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Search Results: 1 - 10 of 141927 matches for " Ann K. Guiffre "
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Platelets and Smooth Muscle Cells Affecting the Differentiation of Monocytes
Michelle W. Y. Williams, Ann K. Guiffre, John P. Fletcher
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088172
Abstract: Background Atherosclerosis is characterised by the formation of plaques. Monocytes play a pivotal role in plaque development as they differentiate into foam cells, a component of the lipid core whilst smooth muscle cells (SMC) are the principal cell identified in the cap. Recently, the ability of monocytes to differentiate into a myriad of other cell types has been reported. In lieu of these findings the ability of monocytes to differentiate into SMCs/smooth muscle (SM)-like cells was investigated. Method and Results Human monocytes were co-cultured with platelets or human coronary aortic SMCs and then analysed to assess their differentiation into SMCs/SM-like cells. The differentiated cells expressed a number of SMC markers and genes as determined by immunofluorescence staining and quantitative polymerase chain reaction (qPCR). CD array analysis identified marker expression profiles that discriminated them from monocytes, macrophages and foam cells as well as the expression of markers which overlapped with fibroblast and mesenchymal cells. Electron microscopy studies identified microfilaments and increased amounts of rough endoplasmic reticulum indicative of the SM- like cells, fibroblasts. Conclusions In the appropriate environmental conditions, monocytes can differentiate into SM-like cells potentially contributing to cap formation and plaque stability. Thus, monocytes may play a dual role in the development of plaque formation and ultimately atherosclerosis.
Positive attitudes towards priority setting in clinical guidelines among Danish general practitioners: A web based survey  [PDF]
Ann Nielsen, Benedicte Carlsen, Pia K. Kjellberg
Health (Health) , 2013, DOI: 10.4236/health.2013.52026

Aims: Increasing focus on improvement and optimisation of the treatment in primary care and reduction of healthcare costs emphasize the need to understand which factors determines adherence and non-adherence to clinical guidelines. In the present study, we examined attitudes towards clinical guidelines in Danish general practitioners (GPs). Methods: We conducted a survey among Danish GPs from all five regions of Denmark. In total, 443 GPs answered the web-based questionnaire that contained questions about attitudes and barriers to clinical guidelines. Results: More than 90% of the GPs reported that they have good knowledge of the guidelines and in general follows the guidelines. A majority of the GPs (81%) found it acceptable that economic considerations are part of the guidelines. The most important factors for non- adherence to guidelines were “need of adjustment to clinical practice” and “lack of confidence in guidelines”. The attitudes to clinical guidelines were not significantly associated with practice characteristics such as gender, years of experience, practice organisation and localisation. Conclusions: Our findings show that clinical guidelines are an integrated or internalised part of everyday practice among GPs in Denmark. Furthermore, the findings indicate that Danish GPs are positive towards applying priority setting in their practice. This is decisive in the light of rising healthcare costs due to development of new expensive technologies and ageing populations that puts pressure on the healthcare system in general and primary healthcare in particular.

Pharmacogenomics of anticoagulants: steps toward personal dosage
Ann K Daly
Genome Medicine , 2009, DOI: 10.1186/gm10
Abstract: Coumarin anticoagulants, including warfarin, are among the most widely prescribed drugs in modern medicine. A difficulty with their use is that dosage needs to be individually determined for each patient, usually by following a standard initial dosing protocol, measuring the coagulation rate regularly (using the international normalized ratio, INR, which is a measure of prothrombin time. A high INR value indicates overcoagulation) and then adjusting the dose until the required rate of coagulation is obtained. Overcoagulation places the patient at risk of potentially fatal hemorrhage, so improving protocols for initiation of anticoagulant treatment remains an important issue. In particular, warfarin has been shown to be frequently implicated in emergency admissions relating to adverse drug reactions in a survey of two UK hospitals [1]. Approximately 10% of Europeans require an unusually low dose of warfarin (1.5 mg/day or less) and these patients could be at increased risk of developing serious bleeds and undesirably high levels of anticoagulation, especially during the initial weeks of treatment [2]. Although the current oral coumarin anticoagulants, such as warfarin, acenocoumarol and phenprocoumon, are likely to be replaced eventually by other drugs under development, such as the specific thrombin inhibitors, the current drugs will probably continue to be the main oral anticoagulants prescribed in the short to medium term.The metabolism of warfarin and the other coumarin anticoagulants is well understood, with the cytochrome P450 enzyme CYP2C9 having a major role in their phase I metabolism (reviewed in [3]). CYP2C9 is subject to a genetic polymorphism affecting its activity, and the fact that this polymorphism contributes to individual anticoagulant dose requirement is now well established, although its effect on phenprocoumon metabolism is less pronounced than that on either warfarin or acenocoumarol [2,4-7]. Coumarin anticoagulants exert their effect by inhibit
Monitoring low birth weight: an evaluation of international estimates and an updated estimation procedure
Blanc,Ann K.; Wardlaw,Tessa;
Bulletin of the World Health Organization , 2005, DOI: 10.1590/S0042-96862005000300010
Abstract: objective: to critically examine the data used to produce estimates of the proportion of infants with low birth weight in developing countries and to describe biases in these data. to assess the effect of adjustment procedures on the estimates and propose a modified estimation procedure for international reporting purposes. methods: mothers' reports about their recent births in 62 nationally representative demographic and health surveys (dhs) conducted between 1990 and 2000 were analysed. the proportion of infants weighed at birth, characteristics of those weighed, extent of misreporting, and mothers' subjective assessments of their children's size at birth were examined. findings: in many developing countries the majority of infants were not weighed at birth. those who were weighed were more likely to have mothers who live in urban areas and are educated, and to be born in a medical facility with assistance from medically trained personnel. birth weights reported by mothers are "heaped" on multiples of 500 grams. conclusion: current survey-based estimates of the prevalence of low birth weight are biased substantially downwards. two adjustments to reported data are recommended: a weighting procedure that combines reported birth weights with mothers' assessment of the child's size at birth, and categorization of one-quarter of the infants reported to have a birth weight of exactly 2500 grams as having low birth weight. averaged over all surveys, these procedures increased the proportion classified as having low birth weight by 25%. we also recommend that the proportion of infants not weighed at birth be routinely reported. efforts are needed to increase the weighing of newborns and the recording of their weights.
SLE – Hematopoietic stem cell transplantation for systemic lupus erythematosus
Richard K Burt, Ann E Traynor
Arthritis Research & Therapy , 2003, DOI: 10.1186/ar786
Abstract: The prognosis of systemic lupus erythematosus (SLE) markedly improved following the introduction of monthly intravenous pulse cyclophosphamide (500–1000 mg/m2). Nevertheless, despite pulse cyclophosphamide and advances in supportive care such as new antihypertensive medications, patients with active SLE involving visceral organs have 2-year and 5-year mortalities of approximately 20% and 35%, respectively. Since SLE is predominately a disease of young women, improvements in disease-related morbidity and mortality were desperately needed.Autologous hematopoietic stem cell transplant regimens for patients with cancer are based on dose escalation of chemotherapeutic drugs that demonstrate effectiveness at standard dosing. Borrowing this concept from the field of oncology, we dose escalated cyclophosphamide, the most effective antilupus medication, to 200 mg/kg. Also borrowing from experience with a hematopoietic stem cell transplantation (HSCT) conditioning regimen for aplastic anemia, where T lymphocytes help to sustain the disease manifestations, a regimen of 200 mg/kg cyclophosphamide (divided as 50 mg/kg over 4 days) and of 90 mg/kg equine antithymocyte globulin (ATG) (divided as 30 mg/kg over 3 days) was selected.To collect hematopoietic stem cells, they need to be mobilized into the peripheral blood with either a hematopoietic colony stimulating factor such as granulocyte-colony stimulating factor or a chemotherapeutic drug such as cyclophosphamide, or both. Since granulocyte-colony stimulating factor is a proinflammatory cytokine that by itself may exacerbate disease, the stem cells were mobilized into the peripheral blood using 2.0 g/m2 cyclophosphamide, granulocyte-colony stimulating factor beginning 72 hours later, and harvest beginning upon white blood cell rebound (usually 10 days after cyclophosphamide). The stem cells are collected on an outpatient basis by apheresis and then purified in the laboratory by positive selection using an antibody to CD34, a pr
Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat
Cara M Hildreth, Ann K Goodchild
BMC Neuroscience , 2010, DOI: 10.1186/1471-2202-11-128
Abstract: Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.Cardiac vagal preganglionic neurons (CVPN) are found predominantly in the nucleus ambiguus (NA) as well as dorsal motor nucleus of the vagus (DMNV) and in the intermediate zone (IZ) between these two nuclei [1-3]. Activation of CVPN has negative chronotropic, dromotropic and ionotropic effects on the heart [4-6] and the activity of these neurons is increased in response to baroreceptor stimulation [7-9] and inhibited during inspiration [10,11].Surprisingly little is known about the functional significance of inputs to CVPN mediated by either ionotropic or g-protein coupled receptors (GPCR). CVPN receive substantial inputs from ionotropic receptors. Microinjection of the GABAA receptor antagonist bicuculline into the NA evokes a profound decrease in HR [12] demonstrating that there is a large GABAergic input to CVPN that plays a role in setting the tonic level of heart rate (HR). GABAergic inputs
Evaluation of Potential for Translocation of Listeria monocytogenes from Floor Drains to Food Contact Surfaces in the Surrounding Environment Using Listeria innocua as a Surrogate  [PDF]
Jasdeep K. Saini, James L. Marsden, Daniel Y. C. Fung, Beth Ann Crozier-Dodson
Advances in Microbiology (AiM) , 2012, DOI: 10.4236/aim.2012.24073

Floor drains in processing environments harbor Listeria spp. due to continuous presence of humidity and organic substrates. Cleaning and washing activities in food-processing facilities can translocate the bacterial cells from the drain to the surrounding environment, thus contaminating food products still in production. This study evaluated the potential for translocation of Listeria monocytogenes from drains to food contact surfaces in the surrounding environment using Listeria innocua as a surrogate. A 7 × 7 × 8-foot polycarbonate flexi-glass chamber with a 10-inch-diameter drain mounted on an aluminum cabinet was used. Stainless steel coupons (6.4 × 1.9 × 0.1 cm, 12 per height) were hung at 1, 3, and 5 feet inside the chamber. Four treatment sets; non-inoculated, non-treated; non-inoculated, treated; inoculated, treated; inoculated non-treated; and two subtreatments of 8 h and 48 h were performed. For the inoculated sets, meat slurry (10 gof ground beef in 900 mL water) and a four-strain cocktail of Listeria innocua at 7 - 8 log CFU/mL were used. For the treated sets, in addition, a commercial cleaner and sanitizer was applied. The drain was cleaned using a pressure hose (40 - 50 psi) after 8 h and 48 h. Coupons were then removed and enriched in listeria enrichment broth to establish if any cell translocated from the drain onto the stainless steel coupons via aerosols generated during washing. Confirmation was done using VIP Listeria rapid test kits. Results indicated translocation at all three heights ranging from 2% - 25%. Significantly higher translocation (p < 0.05) was found at 1 foot (up to 25%), followed by 3 feet (up to 11%) and 5 feet (up to 2.7%). This research indicated that translocation of Listeria spp. from drains to food contact surfaces does occur and increases with increased proximity to the drain.

Factors Associated with First-Line Antiretroviral Therapy Failure amongst HIV-Infected African Patients: A Case-Control Study  [PDF]
Charles M. Kwobah, Ann W. Mwangi, Julius K. Koech, Gilbert N. Simiyu, Abraham M. Siika
World Journal of AIDS (WJA) , 2012, DOI: 10.4236/wja.2012.24036
Abstract: Background: Since 2001, anti-retroviral therapy (ART) has been provided to over 75,000 HIV-infected patients at the USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership in western Kenya. Over 1000 of these patients have switched to second-line ART. We therefore set out to determine factors associated with first-line ART failure amongst these patients. Methods: This case controlled study matched patients (in the ratio 1:2) from the electronic AMPATH Medical Record System on the basis of age, gender, and ART initiation date. Cases were adults (≥18 years) who initiated second-line ART between January 1, 2007 and July 31, 2011 after at least one viral load measurement >5000 copies/ml or satisfying the WHO immunological or clinical failure criteria. Controls were those on non-failing first-line ART with a CD4 count > 400 /ml within the last 12 months, at the time of case incidence. Conditional logistic regression for paired data was used to assess association. We evaluated the strength of association of risk factors using stratified Cox model. Results: Of the 1084 cases and 2149 controls included in the analysis, 62% were female. Median age was 36.5 years (IQR = 30.7 - 43.1); median baseline CD4 cell count was 161 /ml (IQR = 72 - 277); Median time to ART failure was 37 months (IQR = 24 - 47). Low baseline CD4 count < 50 /ml (H.R = 7.07, (95% CI = 4.92 - 10.15); Zidovudine based ART (H.R 1.76, 95% CI = 1.25 - 2.48) and imperfect ART adherence (H.R = 2.77, 95% CI = 2.20 - 3.49) were independently associated with treatment failure. Conclusion: In this setting, low baseline CD4 count, zidovudine-based ART and imperfect adherence are associated with first-line ART treatment failure.
New Findings for Maternal Mortality Age Patterns: Aggregated Results for 38 Countries
Ann K. Blanc, William Winfrey, John Ross
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059864
Abstract: Background With recent results showing a global decline in overall maternal mortality during the last two decades and with the target date for achieving the Millennium Development Goals only four years away, the question of how to continue or even accelerate the decline has become more pressing. By knowing where the risk is highest as well as where the numbers of deaths are greatest, it may be possible to re-direct resources and fine-tune strategies for greater effectiveness in efforts to reduce maternal mortality. Methods We aggregate data from 38 Demographic and Health Surveys that included a maternal mortality module and were conducted in 2000 or later to produce maternal mortality ratios, rates, and numbers of deaths by five year age groups, separately by residence, region, and overall mortality level. Findings The age pattern of maternal mortality is broadly similar across regions, type of place of residence, and overall level of maternal mortality. A “J” shaped curve, with markedly higher risk after age 30, is evident in all groups. We find that the excess risk among adolescents is of a much lower magnitude than is generally assumed. The oldest age groups appear to be especially resistant to change. We also find evidence of extremely elevated risk among older mothers in countries with high levels of HIV prevalence. Conclusions The largest number of deaths occurs in the age groups from 20-34, largely because those are the ages at which women are most likely to give birth so efforts directed at this group would most effectively reduce the number of deaths. Yet equity considerations suggest that efforts also be directed toward those most at risk, i.e., older women and adolescents. Because women are at risk each time they become pregnant, fulfilling the substantial unmet need for contraception is a cross-cutting strategy that can address both effectiveness and equity concerns.
Anatomical Response and Infection of Soybean during Latent and Pathogenic Infection by Type A and B of Phialophora gregata
Ann E. Impullitti, Dean K. Malvick
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098311
Abstract: Growth and anatomical responses of plants during latent and pathogenic infection by fungal pathogens are not well understood. The interactions between soybean (Glycine max) and two types of the pathogen Phialophora gregata were investigated to determine how plants respond during latent and pathogenic infection. Stems of soybean cultivars with different or no genes for resistance to infection by P. gregata were inoculated with wildtype or GFP and RFP-labeled strains of types A or B of P. gregata. Plants were sectioned during latent and pathogenic infection, examined with transmitted light or fluorescent microscopy, and quantitative differences in vessels and qualitative differences in infection were assessed using captured images. During latent infection, the number of vessels was similar in resistant and susceptible plants infected with type A or B compared to the control, and fungal infection was rarely observed in vessels. During pathogenic infection, the resistant cultivars had 20 to 25% more vessels than the uninfected plants, and fungal hyphae were readily observed in the vessels. Furthermore, during the pathogenic phase in a resistant cultivar, P.gregata type A-GFP was limited to outside of the primary xylem, while P.gregata type B-RFP was observed in the primary xylem. The opposite occurred with the susceptible cultivar, where PgA-GFP was observed in the primary xylem and PgB-RFP was limited to the interfascicular region. In summary, soybean cultivars with resistance to BSR produced more vessels and can restrict or exclude P. gregata from the vascular system compared to susceptible cultivars. Structural resistance mechanisms potentially compensate for loss of vessel function and disrupted water movement.
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