Guidelines on the management of Waldenström macroglobulinaemia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Birchall.
Explore the source record for details and available documents.
We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.
BACKGROUND: The skin represents an accessible somatic tissue for therapeutic gene transfer. The superficial lipophilic layer of the skin, the stratum corneum, however, constitutes a major obstacle to the cutaneous delivery of charged macromolecules such as DNA. OBJECTIVES: To determine whether silicon-based microneedles, microfabricated via a novel isotropic etching/BOSCH reaction process, could generate microchannels in the skin of sufficient dimensions to facilitate access of lipid : polycation : pDNA (LPD) nonviral gene therapy vectors. METHODS: Scanning electron microscopy was used to visualize the microconduits created in heat-separated human epidermal sheets after application of the microneedles. Following confirmation of particle size and particle surface charge by photon correlation spectrocopy and microelectrophoresis, respectively, the diffusion of fluorescent polystyrene nanospheres and LPD complexes through heat-separated human epidermal sheets was determined in vitro using a Franz-type diffusion cell. In-vitro cell culture with quantification by flow cytometry was used to determine gene expression in human keratinocytes (HaCaT cells). RESULTS: The diffusion of 100 nm diameter fluorescent polystyrene nanospheres, used as a readily quantifiable predictive model for LPD complexes, through epidermal sheets was significantly enhanced following membrane treatment with microneedles. The delivery of LPD complexes either into or through the membrane microchannels was also demonstrated. In both cases considerable interaction between the particles and the epidermal sheet was observed. In-vitro cell culture was used to confirm that LPD complexes mediated efficient reporter gene expression in human keratinocytes in culture when formulated at the appropriate surface charge. CONCLUSIONS: These studies demonstrate the utility of silicon microneedles in cutaneous gene delivery. Further studies are required to elucidate fully the influence of the physicochemical characteristics of gene therapy vectors, e.g. particle diameter and surface charge, on their diffusion through microchannels and to quantify gene expression in vivo.
Explore the source record for details and available documents.
The parity-violating longitudinal analyzing power, A(z), has been measured in pvectorp elastic scattering at an incident proton energy of 221 MeV. The result obtained is A(z) = [0.84+/-0.29(stat)+/-0.17(syst)]x10(-7). This experiment is unique in that it selects a single parity violating transition amplitude (3P2 - 1D2) and consequently directly constrains the weak meson-nucleon coupling constant h(pp)(rho). When this result is taken together with the existing pvectorp parity violation data, the weak meson-nucleon coupling constants h(pp)(rho) and h(pp)(omega) can, for the first time, both be determined.
The impetus to develop non-viral gene delivery vectors has led to examination of synthetic polycationic polymers as plasmid DNA (pDNA) condensing agents. Previous reports have highlighted superiority (up to x 10-fold) in the in-vitro transfection of pDNA complexes formed by poly-(L)-ornithine (PLO) compared to those formed with poly-(L)-lysine (PLL). The apparent basis for this consistent superiority of PLO complexes remains to be established. This comparative study investigates whether physico chemical differences in the supramolecular properties of polycation:pDNA complexes provide a basis for their observed differential gene transfection. Specifically, particle size distribution and zeta potential of the above complexes formulated over a wide range of polycation:pDNA ratios were found to be consistent with a condensed (150-200 nm) cationic ( + 30-40 mV) system but not influenced by the type of cationic polymer used. A spectrofluorimetric EtBr exclusion assay showed that polycation:pDNA complexes display different pDNA condensation behaviour, with PLO able to condense pDNA at a lower polycation mass compared to both polylysine isomers, and form complexes that were more resistant to disruption following challenge with anionic counter species, i.e. poly-(L)-aspartic acid and the glycosaminoglycan molecule. heparin. We conclude that particle size and surface potential as gross supramolecular properties of these complexes do not represent, at least in a non-biological system, the basis for the differential transfection behaviour observed between these condensing polymers. However, differences in the ability of the polylysine and polyornithine polymers to interact with pDNA and to stabilise the polymer-pDNA assembly could have profound effects upon the cellular and sub-cellular biological processing of pDNA molecules and contribute to the disparity in cell transfection efficiency observed between these complexes.
OBJECTIVE: To identify the causes of dizziness in older patients presenting to the general practitioner and the clinical characteristics at presentation that might guide the general practitioner to the likely cause of dizziness and the most appropriate specialty for subsequent referral if referral is required. DESIGN: A prospective case control study of older patients presenting with dizziness. SETTING: The initial assessment was made in four general practices, three urban practices and one inner city practice (Newcastle). Subsequent investigations were conducted randomly in the Neurocardiovascular Investigation Unit and the Otolaryngology (ENT) Unit at local University hospitals (Newcastle). PARTICIPANTS: Fifty consecutive patients more than 60 years of age presented with dizziness. Twenty-two age- and sex-matched case controls were recruited from the same general practices. MEASUREMENTS: Measurements were of diagnoses attributable to symptoms. RESULTS: Symptoms were of long duration (median 1 year). Forty-six percent of patients had syncope and/or falls in addition to dizziness. Twenty-eight percent had a cardiovascular diagnosis, 18% had a peripheral vestibular disorder, 14% had a central neurological disorder, 18% had more than one diagnosis, and 22% had no attributable cause of symptoms identified. A cardiovascular diagnosis was predicted by the presence of syncope (P < .001), dizziness described as lightheadedness (P < .001), the need to sit or lie down during symptoms (P < .001), pallor with symptoms (P < .001), symptom precipitation by prolonged standing (P < .05), and whether patients had coexisting cardiovascular disease (P < .05). The description of dizziness as "vertigo" predicted a peripheral vestibular disorder (P < .001). The predictive strength of these prognostic indicators was then validated on a separate sample of 50 additional older patients. CONCLUSIONS: Clinical characteristics can predict an attributable cause of dizziness in most older patients and thus guide general practitioners in treatment and appropriate specialist referral. The presence of syncope, falls, or cardiovascular comorbidity increases the likelihood of a cardiovascular diagnosis. Otolaryngological investigations are rarely diagnostic, but vertiginous symptoms do predict peripheral vestibular disorders.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.