Respiratory syncytial virus and neutrophil activation

Respiratory syncytial virus infects almost all children by 2 years of age. Neutrophils are the predominant airway leucocytes in RSV bronchiolitis and they are activated in the presence of infection. However it is not clear whether RSV can directly signal to activate neutrophil cytotoxic function. To investigate this we have used a preparation of RSV washed using a new centrifugal diafiltration method to rapidly remove inflammatory molecules produced by the epithelial cells used to propagate the RSV stock. Human neutrophils were isolated from peripheral blood and activated with either the unwashed crude RSV preparations or the purified intact RSV. Neutrophils were also challenged with purified RSV G-glycoprotein. The effect of challenging human neutrophils with these preparations of intact RSV, or the RSV G-glycoprotein, was assessed by measuring the cell surface expression of CD11b and CD18b, the phagocytic oxidative burst, and intracellular release of calcium pools. Neutrophils challenged with the washed RSV exhibited significantly lower activation of surface marker expression (P < 0.001) and oxidative burst (P < 0.001) than those challenged with unwashed virus or with virus free supernatant. There was no increase in intracellular calcium release on exposure to the washed RSV. Purified G glycoprotein did not stimulate neutrophils, whilst the use of a blocking antibody to the F protein did not prevent unwashed RSV from activating cytotoxic responses. These results suggest that neutrophils have no innate signalling system that recognizes RSV but they are activated at sites of RSV infection as a result of the cytokines and inflammatory molecules released by virally infected cells.     

Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children

Levels of exhaled nitric oxide (eNO) are elevated in subjects with asthma and fall in response to oral or inhaled steroids. This study explored the possibility the measurement of eNO levels could be used to identify subjects who were not adhering to their treatment regimen. Twenty children with asthma attending the respiratory clinic were recruited. Each attended on four occasions 1 month apart when eNO levels were measured. A data logger attached to a pressurised metered dose inhaler was used to objectively monitor use of inhaled corticosteroids (ICSs). The correlation between day and dose compliance with eNO was assessed. The data demonstrated a weak but non-significant correlation between eNO and both day (r = 0.055, P = 0.67) and dose (r = 0.153, P = 0.23). A recorded value of eNO less than 12 was associated with day compliance rates of 3-97%. Of the 19 recorded eNO values greater than 12 ppb almost 80% were from subjects with a day compliance of less than 50% during the preceding month. Of the four values greater than 12 ppb and day compliance > 60% one subject had a poor inhaler technique, one had a mild viral exacerbation and one appeared to be associated with increase pollen exposure. The measurement of eNO may prove to be a useful tool in helping to manage children with asthma but further work is required to define its precise role. Elevated eNO levels in asthmatic children taking ICSs are likely to reflect poor compliance but confounding factors such as disease activity and inhaler technique need to be carefully considered.     

Rasch analysis of the hospital anxiety and depression scale (hads) for use in motor neurone disease

Background

It is important to monitor health related quality of life in order to determine the efficacy of interventions and physical functioning of patients with cystic fibrosis in their daily activities. There is no a single-item global quality of life scale for routine clinical practice for adult patients with cystic fibrosis. We assessed the reliability and validity of a single-item global quality of life scale and compared with the Cystic Fibrosis Quality of Life Questionnaire (CF-QOL) for adult patients with cystic fibrosis.

Method

121 (men = 66, women = 55) adult cystic fibrosis patients self-completed the CF-QOL, the Hospital Anxiety Depression Scale, and the single item global quality of life scale at the out patient clinic. 33 (17 women) completed the repeat questionnaires at home within two weeks. Socio-demographic characteristic and lung function data were extracted from the recent medical notes.

Results

Mean (SD) age was 29.6 (8.9) years and mean (SD) forced expiratory volume in 1 second was 2.20 (0.94) litres. The test-retest reproducibility using the intra-class correlation coefficient (ICC) for the CF-QOL was 0.83, 95% confidence interval 0.68 to 0.91. The single item global quality of life ICC score was 0.78, 95% confidence interval 0.59 to 0.88. Concurrent validity of the single-item global quality of life was examined in relation to all items of the CF-QOL, frequent episodes of readmission, anxiety and depression (all, p < 0.01) were moderately correlated.

Conclusion

The study provides preliminary evidence that the single-item quality of life scale is acceptable, valid and repeatable for adult patients with cystic fibrosis. It is a promising tool that can be easily incorporated into a routine clinical practice to assess patients' quality of life.     

Examining the association of injury with the Functional Movement Screen and Landing Error Scoring System in military recruits undergoing 16 weeks of introductory fitness training

Objectives

To examine the association of injury with the Functional Movement Screen (FMS) and Landing Error Scoring System (LESS) in military recruits undergoing an intensive 16-week training block.

Dialysate flow distribution in hollow fiber hemodialyzers with different dialysate pathway configurations

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, since this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different dialysate compartment designs on dialysate flow distribution and urea clearances. Eighteen hollow fiber 1.3 m2 hemodialyzers were studied, 6 each of 3 designs: Type A--standard fiber bundle (PAN 65DX Asahi Medical, Tokyo, Japan); Type B--spacing filaments external to the fibers (PAN 65SF Asahi Medical, Tokyo, Japan); Type C--fibers waved to give Moiré structure (FB130 Nissho-Nipro, Osaka, Japan). In vitro studies: 3 dialyzers of each type were studied following dye injection into the dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer were undertaken, using a new generation helical CT scanner (X-Press/HS1 Toshiba Corporation, Tokyo, Japan). In vivo studies: 3 dialyzers of each type were studied, in randomized sequence, in 3 different patients under standardized dialysis conditions. Blood- and dialysate-side urea clearances were measured at 30 and 150 minutes of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (Type C) and least homogeneous in the standard dialyzer (Type A). Space yarns (Type B) gave an intermediate dialysate flow distribution. Significantly increased urea clearances (p<0.001) were seen with Types B and C, compared to the standard dialyzer. Type C (Moiré) had the highest clearances although these were not significantly greater than Type B (space yarns). In conclusion, more homogeneous dialysate flow distribution and improved small solute clearances can be achieved by use of spacing yarns or waved (Moiré structure) patterns of fiber packing in the dialyzer. These effects are achieved probably as a result of reduced dialysate channeling resulting in a lower degree of mismatch between blood and dialysate flows. The new radiological technique using the helical CT scanner allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.     

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.     

Incidental durotomy in decompression for lumbar spinal stenosis: incidence,risk factors and effect on outcomes in the Spine Tango registry

Purpose

The three aims of this Spine Tango registry study of patients undergoing decompression for spinal stenosis were to: report the rate of dural tear (DT) stratified by treatment centre; find factors associated with an increased likelihood of incurring a DT; and compare treatment outcomes in relation to DT (none vs. repaired vs. unrepaired DT).

Methods

Multivariate logistic regression was used to assess the association between DT and patient and treatment characteristics. Patient-rated and surgical outcomes were compared in patients with no DT, repaired DT, and unrepaired DT, while adjusting for case-mix.

Results

DT occurred in 328/3254 (10.1%) of included patients. The rate for all 29 contributing hospitals was within 95% confidence intervals of the average. The likelihood of DT increased by 2% per year of age, 1.78 times with previous spine surgery, 1.67 for a minimally/less invasive surgery, 1.58 times with laminectomy, and 1.40, and 2.12 times for BMI 31–35, and >35 in comparison with BMI 26–30, respectively. The majority of DTs (272/328; 82.9%) were repaired. Repairing the DT was associated with a longer duration of surgery (p < 0.001). More patients with repaired than with unrepaired DTs were satisfied with treatment, but the difference was not statistically significant. There was no association between DT and patient-reported outcomes.

Conclusion

The unadjusted rate of incidental DT during decompression for LSS was homogeneous across the participating centres and was associated with age, BMI, previous surgery at the same spinal level, minimally/less invasive surgery, and laminectomy. Non-repair of DTs had no negative association with treatment outcome; however, the unrepaired DTs may have been those that were smaller in size.