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Biomedical subjects

F Clarke

Publications and source records attributed to F Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Minimizing errors of omission: behavioural reenforcement of heparin to avert venous emboli: the BEHAVE study.

OBJECTIVE: To improve patient safety by increasing heparin thromboprophylaxis for medical-surgical intensive care unit patients using a multiple-method approach to evidence-based guideline development and implementation. DESIGN: Prospective longitudinal observational study. SETTING: Medical-surgical intensive care unit. PARTICIPANTS: Multidisciplinary clinicians caring for critically ill patients in a 15-bed medical-surgical closed intensive care unit. INTERVENTIONS: Phase 1 was a 3-month baseline period during which we documented anticoagulation and mechanical thromboprophylaxis. Phase 2 was a 1-yr period in which we implemented a thromboprophylaxis guideline using a) interactive multidisciplinary educational in-services; b) verbal reminders to the intensive care unit team; c) computerized daily nurse recording of thromboprophylaxis; d) weekly graphic feedback to individual intensivists on guideline adherence; and e) publicly displayed graphic feedback on group performance. Phase 3 was a 3-month follow-up period 10 months later, during which we documented thromboprophylaxis. Computerized daily nurse recording of thromboprophylaxis continued in this period. MEASUREMENTS AND MAIN RESULTS: Intensive care unit and hospital mortality rates were similar across phases, although patients in phase 2 had higher Acute Physiology and Chronic Health Evaluation II scores than patients in phases 1 and 3. The proportion (median % [interquartile range]) of intensive care unit patient-days of heparin thromboprophylaxis in phases 1, 2, and 3 was 60.0 (0, 100), 90.9 (50, 100), and 100.0 (60, 100), respectively (p=.01). The proportion (median % [interquartile range]) of days during which heparin thromboprophylaxis was omitted in error in phases 1, 2, and 3 was 20 (0, 53.8), 0 (0, 6.3), and 0 (0, 0), respectively (p<.001). CONCLUSIONS: After development and implementation of an evidence-based thromboprophylaxis guideline, we found significantly more patients receiving heparin thromboprophylaxis. Guideline adherence was maintained 1 yr later. Further research is needed on which are the most effective strategies to implement patient safety initiatives in the intensive care unit.

Aged↗
PubMed1999

A population-based survey of the management of women with cancer of the cervix.

The aim of this study was to investigate the influence of diagnostic throughput on survival outcome for women with cancer of the cervix. We conducted a case note review of 359 women in Lancashire and Greater Manchester diagnosed with cancer of the cervix during 1990, identified from records held by the North Western Regional Cancer Registry. Univariate and multivariate survival analyses were undertaken to investigate the influence on survival of woman, disease and treatment related factors. Following adjustment for woman- and disease-related factors there was no evidence of a statistically significant association between diagnostic throughput and survival. The findings of this study do not support the need for any change in the referral patterns to gynaecologists of women with symptoms suggestive of cancer of the cervix.

Adenocarcinoma↗
PubMed1998

Production and secretion of thioredoxin from transformed human trophoblast cells.

Thioredoxin is a redox active protein which has been implicated in reproductive processes. In this study we investigated the intracellular production and extracellular secretion of placental thioredoxin by human cytotrophoblast cell lines which were used as in-vitro model systems. Results clearly demonstrated that thioredoxin is not only synthesized by these cells but is also secreted and that while the intracellular thioredoxin is present only as a 12 kDa form, it would appear that the extracellular thioredoxin is present in two forms, a predominant 12 kDa form accompanied by a lower amount of a 10 kDa form. The observed localization and possible secretion of thioredoxin at the feto-maternal interface suggest important roles for this protein during pregnancy. Intracellular thioredoxin may be involved in the prevention of cellular damage due to oxidative stress whereas extracellular thioredoxin may act to integrate the actions of the cytokine network operating at the feto-maternal interface thereby assisting with implantation and the successful establishment of pregnancy.

Blotting, Western↗
PubMed1997

Perceptions of the body interior by children with asthma and children with no known chronic disease.

Comparatively little is known about how children perceive their internal bodies. In particular there is a lack of British studies, both of children's normal perceptions and in children experiencing chronic ill health. Such studies are important if information is to be given to children in the most effective way. The current study presents the results of an investigation of 72 children, 36 of whom were chronic asthma sufferers, whilst the others had no known chronic disease. Children at ages 5-6 years, 7-8 years and 10-11 years were asked to draw their internal body parts and to answer questions about the functioning of nine body organs. Data were analysed to examine the effect of age, sex and presence of asthma on the children's responses. Five-year-olds knew significantly less about their lungs than did other groups, boys identified muscle and ribs more frequently than girls, and there was an increase in levels of conceptualisation with age. There were no significant differences between asthmatic and non-asthmatic children. The findings are considered with particular reference to their importance for nursing practice.

Age Factors↗
PubMed1997

Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia.

Infection with certain types of human papillomavirus (HPV) presents a high risk for the subsequent development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Immunological mechanisms are likely to play a role in control of cervical HPV lesions. The HPV E2 protein has roles in virus replication and transcription, and loss of E2 functions may be associated with progression of cervical neoplasia. Accordingly, it is of interest to monitor immune responses to the E2 protein, and previous studies have reported associations between serological reactivity to E2 peptide antigens and cervical neoplasia. In order to investigate serological responses to native, full-length E2 protein, we expressed HPV-16 E2 proteins with and without an N-terminal polyhistidine tag using the baculovirus system. Purified HPV-16 E2 protein was used to develop enzyme-linked immunosorbent assays to detect serological IgG and IgA responses in cervical neoplasia patients and controls. We found that serum IgA levels against the E2 protein were elevated in CIN patients relative to normal control subjects but were not elevated in cervical cancer patients. Moreover, there appeared to be a gradient of response within cervical neoplasia such that the highest antibody levels were seen in lower grades of neoplasia up to CIN 2, whereas lower levels were observed in CIN 3 and still lower levels in cervical carcinoma. These findings suggest that the IgA antibody response to E2 may associate with stage and progression in cervical neoplasia.

Adult↗
PubMed1997

A re-examination of the association of 'early pregnancy factor' activity with fractions of heterogeneous molecular weight distribution in pregnancy sera.

The association of 'early pregnancy factor' ('EPF') activity in early pregnancy sera with multiple fractions of heterogeneous molecular mass was re-examined to test whether previously perplexing observations could be explained by a new multi-factorial model of the serum components required for this activity expression. Gel permeation fractionation of human pregnancy sera revealed 'EPF' activity associated with fractions containing components ranging in MW from < or = 1 kDa to > or = 500 kDa. A significant activity peak was observed eluting on the total volume (Vt) of the column, indicating the presence of active molecules of very low molecular mass. Multiple activity peaks were also observed in the macromolecular fractionation region ranging in apparent molecular weight from 12 kDa, through 25, 70 and 250 to > or = 500 kDa. Analysis of these fractions revealed that they all contained thioredoxin and active moieties of low molecular mass, with the latter probably directly associated with the former. Adsorption with specific anti-thioredoxin antibodies removed from these fractions the capacity to display 'EPF' activity. Further analyses revealed that in these fractions thioredoxin played a permissive role allowing the low molecular mass active moieties to express activity in the bioassay in the presence of otherwise counteracting substances. The results of these studies are consistent with the proposal that 'EPF' activity expression in pregnancy sera is due to the presence of a multi-factorial system in which thioredoxin plays an essential permissive role in concert with active moieties of low molecular mass.

Ammonium Sulfate↗
PubMed1995

Guinea pig serum L-asparaginase: purification, and immunological relationship to liver L-asparaginase and serum L-asparaginases in other mammals.

L-asparaginase, an enzyme used in the treatment of acute lymphocytic leukemia, is found in the serum of only a few mammalian groups, including the guinea pig and its close relatives in the superfamily Cavioidea. This report describes the purification and characterization of L-asparaginase from guinea pig serum. Antiserum against the purified enzyme cross-reacted with sera from other Cavioidean species but not with mouse serum. Relatively weak cross-reaction with unpurified L-asparaginase in guinea pig liver indicates a significant degree of evolutionary divergence.

Animals↗
PubMed1993

Site-directed mutagenesis of human thioredoxin. Identification of cysteine 74 as critical to its function in the "early pregnancy factor" system.

Thioredoxin has been identified as a key component of the "early pregnancy factor" system, a system of components present in pregnancy sera which expresses a lymphocyte modifying activity in an assay known as the rosette inhibition assay. Although thioredoxin alone is inactive, addition of thioredoxin to lymphocytes in combination with nonpregnancy sera or platelet-activating factor results in a positive response. We have changed several amino acids of human thioredoxin by site-directed mutagenesis to investigate the residues required for this cooperative function. Conversion of the two active site residues (cysteines 32 and 35) to serines results in a protein devoid of classical redox activity; however, this protein retained its ability to cooperate with non-pregnancy sera or platelet-activating factor in the rosette inhibition assay. Vertebrate thioredoxins contain an additional conserved pair of cysteine residues in the C-terminal portion of the protein. Changing both to serines resulted in no change in redox activity but completely abolished function in the rosette inhibition assay. Further study revealed this function was solely dependent on cysteine 74 as conversion of only cysteine 74 to serine abolished function, whereas replacement of only cysteine 70 with serine had no effect. The nonfunctional mutants counteracted the action of pregnancy serum in the assay strongly supporting the hypothesis that thioredoxin is an integral part of the early pregnancy factor system with residue cysteine 74 having an important role.

Amino Acid Sequence↗
PubMed1993

Identification of an actin binding region in aldolase.

Fragmentation of the actin binding glycolytic enzyme, aldolase, with cyanogen bromide yields an 18K actin binding fragment which corresponds to residues 1-164 of the aldolase sequence. Within this fragment there is a region of sequence (residues 32-52) which is highly homologous to a region of sequence near the C-terminus of actin itself and which is also found in the actin binding domains of a number of other actin binding proteins. A synthetic peptide corresponding to the aldolase sequence 32-52 encompassing this region of homology binds to F-actin and specifically competes with native aldolase for binding to this cytoskeletal protein.

Actins↗
PubMed1991

Isolation from human placental extracts of a preparation possessing 'early pregnancy factor' activity and identification of the polypeptide components.

Protocols are described for the isolation from human placental extracts of a preparation which is active in the rosette inhibition assay by inducing an increased rosette inhibition titre. In this respect the preparation mimics the effects of pregnancy sera, an ability ascribed to the presence in these sera of a so-called 'early pregnancy factor' (EPF). In addition to this activity in the rosette inhibition assay, the preparation was also shown to modulate the expression of cell surface immunoglobulin on peripheral blood mononuclear cells. The polypeptide composition of the preparation was relatively simple, as revealed by SDS-PAGE. There was a major 12 kd polypeptide previously isolated in a rosette inhibition titre-active preparation from ovine placental extracts, and a small amount of 68 kd polypeptide. N-Terminal amino acid sequence analyses obtained after blotting onto polyvinylidene difluoride membranes identified the latter polypeptide as serum albumin and the major 12 kd polypeptide as human thioredoxin. Gel permeation analysis partially resolved activity expression away from the 12 kd polypeptide as activity expression was also found to be associated with low mol. wt material. It is concluded that EPF activity expression in pregnancy sera involves molecules related to and associated with thioredoxin.

Amino Acid Sequence↗