Survey of nurses' assessment of cancer-related fatigue

Fatigue is now widely recognised as a significant problem for patients with cancer. While research effort into this subject has grown considerably in recent years, the exact mechanisms underlying fatigue remain unclear. Therefore assessing and managing this symptom can be problematic. This paper describes the findings from a survey evaluating how nurses ( n  = 84) in a Cancer Centre in Edinburgh currently define and assess fatigue. The results demonstrate that while the problems associated with fatigue are acknowledged, assessment tools are not widely used and the majority of nurses report that they would benefit from further education on the subject to assist in the care of patients.     

Recruiting donors for autopsy based cancer research

The use of human tissue for scientific research is a highly sensitive issue. A lack of confidence in patient recruitment is one reason for the failure of many studies to be funded and it is important therefore that recruitment procedures are as effective and sympathetic as possible. The authors recruited patients with uveal melanoma into a postmortem study investigating tumour latency in this cancer. Two approaches were used--firstly a direct approach when patients attended clinic and secondly an initial approach by mail followed by telephone contact. In the first year of study the authors had a take up rate of 88.5%, significantly higher than the average rate of 40% quoted by the National Institute for Clinical Excellence (NICE). Key features are a sympathetic personal approach by experienced oncology nurses, the provision of clear information, and the inclusion of the next of kin in the recruitment procedure.     

Online support to facilitate the reintegration of students with brain injury: trials and errors

The reintegration of students after acquired/traumatic brain injury (ABI/TBI) continues to be fraught with difficulties. Presented are (1) case studies exploring the potential of online support for teachers of students with ABI after returning from a paediatric rehabilitation centre; (2) results of Internet-based courses about reintegrating students with ABI; (3) outcomes of videoconferencing-based and Internet email-based support; (4) development of an online support process that uses Questions and Answers as a quick and immediate resource for teachers. The authors recommend that a collaborative process be instituted, in order to generate a relatively small number of high quality online resources about re-integrating students into their school and community. A second recommendation focuses on the development of online support network which may be text or email based or which may use videoconferencing over the Internet. Such networks allow students with ABI to maintain contact with their family and friends in the home community and facilitate their reintegration. An Internet-based support structure also allows professionals to provide consultation, collaboration and continuing input.     

Loss of CD28 expression on CD8(+) T cells is induced by IL-2 receptor gamma chain signalling cytokines and type I IFN, and increases susceptibility to activation-induced apoptosis

CD8(+)CD28(-) T cells are selectively expanded during viral infections, indicating their importance in anti-viral immune responses. Since little is known about the differentiation of CD8(+)CD28(-) cells, we investigated the generation, function and survival characteristics of this subset. In healthy individuals CD8(+)CD28(-) T cells contained more elevated levels of perforin and IFN-gamma than the CD8(+)CD28(+) subset, indicating that they can have an effector function. CD8(+)CD28(-) cells were selectively expanded when activated CD8(+)CD28(+) T cells were cultured in IL-2, IL-7 or IL-15. Moreover, the generation of CD8(+)CD28(-) cells was accelerated by type I IFN suggesting that these cytokines which are released during viral infections influence CD8(+) T cell differentiation. We did not observe re-expression of CD28 by CD8(+)CD28(-) T cells in any of the experiments performed. Activated T cells are susceptible to activation-induced cell death (AICD) if re-stimulated in the absence of co-stimuli. AICD was induced in both CD28(+) and CD28(-) subsets of activated T cells when stimulated with anti-CD3 antibody in the absence of co-stimuli but the magnitude of death was greater in the CD28(-) subset. While co-stimulation through LFA-1 (CD11a and CD18) significantly reduced AICD in the CD8(+)CD28(+) subset, death was not prevented in CD8(+)CD28(-) cells. These results suggest that CD8(+)CD28(-) T cells are more functionally differentiated than the CD8(+)CD28(+) subset and indicate they may represent a terminally differentiated effector population which is destined for clearance by apoptosis at the end of the immune response.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Controlled trial of continuous inflating pressure for hyaline membrane disease

A controlled trial of elective intervention with continuous inflating pressure (CIP) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth. Infants entered the trial if their arterial oxygen tension (PaO2) fell below 60 mmHg while breathing a fractional inspired oxygen concentration (F1O2) greater than 0-95. 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived. 7 treated and 6 control infants required mechanical ventilation. When CIP was started the Pao2 of the treated infants increased, and they breathed high concentrations of oxygen for a significantly shorter period than the control infants. During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial. 37 survived after breathing high concentrations of oxygen (F1O2 greater than 0-60) spontaneously without any ventilatory assistance, and the remaining 70 infants were already being ventilated on their arrival in the unit, usually because they had required mechanical ventilation during transfer from other hospitals. The neonatal survival rate for those infants born in this hospital during the study period was 88% (50 out of 57 infants) and for those referred from other hospitals it was 69% (51 out of 74 infants). The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e. from 77% (101/131) to 82% (107/131).     

Endoscopic retrograde cholangiopancreatography in children

Gastroduodenoscopy and retrograde cholangiopancreatography has been performed on 25 occasions in 20 children aged between 7 and 16. Radiographs of the clinically relevant duct or ducts were achieved in 96% of attempts, with no complications. The diagnostic information proved useful clinically; in particular it provided a precise map if biliary or pancreatic surgery was being contemplated. Several unexpected congenital duct anomalies were found. This and other recent reports, particularly from Germany, indicate that endoscopic retrograde cholangiopancreatography deserves greater application in children, and can also be used in babies.     

2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 2. Synthesis, chirality, and pharmacokinetics

A short stereoselective synthesis of a series of chiral 7-aryl-2,5-diketopiperazines oxytocin antagonists is described. Varying the functionality and substitution pattern of substituents in the 7-aryl ring and varying the chirality of this exocyclic ring have produced potent oxytocin antagonists (pK(i) > 8.5). SAR and pharmacokinetic profiling of this series of (3R,6R,7R)-2,5-diketopiperazines together with the introduction of an ortho F group in the 7-aryl ring to improve rat pK has culminated in the 2',4'-difluorophenyldiketopiperazine derivative 37, a highly potent oxytocin antagonist against the human oxytocin receptor (pK(i) = 8.9) that has >1000-fold selectivity over all three vasopressin receptors V1a, V2, and V1b. It has good bioavailability (46%) in the rat and moderate bioavailability (13-31%) in the dog and is more active in vivo in the rat than atosiban (rat DR(10) = 0.44 mg/kg iv).     

Direct Impairment of Vascular Function by Diesel Exhaust Particulate through Reduced Bioavailability of Endothelium-Derived Nitric Oxide Induced by Superoxide Free Radicals

Background

Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects of air pollution.

Objectives

We assessed the in vitro effects of DEP on vascular function, nitric oxide (NO) availability, and the generation of oxygen-centered free radicals.

Methods

We assessed the direct vascular effects of DEP (10–100 μg/mL) in isolated rat aortic rings using myography. We investigated NO scavenging and oxygen-centered free radical generation using an NO electrode and electron paramagnetic resonance (EPR) with the Tempone-H (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) spin trap, respectively.

Results

Acetylcholine-induced relaxation was attenuated by DEP (maximum relaxation reduced from 91 ± 4% to 49 ± 6% with 100 μg/mL DEP; p < 0.001) but was restored by superoxide dismutase (SOD; maximum relaxation, 73 ± 6%; p < 0.001). DEP caused a modest inhibition of relaxation to NO donor drugs, an effect that could be reversed by SOD (p < 0.01). At 10 μg/mL, DEP did not affect verapamil-induced relaxation (p = 0.73), but at 100 μg/mL DEP inhibited relaxation (p < 0.001) by a mechanism independent of SOD. NO concentrations generated by 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO; 10 μM) were reduced by DEP (100 μg/mL; from 5.2 ± 0.4 to 3.3 ± 0.4 μM; p = 0.002). Free radical generation was increased by DEP (10 μg/mL; 9-fold increase in EPR spectra; p = 0.004) in a manner that could be attenuated by SOD (p = 0.015).

Conclusions

DEP caused oxidative stress through the generation of oxygen-centered free radicals that reduced the bioavailability of endothelium-derived NO without prior interaction with the lung or vascular tissue. These findings provide a mechanism for the adverse cardiovascular effects of particulate air pollution.