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Biomedical subjects

P Lucas

Publications and source records attributed to P Lucas.

At least 55 records · Page 3Linked to original sources

Protein deposition from dry powder inhalers: fine particle multiplets as performance modifiers.

PURPOSE: To evaluate the use of carrier-based dry powder aerosols for inhalation delivery of proteins and examine the effect of fine particle excipients as potential formulation performance modifiers. METHODS: Bovine serum albumin (BSA) was co-processed with maltodextrin by spray-drying to produce model protein particles. Aerosol formulations were prepared by tumble mixing protein powders with alpha-lactose monohydrate (63-90 microns) or modified lactoses containing between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene glycol 6000. Powder blends were characterised in terms of particle size distribution, morphology and powder flow. Formulation performance in Diskhaler and Rotahaler devices was investigated using a twin stage impinger operating at 60.s51 min-1. RESULTS: Inhalation performance of binary ordered mixes prepared using BSA-maltodextrin and lactose (63-90 microns) was improved by addition of FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine particle fraction (0.5-6.4 microns) using the Diskhaler was increased from 31.7 +/- 2.4% to 47.4 +/- 2.2%. Inclusion of FPL and micronised PEG 6000 changed the bulk properties of inhalation powders and reduced powder flow but did not affect device emptying. Unexpectedly, improvements in performance were found to be independent of the order of addition of FPL to the ternary powder formulations. SEM studies revealed that this was probably the result of a redistribution of protein particles between the coarse carrier lactose component and added FPL during mixing. CONCLUSIONS: Fine particle excipients can be used to improve the performance of carrier-based protein dry powder aerosols. Mechanistically, enhancement of performance is proposed to result from a redistribution of protein particles from coarse carrier particles to the fine particle component in the ternary mix.

Aerosols↗

Operative reconstruction after transverse rupture of the tendons of both peroneus longus and brevis. Surgical reconstruction by transfer of the flexor digitorum longus tendon.

Rupture of the tendons of both peroneus longus and peroneus brevis results in considerable disability. We have performed transfer of flexor digitorum longus (FDL) to peroneus brevis in two patients with lateral instability of the hindfoot due to chronic transverse tears of both tendons for which end-to-end repair was not possible. Both patients had excellent function when reviewed after eight and six years, respectively, with no symptoms. CT showed a normal appearance of the FDL in both patients, but the peroneal muscles looked abnormal. Transfer of the FDL provides a reliable solution to lateral instability of the hindfoot resulting from loss of function of both peronei.

Ankle↗

Primary culture of antennal cells of Mamestra brassicae: morphology of cell types and evidence for biosynthesis of pheromone-binding proteins in vitro.

A culture technique for the in vitro growth and differentiation of antennal cells of Mamestra brassicae is described. The morphology of the growing cells is described. At least five morphological cell types can be distinguished in the cultures. Neuronal cells (type A) were characterized morphologically and immunocytochemically with anti-HRP staining and could be separated into two subtypes, A1 and A2, on the basis of the size of the cell body. Non-neuronal cells could be divided into four types. Type-B cells consisted of large and flat cells with a veil-like cytoplasm. They usually adhered to each other and formed groups of 20 to 50 cells. Type C were large and flat cells, highly variable in size and shape. They closely resembled insect glial cells in culture. Type-D cells grew thick processes, up to 100 microm long. These elongated processes resembled trichoid hairs, and D cells are most probably trichogen cells. Type E were spindle-shaped cells present in low number in the cultures. A high proportion of similar cells in the hemolymph of pupae suggests that E cells are hemocytes. Pheromone-binding proteins were detected using specific antisera in the medium of 3- to 4-week-old cultures.

Animals↗

A second DNA polymerase activity in yeast mitochondria.

In eukaryotic cells, there is much evidence to indicate that the replication of the mitochondrial genome is carried out by a specific DNA polymerase named DNA polymerase gamma. In the yeast S. cerevisiae, a DNA polymerase gamma has been partially purified and the gene encoding the catalytic subunit identified. The characteristics of this enzyme are the same as those found in higher eukaryotes, except for the requirement for a higher magnesium concentration. During a purification procedure of yeast mitochondrial DNA polymerase, we have isolated a second DNA polymerase activity. Using different approaches ive have ruled out the possibility of nuclear contamination or a product of proteolysis. From its properties, this new DNA polymerase activity seems to be different from any yeast DNA polymerase. This new mitochondrial DNA polymerase activity provides evidence that the animal model of mitochondrial DNA replication cannot be generalized. The presence of two DNA polymerases in yeast mitochondria could reflect a different replication or repair mechanism.

Cell Fractionation↗

Effects of trifluoromethyl ketones and related compounds on the EAG and behavioural responses to pheromones in male moths.

Trifluoromethyl ketones (TFMKs) and analogues affect pheromone detection and behaviour in male moths. 3-Octylthio-1,1,1-trifluoropropan-2-one (OTFP), one of the most effective antiesterase agents, decreased the EAG amplitude and increased the repolarization time in Spodoptera littoralis. It also modified EAG responses of Mamestra brassicae and Heliothis zea to their pheromones and analogues, containing an acetate, an alcohol or an aldehyde function. In addition, OTFP also reduced the amplitude of the EAG response to linalool, a monoterpenic alcohol, but not its kinetics. The responses of male S. littoralis to the pheromone in the wind tunnel were significantly reduced after pre-exposure to vapours of OTFP. Comparison of the activity of other TFMKs and analogues with that of OTFP revealed a good agreement on EAG and behaviour. The effects of TFMKs on the EAG kinetics are discussed considering the hypothesis of an inhibition of the pheromone deactivation in the antenna.

Acetone↗

Language as a barrier to the acquisition of anatomical knowledge.

The language of instruction for medical students at the University of Hong Kong is English, which is their second language. This presents a potential barrier to their academic learning. We have studied the extent of this problem by looking at the amount of terminology students have to assimilate during their anatomy course and the way in which the terminology is structured and explained (this provides, more generally, an indication of the factual loading to which medical students are exposed). We have also investigated the effect of the quality of students' language skills on their examination results in anatomy class tests and MBBS exams. It was found that students' entrance levels in English correlated well with their final examination results and that the quality and quantity of their English also correlated highly with scores in class tests. On this basis, we conclude that language is one of the most important barriers to students' academic success in the department and that current teaching materials may not be appropriate.

Anatomy↗

Salvage of pseudoarthrosis after tibiotalar arthrodesis.

We retrospectively reviewed the treatment of a selected group of 23 patients with pseudoarthrosis after ankle arthrodesis who underwent revision arthrodesis at an average of 1.7 years (range, 0.3-17.0 years) after the initial, unsuccessful procedure. Fourteen patients underwent isolated revision tibiotalar arthrodesis, and 9 had an additional hindfoot arthrodesis (7 tibiotalocalcaneal, 2 pantalar) performed at the time of the procedure. Rigid internal fixation with screws was performed when possible, and, in patients with poor bone quality, an external fixator was used. Autogenous bone grafting was used in 14 patients where bone loss was present. Twenty-one of 23 patients had successful union (average, 14 weeks; range, 6-48 weeks). Two patients underwent successful arthrodesis but had persistent pain from reflex sympathetic dystrophy. Overall, 19 of 23 patients were satisfied with the surgery. We conclude that revision arthrodesis for tibiotalar pseudoarthrosis is a worthwhile procedure.

Adult↗

Novel fluorinated surfactants for perfluorochemical emulsification: biocompatibility assessments of glycosidic and polyol derivatives.

A novel series of fluoro-surfactants, derived from glycosides (monosaccharides) or polyols (ureas or carbamates), have been produced for use in respiratory gas-carrying perfluorochemical emulsions. Compounds were synthesised via simple, but highly selective, routes using highly fluorinated isocyanates with amino alcohols, polyethoxylated alcohols and partially protected sugars at anomeric carbon; yields were 88-95%. Resultant compounds were perfluoroalkylated with hydroxylic "head" groups. The biocompatibility of surfactants with human blood in vitro was assessed using a conventional haemolysis test. Compounds showing insignificant haemolysis at up to 10 g l-1 were further evaluated (i) for their effects on neutrophil chemiluminescence, and (ii) in a human platelet aggregation assay. Some fluoro-surfactants inhibited spontaneous platelet aggregation, in blood anti-coagulated with hirudin, at concentrations of 0.01% (w/v), suggesting possible applications as antithrombotic agents.

Ampholyte Mixtures↗

Effects of needle exchanges in Hobart, Tasmania.

An examination was conducted of three Tasmanian cohorts of injecting drug users interviewed before the introduction of needle exchanges, during the operation of illegal exchanges and after the introduction of legal exchanges. The drugs reported as used were comparable with reports from Perth and Sydney samples. There are clear downward trends for both males and females toward reduced sharing of injecting equipment and increased use of new equipment which begin when the illegal exchanges were operating and accelerate when the number of exchanges increased and became legal. The use of bleach to clean equipment also increases in the 4-year period. There was a much higher use of open fires to dispose of equipment than has been reported elsewhere. These results strongly suggest that needle exchanges do lead to reduced sharing and to less needles in public places; vital outcomes if AIDS and hepatitis are to be contained.

Journal Article↗

Melanocortin probes for the melanoma MC1 receptor: synthesis, receptor binding and biological activity.

The fate of alpha-melanocyte-stimulating hormone (alpha-MSH) subsequent to binding to the melanoma melanocortin MC1 receptor is of interest with regard to its potential use in targeting cytotoxic drugs or imaging to melanoma. Tools such as iodinated, photoaffinity-labelled, biotinylated and fluorescent melanocortins are required to study the fate of the ligand during its interaction with the receptor. In this study, a series of probes for the receptor based on the potent analogue, [Nle4,Dphe7]alpha-MSH, have been developed and tested for their potential usefulness. All probes contain the core melanocortin motif His-Phe-Arg-Trp. They bind the receptor readily and appear to have similar intrinsic efficacies to the endogenous peptide, so that biological activity is regulated by their receptor binding affinity. Functional photoaffinity-labelled, biotinylated and fluorescent probes are described. The biotinylated probe binds the receptor when coupled to streptavidin, although with reduced affinity.

Animals↗

Intra-renal Doppler wave-form analysis as a screening test for renal artery stenosis.

A double-blinded trial was performed comparing Doppler interrogation of intra-renal arteries with findings at renal angiography in the assessment of renal artery stenosis. Fifty-three consecutive patients were studied. Previously reported parameters and cut-off values were used for predicting the presence of renal artery stenosis with Doppler. Doppler wave-form analysis proved relatively specific (91%) but insensitive (68%) to the presence of renal artery stenosis (of greater than 60%) if acceleration parameters were used alone. The technique of using a difference in mean resistive indices was found to be both insensitive (61%) and non-specific (54%). Patients with fibromuscular dysplasia, branch vessel stenoses, multiple renal arteries and chronic renal impairment proved to cause the most false negatives. Young patients with normal arteries were the source of the few false positive results. The interrogation of intra-renal arteries does not have appropriate sensitivity to be useful as a screening test for renal artery stenosis.

Adult↗

Pancreatitis in children infected with human immunodeficiency virus.

The incidence of pancreatitis in HIV-infected children is not well known. Medical records of 42 children with HIV infection followed at Children's Hospital during a 6-year period were reviewed. Pancreatitis (elevated serum lipase levels) developed in 10 children (23.8%). Three children acquired HIV infection from vertical transmission and seven from contaminated blood products (hemophiliacs). Nine were severely immunosuppressed (CD4+ of < 100 cells/mm3). Lipase values were more often elevated than amylase values. The clinical course was protracted and severe in two children, one had four recurrences, and seven had only a single episode of pancreatitis lasting a few weeks. Opportunistic infections were present in four children and seven were receiving medications previously implicated as cause of pancreatitis. Discontinuation of dideoxynosine (ddI) in one child led to rapid resolution of pancreatitis, but continuation of medications in the other children did not alter the course. The etiology of pancreatitis may be multifactorial. Severe and prolonged clinical course is associated with advanced HIV infection. Determination of serum lipase is more useful than serum amylase for identifying those with pancreatitis.

AIDS-Related Opportunistic Infections↗

Lumbar spinal stenosis: a review.

Lumbar spinal stenosis can usually be identified after a thorough history and physical examination. Most individuals with this condition are successfully treated by non-operative means. Invasive radiologic studies and surgery are reserved for those patients who fail to respond to conservative measures. In these select cases, predictably good results can be expected from lumbar decompression.

Aged↗

[Problems in the adjustment of evaluation and repair of bodily injuries in tomorrow's Europe].

The evaluation of traumatic body damage raises difficult problems when considered in the frame of European Community in view of the major differences currently existing between modes of compensation of such damages in the different countries of the Union. While the economic loss resulting from a given damage should no doubt continue to be fully compensated, obvious financial constraints at the level of insurances will probably make it necessary to consider lump compensation for the non-economic losses which involve the physical and/or psychical integrity of the person. It is proposed to use the term 'personal incapacity' to describe the latter losses whose numerical evaluation now requires the elaboration of new modes of rating (in french, 'barème'). A number of principles are proposed for the actual design and elaboration of this instrument, namely by taking into account the detailed estimation of each of relevant human functions in daily living, thus outside any professional context. Such the new approach proposed should eventually provide an essential instrument for the calculation of these lump compensations, no matter in which country the accident took place nor which are the countries of citizenship of victim, defendant, and insurance companies involved.

Belgium↗