol levels had normalized following vitamin A and E supplementation. Respiratory symptoms, radiographic scores and BL inflammatory indices systematically deteriorated during infancy, reaching significance for free neutrophil elastase activity (9 out of 29 vs 21 out of 33; P = 0.01) and IL-8 levels (79 vs 416; P = 0.046) in BL fluid. No association was seen between serum vitamin levels at diagnosis and airway inflammatory indices at either diagnosis or 12 months later. CONCLUSION: We found in this CF birth cohort no evidence to implicate vitamin A or E deficiency in the development of lung disease or airway inflammation during infancy.

Cystic fibrosis patients and families support cross-infection measures.

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Children's Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients > or=12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person-person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Children's Hospital, Melbourne, Australia.

Pseudomonas cross-infection from cystic fibrosis patients to non-cystic fibrosis patients: implications for inpatient care of respiratory patients.

A 14-year-old boy with bronchiectasis secondary to chronic aspiration developed multiresistant Pseudomonas aeruginosa lower respiratory disease following several inpatient periods where accommodation and physiotherapy services were shared with cystic fibrosis (CF) patients known to be infected with the genetically identical strain of P. aeruginosa. Cross-infection with P. aeruginosa between CF patients and non-CF patients has not previously been described, and this finding raises significant issues relevant to the treatment of patients with non-CF suppurative lung disease.

Early airway infection, inflammation, and lung function in cystic fibrosis.

AIMS: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). METHODS: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. RESULTS: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV(0.5) compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV(0.5) 195 ml and 236 ml respectively). CONCLUSIONS: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients.

Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis.

OBJECTIVE: To determine the clinical consequences of acquiring Pseudomonas aeruginosa infection during early childhood in children with cystic fibrosis (CF). DESIGN: Prospective, observational cohort study of 56 children with CF identified by newborn screening during 1990-92. Each child underwent an annual bronchial lavage during the first 2 to 3 years of life. Clinical outcome was determined at 7 years of age. RESULTS: P aeruginosa infection was diagnosed in 24 (43%) cohort subjects. Four children died before 7 years of age, all of whom had been infected with a multi-resistant, mucoid strain of P aeruginosa (P =.04). In survivors, P aeruginosa infection was associated with significantly increased morbidity as measured by lower National Institutes of Health scores, greater variability in lung function, increased time in the hospital, and higher rates of recombinant human deoxyribonuclease therapy (P <.01). In this young CF cohort, best forced expiratory volume in 1 second was an insensitive measure of increased morbidity. CONCLUSIONS: Acquisition of P aeruginosa was common by 7 years of age in this CF birth cohort and was associated with increased morbidity and mortality. An improved disease severity score would improve the evaluation and study of early CF lung disease.

Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis.

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.

Severe viral respiratory infections in infants with cystic fibrosis.

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991-1996 were recruited into a prospective, multiple-birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL-8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls. During infancy, 31 children (39%) were hospitalized for respiratory disease and 20 (65%) cases had an etiologic agent identified. Respiratory viruses were detected in 16/31 (52%) cases, including four with simultaneous bacterial infection. Another four were infected with Staphylococcus aureus. Respiratory syncytial virus predominated and was found in seven infants. In the absence of bacteria, those with viral infections had acute onset of respiratory distress, were not treated with antibiotics, and had an uncomplicated hospital course. Compared to noninfected CF subjects and controls, infected infants had elevated BAL inflammatory indices (P < 0.01). Eleven of 31 (35%) hospitalized infants followed for 12-60 months acquired Pseudomonas aeruginosa, compared with only three of 49 (6%) subjects not hospitalized for respiratory symptoms during infancy (risk ratio 5.8, CI 1.9, 24). We conclude that respiratory viruses are important causes of hospitalization in CF infants. While viral infections were self-limited, they were accompanied by airway inflammatory changes, and admission to hospital was associated with early acquisition of Pseudomonas aeruginosa and persistent respiratory symptoms.

Lower airway inflammation in infants and young children with cystic fibrosis.

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program. These infants were divided into three groups: 10 had not experienced respiratory symptoms or received antibiotics and pathogens were absent in their BAL fluid; 18 had clear evidence of lower respiratory viral or bacterial (> or = 10(5) CFU/ml) infection; and the remaining 18 had either respiratory symptoms, taken antibiotics, or had < 10(5) CFU/ml of respiratory pathogens. Their BAL cytology, interleukin-8, and elastolytic activity were compared with those from 13 control subjects. In a longitudinal study to assess if inflammation develops or persists in the absence of infection, the results of 56 paired annual BAL specimens from 44 CF infants were grouped according to whether they showed absence, development, clearance, or persistence of infection. In newly diagnosed infants with CF, those without infection had BAL profiles comparable with control subjects while those with a lower respiratory infection had evidence of airway inflammation. In older children, the development and persistence of infection was accompanied by increased inflammatory markers, whereas these were decreased in the absence, or with the clearance, of infection. We conclude that airway inflammation follows respiratory infection and, in young children, improves when pathogens are eradicated from the airways.

Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis.

As collections of lower respiratory tract specimens from young children with cystic fibrosis (CF) are difficult, we determined whether oropharyngeal cultures predicted lower airway pathogens. During 1992-1994, 75 of 90 (83%) infants with CF diagnosed by neonatal screening had 150 simultaneous bronchoalveolar lavage (BAL) and oropharyngeal specimens collected for quantitative bacterial culture at a mean age of 17 months (range, 1-52). Ten children undergoing bronchoscopy for stridor served as controls. Total and differential cell counts and interleukin-8 concentrations were measured in BAL fluid. A subset of bacterial pathogens were typed by pulsed field gel electrophoresis. A non-linear relationship with inflammatory markers supported a diagnosis of lower airway infection when > or = 10(5) colony-forming units/ml were detected. This criterion was met in 47 (31%) BAL cultures from 37 (49%) children. Staphylococcus aureus (19%), Pseudomonas aeruginosa (11%), and Hemophilus influenzae (8%) were the major lower airway pathogens. In oropharyngeal cultures, S. aureus (47%), Escherichia coli (23%), H. influenzae (15%), and P. aeruginosa (13%) predominated. The sensitivity, specificity, and positive and negative predictive values of oropharyngeal cultures for pathogens causing lower respiratory infections were 82%, 83%, 41%, and 97%, respectively. When there was agreement between paired oropharyngeal and BAL cultures, genetic fingerprinting showed some strains of the same organism were unrelated. We conclude that oropharyngeal cultures do not reliably predict the presence of bacterial pathogens in the lower airways of young CF children.

Patients with enteric adenovirus gastroenteritis admitted to an Australian pediatric teaching hospital from 1981 to 1992.

During the period 1981 to 1992, 4,473 fecal specimens collected from children hospitalized with acute gastroenteritis at the Royal Children's Hospital, Melbourne, Australia, were examined by electron microscopy. A monoclonal antibody enzyme immunoassay for enteric adenovirus (EAd) types 40 (Ad40) and 41 (Ad41) was used when adenoviruses were visualized. Fecal samples were positive for adenovirus by both electron microscopy and enzyme immunoassay in 138 patients (3.1%). Ad40 was identified in 19 children (14%), and Ad41 was identified in 119 children (86%). These EAd were identified during each of the 12 years surveyed. EAd were present year-round, but the annual number of hospitalizations was not constant. Yearly prevalence varied from 0.7% (1981) to 6.5% (1985). This was associated with monthly fluctuations in Ad41 activity, with overall peak monthly prevalence in May (late autumn). By contrast, Ad40 numbers remained low and constant year-round. The frequency of Ad41 relative to Ad40 increased from 25% in 1981 to exceed 75% after 1983. Children admitted with EAd infection were more likely to have diarrhea for more than 5 days (P < 0.001) but less likely to be febrile or dehydrated (P < 0.05) than children with rotavirus infection. EAd are responsible for enteric symptoms of only a fraction of hospitalized children with infectious diarrhea but result in a more-protracted illness than rotavirus. Their relationship to persistent diarrhea requires further investigation.

Haptoglobin groups and transferrin subtypes in multiple myeloma.

Haptoglobin and transferrin types were determined for 27 multiple myeloma patients and a series of case controls. No association was found between haptoglobin and the disease, which confirms the findings of an earlier investigation. However, we found a significantly increased relative risk of 2.6 for TFC1C1 individuals. It is suggested that the role of transferrin in erythropoiesis and cell proliferation of both malignant and normal cells, may, at least in part, explain the association. Of additional relevance may be the suggestion that TFC1C1 individuals have higher blood iron levels than other subtypes.

Associations between the two serum proteins haptoglobin and transferrin and leukaemia.

Haptoglobin and transferrin (TF) types were determined for 134 patients with leukaemia of the four most common types: acute lymphocytic (ALL), chronic lymphocytic (CLL), acute myelocytic (AML) and chronic myelocytic leukaemia (CML). The phenotype HP1 was found to have an increased incidence in the total patient group due to an increased incidence in those with AML, ALL and CML compared with controls, but not in those with CLL. Although tests of association applied to each of the samples of the four common types of leukaemia produced no significant chi 2 values, they did indicate that the relative incidence (RI) was just under 2 for the groupings of the acute forms ALL and AML, the myelocytic forms AML and CML and for the combination of ALL, AML and CML, respectively. All these associations were statistically significant (p less than 0.05). Analysis of TF subtypes and leukaemia indicated a significantly increased frequency of TF C1C1 among leukaemia patients compared with controls (p less than 0.005). Analysis of the samples of each of the four common types suggested that while the RI was raised in all but ALL patients, the association was significant only in AML patients (p less than 0.05). However, when the two myelocytic types were combined the RI was 2.3 and the association was highly significant (p less than 0.005). No such association could be detected in the lymphocytic forms.