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Continuous-wave (CW) Doppler recordings of ascending aortic maximal blood flow acceleration (PkA), maximal velocity (PkV) and systolic velocity integral (SVI) were taken at each stage of a graded exercise treadmill test on two separate days with 30 physically active adult males. Signals were measured (Quinton Exerdop) for all cardiac cycles in the 3rd minute of each stage using a hand-held probe positioned at the suprasternal notch. A dedicated microcomputer, programmed to select "valid" beats on the basis of value consistency in the sample set, determined the acceptability of signals. No significant differences were found between the three trial means within each stage on either day for PkA, PkV or SVI. Significant (p <.01) intraclass reliability estimates ranged from r = 0.89 to 0.97 (Pk.A), r = 0.90 to 0.98 (PkV) and r = 0.85 to 0.95 (SVI) . Coefficients of variation were calculated at each stage to estimate the relative consistency of each measure. A gradual reduction of the coefficient of variation was observed for each blood flow measure between stages one and four. The test-retest (between days) reliability coefficients for PkA, PkV and SVI for stages one to four ranged between r = 0.51 to 0.78 (P <.004), but correlations for the pre-exercise baseline and stages five and six were lower. These results indicate that (1) PkA, PkV and SVI demonstrate greater measurement stability within each stage of a graded exercise test than is the case between separate days of measurement at the same stage; and (2) there is modest day-to-day response stability for clinical testing with the Doppler parameter of PkV. Reliability/stability was best in exercise stages which encompass the speed and grade range of 45.0 m•min⁻¹/10%. - 111.7 m•min⁻¹/14%, i.e., those in which all subjects can walk. / Master of Science

There were three objectives of this study. The first was to determine if commercially available fluorochromes could be used to determine the glucocorticoid receptor (GR) density and binding affinity (BA) in equine peripheral blood mononuclear cells. The second was to determine if there was a correlation between elevated plasma cortisol and GR density or binding affinity in healthy adult horses. The third objective was to evaluate the HPA axis in adult horses presenting with systemic inflammatory response syndrome (SIRS), and to determine where any alterations in HPA axis function occur in these patients compared to healthy adults. For the first part of the study, peripheral venous blood was collected from 3 healthy research horses on 3 days. Peripheral blood mononuclear cells were isolated using Ficoll gradient centrifugation. Phycoerythrin (PE)-CD44 was then used to extracellularly label leukocytes, and then an intracellular GR antibody was used to determine a baseline measurement of GR density and fluorescein isothiocyanate (FITC)-dexamethasone was used to determine binding affinity via flow cytometric analysis. Comparison of control samples to those for CD44, GR density, and GR binding affinity showed a statistically significant difference for all samples (P<0.0001, P<0.0001, and P<0.0001 respectively). This showed that the CD44, GR antibody, and FITC-dexamethasone could successfully be used to analyze equine peripheral blood mononuclear cells for GR activity. For the second part of the study, an ACTH stimulation test was performed on 8 healthy horses in order to induce an increase in endogenous cortisol production. Plasma cortisol levels, GR density, and GR binding affinity were measured at baseline, 4, 8, and 24 hours after treatment. Median basal cortisol concentration was 4.9, range 3.2-6.1 μg/dl. This initially increased following ACTH stimulation to 5.6, range 4.8-7.4 μg/dl, then showed a significant decrease by 8 hours post ACTH administration to 1.4, range 1.1-2.7 μg/dl (P=0.0221). No correlation was observed between plasma cortisol concentration in healthy horses and GR density or binding affinity (r=-0.145, P=0.428 and r=0.046, P=0.802, respectively). For the third phase of the study, horses (N=10) with systemic inflammatory response syndrome (SIRS) were compared to healthy, age and sex matched controls (N=10) presenting for lameness evaluation or ophthalmologic examination. Blood was collected from SIRS cases and controls on presentation to the Equine Medical Center. A CBC, serum biochemistry, and serum ACTH and cortisol measurements were performed. GR density and binding affinity were also determined. Nonsurvivors had a significantly decreased GR binding affinity (P=0.008) and demonstrated a trend towards an increase in the ACTH:cortisol ratio. ROC analysis was performed for serum ACTH and cortisol concentrations, the ACTH:cortisol ratio, GR density and GR binding affinity, and triglycerides to determine cut-off values associated with nonsurvival. These were then used to analyze this population using Fischer's exact test to determine the odds ratio (OR) associated with nonsurvival for each variable. This revealed that a serum triglyceride concentration greater than 28.5 mg/dl was associated with nonsurvival (OR=117, 95% CI, 1.94-7060). The other variables were not found to be significantly associated with nonsurvival, although a Delta BA% of less than 35.79% was found to be closely associated with nonsurvival (OR=30.33, 95% CI, 0.96-960.5). Additionally, a significant negative correlation was detected between the plasma ACTH concentration and Delta BA% (r=-0.685, P=0.029) and the ACTH:cortisol ratio and the Delta BA% (r=-0.697, P=0.025). This study showed that nonsurviving horses with SIRS had a significantly decreased GR binding affinity compared to survivors, and a tendency toward an increase in their ACTH:cortisol ratios. This confirms that HPA axis dysfunction occurs in adult horses with SIRS as tissue resistance to glucocorticoids, and potentially relative adrenal insufficiency as well. These results suggest that there are horses with SIRS that might benefit from "physiologic" doses of synthetic glucocorticoids to complement their relative adrenal insufficiency in addition to their poor tissue sensitivity. Further research should focus on methods to more rapidly determine which horses might benefit from treatment with glucocorticoids on presentation, as well as to more accurately determine prognosis for survival. / Master of Science

Yes / Background: Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft–Gault) gives a more accurate estimate of kidney function. Aim: To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. Design and setting: A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. Method: The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft–Gault) was calculated using actual body weight and estimated ideal body weight. Results: Kidney function was too low for recommended prescribing in 4–40% of people aged ≥65 years, and in 24–80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3–28% of those aged ≥65 years, and for 13–58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Conclusion: Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft–Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced.

SANTRAUKA Vilniaus universiteto Medicinos fakultetas Reabilitacijos, sporto medicinos ir slaugos institutas Slaugos magistrantūros programa PACIENTŲ SERGANČIŲ LĖTINIU VENŲ NEPAKANKAMUMU OPERACINIO GYDYMO ĮTAKA GYVENIMO KOKYBEI Slaugos magistro baigiamasis darbas Darbo autorė: Renata Grigonienė Darbo vadovas: dr. Narimantas Markevičius Vilnius, 2008 m. Pagrindinės sąvokos: lėtinis venų nepakankamumas, gyvenimo kokybė prieš operaciją, gyvenimo kokybės pagerėjimas po operacijos, CIVIQ klausimynas. Tyrimo tikslas - ištirti pacientų sergančiųjų lėtiniu venų nepakankamumu gyvenimo kokybę prieš operaciją ir po jos. Tyrimo uždaviniai. Palyginti vyrų ir moterų gyvenimo kokybę sergant lėtiniu venų nepakankamumu prieš operaciją ir po jos. Ištirti gyvenimo kokybės skausmo sritį prieš operaciją ir po jos. Ištirti gyvenimo kokybės fizinę sritį prieš operaciją ir po jos. Ištirti gyvenimo kokybės psichologinę sritį prieš operaciją ir po jos. Ištirti gyvenimo kokybės socialinių santykių sritį prieš operaciją ir po jos. Tyrimo objektas. Tirta pacientų sergančių lėtiniu venų nepakankamumu gyvenimo kokybė prieš operaciją ir po jos. Buvo apklausta 51 respondentas prieš operaciją ir po jos, iš jų 41 (80,4 %) moteris ir 10 (19,6 %) vyrų. Tyrimo metodai. Teorinė mokslinės literatūros, leidinių, publikacijų apžvalga. Pacientų sergančių lėtiniu venų nepakankamumu anketinė apklausa gyvenimo kokybei ištirti prieš operaciją ir po jos. Apklausai naudotas tarptautinis CIVIQ klausimynas. Statistinė analizė... [toliau žr. visą tekstą] / The Influence of Surgical Treatment on Quality of Live of Patients Suffering from Chronic Venous Insufficiency“ Nursing Master’s final paper Author: Renata Grigonienė Supervisor: dr. Narimantas Markevičius Vilnius, 2009 m. Keywords: chronic venous insufficiency, quality of life before surgery, quality of life improvement after surgery, chronic venous insufficiency questionnaire (CIVIQ). The aim of research: to investigate the quality of life of patients suffering from chronic venous insufficiency before and after surgery. The objectives of research: to compare the quality of life of male and female patients with chronic venous insufficiency before and after surgery; to investigate the pain domain of quality of life before and after surgery; to investigate the physical domain of quality of life before and after surgery; to investigate the psychological domain of quality of life before and after surgery; to investigate the social relations domain of quality of life before and after surgery. The subject of research: the quality of life of patients suffering from chronic venous insufficiency before and after surgery. 51 patients took part in the survey before and after surgery, including 41 female (80.4 %) and 10 males (19.6 %). The methods of research: Theoretical review of scientific literature and publications; questionnaire survey designed to investigate the quality of life of patients suffering from chronic venous insufficiency. International CIVIQ questionnaire was used for... [to full text]

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-24T12:08:05Z No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-24T14:01:41Z (GMT) No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-24T14:01:41Z (GMT). No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-04-19 / Hexavalent chromium [Cr(VI)] is a toxic metal that triggers toxicity events in the body, penetrating cell membranes and increasing reactive oxygen species (ROS). These products, in turn, damage cellular macromolecules, inhibiting their functions and enhancing cell death via apoptosis. Therefore, it has been suggested that the use of antioxidants can minimize the damage induced by this metal. In this context, the Eugenia dysenterica DC. (Myrtaceae) plant species, native from Cerrado biome, has been studied because it presents high levels of polyphenols, substances with known antioxidant potential. Moreover, it is traditionally used in folk medicine and presents food and economic importance. In this work, in vitro and in vivo effects of the Eugenia dysenterica DC. leaf hydroalcoholic extract (EDE) on AMJ2-C11 cell line and mice exposed to Cr(VI), respectively, were investigated. In parallel, the antioxidant activity of EDE was also investigated by the methods of 2,2-Diphenyl-1-picrylhydrazyl (DPPH•) free radical capturing and co-oxidation of β-caroteno/linoleic acid. In vitro, pre-treatment of AMJ2-C11 cells with EDE (20, 40 ou 80 μg/mL) followed by exposure to Cr(VI) (100, 250 ou 500 μM) resulted in a concentration-dependent increase of cell viability. Furthermore, mechanistic studies of flow cytometry (cell cycle, annexin V, active caspases, ROS and rhodamine 123) and cell morphology showed that the EDE protected the cells from apoptosis triggered by Cr(VI), and reduced the ROS intracellular levels and prevented the loss of mitochondrial membrane potential. Additionally, significant antioxidant potential of EDE was observed. In vivo, prophylactic treatment for 10 days with EDE (50, 100 ou 200 mg/kg/day) and subsequent exposure to a sublethal dose of Cr(VI) (30 mg/kg) induced a decrease in Cr levels in the kidneys, liver and plasm, besides preventing liver and kidney changes caused by this metal. Moreover, treatment of animals with EDE (50, 100, 125, 200, 250 ou 500 mg/kg/day) followed by exposure to a lethal dose of Cr(VI) (50 mg/kg) induced an increase in the survival of exposed animals, especially at the doses of 50, 100 and 125 mg/kg. Therefore, the present study demonstrated that the EDE showed in vitro and in vivo effect against Cr(VI)-induced oxidative toxicity. / O cromo hexavalente [Cr(VI)] é um metal tóxico capaz de desencadear eventos toxicológicos no organismo, pois ultrapassa as membranas celulares e promove o aumento da produção de espécies reativas de oxigênio (ERO). Esses produtos, por sua vez, danificam as macromoléculas celulares, inibindo suas funções e favorecendo a morte celular por apoptose. Em vista disso, acredita-se que o uso de antioxidantes pode minimizar os danos induzidos por este metal. Nesse contexto, a espécie vegetal Eugenia dysenterica DC. (Myrtaceae), nativa do bioma Cerrado, tem sido estudada por apresentar altos níveis de polifenóis, substâncias que reconhecidamente têm potencial antioxidante. Ademais, é tradicionalmente utilizada na medicina popular e apresenta importância alimentar e econômica. Assim, neste trabalho, os efeitos in vitro e in vivo do extrato hidroalcoólico das folhas da Eugenia dysenterica (EED) sobre a linhagem celular AMJ2-C11 e em camundongos expostos ao Cr(VI), respectivamente, foram investigados. Em paralelo, a atividade antioxidante do EED também foi investigada através dos métodos de captura do radical livre 2,2-difenil-1-picrilidrazila (DPPH•) e da co-oxidação do β-caroteno/ácido linoléico. In vitro, o pré-tratamento das células AMJ2-C11 com EED (20, 40 ou 80 μg/mL) seguido de exposição ao Cr(VI) (100, 250 ou 500 μM) resultou em um aumento da viabilidade celular, de forma concentração dependente. Além disso, estudos mecanísticos utilizando citômetro de fluxo (ciclo celular, anexina V, caspases ativas, ERO e rodamina 123) e de morfologia celular evidenciaram que o EED protegeu as células da apoptose desencadeada pelo Cr(VI), além de reduzir os níveis intracelulares de ERO e impedir a perda do potencial de membrana mitocondrial. Adicionalmente, foi observado relevante potencial antioxidante do EED. In vivo, o tratamento profilático por 10 dias com EED (50, 100 ou 200 mg/kg/dia) e subsequente exposição a uma dose subletal de Cr(VI) (30 mg/kg) promoveu redução dos níveis de Cr nos rins, fígado e plasma, além de prevenir alterações hepáticas e renais causadas por esse metal. Além disso, o tratamento dos animais com EED (50, 100, 125, 200, 250 ou 500 mg/kg/dia) seguido de exposição a uma dose letal de Cr(VI) (50 mg/kg) promoveu um aumento da sobrevida dos animais expostos, principalmente nas doses de 50, 100 e 125 mg/kg. Por conseguinte, o presente estudo demonstrou que o EED

Venous disease is a common vascular condition affecting the lower limbs and causes considerable morbidity in affected patients. National Health Service (NHS) treatment costs are substantial and there is a large demand for treatment much of which cannot be met. Roughly half a million people in the United Kingdom contact their general practitioner each year about varicose veins and associated clinical symptoms. In order to assign priorities and target interventions properly, authorities need to know which patients with venous disease will progress. Although many epidemiological studies have investigated the prevalence of venous disease, information on deterioration is scarce. The overall aim of this study is to determine the natural history of venous disease in the population and to identify lifestyle and clinical factors related to deterioration which might aid clinical decision making and health services policy. The specific objectives were to determine which risk factors were associated with deterioration of venous disease and venous reflux, and to ascertain the natural history of asymptomatic venous incompetence in terms of deteriorating to overt trunk varicose veins and chronic venous insufficiency. The study design was a population based cohort in the Edinburgh Vein Study which the survivors of the 1566 individuals aged 18 to 64 randomly sampled years from the general population at baseline underwent a 13-year follow-up examination. Details of the 1566 participants in the baseline study were sent to the Practitioner Services Division (PSD) of the NHS in Scotland who provided updated addresses and general practitioner registration details. Information collected on each subject at a follow-up clinic included lifestyle factors and medical history, height and weight measurement (by means of a questionnaire), clinical examination for classification of venous disease according to the Basle and CEAP systems, and duplex scanning to assess incompetence of venous valves in the deep and superficial systems of ten vein segments in each leg. Of the subjects from the baseline, 880 participated in the follow-up study, and 576 did not participate, providing a response rate of 60.4% of which 490 were female (55.7%) and 390 were male (44.3%). The study subjects were generally older and slightly more affluent than residents of the City of Edinburgh. For trunk varicose veins, the baseline prevalence was higher in males compared to females (p<0.01), but there was no difference in prevalence among subjects at the follow-up stage of the study (p=0.56). The overall rate of deterioration in trunk varicose veins was 3.55% per annum. More females than males deteriorated (p=0.04). Among subjects who showed deterioration in their trunk varicose veins, the commonest deterioration was from Basle Grade I (mild) at baseline to Grade II (moderate) at follow-up in both the right and left leg (28.1% and 32.9% respectively). Subjects older than 55 years of age (OR=1.59, 95% CI 1.01-2.51), who had a positive family history of varicose veins or venous ulcer (OR=1.92, 95% CI 1.20-3.07), and sat down at work for more than half the working day (OR=1.69, 95% CI 1.04-2.73) had increased risk of deteriorating trunk varicose veins. There was no significant difference between males and females in the prevalence of chronic venous insufficiency (CVI) among subjects at both the baseline and follow-up stage of the study (p=0.15 and 0.16 respectively). The rate of deterioration in CVI was 1.76% per annum. Similarly, among subjects who deteriorated, the commonest deterioration was from Grade I (mild) to Grade II (moderate) CEAP classification in both the right and left leg (42.4% and 45.5% respectively). The risk of worsening of CVI among those older than 55 was nearly three times more than those aged less than 55 (OR=2.85, 95% CI 1.18-6.87), and was still significant when adjusted for gender. The prevalence of telangiectasia was higher in females than in males in both the baseline and follow-up stages of the study (both p<0.01). The rate of deterioration in telangiectasia was 1.6% per annum. The commonest deterioration was from grade I (mild) at baseline to grade II (moderate) follow-up in the left and right leg (using the Basle Classification). Females subjects (OR=1.87, 95% CI 1.35-2.64), those older than 55 (OR=1.68, 95% CI 1.19-2.36), with a positive family history of venous disease (OR=1.60 95% CI 1.14-2.24) were associated with an increased risk of deterioration from telangiectasia compared to male subjects under 55 years of age and with no family history of the disease. The risk of telangiectasia deterioration was more than twice as high in subjects with venous reflux in the greater saphenous vein (origin) (OR=2.34, 95% CI 1.53-3.57), the greater saphenous vein (lower third of the thigh) (OR=2.28, 95% CI 1.59-3.27) and in the small saphenous vein (1.89, 95% CI 1.06-3.36) compared to those with no segments affected. The age and gender adjusted risk was also more than twice as high in subjects with venous reflux in two segments of the superficial system compared to subjects with no venous reflux in any segment (OR=2.06, 95% CI 1.23-3.44), and almost four times as high in subjects with reflux in more than three segments of the superficial system (OR=3.97, 95% CI 2.16-7.31) compared to subjects with no segments affected. On duplex scanning, the prevalence of reflux was higher in females than in males in the superficial system at baseline and follow-up stages of the study (p<0.01 respectively). In the deep system, the prevalence was higher in males than females at the baseline stage (p<0.01) with no significant difference at the follow-up stage (p=0.85). The rate of deterioration in venous reflux was 1.28% per annum. Most subjects deteriorated from one to two vein segments affected in the leg, the majority of which had reflux in the greater saphenous vein (thigh) at baseline and developed reflux in the greater saphenous vein (origin) at follow-up. Subjects more than 55 years of age had significantly more deterioration than those aged less than 55 (p<0.01). Obese or overweight subjects (OR=1.59, 95% CI 1.32-3.67), those aged more than 55 (OR=2.20, 95% CI 1.32-3.67), with a family history of varicose veins (among female subjects only, OR=2.55, 95% CI 1.16-5.56), and who sat down at work more than half the working time (among male subjects only) (OR=2.26, 95%CI 0.97-5.23) had increased risk of showing deterioration in reflux in any leg and in any vein segment from baseline to follow-up. Subjects with venous reflux at baseline were over two and half times more likely to show deterioration in trunk varicose veins compared to those with no reflux (OR=2.69, 95%CI 1.44-5.01), and four times more likely to deteriorate in either trunk varicose veins or chronic venous insufficiency (OR=4.20, 95% CI 2.42-7.29). Subjects with venous reflux at baseline were twice as likely to develop new trunk varicose veins (OR=2.08, 95%CI 1.25-3.46), and 1.78 times more likely to develop either trunk varicose veins or chronic venous insufficiency (OR=1.78, 95%CI 1.12-2.80). Age and gender adjusted risk of trunk varicose veins increased more than fourfold among subjects with venous reflux in the greater saphenous veins (OR=4.04, 95% CI 2.36-6.92), and more than threefold in the greater saphenous vein (lower third of the thigh) (OR=3.13, 95% CI 1.85-5.27) and the small saphenous vein (OR=3.17, 95% CI 1.55-6.48). Subjects with venous reflux in two or more than three vein segments in the superficial system were more than five times more likely to deteriorate from trunk varicose veins (OR=5.39, 95% CI 2.64-10.99 and OR=5.96, 95% CI 2.71-13.10 respectively). The Edinburgh Vein Study follow-up identified factors linked to deterioration of trunk varicose veins and CVI. The findings of this follow-up study have important implications in decision making in NHS and a prognostic tool could be produced to assist clinicians in deciding who should receive treatment or maintained under surveillance. Increasing age, and family history will likely lead to worsening of trunk varicose veins and CVI. The findings also confirm the association between asymptomatic and symptomatic venous valvular incompetence with worsening and developing new cases of venous disease. Such information will be essential for policy makers facing difficult decisions over prioritisation of services in the future. Further research might include trials of surgical and non-surgical interventions designed to limit deterioration in high risk individuals and enable surgeons to target interventions appropriately. Larger prognostic studies of many factors, including genotype, might be conducted to link progression of venous disease, and to provide further information on high risk individuals who might benefit from treatment.