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Biomedical subjects

A Stewart

Publications and source records attributed to A Stewart.

At least 55 records · Page 3Linked to original sources
PubMed2002

Audit of primary care angina management in Sandwell, England.

This audit aimed to assess the identification and treatment of coronary risk factors, lifestyle advice given and use of drug therapy, among patients with angina in Sandwell. It was designed to help general practices evaluate their angina management, and highlight areas where practice could be improved. Criteria were based on Sandwell's published angina audit and local clinical guidelines. Each participating practice was asked to identify all patients with angina, from which a 10% sample was randomly selected. The notes of each selected patient were examined for evidence showing whether agreed standards of care had been achieved. Fifteen practices took part, and contributed data on a total of 358 patients. Of patients without contraindications, 66.5% were taking aspirin, 62.1% were prescribed short-acting nitrates and 58.4% were prescribed beta-blockers. Non-white patients were significantly less likely to receive short-acting nitrates (p < 0.001) and women were significantly less likely to receive beta-blockers (p < 0.01). A total of 83.5% of patients had received smoking cessation advice, 75.1% had weight advice, 75.1% were advised about alcohol use and 64.5% about exercise. Overall, 77.4% had a blood pressure check within the previous twelve months, 40.5% had their cholesterol measured and 33.5% had their blood glucose measured. Non-white patients were significantly less likely to receive smoking cessation, weight, exercise and alcohol advice and were less likely to have their blood pressure checked (all p < 0.0001). Patients aged 65 and over were significantly less likely to receive a cholesterol check (p < 0.0001). None of the auditable standards were actually met. This study shows that there is considerable scope to improve the management of angina patients, with particular regard to aspirin. We recommend that practices develop systems to ensure that the appropriate treatment, advice and checks are given to all patients with angina, paying particular attention to those from ethnic minority backgrounds.

Angina Pectoris↗
PubMed2001

A pyrrolidine-based specific inhibitor of cytosolic phospholipase A(2)alpha blocks arachidonic acid release in a variety of mammalian cells.

We analyzed a recently reported (K. Seno, T. Okuno, K. Nishi, Y. Murakami, F. Watanabe, T. Matsuur, M. Wada, Y. Fujii, M. Yamada, T. Ogawa, T. Okada, H. Hashizume, M. Kii, S.-H. Hara, S. Hagishita, S. Nakamoto, J. Med. Chem. 43 (2000)) pyrrolidine-based inhibitor, pyrrolidine-1, against the human group IV cytosolic phospholipase A(2) alpha-isoform (cPLA(2)alpha). Pyrrolidine-1 inhibits cPLA(2)alpha by 50% when present at approx. 0.002 mole fraction in the interface in a number of in vitro assays. It is much less potent on the cPLA(2)gamma isoform, calcium-independent group VI PLA(2) and groups IIA, X, and V secreted PLA(2)s. Pyrrolidine-1 blocked all of the arachidonic acid released in Ca(2+) ionophore-stimulated CHO cells stably transfected with cPLA(2)alpha, in zymosan- and okadaic acid-stimulated mouse peritoneal macrophages, and in ATP- and Ca(2+) ionophore-stimulated MDCK cells.

Animals↗
PubMed2001

Controls of EGF-induced morphological transformation of human bronchial epithelial cells.

Human bronchial epithelial cells, both normal primary (NHBE) and the BEAS-2B line, respond to epidermal growth factor (EGF) by extruding lengthy filaments, or filapodia. The morphological transformation of BEAS-2B cells maximized at 48 h using 1-10 nM EGF. EGF-induced filapodia extension was inhibited by co-exposure to transforming growth factor beta, which did not affect tyrosine phosphorylation of the EGF receptor (EGFR). Inhibition was also effected by phorbol myristoyl acetate (PMA), which reduced the rate of EGFR tyrosine phosphorylation. Dibutyryl-cAMP had no effect, whereas the protein kinase inhibitor H-89 stimulated the EGF response. The ability to regulate cellular responses to EGF by hormonal and chemical approaches has implications for current investigations into the roles of EGF in lung growth, differentiation, and wound repair.

Bronchi↗
PubMed2001

Deposition of gaseous radionuclides to fruit.

14C, 35S and 3H are released to the environment during the operation of gas-cooled reactors and were identified as radionuclides of interest by the BIOMASS Fruits Working Group. This paper provides a review of the deposition, uptake, allocation and loss of these radionuclides with respect to fruit and conceptual models for gaseous radionuclides. It is concluded that the mechanisms for the uptake of CO35S, HTO and 14CO2 are well understood and that their deposition velocities have been quantified. There is also a reasonable body of work on the translocation of 14C once in the crop, but much less for 35S and 3H, which are considered to follow source-sink relationships. The loss rates of the three radionuclides show large differences, with tritium lost rapidly in the form of HTO but retained longer when converted to OBT. The losses of 14C are less and those of sulphur are minimal post fixation. When fruit crops alone are considered, the quantity of information is further reduced but predictions on possible behaviour of these radionuclide species can be made from the current knowledge.

Air Movements↗
PubMed2001

WaterLOGSY as a method for primary NMR screening: practical aspects and range of applicability.

WaterLOGSY represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. Several relay pathways are used constructively in the experiment for transferring bulk water magnetization to the ligand. The method is particularly useful for the identification of novel scaffolds of micromolar affinity that can be then optimized using directed screening, combinatorial chemistry, medicinal chemistry and structure-based drug design. The practical aspects and range of applicability of the WaterLOGSY experiment are analyzed in detail here. Competition binding and titration WaterLOGSY permit, after proper correction, the evaluation of the dissociation binding constant. The high sensitivity of the technique in combination with the easy deconvolution of the mixtures for the identification of the active components, significantly reduces the amount of material and time needed for the NMR screening process.

Binding, Competitive↗
PubMed2001

The relationship between lumenal and limiting membranes in swollen late endocytic compartments formed after wortmannin treatment or sucrose accumulation.

Immunofluorescence and electron microscopy were used to evaluate the formation of swollen endosomes in NRK cells after treatment with wortmannin or sucrose and to study the relationship between lumenal and limiting membrane. Both treatments resulted in the formation of two populations of swollen late endocytic vacuoles, positive for lysosomal glycoproteins or cation-independent mannose 6-phosphate receptors, but those induced by wortmannin were characterised by time-dependent accumulation of lumenal vesicles, whereas those induced by sucrose uptake did not accumulate lumenal vesicles. In both cases, the distribution of the late endosomal marker, lysobisphosphatidic acid, remained unchanged and was present within the lumen of the swollen vacuoles. Consumption of plasma membrane and peripheral early endosomes, and the appearance of transferrin receptors in swollen late endosomes, indicated that continued membrane influx from early endocytic compartments, together with inhibition of membrane traffic out of the swollen compartments, is sufficient to account for the observed phenotype of cells treated with wortmannin. The accumulation of organelles with the characteristic morphology of endocytic carrier vesicles in cells that have taken up sucrose offers an explanation for the paucity of lumenal vesicles in swollen sucrosomes. Our data suggest that in fibroblast cells the swollen endosome phenotype induced by wortmannin is a consequence of endocytic membrane influx, coupled with the failure to recycle membrane to other cellular destinations, and not the inhibition of multivesicular body biogenesis.

Androstadienes↗
PubMed2001

Towards case-based performance measures: uncovering deficiencies in applied medical care.

Measures are designed to evaluate the processes and outcomes of care associated with the delivery of clinical (and non-clinical) services. They allow for intra- and interorganizational comparison to be used continuously to improve patient health outcomes. The use of performance measures always means to abstract the complex reality (medical scenarios and procedures) in order to provide an understandable and comparable output. Measures can focus on global performance. The more detailed data are available the more specific judgements with respect to the appropriateness of clinical decision-making and implementation of evidence are feasible. Externally reported measures are intended both to inform and lead to action. By providing this information, deficiencies in patient care and unnecessary variations in the care process can be uncovered. Such variations have contributed to disparities in morbidity and mortality. The developments in information technology, especially world-wide interconnectivity, standards for electronic data exchange and facilities to store and manage large amounts of data, offer the opportunity to analyse health-relevant information in order to make the delivery of healthcare services more transparent for consumers and providers. Global performance measures, such as the overall life expectancy (mortality) in a country, can give a rough orientation of how well health systems perform but they do not offer general solutions nor specific insights into care processes that have to be improved. In contrast to population-based measures, case-based performance measures use a defined group of patients depending on specific patient characteristics and features of disease. By means of these measures we are able to compare the number of patients that receive a necessary medical procedure against those patients who do not. The use of case-based measures is a bottom-up approach to improve the overall performance in the long run. They are not only a tool for global orientation but can offer a straightforward link to the areas of deficient care and the underlying procedures. Performance measures are relevant to providers as well as consumers, from their own individual perspective. Cased-based measures focus on the management of individual patient. This approach to performance measurement can inform physicians in a meaningful and constructive way by monitoring their individual performance and by pointing out possible areas of improvement.

Case-Control Studies↗
PubMed2001

Aprotinin reduces blood loss and the need for transfusion in orthognathic surgery.

A randomized, placebo-controlled, double-blind trial (n= 15 in each group) showed that patients given aprotinin intravenously (200 ml, [2000000 kallikrein inactivator units] before the operation and then 50 ml per h until the end of the operation) during simultaneous maxillary Le Fort 1 and mandibular sagittal split osteotomies, lost 52% less blood than controls (calculated by subtracting the volume of saline irrigant used from the volume of blood collected in the aspirator bottle and surgical drains). Patients given aprotinin lost a mean (SD) of 473 (190) ml compared with 986 (356) ml in controls. They also required significantly less transfused blood (1 was given 2 units in the aprotinin group compared with 9 given a mean of 1.5 units (range 1-4) in the control group). There were no complications attributable to this drug.

Adult↗
PubMed2001

Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site.

OBJECTIVE: To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN: Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS: A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patient's hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis.

Adult↗
PubMed2001

The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review.

OBJECTIVE: To determine whether the levonorgestrel-releasing intrauterine device (LNG-IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings. METHODS: A systematic review addressing the effectiveness and cost effectiveness of the LNG-IUS for menorrhagia was undertaken. RESULTS: Five controlled trials and five case series were found which measured menstrual blood loss. Nine studies recorded statistically significant average menstrual blood loss reductions with LNG-IUS (range 74%-97%). Another showed reduction in menstrual disturbance score. The LNG-IUS was more effective than tranexamic acid, but slightly less effective than endometrial resection at reducing menstrual blood loss. In one study, 64% of women cancelled surgery at six months, compared with 14% of control group women. In another, 82% were taken off surgical waiting lists at one year. No cost effectiveness studies were found. DISCUSSION: Small studies of moderate quality indicate the LNG-IUS is an effective treatment for menorrhagia. Costs may be less than for tranexamic acid in primary and secondary care. Although its use may reduce surgical waiting lists, cost effectiveness assessment requires longer follow up. CONCLUSION: Effectiveness and cost effectiveness relative to other treatments and the effect on surgical waiting lists can only be established in larger trials measuring patient-centred outcomes in women with menorrhagia.

Adult↗
PubMed2001

Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling.

Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180% increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and SB203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAIB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle).

Adipocytes↗
PubMed2001

Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders.

The homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1 mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis for these clinical phenotypes, we have examined the impact of these mutations on the regulatory functions of HESX1. We show that Hesx1 is a promoter-specific transcriptional repressor with a minimal 36 amino acid repression domain which can mediate promoter-specific repression by suppressing the activity of homeodomain-containing activator proteins. Mutations in HESX1 associated with pituitary disease appear to modulate the DNA-binding affinity of HESX1 rather than its transcriptional activity. Wild-type HESX1 binds a dimeric homeodomain site with high affinity (K(d) 31 nM) whilst HESX1(S170L) binds with a 5-fold lower activity (K(d) 150 nM) and HESX1(R160C) does not bind at all. Although HESX1(R160C) has only been shown to be associated with the SOD phenotype in children homozygous for the mutation, HESX1(R160C) can inhibit DNA binding by wild-type HESX1 both in vitro and in vivo in cell culture. This dominant negative activity of HESX1(R160C) is mediated by the Hesx1 repression domain, supporting the idea that the repression domain is implicated in interactions between homeodomain proteins. Our data suggest a possible molecular paradigm for the dominant inheritance observed in some pituitary disorders.

Animals↗