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1.
Langmuir ; 35(12): 4270-4277, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30840470

RESUMO

We report on the chemical analysis of ultrathin (10 nm) polymer films using the attenuated total reflectance-Fourier transform infrared (ATR-FTIR) technique based on p-polarized infrared light and two types of enhancing substrates, that is, metallic (Au) and dielectric (Si). We selected low-temperature plasma-treated ∼10 nm thick polystyrene films as a test case for demonstrating the capability of the p-polarized ATR-FTIR, whose performance was further compared with the conventional X-ray photoelectron spectroscopy (XPS) techniques. Although ATR-FTIR cannot be used for quantitatively determining elemental compositions in polymers at which XPS excels, it is able to be operated under nonvacuum conditions and allows the study of hydrogen-containing moieties. By correcting the contact condition between the polymer surface and the ATR prism, the relative concentration of the chemical bonds from different samples can be compared. Because ATR-FTIR and XPS provide complementary information on chemical bonds, their combination provides a powerful approach for studying the chemical composition of polymers.

2.
Nanotechnology ; 28(17): 175301, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28374684

RESUMO

Thermal scanning probe lithography (t-SPL) is applied to the fabrication of chemical guiding patterns for directed self-assembly (DSA) of block copolymers (BCP). The two key steps of the overall process are the accurate patterning of a poly(phthalaldehyde) resist layer of only 3.5 nm thickness, and the subsequent oxygen-plasma functionalization of an underlying neutral poly(styrene-random-methyl methacrylate) brush layer. We demonstrate that this method allows one to obtain aligned line/space patterns of poly(styrene-block-methyl methacrylate) BCP of 18.5 and 11.7 nm half-pitch. Defect-free alignment has been demonstrated over areas of tens of square micrometres. The main advantages of t-SPL are the absence of proximity effects, which enables the realization of patterns with 10 nm resolution, and its compatibility with standard DSA methods. In the brush activation step by oxygen-plasma exposure, we observe swelling of the brush. This effect is discussed in terms of the chemical reactions occurring in the exposed areas. Our results show that t-SPL can be a suitable method for research activities in the field of DSA, in particular for low-pitch, high-χ BCP to achieve sub-10 nm line/space patterns.

3.
J Chem Phys ; 146(5): 052801, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28178847

RESUMO

With the increasing interest in establishing directional etching methods capable of atomic scale resolution for fabricating highly scaled electronic devices, the need for development and characterization of atomic layer etching processes, or generally etch processes with atomic layer precision, is growing. In this work, a flux-controlled cyclic plasma process is used for etching of SiO2 and Si at the Angstrom-level. This is based on steady-state Ar plasma, with periodic, precise injection of a fluorocarbon (FC) precursor (C4F8 and CHF3) and synchronized, plasma-based Ar+ ion bombardment [D. Metzler et al., J. Vac. Sci. Technol., A 32, 020603 (2014) and D. Metzler et al., J. Vac. Sci. Technol., A 34, 01B101 (2016)]. For low energy Ar+ ion bombardment conditions, physical sputter rates are minimized, whereas material can be etched when FC reactants are present at the surface. This cyclic approach offers a large parameter space for process optimization. Etch depth per cycle, removal rates, and self-limitation of removal, along with material dependence of these aspects, were examined as a function of FC surface coverage, ion energy, and etch step length using in situ real time ellipsometry. The deposited FC thickness per cycle is found to have a strong impact on etch depth per cycle of SiO2 and Si but is limited with regard to control over material etching selectivity. Ion energy over the 20-30 eV range strongly impacts material selectivity. The choice of precursor can have a significant impact on the surface chemistry and chemically enhanced etching. CHF3 has a lower FC deposition yield for both SiO2 and Si and also exhibits a strong substrate dependence of FC deposition yield, in contrast to C4F8. The thickness of deposited FC layers using CHF3 is found to be greater for Si than for SiO2. X-ray photoelectron spectroscopy was used to study surface chemistry. When thicker FC films of 11 Å are employed, strong changes of FC film chemistry during a cycle are seen whereas the chemical state of the substrate varies much less. On the other hand, for FC film deposition of 5 Å for each cycle, strong substrate surface chemical changes are seen during an etching cycle. The nature of this cyclic etching with periodic deposition of thin FC films differs significantly from conventional etching with steady-state FC layers since surface conditions change strongly throughout each cycle.

4.
J Vac Sci Technol A ; 34(4): 040603, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27375342

RESUMO

The authors studied the effect of the temperature and chemical state of the chamber wall on process performance for atomic layer etching of SiO2 using a steady-state Ar plasma, periodic injection of a defined number of C4F8 molecules, and synchronized plasma-based Ar+ ion bombardment. To evaluate these effects, the authors measured the quartz coupling window temperature. The plasma gas phase chemistry was characterized using optical emission spectroscopy. It was found that although the thickness of the polymer film deposited in each cycle is constant, the etching behavior changed, which is likely related to a change in the plasma gas phase chemistry. The authors found that the main gas phase changes occur after C4F8 injection. The C4F8 and the quartz window react and generate SiF and CO. The emission intensity changes with wall surface state and temperature. Therefore, changes in the plasma gas species generation can lead to a shift in etching performance during processing. During initial cycles, minimal etching is observed, while etching gradually increases with cycle number.

5.
N Engl J Med ; 365(1): 32-43, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21732835

RESUMO

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).


Assuntos
Dispneia/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Readmissão do Paciente/estatística & dados numéricos , Doença Aguda , Idoso , Método Duplo-Cego , Dispneia/etiologia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Hipotensão/induzido quimicamente , Análise de Intenção de Tratamento , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Natriuréticos/efeitos adversos , Peptídeo Natriurético Encefálico/efeitos adversos , Recidiva
6.
Int J Androl ; 34(5 Pt 2): e487-98, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21831236

RESUMO

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.


Assuntos
Hormônio Antimülleriano/sangue , Síndrome de Down/fisiopatologia , Hipogonadismo/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de Down/complicações , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Hipogonadismo/etiologia , Lactente , Recém-Nascido , Células Intersticiais do Testículo/fisiologia , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Células de Sertoli/fisiologia , Testículo/anatomia & histologia , Testosterona/sangue
7.
Nat Med ; 1(5): 442-7, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7585092

RESUMO

Psoriasis is a hyperproliferative and inflammatory skin disorder of unknown aetiology. A fusion protein composed of human interleukin-2 and fragments of diphtheria toxin (DAB389IL-2), which selectively blocks the growth of activated lymphocytes but not keratinocytes, was administered systemically to ten patients to gauge the contribution of activated T cells to the disease. Four patients showed striking clinical improvement and four moderate improvement, after two cycle of low dose IL-2-toxin. The reversal of several molecular markers of epidermal dysfunction was associated with a marked reduction in intraepidermal CD3+ and CD8+ T cells, suggesting a primary immunological basis for this widespread disorder.


Assuntos
Toxina Diftérica/farmacologia , Imunotoxinas/farmacologia , Interleucina-2/farmacologia , Psoríase/imunologia , Linfócitos T/imunologia , Adulto , Diferenciação Celular , Movimento Celular , Células Cultivadas , Epiderme/imunologia , Feminino , Humanos , Queratinócitos/imunologia , Masculino , Psoríase/patologia , Proteínas Recombinantes de Fusão/farmacologia , Linfócitos T/efeitos dos fármacos
8.
Aust Vet J ; 86(4): 147-52, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18363989

RESUMO

OBJECTIVES AND DESIGN: 1) A prospective study to determine in vitro concentrations for a range of fluoroquinolones, gentamicin and amoxycillin-clavulanate required to inhibit growth of recently collected, feline and canine Escherichia coli and canine Staphylococcus intermedius isolates. 2) A comparative retrospective study to compare the minimum inhibitory concentrations (MICs) of ciprofloxacin, enrofloxacin and amoxycillin-clavulanate for archived canine E coli and S intermedius isolates collected ten to twenty years earlier, with those for recently collected isolates. PROCEDURE: Susceptibility was assessed using disk diffusion, agar dilution susceptibility testing and Epsilometer tests (E-tests) for both recently collected and archived isolates. RESULTS: All feline E coli isolates and recently collected canine S intermedius isolates were susceptible to all fluoroquinolones. There was a statistically significant increase in the MIC range of ciprofloxacin and enrofloxacin for recently collected E coli, and in the MIC range of amoxycillin-clavulanate for recently collected S intermedius isolates compared to archived isolates. Twelve of 59 recently collected canine E coli isolates were resistant to both ciprofloxacin and enrofloxacin. Resistant canine E coli isolates were associated with complicating host or infection site factors. CONCLUSION: This is the first report comparing the MICs for all veterinary fluoroquinolones currently available in Australia for a representative sample of canine and feline E coli and canine S intermedius isolates. Importantly, this study identified 12 of 59 canine E coli isolates resistant to fluoroquinolones and identified the development of low level resistance in canine E coli to ciprofloxacin and enrofloxacin and canine S intermedius to amoxycillin-clavulanate.


Assuntos
Anti-Infecciosos/farmacologia , Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Anti-Infecciosos/uso terapêutico , Doenças do Gato/epidemiologia , Doenças do Gato/microbiologia , Gatos , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Cães , Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Fluoroquinolonas/uso terapêutico , Testes de Sensibilidade Microbiana/veterinária , New South Wales/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus/isolamento & purificação
9.
Mol Cell Endocrinol ; 260-262: 197-204, 2007 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-17084021

RESUMO

FSH is synthesized and secreted in multiple molecular forms with different oligosaccharide structures which are needed for full expression of biological activity. GnRH and sex steroids modulate oligosaccharide structure and composition. In the present study we have assessed the carbohydrate complexity and proportion of circulating FSH isoforms during puberty, aging and after androgen administration to pubertal anorchid boys. Preparative isoelectrofocusing and lectin chromatography were used to isolate FSH isoforms on the basis of charge and internal carbohydrate complexity. Differences in sialic acid content and a progressive increase of isoforms bearing highly branched oligosaccharides were found during puberty. Less acidic, more bioactive FSH isoforms, secreted at mid-puberty may modulate important maturational events in the Sertoli cell population. Androgen administration to pubertal anorchid boys favoured the secretion of this type of isoforms. In adult men, the predominance of FSH isoforms bearing complex type oligosaccharides remained unchanged until very advanced age. These results show that the predominance of FSH isoforms bearing fully processed oligosaccharides in circulation may contribute to the development and maintenance of seminiferous epithelium function in men.


Assuntos
Carboidratos/química , Concanavalina A/metabolismo , Hormônio Foliculoestimulante/sangue , Isoformas de Proteínas/sangue , Adolescente , Adulto , Idoso , Envelhecimento/sangue , Criança , Humanos , Concentração de Íons de Hidrogênio , Focalização Isoelétrica , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Puberdade/sangue , Testículo/anormalidades , Testosterona/sangue
11.
J Interv Card Electrophysiol ; 17(1): 65-72, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17235681

RESUMO

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are effective at reducing mortality in patients at high risk for sudden cardiac death (SCD) but can cause psychological distress and reduce quality of life (QOL). The full benefits of ICDs can only be achieved when the patient's QOL and psychological status are maintained. We examined psychological status and QOL post ICD implantation; the relationship of psychological status to QOL; the relationship of time since implantation to psychological status and QOL; and the relationship of time since ICD implantation and age of patient to these variables. METHODS AND RESULTS: A cross-sectional self-administered assessment of QOL, depression, anxiety, demographic characteristics and cardiovascular health history of patients (n = 48) who had received ICDs within the past 10 years at an urban hospital. Patients who had ICDs for longer experienced worse depression and QOL. Patients who were younger had worse depression, anxiety, and QOL. The combination of anxiety, depression, age, and time since ICD implant significantly predicted overall QOL and the psychosocial and physical dimensions of QOL explaining 55.5, 54, and 34.9% of the variance, respectively. CONCLUSION: Younger ICD patients are at highest risk for psychological distress and poor QOL. Longitudinal research would facilitate determination of the trajectory of changes in psychological status and QOL over the duration of the ICD experience.


Assuntos
Ansiedade/epidemiologia , Desfibriladores Implantáveis/psicologia , Desfibriladores Implantáveis/estatística & dados numéricos , Depressão/epidemiologia , Qualidade de Vida , Medição de Risco/métodos , Perfil de Impacto da Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Comorbidade , Depressão/psicologia , Humanos , Incidência , Maryland/epidemiologia , Pessoa de Meia-Idade , Psicologia/estatística & dados numéricos , Fatores de Risco
12.
AIDS ; 30(17): 2707-2714, 2016 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-27536979

RESUMO

OBJECTIVES: HIV-2-infected individuals usually initiate antiretroviral therapy (ART) at an advanced age compared with HIV-1 patients, with a potential impact on treatment outcomes. This study aimed to investigate the effect of sex and age on mortality and loss to follow-up (LTFU) among HIV-2-infected individuals initiating ART. METHODS: Analyses were conducted using the database of the International Epidemiological Databases to Evaluate AIDS's collaboration in West Africa. LTFU was considered if the interval between the last visit and the closing date for this analysis was more than 180 days. Probability of death and LTFU were estimated with Kaplan-Meier methods. A Cox regression model was used to identify factors associated with death and LTFU over the first 24 months on ART. RESULTS: A total of 1825 HIV-2-infected individuals, including 60% women were considered for this analysis. The median age, baseline CD4 cell count, and follow-up duration were 45 years [interquartile range (IQR; 38-52)], 185 cells/µl [IQR (95-297)], and 28.8 months [IQR (9.8-58.9)], respectively. Over the first 24 months, the mortality rate was 5.2/100 person-years of observation [95% confidence interval (CI; 4.4-6.1)] and 469 (25.7%) were LTFU. Male sex [hazard ratio (HR) = 1.9; 95% CI (1.4; 2.8)], baseline CD4 cell count less than 100 cell/µl [HR = 4.4 95% CI (1.7; 11.1); ref at least 350 cell/µl], haemoglobin 7.5-10 g/dl [HR = 2.4 95% CI (1.3; 4.4); ref at least 12 g/dl], and BMI less than 18 kg/m [HR = 2.1 95% CI (1.3; 3.4); ref = 18-25 kg/m] were associated with higher mortality over the first 24 months. Similar associations were found for LTFU. CONCLUSION: Mortality and LTFU are high among ART-receiving HIV-2-infected individuals and higher in men than in women. There is a critical need to further determine the causes of poor retention and implement sex-specific solutions that improve outcomes in HIV-2 ART programmes.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-2/isolamento & purificação , Adolescente , Adulto , África Ocidental , Fatores Etários , Idoso , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
13.
Circulation ; 102(20): 2484-90, 2000 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-11076821

RESUMO

BACKGROUND: Previous studies have suggested that women with acute myocardial infarction (AMI) are less aggressively managed than are men. The aim of this study was to assess sex differences in medical and invasive coronary procedures (angiography, PTCA, and CABG) in AMI patients admitted to cardiac care units (CCUs) in Israel in the mid 1990s and their association with early and 1-year prognosis. METHODS AND RESULTS: We studied 2867 consecutive AMI patients (2125 men, 74%) hospitalized in all 25 CCUs in Israel from 3 prospective nationwide surveys conducted in 1992, 1994, and 1996. Women were, on average, older than men (69 versus 61 years, P:<0.0001) and had a higher prevalence of hypertension, diabetes, Killip class >/=II on admission, and in-hospital complications. Women received aspirin and beta-blockers less often than did men, but these differences were not significant after age adjustment. The unadjusted rates of thrombolysis, angiography, and PTCA/CABG use were lower in women than in men but not after covariate adjustment: 42% versus 48% (adjusted odds ratio [OR] 0.92, 95% CI 0.77 to 1.11), 23% versus 31% (OR 0.88, 95% CI 0.70 to 1.09), and 15% versus 19% (OR 0.93, 95% CI 0.72 to 1.19), respectively. The 30-day mortality was higher in women than in men (17.6% versus 9.6%, respectively; OR 1.39, 95% CI 1.06 to 1.82), but the 30-day to 1-year mortality rate was not (9.1% versus 5.6%, respectively; hazard ratio 1.18, 95% CI 0.84 to 1.66). CONCLUSIONS: This prospective nationwide observational community-based study of consecutive AMI patients hospitalized in the CCUs in the mid 1990s indicates that women fare significantly worse than do men at 30 days but not thereafter at 1-year. The difference in 30-day outcome was not influenced by the use of different therapeutic modalities, including thrombolysis and invasive coronary procedures, but was rather due to the older age and greater comorbidity of women; these findings seem also to explain the less frequent use of invasive procedures in women.


Assuntos
Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Saúde da Mulher , Distribuição por Idade , Fatores Etários , Idoso , Angiografia/estatística & dados numéricos , Angioplastia Coronária com Balão/estatística & dados numéricos , Comorbidade , Ponte de Artéria Coronária/estatística & dados numéricos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Razão de Chances , Prevalência , Prognóstico , Estudos Prospectivos , Distribuição por Sexo , Fatores Sexuais , Terapia Trombolítica/estatística & dados numéricos
14.
Circulation ; 102(18): 2222-7, 2000 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-11056096

RESUMO

BACKGROUND: We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. METHODS AND RESULTS: One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) who had a pulmonary capillary wedge pressure >/=15 mm Hg and a cardiac index

Assuntos
Cardiotônicos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hidrazonas/administração & dosagem , Piridazinas/administração & dosagem , Vasodilatadores/administração & dosagem , Cardiotônicos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Testes de Função Cardíaca/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidrazonas/efeitos adversos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pressão Propulsora Pulmonar/efeitos dos fármacos , Piridazinas/efeitos adversos , Índice de Gravidade de Doença , Simendana , Resultado do Tratamento , Vasodilatadores/efeitos adversos
15.
Circulation ; 101(25): 2922-7, 2000 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-10869264

RESUMO

BACKGROUND: Elevated plasma endothelin-1 (ET-1) levels in patients with chronic heart failure correlate with pulmonary artery pressures and pulmonary vascular resistance. ET(A) receptors on vascular smooth muscle cells mediate pulmonary vascular contraction and hypertrophy. We determined the acute hemodynamic effects of sitaxsentan, a selective ET(A) receptor antagonist, in patients with chronic stable heart failure receiving conventional therapy. METHODS AND RESULTS: This multicenter, double-blind, placebo-controlled trial enrolled 48 patients with chronic New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) treated with ACE inhibitors and diuretics. Patients with a baseline pulmonary capillary wedge pressure >/=15 mm Hg and a cardiac index

Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Baixo Débito Cardíaco/fisiopatologia , Antagonistas dos Receptores de Endotelina , Circulação Pulmonar/efeitos dos fármacos , Vasodilatação , Vasodilatadores/uso terapêutico , Doença Crônica , Método Duplo-Cego , Endotelina-1/sangue , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Receptor de Endotelina A , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise , Vasodilatadores/efeitos adversos
16.
J Gen Physiol ; 52(3): 643-65, 1968 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19873637

RESUMO

Embryonic chick heart cells were cultured on a plastic surface in sparse sheets of 2-50 cells mutually in contact, or isolated as single cells. Conditions are described which permitted conjoint cells to be impaled with recording microelectrodes with 75% success, and isolated single cells with 8% success. It is proposed that cells in electrical contact with neighbors are protected from irreversible damage by the penetrating electrode, by a flow of ions or other substances from connected cells across low-impedance intercellular junctions. Action potentials recorded from conjoint and isolated single cells were similar in form and amplitude. The height or shape of the action potential thus appears not to depend upon spatial relationships of one cell to another. As the external potassium concentration was increased from 1.3 mM to 6 mM, cells became hyperpolarized while the afterhyperpolarization was reduced. At higher potassium levels, the afterhyperpolarization disappeared, the slope of the slow diastolic depolarization decreased, and resting potential fell along a linear curve with a slope of 61 mv per 10-fold increase in potassium. In pacemaker cells the diastolic depolarization consists of two phases: (a) recovery from the afterpotential of the previous action potential and (b) the pacemaker potential. These phases are separated by a point of inflection, and represent manifestations of different mechanisms. Evidence is presented that it is the point of inflection (PBA) rather than the point of maximal diastolic potential, that should be taken as the resting potential.

17.
J Gen Physiol ; 52(4): 643-65, 1968 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-5693166

RESUMO

Embryonic chick heart cells were cultured on a plastic surface in sparse sheets of 2-50 cells mutually in contact, or isolated as single cells. Conditions are described which permitted conjoint cells to be impaled with recording microelectrodes with 75 % success, and isolated single cells with 8 % success. It is proposed that cells in electrical contact with neighbors are protected from irreversible damage by the penetrating electrode, by a flow of ions or other substances from connected cells across low-impedance intercellular junctions. Action potentials recorded from conjoint and isolated single cells were similar in form and amplitude. The height or shape of the action potential thus appears not to depend upon spatial relationships of one cell to another. As the external potassium concentration was increased from 1.3 mM to 6 mM, cells became hyperpolarized while the afterhyperpolarization was reduced. At higher potassium levels, the afterhyperpolarization disappeared, the slope of the slow diastolic depolarization decreased, and resting potential fell along a linear curve with a slope of 61 mv per 10-fold increase in potassium. In pacemaker cells the diastolic depolarization consists of two phases: (a) recovery from the afterpotential of the previous action potential and (b) the pacemaker potential. These phases are separated by a point of inflection, and represent manifestations of different mechanisms. Evidence is presented that it is the point of inflection (PBA) rather than the point of maximal diastolic potential, that should be taken as the resting potential.


Assuntos
Potenciais de Ação , Embrião de Galinha/fisiologia , Miocárdio/citologia , Animais , Meios de Cultura/análise , Técnicas de Cultura , Eletrofisiologia , Sistema de Condução Cardíaco/fisiologia , Potenciais da Membrana , Potássio/farmacologia
18.
J Am Coll Cardiol ; 17(3): 743-51, 1991 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-1993796

RESUMO

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Doença das Coronárias/complicações , Digoxina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Doença Crônica , Teste de Esforço , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Troca Gasosa Pulmonar/fisiologia , Volume Sistólico/fisiologia , Vasodilatadores/uso terapêutico
19.
J Am Coll Cardiol ; 26(4): 967-73, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7560625

RESUMO

OBJECTIVES: This prospective study assessed the initial hemodynamic effects and long-term clinical benefits of dual-chamber pacing with a short atrioventricular (AV) delay in patients with chronic heart failure who had no traditional indication for pacemaker implantation. BACKGROUND: Dual-chamber pacing with a short AV delay has been proposed as a nonpharmacologic treatment for drug-refractory heart failure. Both initial and long-term hemodynamic as well as functional benefits have been reported. All previous studies have used an AV delay of 100 ms. Despite encouraging results, these previous studies have been anecdotal and uncontrolled. METHODS: This double-blind, randomized, crossover trial included 12 subjects with chronic congestive heart failure despite optimal medical therapy. Patients were required to be in sinus rhythm with no evidence of significant bradyarrhythmias. On the day after implantation of a dual-chamber pacemaker, invasive hemodynamic measurements were made at varying AV delays between 100 and 200 ms. Patients were then randomized to either dual-chamber pacing with a 100-ms AV delay or backup mode (VVI at 40 beats/min). After 4 to 6 weeks, crossover to the other pacing mode was programmed. RESULTS: Hemodynamic measurements on the day after pacemaker implantation demonstrated no benefit of pacing with any AV delay compared with intrinsic conduction. At the optimal AV interval for each patient, neither cardiac output (4.5 +/- 1.5 vs 4.7 +/- 1.6 liters/min [mean +/- SD]) nor wedge pressure (16 +/- 10 vs 17 +/- 8 mm Hg) improved significantly from baseline measurements during intrinsic conduction. The long-term pacing protocol was completed in nine patients. Ejection fraction was 16 +/- 6% with dual-chamber (VDD mode) pacing and 18 +/- 4% in backup mode (p = NS). No patient had an increase in ejection fraction by > or = 5% with VDD pacing, nor did any patient improve in New York Heart Association functional class with short AV delay dual-chamber pacing. Also, there were no significant reductions in body weight or diuretic requirements during this pacing period. CONCLUSIONS: Dual-chamber pacing with a short AV delay does not improve hemodynamic and clinical status or ejection fraction measured on the day after pacemaker implantation in patients with chronic congestive heart failure. Routine use of pacemaker therapy with a short AV delay aas a primary treatment of heart failure in patients without standard arrhythmic indications is unwarranted.


Assuntos
Estimulação Cardíaca Artificial/métodos , Insuficiência Cardíaca/terapia , Hemodinâmica/fisiologia , Marca-Passo Artificial , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Volume Sistólico/fisiologia , Fatores de Tempo
20.
J Am Coll Cardiol ; 13(7): 1534-9, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2524515

RESUMO

Several circulating neurohormones have been shown to have prognostic significance in patients with chronic heart failure, but the relation between plasma levels of atrial natriuretic peptide and mortality in this disorder remains unknown. Plasma levels of immunoreactive atrial natriuretic peptide were measured in 102 patients in whom left ventricular ejection fraction, ventricular arrhythmias on ambulatory electrocardiographic recording and plasma levels of norepinephrine, renin activity, aldosterone and arginine vasopressin were also measured. Compared with patients with atrial natriuretic peptide concentrations below the median value of 125 pg/ml, patients with higher levels of the peptide had a higher plasma renin activity (8.9 +/- 1.8 versus 2.6 +/- 0.4 ng/ml per h) and plasma norepinephrine (858 +/- 116 versus 538 +/- 45 pg/ml), more frequent premature ventricular depolarizations (4,485 +/- 715 versus 2,004 +/- 495/day) and more advanced hemodynamic abnormalities (all p less than 0.05). During the subsequent 13 to 25 months of follow-up, patients with high levels of atrial natriuretic peptide had a significantly lower rate of survival than did those whose initial circulating peptide concentrations were normal or mildly increased (p = 0.01). These data indicate that, in patients with chronic heart failure, plasma atrial natriuretic peptide provides important prognostic information. This may relate to the ability of the hormone to reflect the interplay of several pathophysiologic factors that contribute to mortality in this disease.


Assuntos
Fator Natriurético Atrial/sangue , Insuficiência Cardíaca/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Prognóstico , Fatores de Risco , Volume Sistólico , Fatores de Tempo
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