Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation.

Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst. The respiratory burst activity of neutrophils isolated from stable DeltaF508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR. The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates. CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.

Variable antibiotic susceptibility in populations of Pseudomonas aeruginosa infecting patients with bronchiectasis.

OBJECTIVES: To investigate variability in colony morphology and antibiotic susceptibility in populations of Pseudomonas aeruginosa from sputa of patients with bronchiectasis without cystic fibrosis (CF) compared with P. aeruginosa isolated from patients with CF, and from other infections as controls. METHODS: P. aeruginosa was cultured from 31 patients with non-CF bronchiectasis, 24 with CF, 7 ventilated patients and 9 skin swabs. Four colonies of each morphotype of P. aeruginosa were tested for susceptibility to 12 antibiotics by disc diffusion. The variability in susceptibility between the isolates in each patient's population of P. aeruginosa was investigated. RESULTS: The classic morphotype of P. aeruginosa was cultured from control samples with an average variation in zone size of 2 mm (range 0-4 mm) for the four colonies tested. Non-CF bronchiectasis sputa contained 1-3 colonial morphotypes of P. aeruginosa; the average difference between the largest and smallest zone sizes found in all examples of the morphotypes present in each sample varied from 3 mm (1-9 mm) for colistin to 8 mm (0-24 mm) for piperacillin/tazobactam. CF sputa contained 2-6 morphotypes of P. aeruginosa with a wider variation of susceptibility. There was variation between bacteria of the same morphotype from non-CF bronchiectasis and CF sputa. CONCLUSIONS: Phenotypic variation in colonial form and antibiotic susceptibility is not unique to chronic infection in CF but is also found in non-CF bronchiectasis. This questions the use of current susceptibility testing methods for the complex populations of bacteria found in chronic lung infection.

Microbiological evaluation of UV disinfection effectiveness in a specialist cystic fibrosis clinic.

The aim of the study was to evaluate the impact of manual cleaning and manual cleaning followed by Ultraviolet-C disinfection on the colony forming units of bacteria retrievable from equipment and surfaces within clinic rooms following a CF outpatient encounter. While UV disinfection has proven to be effective within general healthcare settings, it has not been evaluated in a CF centre. Microbiological sampling was performed following outpatient encounters involving 11 adult patients with CF and chronic infection with P.aeruginosa, MRSA or E. coli ESBL. The results of this study suggest that manual cleaning followed by UV-C disinfection is more effective than manual cleaning alone at reducing environmental contamination within a CF clinic and that UV-C isinfection is likely to reduce the risk of fomite transmission in the CF outpatient setting.

Clostridium difficile pancolitis in adults with cystic fibrosis.

We report three cases of Clostridium difficile pancolitis in adults with cystic fibrosis (CF) in whom the presenting symptoms were atypical. All three required treatment with systemic steroids, in addition to oral vancomycin and metronidazole to achieve resolution of the colitis. This experience suggests that C. difficile colitis should be considered in individuals with CF presenting with non-specific abdominal symptoms.

A single centre experience of liver disease in adults with cystic fibrosis 1995-2006.

BACKGROUND: Liver disease is an important cause of death in adults with cystic fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices and timely evaluation for liver transplantation are important. METHODS: Adults with CF underwent annual review. Abnormalities of liver function tests or ultrasound prompted referral to the CF/liver clinic where UDCA was commenced. Endoscopic surveillance for varices was undertaken if ultrasound suggested portal hypertension. RESULTS: 154 patients were followed for a median 5 years. 43 had significant liver disease, 29 had cirrhosis with portal hypertension and 14 had ultrasound evidence of cirrhosis without portal hypertension. All started UDCA. Only one patient developed chronic liver failure and none required liver transplantation. 27 underwent endoscopy; 1 required variceal banding, the others had insignificant varices. Ultrasound was normal in 97 patients while five had steatosis; nine further patients had splenomegaly but no other evidence of portal hypertension. Neither spleen size nor platelet count correlated with portal hypertension. CONCLUSIONS: Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.

Bone histomorphometry in adult patients with cystic fibrosis.

STUDY OBJECTIVE: Low bone mineral density is a common complication of cystic fibrosis (CF), and recent studies have implicated vitamin D insufficiency as a significant etiologic factor. The aim of this study was to establish whether there was bone biopsy evidence of vitamin D deficiency osteomalacia in patients with CF and to document the general histomorphometric characteristics of CF bone. PATIENTS AND METHODS: A retrospective descriptive and histomorphometric study of postmortem L2/L3 vertebral bone biopsy specimens was undertaken on tissue from 11 posttransplant CF patients and 4 nontransplanted CF patients. Control data were derived from postmortem bone specimens from 15 young adults. RESULTS: Bone from all CF patients was characterized by severe osteopenia in both trabecular and cortical bone. At the cellular level, there was decreased osteoblastic and increased osteoclastic activity. The reduction in osteoblastic activity was due to both a decrease in osteoblast number and a decrease in the biosynthetic potential of osteoblasts. The osteoclastic changes were due to an increase in the number of osteoclasts. The increase in osteoclasis and the uncoupling of osteoblastic and osteoclastic activity resulted in an increase in resorptive surfaces. Although there were few significant differences between the transplanted and nontransplanted CF groups, both cortical and trabecular bone mass tended to be lower after transplantation. None of the CF undecalcified biopsy specimens showed osteoid parameters characteristic of vitamin D deficiency osteomalacia. CONCLUSIONS: CF patients have an unusual and complex pattern of cellular changes within bone that are not typical of vitamin D deficiency osteomalacia.

Middle fossa arachnoid cyst eroding into the middle ear: case report.

We describe an unusual presentation of a large middle fossa cyst which eroded through the anterior petrous ridge into the middle ear. The significance of this and considerations related to its treatment are discussed.

Stab wounds to the temporal fossa.

Stab wounds to the temporal fossa appear as a characteristic clinical entity. Patients admitted with stab wounds to the head during the period 1970 to 1986 were reviewed retrospectively. Of these, 10 met the criteria of having suffered a stab wound that penetrated the skull and dura mater of the temporal fossa. Injury to the internal carotid artery-cavernous sinus complex (3 patients) or to the basilar artery-pons region (5 patients) was frequent. Two other patients experienced injury to the trigeminal nerve and the petrous ridge. The mechanical, neurological, radiological, and prognostic features of knife wounds to this region are discussed.

Modified prone position for cranial remodeling procedures in children with craniofacial dysmorphism: a technical note.

A new head position for use during operation on young children with cranial deformities is described. The position allows exposure of the entire calvarium from the supraorbital ridges to the posterior rim of the foramen magnum. It is a modification of the conventional prone position involving hyperextension of the neck. The authors have safely used this position to perform one-stage radical cranial remodeling procedures that previously required two stages. The advantages of this position and the methods for achieving it are discussed.

A neurosurgical approach to far-lateral disc herniation. Technical note.

A technique for exposing far-lateral intervertebral disc herniations without disrupting the facet is described. This technique is a simple modification of the standard neurosurgical approach.

Optic pathway glioma infiltrating into somatostatinergic pathways in a young boy with gigantism. Case report.

The authors report gigantism in a 16-month-old boy with an extensive optic pathway glioma infiltrating into somatostatinergic pathways, as revealed by magnetic resonance imaging and immunocytochemical studies. Stereotactic biopsies of areas showing hyperintense signal abnormalities on T2-weighted images in and adjacent to the involved visual pathways provided rarely obtained histological correlation of such areas. The patient received chemotherapy, which resulted in reduction of size and signal intensity of the tumor and stabilization of vision and growth velocity.

Osteoporosis in adults with cystic fibrosis.

Osteoporosis is prevalent in adults with CF Longitudinal data have not been collected and so the natural history is unknown. The aetiology is not known. There are no published randomized controlled trials evaluating treatments for osteoporosis in CF patients.

Characteristics of adults with and without cystic fibrosis-related diabetes.

AIMS: The prevalence of diabetes in adults with cystic fibrosis (CF) approximates 25%, yet few studies have defined risk factors. We examined the association between biochemical and clinical factors and CF-related diabetes. METHODS: We performed a study in adults with CF in 2004 in Cambridgeshire, UK. Of 160 individuals, 51 had diabetes (cases) on the basis of medical history or screening using a 75-g oral glucose tolerance test, and 107 did not have diabetes (control subjects); two were excluded. We used logistic regression to model the cross-sectional association between potential risk factors and diabetes. RESULTS: The mean age was 26 (16-58) years, mean body mass index (BMI) was 21 (16-28) kg/m(2), and mean forced expiratory volume in 1 s was 60 +/- 24% (mean +/- sd). All of the cases and 88% of control subjects had pancreatic insufficiency. Cases did not differ from control subjects with respect to age, sex, body mass index, or dose of oral pancreatic enzymes. Cases were more likely to have low serum magnesium, haemoglobin, and pulmonary function, and higher serum gamma-glutamyl transferase (GGT) activity, plasma fibrinogen levels, erythrocyte sedimentation rate, use of oral corticosteroids, and number of CF-related complications. In multivariate analyses, GGT, previous organ transplantation, plasma fibrinogen and the presence of CF-related complications were independently associated with diabetes, after controlling for corticosteroid use. CONCLUSIONS: These data confirm the high prevalence of diabetes in adults with CF, and identify plasma fibrinogen and GGT, and organ transplantation as factors independently associated with CF-related diabetes. A prospective study would clarify the nature of these associations.

Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.

Staphylococcus aureus ventriculitis treated with single-dose intraventricular vancomycin or daptomycin (LY146032): bacterial and antibiotic kinetics in hydrocephalic rabbits.

Vancomycin and a new antibiotic, daptomycin (LY146032), were tested in vitro and in vivo against Staphylococcus aureus. In vivo tests were performed with rabbits with kaolin-induced hydrocephalus. Five groups of rabbits were studied: untreated ventriculitis, intraventricular vancomycin only, and ventriculitis treated with intraventricular vancomycin (30 micrograms or 120 micrograms) or daptomycin (7.5 micrograms). Results of this study were as follows. (i) S. aureus demonstrated static growth in cerebrospinal fluid in vitro and in ventriculitis at a maximum titer of 10(5) to 10(6) CFU/ml. (ii) In vitro time kill curves in cerebrospinal fluid matched those in vivo. (iii) Single-dose intraventricular vancomycin did not lower S. aureus concentrations over 8 h, whereas daptomycin did. (iv) Ventriculitis did not significantly alter the clearance of intraventricular vancomycin. (v) Intraventricular half-lives were approximately 2.8 h (maximum) for vancomycin and 4.5 h for daptomycin. (vi) Vancomycin was detectable in the periventricular white matter only in the presence of ventriculitis. Daptomycin was also detectable in the periventricular white matter of rabbits with ventriculitis, but in amounts too small to quantitate. We concluded that daptomycin achieved greater bactericidal activity, more rapid killing kinetics, and a longer half-life in the ventricle than vancomycin did in this model.