Danish ethics council rejects brain death as the criterion of death -- commentary 1: wanting it both ways

In this commentary on the recommendations of the Danish Council of Ethics (DCE) concerning criteria for death it is argued that whilst the DCE is correct in stressing the cultural aspects of death, its adoption of cardiac-oriented criteria raises several problems. There are problems with its notion of a 'death process', which purportedly begins with brain death and ends with cessation of cardiac function, and there are serious problems regarding its commitment to a cardiac-oriented definition whilst permitting transplantation when the heart is still beating.     

Dornase alfa. A review of pharmacoeconomic and quality-of-life aspects of its use in cystic fibrosis

Cystic fibrosis (CF) is a fatal hereditary disease; patients with CF have an average lifespan of 30 years. By cleaving neutrophil-derived DNA, dornase alfa (recombinant human deoxyribonuclease I) decreases the adhesiveness and visco-elasticity of sputum in the infected lungs of patients with CF. As a result, respiratory function is improved in patients with all degrees of disease severity, and the relative risk of pulmonary exacerbations is reduced in patients with mild to moderate disease. Resource utilisation (days spent in hospital or receiving parenteral antibiotics) in patients with mild to moderate disease is also reduced by dornase alfa, as evidenced by a placebo-controlled trial in > 900 patients. Cost savings generated by these reductions in resource use during 24 weeks of dornase alfa therapy offset about 17 to 37.5% of the acquisition cost of the drug, depending on local cost data for various countries. Reductions in resource utilisation with dornase alfa have not been observed in patients with severe disease. Available cost-effectiveness and cost-utility analyses are not fully published. One analysis estimated that the incremental cost of avoiding one hospitalisation was about $Can 15,000 relative to standard therapy after 1 year of treatment. Informal analysis in the UK suggests a cost per quality-adjusted life-year of 25,000 Pounds for dornase alfa. Some quality-of-life (QOL) domains (mainly cough frequency and chest congestion) have shown modest improvement in patients treated with dornase alfa, mainly those with mild CF. Persuasive evidence of QOL benefit is lacking in those with more severe disease. Identifying patients most likely to benefit from dornase alfa therapy is essential to maximise clinical and cost benefits. The lack of a demonstrated reduction in resource utilisation in patients with severe CF makes its use more difficult to justify economically in this group than in those with less severe disease. However, in the absence of other treatments for this group, economic considerations must be weighed against clinical benefits. In conclusion, the acquisition cost of dornase alfa is partially offset by savings gained by reducing resource utilisation in patients with mild to moderate CF, and the drug appears to improve quality of life in some patients, mostly those with less severe disease. However, in the absence of guidance from definitive cost-effectiveness analyses, individual healthcare providers must make their own decisions about how best to provide dornase alfa to patients with CF in a rational and cost-justifiable manner.     

Iso-electric focusing of aqueous humour IgG in multiple sclerosis

Samples of aqueous fluid were obtained from 35 controls who were people undergoing routine cataract surgery. Similar samples were taken from seven patients with clinically definite multiple sclerosis (MS) and a previous history of optic neuritis, either at cataract surgery or as an elective procedure. Oligoclonal bands were found in only one subject who suffered from the MS-uveitis syndrome.     

ANEURYSM OF SINUS OF VALSALVA DISSECTING INTO THE INTERVENTRICULAR SEPTUM – ECHOCARDIOGRAPHIC DIAGNOSIS (A Case Report)

Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare entity. We report one such case who was incidentally diagnosed by echocardiography to have this abnormality during evaluation of a clinically suspected isolated aortic regurgitation.KEY WORDS: Aneurysm – dissecting – sinus of Valsalva, Echocardiography     

Discriminated conditioned taste aversion for studying multi-element stimulus control

The effects of morphine pre-treatment interval on the stimulus control exerted by a multi-element stimulus consisting of morphine (5.6mg/kg), saccharin (0.2%, w/v), and a ball-bearing drinking nozzle in a discriminated taste aversion procedure were examined. In this discriminated aversion procedure, rats received injections of LiCI following presentation of this multielement stimulus, and injections of saline following the saline, water, and non-ball-bearing nozzle composite stimulus. These paired rats were compared to unpaired rats that received saline injections rather than LiCI injections following presentation of the multi-element stimulus. Morphine pre-treatment times of 5, 10, and 20min were examined in groups of 12 paired and 6 unpaired rats. The discrimination was rapidly learned under all three pre-treatment intervals. In subsequent testing with each individual stimulus element and combinations of two stimulus elements, stimulus control was clearly exerted by both morphine and saccharin. Paired rats drank less saccharin than unpaired rats, and less saccharin than water. Similarly, paired rats drank less fluid following morphine administration than following saline administration, and less fluid than unpaired rats following morphine administration. Control by the nozzle type was also apparent in significant interactions between the nozzle and morphine or saccharin and pairing with LiCI. In general, pre-treatment time did not influence the stimulus control that developed. However, at the two shorter pre-treatment times there was some indication that a conditioned taste aversion to morphine was developing in the unpaired rats. These experiments indicate that such discriminated taste aversion procedures may be viable methods for studying the contextual control of how drugs function as discriminative stimuli, and that longer drug pre-treatment times may be desirable in such procedures.     

Linked suppression in peripheral T cell tolerance to the house dust mite derived allergen Der p 1

BACKGROUND: Peripheral tolerance is required to maintain balance within the immune system. A feature of peripheral tolerance is linked suppression, in which tolerance induced to a single T cell epitope inhibits the response to all epitopes in the same protein. It is suggested that this phenomenon is mediated by regulatory T cells through either the activity of immunopressive cytokines or direct cell contact. In previous experiments we failed to detect inhibitory cytokines when T cells from mice rendered tolerant by intranasal delivery of the immunodominant peptide of Der p 1 (p 1, 110-131) were restimulated with peptide in vitro. Therefore, the aim of this study was to determine if cognate interactions between T cells mediated by Notch/Delta signaling induce and maintain peripheral T cell tolerance. METHODS: Using in situ hybridization and viral mediated gene transfer, the expression and function of Delta1 were investigated in a murine model of T cell tolerance to Der p 1 in vivo. RESULTS: Delta1 expression is increased on peripheral T cells during the induction of tolerance with high-dose peptide delivered intranasally and when tolerant animals are rechallenged under immunogenic conditions. Peptide p 1, 110-131-specific CD4+ T cells transfected with Delta1 inhibited the response of antigen-primed T cells and induced linked suppression. CONCLUSIONS: High-dose peptide delivered intranasally induces transient expression of Delta 1 on inhibitory CD4+ T cells. Ligation of the Notch1 receptor on neighbouring T cells by Delta1+ regulatory T cells inhibits clonal expansion of the former and mediates linked suppression.