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Biomedical subjects

A Shaw

Publications and source records attributed to A Shaw.

At least 19 recordsLinked to original sources
PubMed2005

Patient perspectives on multiple medications versus combined pills: a qualitative study.

BACKGROUND: A growing number of patients are taking multiple medications. Unfortunately, adherence may fall as drug numbers and procedural complexity increase. While there are plausible theoretical reasons why combining pills might improve non-adherence, patients' attitudes are unknown. AIM: To explore attitudes and practices to medication regimens among patients already in receipt of multiple medications, and to assess whether a combined tablet would be perceived as advantageous. DESIGN: Qualitative study. METHODS: Ninety-two men and women aged >40 years currently receiving both antihypertensive and cholesterol-lowering medications took part in 14 focus groups. RESULTS: Drugs were seen as unwelcome but necessary. Some took drugs flexibly by changing dose timing, thereby increasing the complexity of their regimen. A routine was seen as the key to coping with multiple medications, although it was sometimes threatened by changes in prescriptions and life circumstances. While some participants welcomed a combined pill, there was uncertainty about whether a combination that mirrored their current doses would be available. There were also concerns about tablet size, allergies, the attribution of side-effects, timing of tablets throughout the day, and the ability to alter dose levels. CONCLUSION: While some patients would be willing to try a combined pill and would appreciate the associated convenience, they are likely to have a number of concerns that prescribers should address. Willingness to move to combined therapy may be hindered if drug combinations that mirror personalized and trusted regimens are not available.

Aged↗
PubMed2005

A safety evaluation of drotrecogin alfa (activated) in hematopoietic stem cell transplant patients with severe sepsis: lessons in clinical research.

We conducted an open-label, multicenter, single-arm clinical trial to investigate the safety and efficacy of drotrecogin alfa (activated) (Drot AA) in hematopoietic stem cell transplant (HSCT) patients with severe sepsis. Drot AA was administered as a continuous i.v. infusion of 24 microg/kg/h for 96 h. The target enrollment was 250 patients in 15-20 transplant centers over a 2-year period (March 2003-March 2005). However, after only 10 months, in December 2003, the trial was stopped due to a low enrollment of seven patients at three of the 15 sites that were open for accrual. Six of the seven patients completed the drug infusion. Two patients experienced serious bleeding events. The first patient developed a nonfatal diffuse alveolar hemorrhage 2 days after study-drug completion. The second patient had severe coagulopathy and developed a fatal intracranial hemorrhage on the third day of drug infusion. Three of the seven patients were alive 100 days after the HSCT. The slow enrollment rate was attributed to changes in transplant preparatory regimens, enhancements in antimicrobial prophylactic protocols and the use of antimicrobial-coated catheters. The small number of patients in this report precludes a definitive assessment of the safety and efficacy of Drot AA in HSCT patients.

Adult↗
PubMed2005

Microbial ecology of the cystic fibrosis lung: does microflora type influence microbial loading?

This study aims to examine the association between the numbers of culturable microbial species forming the microflora of the lung in patients with cystic fibrosis (CF) and microbial loading (i.e., type[s] versus numbers). Additionally, it examines qualitative combinations of the microflora present in a large adult CF centre (n=138) in order to ascertain ecological relationships between the taxa present. The culturable microflora of sputum from 34 adults patients with CF are enumerated using a spread plate technique on non-selective agar, and the microflora identified phenotypically employing the API 20NE scheme. Microbiological examination of the 34 adult patients demonstrated that their sputum contained between one and three taxa, with a mean cell density of 8.25 +/- 0.85 log colony-forming units (cfu)/g sputum and a range of 5.91-9.74 log cfu/g sputum. Most colonising patterns demonstrated only Gram-negative infection (22/34), followed by a mixed Gram-positive/Gram-negative infection pattern (10/34). Only 2/34 patients had a single Gram-positive infection. Most patients (53%) were colonised by only one organism, with 38% of patients colonised by two organisms, and the remainder (4%) colonised with three organisms. There was no statistical difference (P>0.05) between microbial cell density and the number of taxa present (i.e., the greater number of taxa present in sputum did not produce a higher cell density). However, there was a significantly higher cell density (log 0.59 cfu/g sputum) noted for those patients who had only Gram-negative infection, compared to those who had a mixed Gram-negative/Gram-positive infection pattern (P=0.02). Relatively little is known about the ecological interactions that exist between the microflora in the CF lung. Further work is required to explore these interactions in order to aid understanding of the succession and dominance of Gram-negatives in chronic chest infections. Ultimately, a greater understanding of such interactions may allow the opportunity to manipulate the ecology of the lung to control otherwise problematic pathogens

Adult↗
PubMed2004

Assessing the patterns of health-seeking behaviour and awareness among sleeping-sickness patients in eastern Uganda.

For those with sleeping sickness, the consequences of delayed diagnosis include poor prognosis at treatment and an increased risk of tsetse infection. Data on their socio-demographic and clinical characteristics, health-seeking behaviour and delays in presentation and diagnosis were collected from 119 diagnosed cases of rhodesiense sleeping sickness in eastern Uganda. The median total delay, from onset of the illness to diagnosis, was 60 days. The median service-provider delay (30 days) was markedly longer than the median patient delay (17 days). Each of these delays was, however, considerable and independently associated with patients presenting with late-stage sleepiness, giving odds ratios and (95% confidence intervals) of 7.29 (3.10-17.14) and 2.98 (1.38-6.43), respectively. A blood examination at the first visit was also associated with the service-provider delay (odds ratio = 0.45; 95% confidence interval = 0.22-0.95). Most of the patients (77.4%) had either been referred to the local sleeping-sickness hospital by other members of their community or presented at the hospital on their own initiative; few had been referred by other components of the local health system. The results are disappointing, not only in showing long delays in diagnosis (and therefore in treatment) but also in indicating that much of the delay is attributable to the service provider failing to diagnose sleeping sickness among symptomatic individuals.

Adolescent↗
PubMed2003

Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory syncytial virus and other respiratory viral infections.

Respiratory syncytial virus (RSV) infection, one of the most common causes of hospitalization of children in developed countries, has been implicated as a cause of asthma. We aimed to characterize the cytokine profile in nasopharyngeal aspirates (NPAs) taken from infants during upper respiratory tract infection to investigate whether RSV induced a unique immune response as compared with other viruses. Additionally, we sought to determine whether this profile was influenced by the infants' atopic status. A prospective birth cohort of babies at high risk of atopy was recruited. Ratios of a T-helper 1 (Th1) cytokine, interferon gamma (IFN-gamma) and a T-helper 2 (Th2)-like cytokine, interleukin-10 (IL-10), in NPAs were determined during episodes of respiratory tract infections in the first year. The viral aetiology of the respiratory tract infections was determined using polymerase chain reaction (PCR), culture and immunofluorescence. Atopic status was ascertained at 1 year of age using skin prick tests. Participants were recruited antenatally and subsequently followed in the community. Sixty babies with one or both parents atopic were enrolled into the study. IFN-gamma : IL-10 ratios in NPAs during upper respiratory tract infections and their correlation with viral aetiology and atopic status were the main outcome measures. The mean IFN-gamma : IL-10 ratio was significantly lower (due to lower IFN-gamma) during RSV infections than during infections with other viruses (P = 0.035). The cytokine ratio, however, did not differ between infants with or without wheeze during URTIs (P = 0.44), or between infants who were atopic or non-atopic (P = 0.49). This study suggests that RSV is associated with lower IFN-gamma production in young babies, regardless of their atopic status, compared to upper respiratory tract infections where either another virus is detected or where no viral identification is made.

Follow-Up Studies↗
PubMed2002

A novel combination of two classic catalytic schemes.

The crystal structure of an alkaline Bacillus cellulase catalytic core, from glucoside hydrolase family 5, reveals a novel combination of the catalytic machinery of two classic textbook enzymes. The enzyme has the expected two glutamate residues in close proximity to one another in the active-site that are typical of retaining cellulases. However, the proton donor, glutamate 139 is also unexpectedly a member of a serine-histidine-glutamate catalytic triad, forming a novel combination of catalytic machineries. Structure and sequence analysis of glucoside hydrolase family 5 reveal that the triad is highly conserved, but with variations at the equivalent of the serine position. We speculate that the purpose of this novel catalytic triad is to control the protonation of the acid/base glutamate, facilitating the first step of the catalytic reaction, protonation of the substrate, by the proton donor glutamate. If correct, this will be a novel use for a catalytic triad.

Bacillus↗
PubMed2001

Solution structure and interaction surface of the C-terminal domain from p47: a major p97-cofactor involved in SNARE disassembly.

p47 is the major protein identified in complex with the cytosolic AAA ATPase p97. It functions as an essential cofactor of p97-regulated membrane fusion, which has been suggested to disassemble t-t-SNARE complexes and prepare them for further rounds of membrane fusion. Here, we report the high-resolution NMR structure of the C-terminal domain from p47. It comprises a UBX domain and a 13 residue long structured N-terminal extension. The UBX domain adopts a characteristic ubiquitin fold with a betabetaalphabetabetaalphabeta secondary structure arrangement. Three hydrophobic residues from the N-terminal extension pack closely against a cleft in the UBX domain. We also identify, for the first time, the p97 interaction surface using NMR chemical shift perturbation studies.

Adenosine Triphosphatases↗
PubMed2001

The X-ray crystal structure of the Trichoderma reesei family 12 endoglucanase 3, Cel12A, at 1.9 A resolution.

We present the three-dimensional structure of Trichoderma reesei endoglucanase 3 (Cel12A), a small, 218 amino acid residue (24.5 kDa), neutral pI, glycoside hydrolase family 12 cellulase that lacks a cellulose-binding module. The structure has been determined using X-ray crystallography and refined to 1.9 A resolution. The asymmetric unit consists of six non-crystallographic symmetry-related molecules that were exploited to improve initial multiple isomorphous replacement phasing, and subsequent structure refinement. The enzyme contains one disulfide bridge and is glycosylated at Asp164 by a single N-acetyl glucosamine residue. The protein has the expected fold for a glycoside hydrolase clan-C family 12 enzyme. It contains two beta-sheets, of six and nine strands, packed on top of one another, and one alpha-helix. The concave surface of the nine-stranded beta-sheet forms a large substrate-binding groove in which the active-site residues are located. In the active site, we find a carboxylic acid trio, similar to that of glycoside hydrolase families 7 and 16. The strictly conserved Asp99 hydrogen bonds to the nucleophile, the invariant Glu116. The binding crevice is lined with both aromatic and polar amino acid side-chains which may play a role in substrate binding. The structure of the fungal family 12 enzyme presented here allows a complete structural characterization of the glycoside hydrolase-C clan.

Amino Acid Sequence↗
PubMed2001

Histometrics: improvement of the dynamic range of fluorescently stained proteins resolved in electrophoretic gels using hyperspectral imaging.

Most image-based analyses, using absorbance or fluorescence of the spatial distribution of identifiable structures in complex biological systems, use only a very small number of dimensions of possible spectral data for the generation and interpretation of the image. We here extend the concepts of hyperspectral imaging, being developed in remote sensing, into analytical biotechnology. The massive volume of information contained in hyperspectral spectroscopic images requires multivariate analysis in order to extract the chemical and spatial information contained within the data. We here describe the use of multivariate statistical methods to map and quantify common protein staining fluorophores (SYPRO Red, Orange and Tangerine) in electrophoretic gels. Specifically, we find (a) that the 'background' underpinning limits of detection is due more to proteins that have not migrated properly than to impurities or to ineffective destaining, (b) the detailed mechanisms of staining of SYPRO red and orange are apparently not identical, and in particular (c) that these methods can provide two orders of magnitude improvement in the detection limit per pixel, to levels well below the limit observable optically.

Biotechnology↗