Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Cardiovasc J Afr ; 30(5): 279-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512717

RESUMO

BACKGROUND: Alirocumab reduces low-density lipoprotein cholesterol (LDL-C) levels by up to 61%. The ODYSSEY Open-Label Extension study investigated the effect of alirocumab in patients with heterozygous familial hypercholesterolaemia (HeFH) over 144 weeks. METHODS: Eligible patients with HeFH had completed an earlier double-blind, randomised, placebo-controlled parent study. Patients were initiated on 75 mg alirocumab Q2W subcutaneous (SC) unless baseline LDL-C was > 8.9 mmol/l, in which case they received 150 mg alirocumab Q2W. Dose titration to 150 mg Q2W was at the investigator's discretion. RESULTS: The study enrolled 167 patients and the parent study mean (± SD) baseline LDL-C level was 3.65 ± 1.9 mmol/l. Mean LDL-C level was reduced by 48.7% at week 144; mean on-treatment LDL-C was 2.30 ± 1.24 mmol/l. Eight patients reported injection-site reactions, with one treatment discontinuation. Treatment emergent anti-drug antibodies were identified in five patients but these did not affect the efficacy. CONCLUSIONS: Alirocumab effectively and safely reduced LDL-C in these patients.

2.
Circulation ; 131(1): 54-61, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25403646

RESUMO

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Progressão da Doença , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Tetrazóis/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fatores de Risco , Volume Sistólico/fisiologia , Sobreviventes , Resultado do Tratamento , Troponina/sangue
3.
PLoS One ; 7(11): e49006, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23152839

RESUMO

OBJECTIVES: Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. METHODS AND RESULTS: Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. MAIN OUTCOME: percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). CONCLUSION: Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00794664.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Oligodesoxirribonucleotídeos Antissenso/administração & dosagem , Oligodesoxirribonucleotídeos Antissenso/efeitos adversos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Resultado do Tratamento
4.
Nutrition ; 25(10): 1006-10, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19487103

RESUMO

OBJECTIVE: Hypoalbuminemia is known to occur in critically ill patients and is associated with increased mortality. Severe hypoalbuminemia is defined in the literature as serum albumin levels lower than 24 g/L. METHODS: Albumin levels were measured in our laboratory using the bromocresol purple method on the Synchron CX9 (Beckman Coulter); the lower detection limit on this apparatus is 10 g/L. RESULTS: We report two cases of severe hypoalbuminemia with levels lower than 10 g/L-one in a complete paraplegic patient with severe pressure ulcers and the other in a patient positive for the human immunodeficiency virus with chronic renal failure. CONCLUSION: Although cases of severe hypoalbuminemia (<10 g/L) are very rare in the literature, chemical pathologists should be aware of the causes of serum albumin levels of this magnitude. These cases describe two different disease states that lead to severe hypoalbuminemia by means of a similar underlying cause, namely severe inflammation or infection.


Assuntos
Hipoalbuminemia/etiologia , Adulto , Anemia/complicações , Eletroforese das Proteínas Sanguíneas , Púrpura de Bromocresol , Feminino , Infecções por HIV/complicações , Humanos , Hipoalbuminemia/mortalidade , Indicadores e Reagentes , Masculino , Nefelometria e Turbidimetria , Lesão por Pressão/complicações , Insuficiência Renal/complicações , Albumina Sérica/análise , Espectrofotometria
5.
S Afr Med J ; 99(9): 668-71, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20073294

RESUMO

BACKGROUND: Various publications have highlighted the significance of laboratory errors in the pre- and post-analytical phases and their impact on results. Thyroid-stimulating hormone (TSH) is a first-line thyroid function test and, if abnormal, reflex thyroxine (T4) or tri-iodothyronine (T3) testing is requested, depending on clinical and medication data provided. Interpretative comments are added to all TFT results. OBJECTIVES: In view of the paucity of articles describing such errors, we audited laboratory request forms requesting thyroid function tests (TFT), received from primary care clinics and regional hospitals at our laboratory. DESIGN: We assessed 482 laboratory request forms for TFT from primary health care clinics for specific parameters. RESULTS: A total of 482 forms were analysed. Medication/s used by the patient (74.5%) and doctor's contact number (65.1%) were the most commonly incomplete parameters. Of the 123 patients with medication details, 62 (50.4%) were on thyroxine. CONCLUSIONS: There are few studies examining the frequency and impact of incomplete laboratory forms on laboratory errors, and even fewer studies examining interpretative comments accompanying clinical biochemistry results. We studied how pre-analytical errors in completing request forms may lead to incorrect interpretative comments and inappropriate reflex testing, and so influence the quality of the post-analytical phase.


Assuntos
Erros de Diagnóstico/prevenção & controle , Documentação/normas , Laboratórios Hospitalares/normas , Patologia Clínica , Garantia da Qualidade dos Cuidados de Saúde , Testes de Função Tireóidea , Química Clínica , Testes de Química Clínica , Humanos , Patologia Clínica/normas , Estudos Retrospectivos , Suécia
6.
Cardiovasc J S Afr ; 17(5): 233-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17117227

RESUMO

OBJECTIVES: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-tuberculous therapy in patients with tuberculous pericarditis. METHODS: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. RESULTS: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and/or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. CONCLUSIONS: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive tuberculous pericarditis could not be demonstrated in this three-year study.


Assuntos
Glucocorticoides/administração & dosagem , Infecções por HIV/tratamento farmacológico , Pericardite Tuberculosa/tratamento farmacológico , Prednisona/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pericardite Tuberculosa/complicações , Pericardite Tuberculosa/diagnóstico , Pericardite Tuberculosa/mortalidade
7.
Clin Chim Acta ; 366(1-2): 357-60, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16289427

RESUMO

INTRODUCTION: Pseudohyponatraemia is uncommonly associated with severe hypercholesterolaemia. Severe hypercholesterolaemia encountered in obstructive jaundice due to an abnormal lipoprotein, lipoprotein X (LpX), may result in pseudohyponatraemia. CASE REPORT: We report a case of falsely low sodium measurements in a patient with severe hypercholesterolaemia due to obstructive liver disease. The pathophysiology, complications and analytical effects of LpX are briefly discussed. CONCLUSION: The possibility of pseudohyponatraemia should be considered in severely hypercholesterolaemic samples.


Assuntos
Hiponatremia/diagnóstico , Icterícia Obstrutiva/complicações , Adulto , Diagnóstico Diferencial , Eletroforese em Gel de Ágar , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etiologia , Hiponatremia/etiologia , Icterícia Obstrutiva/metabolismo , Lipoproteína-X/análise
8.
Tuberculosis (Edinb) ; 86(2): 125-33, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16360340

RESUMO

OBJECTIVE: To investigate the immunopathogenesis of pericardial tuberculosis (TB) and the influence of human immunodeficiency virus (HIV) on the anti-tuberculous immune response. DESIGN: Consecutive patients presenting with large pericardial effusions were subjected to a full clinical examination and pericardiocentesis. Aspirated fluid was sent for biochemistry, differential leukocyte count, flow cytometric analysis and determination of cytokine levels. Pericardial tissue was sent for TB culture and histopathological evaluation. Diagnoses were made according to pre-determined criteria. RESULTS: Fifty-six patients were included and divided into HIV positive TB (n = 22), HIV negative TB (n = 21) and non-tuberculous effusions (n = 13). Peripheral blood neutrophil, lymphocyte and monocyte counts were significantly lower in HIV positive TB patients. Lymphocytes were the dominant cell type in tuberculous pericardial effusions. CD4+ cells dominated in HIV negative tuberculous effusions, whereas CD8+ cells dominated in HIV positive TB. The difference in the concentration of IFN-gamma levels in the tuberculous and non-tuberculous pericardial effusions was statistically significant. Despite significant differences in pericardial CD4+ cell counts, IFN-gamma levels were similarly elevated in HIV negative and HIV positive tuberculous effusions. Highest levels of pericardial IL-10 were observed in samples associated with least tissue necrosis, suggesting the possibility of a tissue protective immunoregulatory role for IL-10. CONCLUSIONS: Tuberculous pericardial effusions result from a T helper1 (Th1)-dominant immune response. IFN-gamma producing CD4+ lymphocytes dominate in HIV negative patients, whereas CD8+ seem to play a more important role in HIV positive patients. Infection with HIV leads to the depletion of immunocompetent cells such as monocytes, NK cells and neutrophils.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Derrame Pericárdico/imunologia , Pericardite Tuberculosa/imunologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/análise , Citometria de Fluxo , Infecções por HIV/imunologia , Humanos , Interferon gama/análise , Interleucina-10/análise , Contagem de Leucócitos , Necrose , Derrame Pericárdico/microbiologia , Pericardite Tuberculosa/patologia , Pericárdio/patologia , Estudos Prospectivos , Células Th1/imunologia
9.
Circulation ; 112(23): 3608-16, 2005 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-16330703

RESUMO

BACKGROUND: The incidence of tuberculous pericarditis is increasing in Africa as a result of the human immunodeficiency virus (HIV) epidemic. The primary objective of this article was to review and summarize the literature on the pathogenesis, diagnosis, and management of tuberculous pericarditis. METHODS AND RESULTS: We searched MEDLINE (January 1966 to May 2005) and the Cochrane Library (Issue 1, 2005) for information on relevant references. A "definite" diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on a histological section of the pericardium; "probable" tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated adenosine deaminase levels, and/or appropriate response to a trial of antituberculosis chemotherapy. Treatment consists of the standard 4-drug antituberculosis regimen for 6 months. It is uncertain whether adjunctive corticosteroids are effective in reducing mortality or progression to constriction. Surgical resection of the pericardium remains the appropriate treatment for constrictive pericarditis. The timing of surgical intervention is controversial, but many experts recommend a trial of medical therapy for noncalcific pericardial constriction, and pericardiectomy in nonresponders after 4 to 8 weeks of antituberculosis chemotherapy. CONCLUSIONS: Research is needed to improve the diagnosis, assess the effectiveness of adjunctive steroids, and determine the impact of HIV infection on the outcome of tuberculous pericarditis.


Assuntos
Pericardite Tuberculosa/diagnóstico , Pericardite Tuberculosa/tratamento farmacológico , África/epidemiologia , Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Humanos , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/tratamento farmacológico , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/tratamento farmacológico , Pericardite Tuberculosa/etiologia
10.
Chest ; 122(3): 900-5, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12226030

RESUMO

BACKGROUND: Traditional diagnostic tests for pericardial tuberculosis (TB) are insensitive and often require long culture periods, and this has led to more emphasis being placed on biochemical tests such as the pericardial adenosine deaminase (ADA) test. However, controversy exists as to its diagnostic utility. In addition, the use of interferon (IFN)-gamma, which is a reliable indicator of pleural and peritoneal TB, has not been explored in pericardial effusions. We investigated ADA and IFN-gamma levels in pericardial effusions of different etiologies. METHODS AND RESULTS: A prospective study was carried out from February 1995 to February 1998 at Tygerberg Hospital (South Africa), with pericardial taps being performed under echocardiographic guidance. During this period, 110 consecutive patients presenting with large pericardial effusions were included in the study. Diagnoses were made according to predetermined criteria, and they included TB (n = 64), malignancy (n = 12), nontuberculous infections (n = 5), other effusions (n = 19), and effusions of uncertain origin (n = 10). The median ADA level in the tuberculous group was 71.7 U/L (range, 10.3 to 303.6 U/L), which was significantly higher than that in any other group (p < 0.05). With a cutoff level for ADA activity of 30 U/L, sensitivity was 94%, specificity was 68%, and positive predictive value was 80%. IFN-gamma levels were determined in 30 subjects. The median IFN-gamma concentration in the tuberculous group was > 1,000 pg/L, which was significantly higher than in any other diagnostic group (p < 0.0005). A cutoff value of 200 pg/L for IFN-gamma resulted in a sensitivity and specificity of 100% for the diagnosis of pericardial TB. CONCLUSION: Pericardial fluid levels of ADA and IFN-gamma are useful in the diagnosis of tuberculous pericarditis.


Assuntos
Adenosina Desaminase/análise , Interferon gama/análise , Derrame Pericárdico/química , Pericardite Tuberculosa/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/etiologia , Pericardite Tuberculosa/enzimologia , Valor Preditivo dos Testes , Estudos Prospectivos , África do Sul
11.
Chest ; 121(2): 495-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11834663

RESUMO

STUDY OBJECTIVES: To determine the biochemical characteristics of large pericardial effusions in various disease states, and to assess their utility as diagnostic tools. SETTING: An academic university hospital in the Western Cape, South Africa. DESIGN: Consecutive, prospective case series. PATIENTS: One hundred ten hospital patients > 12 years old, who presented to the echocardiography department with large pericardial effusions, and 12 control subjects who underwent open-heart surgery (coronary artery bypass graft or aortic valve replacement). MEASUREMENTS: Fluid was sent for examination of biochemistry, adenosine deaminase, microbiology, hematology, and cytology. The etiology of each pericardial fluid sample was established using predetermined criteria. RESULTS: The biochemistry of pericardial exudates differed significantly from pericardial transudates. Light' s criteria (whereby an exudate is defined as having one or more of the following: pleural fluid/serum protein ratio > 0.5; pleural fluid/serum lactate dehydrogenase [LDH] ratio > 0.6; and/or pleural fluid LDH level > 200 U/L) were applied to pericardial fluids and demonstrated to be the most reliable diagnostic tool for identifying pericardial exudates. The corresponding sensitivity was 98%. CONCLUSION: Although laboratory tests are a useful guideline when assessing the etiology and pathophysiology of pericardial effusions, the majority of large, clinically significant pericardial effusions result from exudative causes.


Assuntos
Derrame Pericárdico/diagnóstico , Bilirrubina/análise , Colesterol/análise , Humanos , L-Lactato Desidrogenase/análise , Derrame Pericárdico/metabolismo , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA