Objective and behavioural assessment of the emergence from post-traumatic amnesia (PTA)

Primary objective: To determine the profile of resolution of typical PTA behaviours and describe new learning and improvements in self-care during PTA. Research design: Prospective longitudinal study monitoring PTA status, functional learning and behaviours on a daily basis. Methods and procedures: Participants were 69 inpatients with traumatic brain injury who were in PTA. PTA was assessed using the Westmead or Oxford PTA assessments. Functional learning capability was assessed using a routine set of daily tasks and behaviour was assessed using an observational checklist. Data was analysed using descriptive statistics. Main outcomes and results: Challenging behaviours that are typically associated with PTA, such as agitation, aggression and wandering resolved in the early stages of PTA and incidence rates of these behaviours were less than 20%. Independence in self-care and bowel and bladder continence emerged later during resolution of PTA. New learning in functional situations was demonstrated by patients in PTA. Conclusions: It is feasible to begin active rehabilitation focused on functional skills-based learning with patients in the later stages of PTA. Formal assessment of typically observed behaviours during PTA may complement memory-based PTA assessments in determining emergence from PTA.

PRN Sedation-patterns of prescribing and administration in a child and adolescent mental health inpatient service

Objective: To identify utilisation rates of prn (pro re nata) sedation in children and adolescents receiving inpatient psychiatric treatment, and to compare correlates of prn prescribing and administration. Method A retrospective chart review examined 122 medical charts from a child and youth mental health inpatient service. Results 71.3% of patients were prescribed prn sedation and 50.8% were administered prn sedation. Patients received an average of 8.0 doses of prn sedation, with 9.8% receiving 10 or more doses. Chlorpromazine and diazepam were the most commonly utilised agents. Prescribing of prn sedation was only related to use of regular medications (p < 0.01), and non-parent carers (p < 0.01). In contrast, administration of prn sedation was associated with multiple diagnoses (p < 0.01), pervasive development disorder (p < 0.01), mental retardation (p < 0.01) ADHD (p < 0.01), longer hospital admission (p < 0.01), use of atypical antipsychotics (p < 0.01) and polypharmacy (p < 0.01). Conclusions Despite lack of data to inform practice, prn sedation is widely utilised, especially in complex patients. Future research in this area needs to incorporate nurses and examine whether patients benefit from prn sedation, which drugs and dosing patterns optimise safety and efficacy, and what is the role of prn sedation in the context of other medication.

In-vitro study of the spontaneous calcification of PHEMA-based hydrogels in simulated body fluid

In-vitro calcification of poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogels in simulated body fluid (SBF) under a steady/batch system without agitation or stirring the solutions has been investigated. It was noted that the formation of calcium phosphate (CaP) deposits primarily proceeded through spontaneous precipitation. The CaP deposits were found both on the surface and inside the hydrogels. It appears that the effect of chemical structure or reducing the relative number of oxygen atoms in the copolymers on the degree of calcification was only important at the early stage of calcification. The morphology of the CaP deposits was observed to be spherical aggregates with a thickness of the CaP layer less than 0.5 mu m. Additionally, the CaP deposits were found to be poorly crystalline or to have nano-size crystals, or to exist mostly as an amorphous phase. Characterization of the CaP phases in the deposits revealed that the deposits were comprised mainly of whitlockite [Ca9MgH(PO4)(7)] type apatite and DCPD (CaHPO4 center dot 2H(2)O) as the precursors of hydroxyapatite [Ca-10(PO4)(6)(OH)(2)]. The presence of carbonate in the deposits was also detected during the calcification of PHEMA based hydrogels in SBF solution.

Sex Differences in Symptoms of Depression in Unrelated Individuals and Opposite-Sex Twin and Sibling Pairs

Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association requires 5 out of 9 symptoms to be present. Therefore, individuals may differ in the specific symptoms they experience and reach a diagnosis of depression via different pathways. It has been suggested that depressed women more often report symptoms of sleep disturbance, appetite or weight disturbance, fatigue, feelings of guilt/worthlessness and psychomotor retardation than depressed men. In the current study, we investigate whether depressed men and women differ in the symptoms they report. Two samples were selected from a sample of Dutch and Australian twins and siblings. First, Dutch and Australian unrelated depressed individuals were selected. Second, a matched epidemiological sample was created consisting of opposite-sex twin and sibling pairs in which both members were depressed. No sex differences in prevalence rates for symptoms were found, with the exception of decreased weight in women in the sample of unrelated individuals. In general, the similarities in symptoms seem to far outweigh the differences in symptoms between men and women. This signifies that men and women are alike in their symptom profiles for major depression and genes for depression are probably expressed in the same way in the two sexes.

INTERVENÇÃO PSICOMOTORA LÚDICA EM CRIANÇAS COM DIFICULDADES DE APRENDIZAGEM

Este estudo investiga evidências da influência de uma intervenção psicomotora lúdica na construção do pensamento operatório concreto e desempenho neuromotor de alunos com dificuldade de aprendizagem da 2ª série do ensino fundamental, de escola pública do Estado de São Paulo. Utiliza-se de método experimental. Manipula a intervenção psicomotora lúdica, (Variável Independente-VI), com o objetivo de verificar a sua possível influência no desempenho cognitivo relativo a noções de Conservação, Classificação, Seriação e Aritmética, assim como no neuromotor relativo a Agilidade e Orientação Direita-Esquerda (Variáveis Dependentes - VDs) - totalizando 6 VDs. A amostra compõe-se por 18 escolares, na faixa etária de 7 a 11 anos, de ambos os sexos, organizados em dois grupos: experimental (N=9) e controle (N=9). O procedimento experimental desenvolve-se em 16 sessões, constando de três etapas. Aos dois grupos são aplicados, individualmente, pré-teste (1ª etapa) e pós-teste (3ª etapa), constando de duas sessões individuais em cada etapa, com a utilização dos seguintes instrumentos: Provas Operatórias de Piaget, teste Piaget-Head de Orientação Direita-Esquerda e subteste de Aritmética do teste de Desempenho Escolar de Stein, teste de Shuttle Run . A 2ª etapa, exclusiva do grupo experimental, consta da intervenção psicomotora lúdica, em 12 sessões grupais de 50 minutos cada. Utilizou-se da prova de Wilcoxon, para comparação dos resultados entre os grupos. Os resultados referentes às noções de Classificação ( p=0,010), Seriação (p=0,034), Aritmética (p=0,157) e Orientação Direita- Esquerda (p=0,007), indicam que ocorreu uma diferença significativa estatisticamente, considerando-se que os participantes apresentaram desempenho superior nos pós-testes. Nas demais provas, foi observado melhor desempenho nos dois grupos, o que, portanto, não pode ser atribuído à intervenção. Conclui-se que o objetivo do trabalho foi atingido, visto que o programa mostrou-se eficiente para desenvolver o pensamento operatório e o neuromotor em relação a Orientação Direita-Esquerda dos participantes.(AU)

Liposomes:Formulation and characterisation as contrast agents and as vaccine delivery systems

Liposome systems are well reported for their activity as vaccine adjuvants; however novel lipid-based microbubbles have also been reported to enhance the targeting of antigens into dendritic cells (DCs) in cancer immunotherapy (Suzuki et al 2009). This research initially focused on the formulation of gas-filled lipid coated microbubbles and their potential activation of macrophages using in vitro models. Further studies in the thesis concentrated on aqueous-filled liposomes as vaccine delivery systems. Initial work involved formulating and characterising four different methods of producing lipid-coated microbubbles (sometimes referred to as gas-filled liposomes), by homogenisation, sonication, a gas-releasing chemical reaction and agitation/pressurisation in terms of stability and physico-chemical characteristics. Two of the preparations were tested as pressure probes in MRI studies. The first preparation composed of a standard phospholipid (DSPC) filled with air or nitrogen (N2), whilst in the second method the microbubbles were composed of a fluorinated phospholipid (F-GPC) filled with a fluorocarbon saturated gas. The studies showed that whilst maintaining high sensitivity, a novel contrast agent which allows stable MRI measurements of fluid pressure over time, could be produced using lipid-coated microbubbles. The F-GPC microbubbles were found to withstand pressures up to 2.6 bar with minimal damage as opposed to the DSPC microbubbles, which were damaged at above 1.3 bar. However, it was also found that DSPC-filled with N2 microbubbles were also extremely robust to pressure and their performance was similar to that of F-GPC based microbubbles. Following on from the MRI studies, the DSPC-air and N2 filled lipid-based microbubbles were assessed for their potential activation of macrophages using in vitro models and compared to equivalent aqueous-filled liposomes. The microbubble formulations did not stimulate macrophage uptake, so studies thereafter focused on aqueous-filled liposomes. Further studies concentrated on formulating and characterising, both physico-chemically and immunologically, cationic liposomes based on the potent adjuvant dimethyldioctadecylammonium (DDA) and immunomodulatory trehalose dibehenate (TDB) with the addition of polyethylene glycol (PEG). One of the proposed hypotheses for the mechanism behind the immunostimulatory effect obtained with DDA:TDB is the ‘depot effect’ in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. The depot effect has been suggested to be primarily due to their cationic nature. Results reported within this thesis demonstrate that higher levels of PEG i.e. 25 % were able to significantly inhibit the formation of a liposome depot at the injection site and also severely limit the retention of antigen at the site. This therefore resulted in a faster drainage of the liposomes from the site of injection. The versatility of cationic liposomes based on DDA:TDB in combination with different immunostimulatory ligands including, polyinosinic-polycytidylic acid (poly (I:C), TLR 3 ligand), and CpG (TLR 9 ligand) either entrapped within the vesicles or adsorbed onto the liposome surface was investigated for immunogenic capacity as vaccine adjuvants. Small unilamellar (SUV) DDA:TDB vesicles (20-100 nm native size) with protein antigen adsorbed to the vesicle surface were the most potent in inducing both T cell (7-fold increase) and antibody (up to 2 log increase) antigen specific responses. The addition of TLR agonists poly(I:C) and CpG to SUV liposomes had small or no effect on their adjuvanticity. Finally, threitol ceramide (ThrCer), a new mmunostimulatory agent, was incorporated into the bilayers of liposomes composed of DDA or DSPC to investigate the uptake of ThrCer, by dendritic cells (DCs), and presentation on CD1d molecules to invariant natural killer T cells. These systems were prepared both as multilamellar vesicles (MLV) and Small unilamellar (SUV). It was demonstrated that the IFN-g secretion was higher for DDA SUV liposome formulation (p<0.05), suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs.

Mass transfer characteristics of two-aqueous-phase liquid-liquid mixtures

Mass transfer rates were studied using the falling drop method. Cibacron Blue 3 GA dye was the transferring solute from the salt phase to the PEG phase. Measurements were undertaken for several concentrations of the dye and the phase-forming solutes and with a range of different drop sizes, e.g. 2.8, 3.0 and 3.7 mm. The dye was observed to be present in the salt phase as finely dispersed solids but a model confirmed that the mass transfer process could still be described by an equation based upon the Whitman two-film model. The overall mass transfer coefficient increased with increasing concentration of the dye. The apparent mass transfer coefficient ranged from 1 x 10-5 to 2 x 10 -4 m/s. Further experiments suggested that mass transfer was enhanced at high concentration by several mechanisms. The dye was found to change the equilibrium composition of the two phases, leading to transfer of salt between the drop and continuous phases. It also lowered the interfacial tension (i.e. from 1.43 x 10-4 N/m for 0.01% w/w dye concentration to 1.07 x 10-4 N/m for 0.2% w/w dye concentration) between the two phases, which could have caused interfacial instabilities (Marangoni effects). The largest drops were deformable, which resulted in a significant increase in the mass transfer rate. Drop size distribution and Sauter mean drop diameter were studied on-line in a 1 litre agitated vessel using a laser diffraction technique. The effects of phase concentration, dispersed phase hold-up and impeller speed were investigated for the salt-PEG system. An increase in agitation speed in the range 300 rpm to 1000 rpm caused a decrease in mean drop diameter, e.g. from 50 m to 15 m. A characteristic bimodal drop size distribution was established within a very short time. An increase in agitation rate caused a shift of the larger drop size peak to a smaller size.

NMR spectroscopy in the presence of ultrasound and other perturbations

The work described in this thesis has been concerned with exploring the potential uses of ultrasound in Nuclear Magnetic Resonance (NMR) spectroscopy, The NMR spectra of liquids provide detailed structural information that may be deduced from the chemical shifts and spin-spin coupling, that are evident in the narrow resonances, arising from some of the nuclear broadening interactions being reduced to zero. In the solid state, all of the nuclear broadening interactions are present and broad lines in the NMR spectrum are observed. Current techniques employed to reduce the line widths in solids are based on coherent averaging techniques such as MAS NMR1,2 which can remove first order interactions. Recently DOR3 and DAS4 have become available to remove higher order interactions. SINNMR (Sonically Induced Narrowing of the NMR spectra of solids) has been reported by Homer et al5 and developed by Homer and Howard6 to reduce the line widths of solids. The basis of their work is the proposal that a colloidal suspension of solid particles can be made to move like large molecules by using ultrasonic agitation. The advantage of the technique is that the particles move incoherently removing all of the nuclear interactions responsible for broad lines. This thesis describes work on the extension of SINNMR by showing that the line width of 27AI and 11B for the glass Na20/B203/AI203 can be reduced by placing solid particles in a colloidal suspension. Further line width reduction is possible by applying ultrasound, at 2 MHz, of sufficient intensity. It is proposed that a cavitation field is responsible for imparting sufficient rotational motion to the solid particles to partially average the nuclear interactions responsible for broad lines. Rapid stirring of the colloidal suspension generates turbulent flow, however, the motion is insufficient to narrow the line widths for 27AI in the glass. Investigations of sonochemical reactions for in situ rate measurements by NMR have been made. 8y using the Weissler reaction7, it has been shown that ultrasonic cavitation is possible up to 10MHz. Preliminary studies have been carried out into the rate of ultrasonic polymerisation of methylmethacrylate by NMR. Long range order in liquid crystals can imposed when they are aligned in the presence a magnetic field. The degree of alignment can be monitored by NMR using, for example a deuterated solute added to the liquid crystal8. Ultrasonic streaming can then be employed to deflect the directors of the liquid crystal from their equilibrium position, resulting in a change In the NMR spectrum. The angle of deflection has been found for the thermotropic liquid crystal (I35) to be ca, 35° and for the lyotropic (ZLI-1167) to be ca, 20°, Mechanical stirring can used to re- orientate the liquid crystal but was found to give a smaller deflection, In a separate study, that did not use ultrasound, it has been found that the signal to noise ratio of 13C NMR signals can be enhanced by rapidly stirring a Iiquid. Accelerating the diffusion of nuclei out of the coil region enables M0 to be re-established more rapidly than the normal relaxation process. This allows the pulse repetition rate to be reduced without saturating the spin system. The influence of varying the relaxation delay, acquisition time and inter-pulse delay have been studied and parameters optimised. By studying cholesterol the technique was found to be most effective for nuclei with long relaxation times, such as quaternary carbon sites. Key Worde: NMR, Ulf.rasciund, 1,.lqi.fi!:l cryllltalt!h SCll1C1otlemlstryl I!r1hano~d algnflllf

Fermentation methods for dextransucrase production

Several fermentation methods for the production of the enzyme dextransucrase have been employed. The theoretical aspects of these fermentation techniques have been given in the early chapters of this thesis together with a brief overview of enzyme biotechnology. A literature survey on cell recycle fermentation has been carried out followed by a survey report on dextransucrase production, purification and the reaction mechanism of dextran biosynthesis. The various experimental apparatus as employed in this research are described in detail. In particular, emphasis has been given to the development of continuous cell recycle fermenters. On the laboratory scale, fed-batch fermentations under anaerobic low agitation conditions resulted in dextransucrase activities of about 450 DSU/cm3 which are much higher than the yields reported in the literature and obtained under aerobic conditions. In conventional continuous culture the dilution rate was varied in the range between 0.375 h-1 to 0.55 h-1. The general pattern observed from the data obtained was that the enzyme activity decreased with increase in dilution rate. In these experiments the maximum value of enzyme activity was ∼74 DSU/cm3. Sparging the fermentation broth with CO2 in continuous culture appears to result in a decrease in enzyme activity. In continuous total cell recycle fermentations high steady state biomass levels were achieved but the enzyme activity was low, in the range 4 - 27 DSU/cm3. This fermentation environment affected the physiology of the microorganism. The behaviour of the cell recycle system employed in this work together with its performance and the factors that affected it are discussed in the relevant chapters. By retaining the whole broth leaving a continuous fermenter for between 1.5 - 4 h under controlled conditions, the enzyme activity was enhanced with a certain treatment from 86 DSU/cm3 to 180 DSU/cm3 which represents a 106% increase over the enzyme activity achieved by a steady-state conventional chemostat. A novel process for dextran production has been proposed based on the findings of this latter part of the experimental work.

BTX extraction by sulfolane in a mixer-settler cascade

The literature relating to the extraction of the aromatics, benzene, toluene and xylene (BTX) using different commercial solvents, and to mixer-settler design and performance, has been reviewed. Liquid-liquid equilibria of the ternary systems: hexane-benzene-sulfolane, n-heptane-toluene-sulfolane, and octane-xylene-sulfolane were determined experimentally at temperatures of 30oC, 35oC, and 40oC. The work was then extended to a multicomponent system. The data were correlated by using Hand's method and were found to be in a good agreement with theoretical predictions using the UNIFAC method. A study was made of the performance of a 10-stage laboratory mixer-settler cascade for the extraction of BTX from a synthetic reformate utilizing sulfolane as a solvent. Murphree stage efficiency decreased with stage number but 99% extraction was achievable within 4 stages. The effects of temperature, phase ratio, and agitator speed were investigated. The efficiency increased with agitator speed but > 1050 rpm resulted in secondary haze formation. An optimum temperature of 30oC was selected from the phase equilibria; the optimum solvent: feed ratio was 3:1 for 4 stages. The experimental overall mass transfer coefficients were compared with those predicted from single drop correlations and were in all cases greater, by a factor of 1.5 to 3, due to the surface renewal associated with drop break-up and coalescence promoted by agitation. A similar investigation was performed using real reformate from the Kuwait Oil Company. The phase ratios were in the range 0.5 to 1 to 3.25 to 1, the agitator speed 1050 rpm, and the operating temperature 30oC. A maximum recovery of 99% aromatics was achieved in 4 stages at a phase ratio of 3.25 to 1. A backflow model was extended to simulate conditions in the mixer-settler cascade with this multicomponent system. Overall mass transfer coefficients were estimated by obtaining the best fit between experimental and predicted concentration profiles. They were up to 10% greater than those with the synthetic feed but close agreement was not possible because the distribution coefficient and phase ratio varied with stage number. Sulfolane was demonstrated to be an excellent solvent for BTX recovery and a mixer-settler cascade was concluded to be a technically viable alternative to agitated columns for this process.

The production of the enzyme dextransucrase by batch and continuous fermentation techniques

A review of the literature of work carried out on dextransucrase production, purification, immobilization and reactions has been carried out. A brief review has also been made of the literature concerning general enzyme biotechnology and fermentation technology. Fed-batch fermentation of the bacteria Leuconostoc mesenteroides NRRL B512 (F) to produce dextransucrase has formed the major part of this research. Aerobic and anaerobic fermentations have been studied using a 16 litre New Brunswick fermenter which has a 3-12 litre working volume. The initial volume of broth used in the studies was 6 litres. The results of the fed-batch fermentations showed for the first time that yields of dextransucrase are much higher under the anaerobic conditions than during the aerobic fermentations. Dextransucrase containing 300-350 DSU/cm3 of enzyme activity has been obtained during the aerobic fermentations, while in the anaerobic fermentations, enzyme yields containing 450-500 DSU/cm3 have been obtained routinely. The type of yeast extract used in the fermentation medium has been found to have significant effects on enzyme yield. Of the different types studied, the Gistex Standard was found to be the type that favoured the highest enzyme production. Studies have also been carried out on the effect of agitation rate and antifoam on the enzyme production during the anaerobic experiments. Agitation rates of up to 600 rpm were found not to affect the enzyme yield, however, the presence of antifoam in the medium led to a significant reduction in enzyme activity (less than 300 DSU/cm3). Scale-up of the anaerobic fermentations has been performed at up to the 1000 litre level with enzyme yields containing more than 400 DSU/cm3 of activity being produced. Some of the enzyme produced at this scale was used for the first time to produce dextran on an industrial scale via the enzyme route, with up to 99% conversion of sucrose to dextran being obtained. An attempt has been made at continuous dextransucrase production. Cell washout was observed to occur at dilution rates of greater than 0.4 h-1. Dextransucrase containing up to 25 DSU/cm3/h has been produced continuously.

Inhibition of microbial colonization of shipboard fuel systems

The aim of the investigation was to study the problem of colonization of shipboard fuel systems and to examine the effect of a number of environmental factors on microbial growth and survival in order to find potential preservative treatments. A variety of microbial species were isolated from samples taken from fuel storage tanks. Bacteria were more numerous than yeasts or fungi and most microorganisms were found at the fuel/water interface. 1he salinity, pH and phosphate concentration of some water bottoms were characteristic of sea water. Others were brackish, acidic and varied in phosphate content. Microorganisms were cultured under a number of environmental conditions. After prolonged incubation, the inoculum size had no effect on the final biomass of Cladosporium resinae but the time required to achieve the final mass decreased with increasing spore number. Undecane supported better growth of the fungus than diesel fuel and of four types of diesel fuel, two allowed more profuse growth. With sea water as the aqueous phase, a number of isolates were inhibited but the addition of nutrients allowed the development of many of the organisms. Agitation increased the growth of C. resinae on glucose but inhibited it on hydrocarbons. The optimum temperature fgr growth of C. resinae on surface culture lay between 25º C and 30º C and growth was evident at 5º C but not at 45º C. In aqueous suspension, 90% of spores were inactivated in around 60 hours at 45ºC and the same proportion of spores of C. resinae and Penicillium corylophilum were destroyed after about 30 seconds at 65ºC. The majority of bacteria and all yeasts in a water bottom sample were killed within 10 seconds at this temperature. An increase in the concentration of an organo-boron compound caused more rapid inactivation of C. resinae spores and raising the temperature from 25ºC to 45°C significantly enhanced the potency of the biocide.

The postantibiotic effect of the carbapenem antibiotics on gram-negative bacteria

Postantibiotic effect (PAE) describes the suppression of microbial growth occurring after a short exposure to an antimicrobial agent. PAE appears to be a property of the majority of antimicrobial agents and is demonstrated by a wide variety of microorganisms. At present, carbapenems and penems are the only members of the -lactam group of antimicrobial agents that exhibit a significant PAE on Gram-negative bacilli. A standardised method was developed to evaluate the in vitro PAE of three carbapenems; imipenem, meropenem and biapenem on Gram-negative bacteria under reproducible laboratory conditions that partially mimicked those occurring in vivo. The effects on carbapenem PAE of the method of antimicrobial removal, concentration, exposure duration, inoculum size, inoculum growth phase, multiple exposures and pooled human serum were determined. Additionally, the reproducibility, susceptibility prior to and after PAE determination and inter-strain variation of carbapenem PAE were evaluated. The method developed determined PAE by utilising viable counts and demonstrated carbapenem PAE to be reproducible, constant over successive exposures, dependent on genera, concentration, duration of exposure, inoculum size and growth phase. In addition, carbapenem PAE was not significantly effected either by agitation, the antimicrobial removal method or the viable count diluent. At present, the mechanism underlying PAE is undetermined. It is thought to be due to either the prolonged persistence of the antimicrobial at the cellular site of action or the true recovery period from non-lethal damage. Increasing the L-lysine concentration and salinity at recovery decreased and increased the carbapenem and imipenem PAE of Pseudomonas aeruginosa, respectively. In addition, no apparent change was observed in the production of virulence factors by P.aeruginosa in PAE phase. However, alterations in cell morphology were observed throughout PAE phase, and the reappearance of normal cell morphology corresponded to the duration of PAE determined by viable count. Thus, the recovery of the penicillin binding protein target enzymes appears to be the mechanism behind carbapenem PAE in P. aeruginosa.

The use of anticholinergic agents to treat excessive oropharyngeal and tracheal secretions in palliative care

Palliative care involves a multi-professional team approach to the provision of active, holistic care for patients and their families when the patient's disease is no longer responsive to curative treatment. Patient care encompasses medical and pharmacological intervention for symptom control, together with psychological, spiritual and social support for patients and families. Care is provided by teams in hospice, hospital or community environments. Although traditionally associated with providing care for cancer patients, palliative care services are increasingly providing for patients with non-malignant disease. Symptoms commonly associated with terminal phase of disease include pain, nausea, agitation, respiratory symptoms and general fatigue. During the last few days of life, patients may become weak, resulting in difficulty taking oral medication and have periods of unconsciousness. Some patients may require drug administration via subcutaneous infusion. A proportion of patients may develop difficulty clearing respiratory secretions causing a characteristic ‘death rattle’, which although not generally considered to be distressing for the patient, is often treated with a variety of anticholinergic drugs in an attempt to reduce the ‘noisy breathing’ for the benefit of relatives and others who may be closely associated with the patient.This study examined treatment of death rattle in two Hospices focusing on objective and subjective outcome measures in order to determine the efficacy of anticholinergic regimens in current use. Qualitative methods were employed to elicit attitudes of professionals and carers working closely with the patient. The number of patients recruited and monitored were small, many confounding factors were identified which questioned firstly the clinical rationale for administering anticholinergic drugs routinely to treat death rattle and secondly, the ethics of administering drug regimens to patients to treat death rattle with the primary aim of relieving distress for others. Ethnical issues, including those of consent are discussed in relation to their impact on the methodology of end of life studies in medicines management in palliative care.