Biomedical subjects
R Jones
Publications and source records attributed to R Jones.
Effectiveness of rivastigmine in Alzheimer's disease. Participation in trials should be based on clinical uncertainty, not enforcement.
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Hydrogen interaction with dislocations in Si
An H plasma has a remarkable effect on dislocation mobility in silicon, reducing its activation energy to 1.2 eV. Applying density functional theory to the interactions of H and H2 with the core of the 90 degrees partial dislocation in Si, we have identified a path for motion involving kink formation and migration at hydrogenated core bonds which conforms exactly to the experimentally measured activation energy.
A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads.
The present study reports on the solution structure of the guanine plus adenine rich d(A(2)G(2)T(4)A(2)G(2)) 12-mer sequence which forms a unique fold in moderate NaCl solution. Proton resonance assignments for this sequence, which contains a pair of AAGG repeats separated by a T(4) linker segment, were aided by site-specific (15)N-labeling of guanine and adenine bases, as well as site-specific incorporation of 2,6-diaminopurine and 8-bromoadenine for adenine, 8-bromoguanine, 7-deazaguanine and inosine for guanine, and uracil and 5-bromouracil for thymine. The solution structure, which was solved by a combined NMR and intensity-refined computational approach, consists of a diamond-shaped architecture formed through dimerization of a pair of d(A(2)G(2)T(4)A(2)G(2)) hairpins. This 2-fold symmetric structure contains a quadruplex core consisting of a pair of symmetry-related G(syn).G(syn).G(anti). G(anti) tetrads, where adjacent strands have both parallel and anti-parallel neighbors and connecting T(4) segments which form diagonal loops. Each of the G(syn).G(syn).G(anti).G(anti) tetrads forms a platform on which stacks a T(anti).[A(syn)-A(anti)] triad containing a novel A(syn)-A(anti) platform step and a reversed Hoogsteen A(syn).T(anti) pair. We observe both base-base and base-sugar stacking interactions, with the latter occuring at a sheared A-G step where the sugar of the A stacks on the purine plane of the G. Unexpectedly, the topology of this sheared A(anti)-G(syn) step has many similarities with the C(anti)-G(syn) step in left-handed Z-DNA. The T.(A-A) triad is sandwiched between the G-tetrad on one side and a reversed Hoogsteen A(anti).T(anti) pair on the other. This intercalative topology is facilitated by a zipper-like motif where the A(anti) residue of the triad is interdigitated within a stretched A(anti)-G(syn) step. Our structural study reports on new aspects of A-A platforms, base triads, zipper-like interdigitation and sheared base steps, together with base-base and base-sugar stacking defining a diamond-like architecture for the d(A(2)G(2)T(4)A(2)G(2)) sequence. One can anticipate that mixed guanine-adenine sequences will exhibit a rich diversity of polymorphic architectures that will provide unique topologies for recognition by both nucleic acids and proteins.
Availability of equine medicines.
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False-positive maternal serum screening in systemic lupus erythematosis: a case report.
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Experimental evaluation of a short transitional edge protection balloon for intracoronary stent deployment.
The purpose of this study was to determine if balloon injury to the adjacent arterial wall during intracoronary stent deployment influences late in-stent neointimal formation. Stent design and deployment techniques are considered important factors in determining acute and long-term success with intracoronary stenting. Experimental and clinical studies support that the extent of neointimal formation and the probability for restenosis are influenced by the magnitude of arterial trauma induced with stenting. Nineteen 18-mm-long balloon-expandable stainless steel stents (MULTI-LINK Duet) were implanted at a 1:1 stent-to-artery ratio in the coronary arteries of swine with a conventional noncompliant balloon (n = 10) or a novel noncompliant balloon with short tapered shoulders to prevent edge dissection (n = 9). Quantitative coronary angiography and histology were used to evaluate balloon and artery interactions and the chronic vascular responses to the stents. Nineteen stents were implanted in the coronary arteries of seven swines at an inflation pressure of 14 atm using a standard noncompliant (n = 10) or a unique short transitional edge protection (n = 9) balloon. Histologic analysis at 28 days demonstrated balloon-associated barotrauma in 13 of 20 (65%) of adjacent nonstented arterial segments with the conventional balloon and only 3 of 18 (17%) of the adjacent nonstented arterial segments with the short transition edge protection balloon (P = 0.022). In-stent neointimal area and % stenosis correlated with the severity of peristent arterial injury (r = 0.43, P = 0.01). In-stent vessel injury scores were similar for stents with peristent injury (1.0+/-0.3) versus stents without peristent injury (1.0+/-0.03, P = 0.73). In-stent neointimal area and % stenosis were greater for stents with peristent injury (2.36+/-0.74 mm(2), 32%+/-9%) as compared to stents without peristent injury (1.39+/-0.70 mm(2), 20%+/-10%, P = 0.01). Arterial wall injury adjacent to a stent after high-pressure deployment contributes to late in-stent neointimal hyperplasia in this model. These experimental data suggest that further study is warranted to refine stent implantation techniques and that modifications of balloon shape or material may be useful to optimize stent deployment and reduce arterial trauma.
Characterization of bovine collagens using capillary electrophoresis.
A capillary electrophoresis method was developed and characterized for analyzing the spectrum of collagen subspecies in collagen preparations. The Bio-Rad CE-SDS protein kit was used for the dynamic sieving separation of collagen subspecies in this CE method (DSCE). The optimized method utilized a 36 cm (or 24 cm) x 50 microm uncoated capillary, electrophoretic injection at 10 kV for 10 s, a run voltage of 15 kV, a capillary temperature of 20 degrees C, and UV detection at 220 nm. A preliminary validation of the method was performed. The assay had good repeatability (RSDs for peaks were 15%), and responses were linear for assay solutions with collagen concentrations from 0.125 to 1.25 mg/ml. The DSCE electropherogram of bovine skin collagen provided a profile of subspecies similar in number and relative abundance to that generated by scanning of Coomassie-stained SDS-PAGE gels.
Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.
Peripheral blood stem cell grafts from patients with lymphoma are often contaminated with neoplastic cells. Administration of a lymphoma-specific monoclonal antibody before collecting stem cells may be one way of reducing the contamination. Similarly, an antibody after transplantation at a time of minimal residual disease may increase the efficacy of the procedure. The objective of this study was to determine the safety of using rituximab as both an in vivo purging agent and a posttransplantation adjuvant. Eligible patients with lymphoma received 375 mg/m2 rituximab intravenously IV) on day 1, 2.5 g/m2 cyclophosphamide IV on day 4, and 10 microg/kg per day filgrastim starting on day 5 and continuing until completion of leukapheresis. Patients subsequently received a standard preparative regimen and then received 375 mg/m2 rituximab IV 7 days after platelet independence was achieved. Twenty-five patients (14 men, 11 women; median age, 51 years) were enrolled. Of the 25 patients, 23 received transplants after at least 2.0 x 10(6) CD34+ cells/kg were harvested. As determined with a sensitive polymerase chain reaction assay, 6 of 7 stem cell products tested were free of tumor contamination. All patients engrafted promptly, and the rituximab infusions were well tolerated. Transient neutropenia of uncertain etiology occurred in 6 patients a median of 99.5 days post-transplantation. An additional patient developed progressive pancytopenia. Rituximab used as an in vivo purging agent and adjuvant immunotherapy with peripheral blood stem cell transplantation for non-Hodgkin's lymphoma is a well-tolerated regimen. However, the ultimate determination of efficacy will require the results of ongoing studies.
HCV prevalence in pregnant women in the UK.
The objective of the study was to assess the prevalence and epidemiology of hepatitis C virus (HCV) infection in pregnant women in the North Thames region, and in the UK in general. Demographic data were linked to neonatal samples prior to anonymization and testing by anti-HCV EIA, and with RIBA 3 confirmation. Risk factors for maternal infection were explored. Area-specific seroprevalence rates were multiplied into population sizes to estimate HCV prevalence in pregnant women in the UK. A total of 241/126,009 samples were confirmed anti-HCV positive, and a further 40 were indeterminate, representing a seroprevalence of 0.19-0.22%; 51% of maternal HCV infections were in UK-born women (71% of the population), and 22% in women from continental Europe (5% of the population). Among European-born women, HCV prevalence was associated with birth in continental Europe, partner not being notified at birth registration, partner born in a different region to the mother, and inner city residence. Four of the 241 anti-HCV positive samples (1.7%) were also anti-HIV-1 positive. It was estimated that each year an estimated 1150 out of 730,000 pregnancies in the UK would involve a woman infected with HCV (uncertainty range 660-1850), a prevalence of 0.16% (0.09-0.25%). On the basis of reported rates of mother-to-child transmission of HCV, this would represent approximately 70 paediatric HCV infections per year.
Programmed cell death in cereal aleurone.
Progress in understanding programmed cell death (PCD) in the cereal aleurone is described. Cereal aleurone cells are specialized endosperm cells that function to synthesize and secrete hydrolytic enzymes that break down reserves in the starchy endosperm. Unlike the cells of the starchy endosperm, aleurone cells are viable in mature grain but undergo PCD when germination is triggered or when isolated aleurone layers or protoplasts are incubated in gibberellic acid (GA). Abscisic acid (ABA) slows down the process of aleurone cell death and isolated aleurone protoplasts can be kept alive in media containing ABA for up to 6 months. Cell death in barley aleurone occurs only after cells become highly vacuolated and is manifested in an abrupt loss of plasma membrane integrity. Aleurone cell death does not follow the apoptotic pathway found in many animal cells. The hallmarks of apoptosis, including internucleosomal DNA cleavage, plasma membrane and nuclear blebbing and formation of apoptotic bodies, are not observed in dying aleurone cells. PCD in barley aleurone cells is accompanied by the accumulation of a spectrum of nuclease and protease activities and the loss of organelles as a result of cellular autolysis.
The prevalence of gastro-oesophageal reflux symptoms in a UK population and the consultation behaviour of patients with these symptoms.
BACKGROUND: Patients consulting with gastro-oesophageal reflux symptoms (GORS) may differ from nonconsulters. AIM: To describe these differences in a UK population. METHODS: A postal questionnaire was sent to 4432 adults. Definitions used were GORS (either heartburn or acid regurgitation on more than six occasions during the previous year), dyspepsia (upper abdominal pain or discomfort on more than six occasions during the previous year) and irritable bowel syndrome (abdominal pain with three or more Manning criteria). Socio-economic status was identified by the Standard Occupational Classification. RESULTS: With a 71.7% response, GORS were reported by 28.7% of the sample, it was unaffected by gender and age but was more common among the socially disadvantaged (P < 0. 005). Less than 25% of GORS patients consulted during the previous year. Increasing age (chi2 for trend; P < 0.001) and coexisting upper abdominal symptoms (chi2 P < 0.001) positively influenced consultation behaviour, but it was unaffected by socio-economic status, gender, or the coexistence of irritable bowel syndrome. Dyspepsia and nausea independently predicted consultation. CONCLUSIONS: GORS are especially common among the deprived. Socio-economic variables do not affect consultation behaviour, but the patient's age and the burden (number and type) of associated symptoms do.
Parenteral narcotic analgesic for labour pain 2.
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Drug information leaflets: adolescent and professional perspectives.
This study was undertaken to evaluate a range of drug information leaflets from both an adolescent and professional perspective. 72 adolescents were interviewed in focus groups within school settings. Fifteen paediatricians were also interviewed individually. Participants were asked to consider the leaflets under the following categories: initial impact, content and overall suitability for adolescents. Paediatricians were not good judges of which leaflets would appeal to adolescents. They tended to choose the leaflets with comic strip illustrations and those written in a 'cool' or witty style. In contrast the adolescents seemed to prefer a more sober approach with high quality factual information combined with clear illustrations.
Renal hemodynamics and pharmacokinetics of bosentan with and without cyclosporine A.
UNLABELLED: Renal hemodynamics and pharmacokinetics of bosentan with and without cyclosporine A. BACKGROUND: Endothelins may play an important role in cyclosporine A (CsA)-induced renal vasoconstriction. Therefore, the effects of a mixed endothelin A and B receptor antagonist, bosentan (BO), on CsA were studied. METHODS: BO was given either alone or combined with CsA to healthy subjects in a double-blind, placebo-controlled, cross-over study. Standardized renal hemodynamics took place after a single dose of BO or placebo and after seven days of regular intake of CsA + BO or CsA + placebo. CsA was administered as a dose-adjusted regimen to achieve predetermined target trough levels. A pharmacokinetic study of CsA and BO was performed. RESULTS: A single dose of BO did not affect renal hemodynamics. After seven days of coadministration with CsA, BO significantly attenuated both the overall CsA-induced fall of renal plasma flow (RPF; placebo, 594 +/- 85; CsA + placebo, 490 +/- 93; CsA + BO, 570 +/- 106* mL/min, *P < 0.01) and the maximal RPF fall (P < 0.01) observed five hours after CsA intake. The CsA-induced rise of blood pressure and the decrease of glomerular filtration rate (GFR) were not influenced by comedication with BO. After seven days of CsA + BO, the area under the curve (AUC) of BO was nearly doubled compared with the AUC after a single dose of BO (P < 0.05). To reach the CsA target trough levels after seven days, the average CsA dose was increased by 35% when given with BO, as compared with placebo (P = 0.01). CsA exposure (trough levels, AUC) was not statistically different after CsA + placebo and after CsA + BO. CONCLUSIONS: Assuming CsA nephrotoxicity is mainly due to vasoconstriction, BO has the potential to attenuate the CsA renal toxicity by markedly blunting the renal hypoperfusion effect of CsA. A complex drug interaction between BO and CsA was observed.
Primary care research: ends and means.
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Good publication practice
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