11 |
Effect of Nebivolol and Lifestyle Modification on Large Artery Stiffness in Middle-Aged and Older Hypertensive AdultsWerner, Timothy Jason 24 July 2013 (has links)
For more than half a century cardiovascular disease has been the leading cause of death in the United States. Aging, hypertension, and obesity are major risk factors for cardiovascular disease and clearly associated with arterial stiffness. Arterial stiffness generates higher afterloads and diminishes coronary perfusion thereby causing ventricular hypertrophy and ischemia. Importantly, arterial stiffness is an independent predictor of cardiovascular disease risk and all-cause mortality. Current strategies such as inhibition of angiotensin II or angiotensin converting enzyme, reduction of smooth muscle tone, blood volume, or inflammatory mediators, and improving glucose homeostasis are effective destiffening options. Nebivolol, a third generation beta-blocker, has unique vasodilatory characteristics and may be particularly efficacious as a destiffening agent. Only a few studies have addressed this issue while relying on indirect, blood pressure-dependent stiffness indices precluding clear understanding of study outcomes. There remains a need to determine the potential utility of nebivolol therapy as an arterial destiffening strategy. Thus, we hypothesized that the combination of nebivolol and lifestyle modification would reduce central arterial stiffness in middle-aged and older hypertensive adults more than either intervention alone. To test this hypothesis, we randomized 45 hypertensive adults to receive lifestyle modification, nebivolol, or combination for 12 weeks. β-stiffness index, pulse wave analysis, and arterial compliance were measured at baseline and following the intervention. No baseline differences in variables of interest were observed between groups. In contrast to our hypothesis, lifestyle modification, nebivolol, and combination groups had similar (P>0.05) reductions in beta-stiffness index (-1.87±0.83; -2.03±0.60; and -2.51±0.90 U), respectively, while carotid-femoral pulse wave velocity declined only in the nebivolol and combination groups. Our findings suggest combination of nebivolol and lifestyle modification reduces arterial stiffness to a similar degree as either intervention alone in middle-aged and older hypertensive adults. Further studies are needed to determine if the changes in arterial stiffness continue to occur or remain clinically significant over longer durations. / Ph. D.
|
12 |
Avaliação da eficácia e segurança de protocolos para obtenção de midríase com uso tópico de brometo de rocurônio em papagaios do gênero Amazona (Amazona aestiva e Amazona amazonica) / Evaluation of the efficacy and safety of protocols for obtaining mydriasis using rocuronium bromide in Amazon parrots (Amazona aestiva and Amazona amazonica)Dongo, Pamela Silvana Juárez 13 May 2016 (has links)
O exame oftálmico, em aves, demanda conhecimentos sobre as particularidades do olho e de seus anexos, já que, por exemplo, a predominância de fibras musculares estriadas, na íris, impede a obtenção de midríase com fármacos convencionais, como parassimpatolíticos e simpatomiméticos. Objetivando-se estabelecer protocolo efetivo e seguro para a obtenção de midríase em duas espécies de papagaios do gênero Amazona, optou-se por utilizar a aplicação tópica do brometo de rocurônio (10 mg/ml), em ambos os olhos. Foram avaliados 12 papagaios-verdadeiros (Amazona aestiva) e 12 papagaios-do-mangue (Amazona amazônica), adultos, com sexo indeterminado, sadios e sem oftalmopatias, os quais foram submetidos a três protocolos com doses crescentes de rocurônio, aplicadas com pipeta: ROC1 (instilação única de 20 µl); ROC2 (instilação dupla de 20 µl, a cada 15 minutos) e ROC3 (instilação tripla de 20 µl, a cada 15 minutos). Presença ou não de resposta pupilar à luz (RPL) por estímulo direto com transiluminador de Finoff e mensuração do diâmetro pupilar com paquímetro digital foram verificadas antes (M0) e após os tratamentos, nos tempos de 15 (M15), 30 (M30), 45 (M45), 60 (M60), 120 (M120), 180 (M180), 240 (M240), 300 (M300) e 360 (M360) minutos, assim como após 24 horas (M24H). A ocorrência de sinais adversos locais e sistêmicos foi monitorada durante os períodos de avaliação. Quanto ao diâmetro pupilar, diferenças significativas (p<0,05) foram observadas comparando-se ROC1 com ROC2, em M45 e M60 e, em ROC1 com ROC3, de M15 a M60, nos papagaios-verdadeiros. Nos papagaios-do-mangue, diferenças foram observadas comparando-se ROC1 com ROC2 e ROC1 com ROC3, de M15 a M360. Em relação aos protocolos ROC2 com ROC3, diferenças estiveram presentes em M15, M30 e M120. RPL diminuída foi observada em 16,7% dos papagaios-verdadeiros e 25% dos papagaios-do-mangue, em ROC1; ausência foi manifesta por dois papagaios-verdadeiros (16,7%). Em ROC2, diminuição da intensidade da RPL ocorreu em 50% dos papagaios-verdadeiros e 25% dos papagaios-do-mangue; RPL foi ausente em um papagaio-verdadeiro (8,3%) e 25% dos papagaios-do-mangue. Em ROC3, verificou-se resposta pupilar atenuada em 25% dos papagaios-verdadeiros e dos papagaios-do-mangue; a mesma esteve ausente em dois papagaios-verdadeiros (16,7%) e 41,7% dos papagaios-do-mangue. Diferenças significativas quanto ao parâmetro, entre os três protocolos, não foram observadas nos papagaios-verdadeiros; já nos papagaios-do-mangue, ocorreram entre ROC1 e ROC3, de M15 a M120. Efeitos adversos locais não foram verificados e dentre os sistêmicos, constatou-se somente paralisia palpebral transitória em graus variáveis. Em ROC1, paralisia ocorreu em um papagaio-verdadeiro (8,3%); com ROC2, em 33,3% dos papagaios-verdadeiros e 16,7% dos papagaios-do-mangue e, em ROC3, em 50% dos papagaios-verdadeiros e 58,3% dos papagaios-do-mangue. Diferenças significativas (p<0,05) quanto à paralisia palpebral, não foram observadas entre ROC1 e ROC2, nos papagaios-verdadeiros, sendo identificadas em M15, à comparação de ROC1 com ROC3. Nos papagaios-do-mangue, ocorreram entre ROC1 e ROC3 e ROC2 e ROC3, em M15. Os resultados permitiram concluir que midríase superior e duradoura foi obtida nos protocolos ROC2 e ROC3, considerados mais efetivos e relativamente seguros mediante a ocorrência de efeitos colaterais brandos / The ophthalmic examination in birds demands knowledge about the ophthalmic particularities. For example, the predominance of striated muscle fibers in the iris prevents mydriasis with conventional drugs, such as parasympatholytic and sympathomimetics. The purpose of this study was to establish an effective and safe protocol to obtain mydriases in two species of parrots (Amazona aestiva and Amazona amazonica) by the topical application of rocuronium bromide (10 mg/ml) in both eyes. Twelve blue-fronted Amazon parrots (Amazona aestiva) and twelve orange-winged Amazon parrots (Amazona amazonica), adults, with undetermined sex, healthy and without ocular diseases, were submitted to three protocols with different doses of rocuronium, applied with a pipette: ROC1 (20 µl of rocuronium, single dose), ROC2 (20 µl of rocuronium, two doses with 15 minutes apart) and ROC3 (20 µl of rocuronium, three doses with 15 minutes apart). Pupillary light reflex (PLR) was tested by direct stimulation with Finoff transilluminator and pupillary diameter was measured with digital caliper before (M0) and after treatments in times of 15 (M15), 30 (M30), 45 (M45), 60 (M60), 120 (M120), 180 (M180), 240 (M240), 300 (M300) and 360 (M360) minutes, and after 24 hours (M24H). The occurrence of local and systemic adverse signs was monitored. Considering pupillary diameter, significant differences (p <0.05) were observed comparing ROC1 with ROC2, in M45 and M60, and ROC1 with ROC3, M15 to M60, in Amazona aestiva. Differences were observed comparing ROC1 with ROC2 and ROC1 with ROC3, from M15 to M360, in Amazona amazonica. Regarding ROC2 with ROC3 protocols, there were differences in M15, M30 and M120. Diminished PLR was observed in 16.7% of Amazona aestiva and in 25% of Amazona amazonica, in ROC1; absence was manifested by 16.7% of Amazona aestiva. In ROC2, decreased PLR occurred in 50% of Amazona aestiva and 25% of Amazona amazonica; PLR was absent in one Amazona aestiva (8.3%) and 25% of Amazona amazonica. In ROC3, there was attenuated pupillary reflex in 25% of both species, and absent in 16,7% of Amazona aestiva and 41.7% of Amazona amazonica. Significant differences between the three protocols were not observed in Amazona aestiva, however, in Amazona amazonica, there was significant difference between ROC1 and ROC3, from M15 to M120. Local adverse effects were not observed. Regarding to systemic effects, only transient lower eyelid paresis was noted in varying degrees. In ROC1, paresis occurred in one Amazona aestiva (8.3%), in ROC2, in 33.3% of Amazona aestiva and 16,7% of Amazona amazonica, in ROC3, in 50% of Amazona aestiva and 58.3%. of Amazona amazonica. Significant differences (p<0.05) regarding palpebral paresis were not observed between ROC1 with ROC2, in Amazona aestiva, but they were identified in M15, comparing ROC1 with ROC3. In Amazona amazonica, differences occurred in M15, comparing ROC 1 with ROC3 and ROC2 with ROC3. The results of this study indicate that a greater and more lasting mydriasis was obtained in ROC2 and ROC3. These two protocols were considered most effective and relatively safe because of mild side effects manifested
|
13 |
Cardioprotective effect of Na+/Ca2+ exchange inhibition in cardioplegic arrest by SEA0400Egar, Jeanne 06 August 2013 (has links)
This study investigated the effects of SEA0400, a Na+/Ca2+ exchange inhibitor, in
cardioplegia on rat myocyte contractile function. SEA0400 significantly reduced the
accumulation of diastolic Ca2+ throughout cardioplegic arrest compared to ischemic
control and cardioplegia. Cells treated with SEA0400 during cardioplegic arrest showed
significantly larger Ca2+ transient amplitudes and contractions throughout reperfusion
compared to cells treated with cardiopelgia alone. Intracellular Ca2+ stores were similar in both cardioplegic groups at baseline and during reperfusion. Together these results suggest that SEA0400 has beneficial effects at protecting ventricular myocytes during cardioplegic arrest and that SEA0400 in cardioplegia may affect myofilament Ca2+ sensitivity.
|
14 |
Effekte einer b-Rezeptor-Blockade auf die funktionellen Auswirkungen der sympathischen Reinnervation am orthotop transplantierten HerzenKarja, Jessica. Unknown Date (has links) (PDF)
Techn. Universiẗat, Diss., 2005--München.
|
15 |
Kisspeptin and neurokinin B in the regulation of the human hypothalamic-pituitary-gonadal axisSkorupskaite, Karolina January 2017 (has links)
Background: Hypothalamic kisspeptin and neurokinin B (NKB) are central regulators of GnRH and thus gonadotropin (LH and FSH) secretion. Men and women with loss-of-function mutations in NKB-kisspeptin pathway show hypogonadotropic pubertal delay with reduced GnRH/LH pulsatility. Studies in patients with defects in NKB signalling suggest that kisspeptin is functionally downstream of NKB, although there are very limited data on the relevance of the NKB pathway in normal men or women, and no hierarchical data on this. The studies described in this thesis have investigated the interaction between these neuropeptides in the control of human reproduction in conditions of varying sex-steroid environment, and in states of fast and slow LH secretion (men, menopause, various stages across the menstrual cycle). Overall hypothesis: Pharmacological blockade of NKB signalling will decrease LH secretion by modulating GnRH/LH pulsatility, indicating the involvement of the NKB pathway in normal human reproductive function. It is also hypothesised that this will not abrogate the stimulatory kisspeptin response, revealing a functional hierarchy whereby NKB signalling is upstream of kisspeptin. Research strategy: A specific neurokinin-3 receptor antagonist (NK3R antagonist, AZD4901) was administered 40 mg twice daily orally for 7 days with and without kisspeptin-10 (KP-10) challenge. Response of reproductive hormones (serum and urinary where applicable) was measured. LH was sampled every 10 minutes for 8 hours to assess LH pulsatility by blinded deconvolution. Results: Role of neurokinin B and kisspeptin in healthy men Six healthy men underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist reduced LH and testosterone secretion, whilst stimulatory LH response to KP-10 was unaffected. LH pulse frequency was unchanged by the NK3R antagonist but basal (nonpulsatile) and pulsatile LH secretion was markedly reduced. Role of neurokinin B and kisspeptin in postmenopausal women Eleven postmenopausal women underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist decreased LH secretion. Basal (nonpulsatile) LH secretion also fell and while LH pulse frequency did not change in a group as a whole, it did fall in the 8 of 11 postmenopausal womenwith hot flushes. These women reported a reduction in hot flush frequency (3.4±1.2 vs 1.0± 0.6 flushes/day with NK3Ra, p=0.008) and severity whilst on NK3R antagonist. LH response to KP-10 was minimal and unaffected by the NK3R antagonist. Role of neurokinin B across different phases of menstrual cycle The effect of NK3R antagonist on ovarian function was compared in early follicular (n=13), late follicular (n=6) and luteal phase (n=6) to no treatment control cycle. Early follicular: NK3R antagonist was commenced from cycle day 5-6. The diameter of the leading follicle was smaller than in controls at the end of treatment (9.3±0.4 vs 15.1±0.9 mm, p < 0.0001). Serum estradiol was also reduced and the endometrium was thinner. Although NK3R antagonist had no effect on LH pulse frequency, basal (nonpulsatile) LH secretion was decreased, suggesting that NKB modulates GnRH secretion. After stopping treatment, follicle development resumed and estradiol secretion increased thereby delaying the LH surge in 11/13 women (LH surge cycle day 22±1 vs 15±1, p=0.0006). The delayed LH surge and ovulation were confirmed by a similarly delayed rise in urinary progesterone and prolonged cycle length. NK3R antagonist did not affect luteal function. Late follicular: NK3R antagonist was administered from the emergence of a dominant follicle (≥12mm). Whilst there was an LH surge in all treated cycles, estrogen feedback was perturbed by the NK3R antagonist, as there was increased variation in the timing of LH surge compared to control cycle. NK3R antagonist had no effect on the growth of a dominant follicle and luteal function was unaffected. Luteal: NK3R antagonist was administered from day +2-3 of the disappearance of the dominant follicle. NK3R antagonist reduced the variation in the timing of peak estradiol secretion. Estradiol and progesterone concentrations remained unchanged, suggesting that luteal function was overall unaffected by this treatment. No difference in mean LH was observed, although LH pulsatility was not assessed. Role of neurokinin B and kisspeptin in the mid-cycle LH surge A model of follicular phase (cycle day 9-11) administration of estradiol (200μg/day) to induce LH secretion at 48 hours was used in twenty women, mimicking LH surge. In this model, KP-10 infusion (4μg/kg/hr for 7 hours) enhanced LH secretion, the response of which was directly correlated with estrogen concentration, indicating a role of kisspeptin in estrogen feedback. Pre-treatment with NK3R antagonist decreased LH pulse frequency and whilst the immediate LH response to KP-10 was unaffected, it blunted the duration of this response and abolished the relationship between estradiol and kisspeptin-induced LH secretion. Conclusions: These data indicate the role of NKB-KP pathway in regulating human reproductive function and that this is via the modulation of pulsatile GnRH secretion. Whilst NKB is predominantly proximal to kisspeptin, the hierarchy is more complex than simply linear in the control of human HPG axis. Manipulation of NKB-KP signalling has therapeutic potential in regulating GnRH/LH secretion in wide range of clinical settings, including contraception, sex-steroid dependent disorders and in the treatment of hot flushes.
|
16 |
Therapeutic misadventure with a beta blocker during a thyroid storm in an undiagnosed hyperthyroid Patient.Obeng, George, Trofimovitch, Diana, MD, Addo-yobo, Emmanuel, Vijayan, Karthik, Zaietta, Gabriel A 05 April 2018 (has links)
Thyroid storm (TS) is a rare life threatening endocrine emergency. Estimates for mortality rate for untreated TS ranges from 50%-90%[1,2].; however if managed appropriately, mortality drops to less than 20%[2]. Management can include glucocorticoids, propranolol, propylthiouracil(PTU) or methimazole and iodine solution. Each have established roles in controlling the hyperdynamic state in the storm. What is not well established is subclinical cardiomyopathy that may exist with chronic uncontrolled hyperthyroidism. We present a case in which propranolol, used appropriately, led to cardiovascular collapse during the management of a thyroid storm.
48 year old female with a medical history significant for hypertension presented with a 1 day history of severe dyspnea. On arrival vitals were: BP 177/103, pulse 127, RR 28 and pulse ox 92% on room air. She had anasarca and a GCS of 6. She was intubated for airway protection. Head CT was normal. Labs were sodium 128, bicarbonate 18, glucose 38, anion gap 14, lactic acid 5, leukocytes of 12000, Hb 7.3. ABG was pH 7.04, PCO2 45, PaO2 138 on 100% O2 at PEEP of 10, immediately after intubation. TSH was undetectable, FT4 was > 8ng/dL with FT3 of 11pg/mL. Echocardiogram showed EF of 45%, RV dilation and biatrial enlargement. She received glucocorticoids, PTU and oral propranolol. Shortly afterwards she became bradycardic, hypotensive then developed pulseless electrical activity (PEA) despite glucagon and aggressive IV fluids. ROSC was achieved after 8 minutes of ACLS protocol. Within minutes she became bradycardic and hypotensive again then became pulseless again despite glucagon and attempts at transcutaneous pacing. After ROSC with ACLS protocol, she was eventually stabilized with aggressive IV fluid, 5 vasopressors and a bicarbonate drip. That night, she had a third cardiac arrest. After ROSC, an emergency bedside laparotomy was performed for decompression of compartment syndrome. Her hospital course was complicated by hematologic abnormalities requiring multiple blood products, gastrointestinal blood loss, NSTEMI and dialysis dependent renal failure.
The concept of thyrocardiac disease must be kept in mind when managing a thyroid storm. In long standing hyperthyroidism, the resulting cardiomyopathy is compensated by tachycardia and increased sensitivity to catecholamines [3]. This compensatory mechanism depends on tachycardia to maintains adequate cardiac output. Failure to consider this led to our therapeutic misadventure.
Current management of TS includes the use of propranolol to lessen the adrenergic effect on the heart and to inhibit peripheral conversion of T4 to T3. This patient’s experience suggested that abrupt disruption of this compensatory state with beta blockade puts the body at risk for cardiovascular collapse. Until management guidelines are updated, it is imperative to for clinicians to avoid beta blockers or use short acting beta blockers with extreme caution when managing TS.
|
17 |
β-Blocker therapy and cardiovascular outcomes in patients who have undergone percutaneous coronary intervention after ST-elevation myocardial infarction / ST上昇型急性心筋梗塞患者におけるβ遮断薬と心血管予後の関係Bao, Bingyuan 24 March 2014 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18162号 / 医博第3882号 / 新制||医||1003(附属図書館) / 31020 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 佐藤 俊哉, 教授 坂田 隆造 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
|
18 |
Cyclosporine populational pharmacodynamic studies in dogsAlmeida Lupiano, Henrique Ellrich de 13 May 2022 (has links) (PDF)
Background: Cyclosporine is an immunosuppressive agent used to treat immune-mediated and inflammatory diseases in dogs. We have developed a pharmacodynamic (PD) assay that measures interleukin-2 (IL-2) produced by activated T cells to measure the immunosuppressive effects of cyclosporine. Hypothesis/objectives: Our retrospective study extracted data from samples submitted to our laboratory to obtain descriptive statistics, to determine whether assay results predicted treatment effectiveness, and to determine whether cyclosporine formulation or breed affected PD responses. Animals: 1,110 samples were analyzed over 4 years. Methods: Extracted data was analyzed to determine whether there was a relationship between assay results and clinical control, and whether either formulation or breed affected results. Results: We found no relationship between assay results and control of signs, and found that breed did not affect results. At comparable doses, proprietary modified cyclosporine was more immunosuppressive than proprietary non-modified cyclosporine, and both proprietary and generic modified formulations had similar efficacy.
|
19 |
The Nurse Executive Role in Implementing Evidence Based Practice (EBP) at the Point of CareMalcolm, Kimberly Ann, Mrs. 13 April 2016 (has links)
No description available.
|
20 |
Influence of three-tier cost sharing on patient compliance with and switching of cardiovascular medicationsDowell, Margaret Anne January 2002 (has links)
No description available.
|
Page generated in 0.0412 seconds