RESUMO
An informed consent is a prerequisite for participating in medical trials, whereby the person asked to take part in the trial shall understand what he is committing himself to, and that the consent is given voluntarily. Voluntariness can be undermined by so-called therapeutic optimism, i.e. belief in personal benefit brought about by the trial, as well as the difficulty of understanding how conventional treatment and the trial differ from each other, i.e. the so-called therapeutic misconception. The investigator, especially if he is also the attending physician, may influence the development of therapeutic misconception, because the participant may assume that the physician works as an investigator for the best benefit of the patients. It is important to recognize unrealistic optimism and therapeutic misconception of the trial, because for the participant they may result in disappointment and loss of confidence during the trial.
Assuntos
Ensaios Clínicos como Assunto/ética , Tratamento Farmacológico , Ética em Pesquisa , Consentimento Livre e Esclarecido , Mal-Entendido Terapêutico , HumanosRESUMO
Persons taking part in a clinical study are patients in the need of treatment. Although the values of the study and the treatment are largely consistent with each other, their goals, methods and ethics differ. Randomized studies in particular involve features that are strange to conventional treatments, such as blinding and placebo medication. Anyone participating in a study should understand that instead of obtaining a health benefit for an individual participant, its primary goal is generalizable knowledge. Any misunderstanding of the therapeutic meaning of the study may lead to disappointment of the participant.
Assuntos
Experimentação Humana , Projetos de Pesquisa , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
To meet all physicians' needs for ethics consultation in Finland, a novel form of service, the Physicians' Ethics Forum, was founded in 2003. The Forum is a cost-efficient service based on electronic communication. In this paper, experiences throughout its first 6 years are described.
Assuntos
Consultoria Ética/organização & administração , Sistemas On-Line , Atitude do Pessoal de Saúde , Eticistas , Finlândia , Humanos , Internet , MédicosRESUMO
OBJECTIVE: Anti-carbonic anhydrase II (anti-CA II) antibodies have been related to renal manifestations of primary SS (pSS), and animal studies have even suggested a pathogenic role for them. However, not all pSS patients with renal tubular acidosis (RTA) present with anti-CA II antibodies. Recently, several novel CA isoenzymes have been recognized and we aimed to investigate whether antibodies to these are associated with renal manifestations of pSS. METHODS: We examined anti-CA II antibodies as well as anti-CA I, VI, VII and XIII antibodies by ELISA tests in 74 pSS patients on whom detailed nephrological examinations had been performed and, as controls, in 56 subjects with sicca symptoms, but no pSS. RESULTS: The levels of anti-CA I, II, VI and VII antibodies were significantly higher in patients with pSS compared with subjects with sicca symptoms but no pSS. None of the anti-CA antibodies was associated with the presence of complete or incomplete RTA or proteinuria or urinary α1m excretion in patients with pSS. However, levels of anti-CA II, VI and XIII antibodies correlated significantly with urinary pH, and inversely with serum sodium concentrations. The degree of 24-h urinary protein excretion correlated weakly with levels of anti-CA VII antibodies. CONCLUSION: Not only antibodies to CA II, but also anti-CA VI and XIII antibodies seem to be associated with renal acidification capacity in patients with pSS.
Assuntos
Acidose Tubular Renal/patologia , Autoanticorpos/sangue , Anidrases Carbônicas/imunologia , Síndrome de Sjogren/patologia , Acidose Tubular Renal/enzimologia , Acidose Tubular Renal/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos/imunologia , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Concentração de Íons de Hidrogênio , Isoenzimas/imunologia , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/enzimologia , Síndrome de Sjogren/imunologia , Sódio/sangueRESUMO
BACKGROUND/AIMS: We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and blood pressure in patients 6 years after acute nephropathia epidemica (NE) compared with seronegative controls. The present aim was to establish whether the long-term outcome is determined by the severity of acute illness. METHODS: Serial plasma interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), creatinine, C-reactive protein, blood cell count as well as 24-hour urinary protein and overnight α(1)-microglobulin and albumin excretions were measured in 37 patients with acute NE. Human leucocyte antigen (HLA)-B, HLA-DRB1, TNF-α(-308) and IL-6(-174) alleles were also analyzed. After 6 years, GFR, blood pressure and urinary protein excretion were examined. RESULTS: There were no associations between the clinical severity of acute NE or the genetic factors determined and the increased GFR, hypertension or 24-hour urinary protein excretion observed 6 years later. The degree of inflammation during the acute phase was higher in patients who had increased urinary excretion of α(1)-microglobulin 6 years later compared with those with no α(1)-microglobulin excretion. CONCLUSION: Neither the severity of acute NE nor the host genetic factors determined the predicted renal function, blood pressure or 24-hour urinary protein excretion 6 years later.
Assuntos
Febre Hemorrágica com Síndrome Renal/sangue , Febre Hemorrágica com Síndrome Renal/patologia , Virus Puumala , Índice de Gravidade de Doença , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined. METHODS: A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self-reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT), glutamyl transferase, gamma-CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde-protein adducts. RESULTS: In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and gamma -CDT, p < 0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake. CONCLUSIONS: These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted.
Assuntos
Acetaldeído/imunologia , Consumo de Bebidas Alcoólicas/imunologia , Adutos de DNA/imunologia , Glomerulonefrite por IGA/imunologia , Imunoglobulina A/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Glomerulonefrite por IGA/diagnóstico , Humanos , Imunoglobulina A/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: IgA glomerulonephritis (IgAGN) is a kidney disease with variable prognosis. Several known risk factors exist for a more progressive course. Some population studies indicate that moderate alcohol consumption might protect kidney function, but the relationship between alcohol intake and IgAGN has not previously been examined. METHODS: We examined 158 (95 men) IgAGN patients (37 abstainers, 80 light drinkers, 25 moderate drinkers and 16 heavy drinkers) in a cross-sectional study. The definition of alcohol consumption was based on interviews on the amounts of alcohol intake combined with measurements of serum carbohydrate-deficient transferrin, a specific biomarker of alcohol abuse. Longitudinal data on renal function were available from 117 patients (76 men) in whom an analysis with respect to progression was also performed. RESULTS: Moderate drinkers showed the best kidney function. When adjusted by hypertension and 24-hour protein excretion, moderate alcohol consumption in a cross-sectional multivariate analysis, and both light and moderate alcohol consumption in a longitudinal multivariate analysis were significant factors of better kidney function. When the study population was divided by gender, the best kidney function was among light drinkers in women and among moderate drinkers in men. CONCLUSIONS: Moderate alcohol consumption might have a favorable impact on the progression of IgAGN. Light alcohol consumption in women and moderate consumption in men are associated with improved indices of the glomerular filtration estimates in patients with IgAGN.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/epidemiologia , Testes de Função Renal/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND/AIMS: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. METHODS: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. RESULTS: Six years after NE, the prevalence of elevated urinary alpha(1)-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs. 109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/- 9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p = 0.035) than the controls. CONCLUSIONS: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.
Assuntos
Taxa de Filtração Glomerular , Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/etiologia , Proteinúria/diagnóstico , Proteinúria/etiologia , Adulto , Idoso , Feminino , Humanos , Túbulos Renais Proximais/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Working as a physician requires versatile competence, which has been dissected by using various models. Most of these include medical knowledge, patient work, interactive skills, multiprofessional collaboration, management of operational processes within medical and health care, and information technology skills. Without feedback, the ability of physicians to evaluate their developmental needs is poor, whereby the development of competence should be tied on the basis of needs to on-the-job learning and functionality. Different perspectives should be used in its planning and evaluation. After the evaluation, a development plan should be devised and resources created for its implementation.
Assuntos
Competência Clínica , Médicos , Humanos , Avaliação das NecessidadesRESUMO
BACKGROUND: IgA glomerulonephritis (IgAGN) composes a variable prognosis with 15-40% of the patients eventually progressing to end-stage renal failure. Known risk factors for progressive course of IgAGN include hypertension, proteinuria and renal insufficiency. Although markers of inflammation such as serum or urinary interleukin-6 (IL-6) and serum albumin have predicted progression in some studies, sensitive CRP (hs-CRP) has not been directly linked to the progression of IgAGN. METHODS: A total of 174 (70 females) patients were invited for two visits 11 and 16 years (medians) after IgAGN was diagnosed in renal biopsy. All patients had been diagnosed at least 5 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the visits, or kidney transplantation or start of dialysis. Cystatin-C and creatinine clearance, serum hs-CRP, s-albumin, s-IL-6 and white blood cell count (WBC) were available for analysis from 118 patients. RESULTS: IgAGN was progressive in 19.5% of the patients on the second visit. Hs-CRP, s-albumin and WBC of the first visit were significantly associated with the progression of IgAGN (P = 0.014; P = 0.0001; P = 0.023, respectively). S-IL-6 was not associated with the progression. All inflammatory variables correlated significantly with the concurrent level of kidney function. Possible study limitations are the relatively low number of outcomes in the study groups, and the lack of generally accepted definitions for disease progression. CONCLUSIONS: Our results suggest that inflammatory markers hs-CRP, s-albumin and WBC are associated with the progression of IgAGN.
Assuntos
Proteína C-Reativa/metabolismo , Cistatinas/sangue , Glomerulonefrite por IGA/metabolismo , Interleucina-6/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Biópsia , Pressão Sanguínea/fisiologia , Creatinina/sangue , Creatinina/urina , Cistatina C , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Visita a Consultório Médico , Prognóstico , Inibidores de Proteases , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Secondary hyperparathyroidism, malnutrition and inflammation have been reported to associate with adverse outcomes in dialysis patients. However, little is known about the implications of these conditions for treatment costs. METHODS: The cost data of all adult patients who had entered dialysis therapy at Tampere University Hospital between 1991 and 1996 and had remained on dialysis for at least 1 year were collected. results of measurements of parathyroid hormone (PTH), calcium, phosphorus, albumin and C-reactive protein (CRP) were obtained from the database of the hospital. RESULTS: Patients (n = 109), aged 57.0 +/- 14.9 years, included 57% men and 37% diabetics; 62% started on hemodialysis and 38% on peritoneal dialysis. Average daily costs were USD 161 (range 95-360). After controlling for patients' age, body mass index, gender, dialysis modality and primary renal disease, there was a positive correlation between average CRP and average costs and a negative correlation between albumin and costs. Correlations between mineral metabolism markers and costs were not found, but there was a trend towards lower cost among patients who achieved the Kidney Disease Outcomes Quality Initiative targets of calcium, phosphorus and PTH (USD 145 +/- 31) compared with those with nonoptimal levels (USD 165 +/- 48; p = 0.095). Costs of patients with at least one in-target PTH measurement were lower than costs of patients with constantly low PTH (USD 148 +/- 31 vs. 170 +/- 48; p = 0.01). CONCLUSION: Serum levels of albumin and CRP correlated with dialysis patients' treatment costs. Achieving the Kidney Disease Outcomes Quality Initiative targets may be associated with lower costs.
Assuntos
Proteína C-Reativa/análise , Custos de Cuidados de Saúde/estatística & dados numéricos , Minerais/sangue , Diálise Renal/economia , Diálise Renal/estatística & dados numéricos , Insuficiência Renal , Albumina Sérica/análise , Biomarcadores/sangue , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/sangue , Insuficiência Renal/economia , Insuficiência Renal/epidemiologia , Insuficiência Renal/reabilitaçãoRESUMO
BACKGROUND: Dialysis treatment requires considerable resources and it is important to improve the efficiency of care. METHODS: Files of all adult end-stage renal disease (ESRD) patients who entered dialysis therapy between 1991 and 1996, were studied and all use of health care resources was recorded. A total of 138 patients started with in-center hemodialysis (HD) and 76 patients with continuous ambulatory peritoneal dialysis (CAPD). Four alternative perspectives were applied to assess effectiveness. An additional analysis of 68 matched CAPD-HD pairs with similar characteristics was completed. RESULTS: Cost-effectiveness ratios (CER; cost per life-year gained) were different in alternative observation strategies. If modality changes and cadaveric transplantations were ignored, annual first three years' CERs varied between $41220-61465 on CAPD and $44540-85688 on HD. If CAPD-failure was considered as death, CERs were $34466-81197 on CAPD. When follow-up censored at transplantation but dialysis modality changes were ignored, CERs were $59409-95858 on CAPD and $70042-85546 on HD. If observation censored at any change of primarily selected modality, figures were $57731-66710 on CAPD and $74671-91942 on HD. There was a trend of lower costs and better survival on CAPD, the only exception was the strategy in which technical failure of modality was considered as death. Figures of the matched CAPD-HD pairs were very close to the figures of the entire study population. CONCLUSIONS: Compared to HD, CERs were slightly lower on CAPD.
Assuntos
Diálise Peritoneal Ambulatorial Contínua/economia , Diálise Renal/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
BACKGROUND: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with mesangial IgM deposition. The etiology of the depositions and possible association of serum and mesangial immunoglobulins and complement findings with renal outcome in IgMN remain unknown. Here we brought out data supplementary to our previous findings by reporting associations of immunological parameters with the outcome of IgMN. METHODS: Serum IgA, IgG, IgM, C3 and C4 were measured in 110 IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA, IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/-. Seven histopathological parameters were semiquantitatively graded into three classes. The relationship of serum and mesangial immunoglobulin and complement findings with the clinical outcome and prognosis of IgMN was examined. RESULTS: We found significantly lower serum IgG and higher serum C3 levels in patients with nephrotic syndrome. Serum C3 correlated with the severity of glomerular histopathological changes. Of immunological parameters evaluated a low serum IgG/C3 ratio correlated best with the progression of renal disease. However, serum C3 was associated independently with progression in the case of patients without nephrotic syndrome. CONCLUSIONS: In addition to previously reported factors, immunological parameters may also be helpful in determining the prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated with high-grade proteinuria, severe histopathological changes and progression.
Assuntos
Complemento C3/análise , Glomerulonefrite/sangue , Glomerulonefrite/imunologia , Imunoglobulina M , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD). METHODS AND RESULTS: We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of IHD, an effect modulated by the L162V polymorphism CONCLUSIONS: The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.
Assuntos
Arteriosclerose/genética , Polimorfismo Genético , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genética , Idoso , Alelos , Substituição de Aminoácidos , Arteriosclerose/epidemiologia , Arteriosclerose/terapia , Ensaios Clínicos como Assunto , Estudos de Coortes , Comorbidade , Ponte de Artéria Coronária , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/prevenção & controle , Progressão da Doença , Finlândia/epidemiologia , Genfibrozila/uso terapêutico , Frequência do Gene , Predisposição Genética para Doença , Humanos , Hipolipemiantes/uso terapêutico , Íntrons , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: Alpha1-Antitrypsin (AAT) protects elastic tissue and may play a role in atherogenesis. The association of atherosclerosis progression with common AAT variants was considered in 2 clinical trials. METHODS AND RESULTS: We examined the association of AAT V213A, S and Z deficiency alleles, and the functional 3' UTR 11478G>A with change in minimal luminal diameter, a measure of focal disease, in the Lopid Coronary Angiography Trial gemfibrozil study of post-bypass men. S or Z carriers (n=14) showed strong progression of disease on placebo (11.5%) but responded well to treatment (3% regression). 11478A carriers treated with placebo or gemfibrozil showed significantly more disease progression (n=8, -14.5% and n=16, -4.0%, respectively) than 11478GG men (n=107, -7.0% and n=108, -1.4%, respectively; overall, P=0.003). VV213 men treated with gemfibrozil (n=68) showed -4.8% progression, whereas A213 carriers (n=55) showed +1.4% regression of disease (P=0.001). No V213A effect was seen on placebo (P=0.11). In the Diabetes Atherosclerosis Intervention Study fenofibrate trial of angiographic progression in type 2 diabetes, the association of 11478A with increased disease progression was confirmed in the treatment group, but not the gemfibrozil-treated A213 association with regression, suggesting a pharmacogenetic difference. CONCLUSIONS: Disease progression is associated with variation in AAT, and low AAT levels promote atherogenesis.
Assuntos
Doença da Artéria Coronariana/genética , Deficiência de alfa 1-Antitripsina/complicações , alfa 1-Antitripsina/genética , Regiões 3' não Traduzidas/genética , Idoso , Alelos , Substituição de Aminoácidos , Estudos de Coortes , Terapia Combinada , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/complicações , Progressão da Doença , Feminino , Fenofibrato/química , Fenofibrato/uso terapêutico , Genfibrozila/química , Genfibrozila/uso terapêutico , Humanos , Hipolipemiantes/química , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Elastase Pancreática/antagonistas & inibidores , Ligação Proteica , Conformação Proteica , Prevenção Secundária , Relação Estrutura-Atividade , alfa 1-Antitripsina/química , alfa 1-Antitripsina/fisiologia , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
The present study aimed to assess the effect of gemfibrozil on serum total homocysteine (tHcy) concentration and to evaluate the influence of tHcy on the angiographically determined progression of coronary atherosclerosis in a randomised, placebo-controlled trial of 395 post-coronary bypass men with low HDL cholesterol levels. The baseline levels of tHcy and those after 16 months of randomised therapy were measured by high-pressure liquid chromatography. Patients were genotyped for the thermolabile variant of N5,N10-methylenetetrahydrofolate reductase (MTHFR) (677C > T substitution). Gemfibrozil therapy was associated with a median 18% increase in tHcy levels (P < 0.01). In the gemfibrozil group increases in tHcy and HDL cholesterol were related (r = 0.217, P = 0.004), but changes in tHcy and triglycerides were not. Levels of tHCy were not associated with baseline extent or progression of coronary-artery disease. Subjects homozygous for the rare MTHFR T allele had 34% higher median tHcy concentrations than CC homozygotes or CT heterozygotes, but responses to gemfibrozil did not differ significantly among genotypes. The MTHFR genotype was not associated with extent or progression of coronary atherosclerosis. We conclude that gemfibrozil causes a significant elevation in tHcy levels, but the clinical relevance of this is unknown at present.
Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Genfibrozila/uso terapêutico , Homocisteína/sangue , Hipolipemiantes/uso terapêutico , HDL-Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Progressão da Doença , Método Duplo-Cego , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Triglicerídeos/sangueRESUMO
The 643R allele of R643G polymorphism (also known as R670G in the premature protein) in PECAM-1 has been associated with risk of myocardial infarction (MI), while the 643G allele has been associated with risk of coronary artery stenosis (CAS). The aim of this study was to investigate this apparently conflicting association. The association of R643G with risk of MI was determined in the second Northwick Park Heart study (2037 men with 138 CHD events; mean age: 56 years). Smokers homozygous for the 643R allele showed increased risk of MI with a hazard ratio of 2.47 (95% CI: 1.23-4.97; P=0.01) compared to smokers homozygous for the 643G allele. Progression of disease was determined in the Lopid Coronary Angiography Trial (279 men; mean age: 58.9 years). The 643G homozygotes showed greater focal (-0.08 +/- 0.02 mm) and diffuse (-0.01 +/- 0.01 mm) progression of CAS compared to 643R homozygotes (-0.02 +/- 0.02 mm and 0.001 +/- 0.01 mm, respectively; P=0.04). While there was no genotype effect on platelet aggregation, PECAM-1 tyrosine phosphorylation in HUVECs of GG genotype was 2.4-fold greater (P <0.01) than cells of RR genotype, and the level of transendothelial migration of monocytes of GG genotype was greater than that of monocytes of RR genotype following stimulation with either IL-1beta (12% higher, P <0.01) or TNF-alpha (10% higher, P=0.05). These data confirm the association of the R643G polymorphism with MI and CAS and suggest that greater influx of monocytes in individuals homozygous for the 643G may explain the association with CAS.
Assuntos
Movimento Celular/fisiologia , Doença das Coronárias/genética , Monócitos/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Polimorfismo Genético , Células Cultivadas , Progressão da Doença , Endotélio Vascular/citologia , Humanos , Agregação Plaquetária , Fatores de RiscoRESUMO
A 53G>A polymorphism identified in the 5' untranslated region (5'UTR) of the platelet endothelial cell adhesion molecule-1 (PECAM-1) gene alters a putative shear stress responsive element (SSRE). PECAM-1 was shown to be responsive to shear stress and transient transfection of human umbilical vein endothelial cell (HUVECs) with two luciferase reporter constructs driven by the PECAM-1 promoter and 5'UTR showed a response of the 53G allele, not the 53A allele, to shear stress. Association between the 53G>A, and the previously published L125V polymorphism, and coronary atherosclerosis was examined in two angiographic studies. The frequencies of the rare alleles of the 53G>A and L125V polymorphisms were 0.01 and 0.49, respectively, in the Lopid Coronary Angiography Trial (LOCAT) study and 0.02 and 0.49, respectively, in the Regression Growth Evaluation Statin Study (REGRESS) study. Compared with 53G homozygotes, carriers of the 53A allele showed less focal progression of disease in the LOCAT study and a similar trend in the diffuse progression of disease in the REGRESS study, whereas no association between L125V and coronary atherosclerosis was observed in either study. These data demonstrate that the PECAM-1 gene is responsive to shear stress in vitro and that decreased PECAM-1 gene expression in 53A carriers may influence reduced progression of vessel stenosis in patients with coronary artery disease.
Assuntos
Doença da Artéria Coronariana/genética , Ordem dos Genes/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Polimorfismo Genético/genética , Idoso , Alelos , Sistemas Computacionais , Angiografia Coronária , Doença da Artéria Coronariana/tratamento farmacológico , DNA Complementar/genética , Progressão da Doença , Endotélio Vascular/química , Endotélio Vascular/citologia , Finlândia , Seguimentos , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Gliceraldeído-3-Fosfato Desidrogenases/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Molécula 1 de Adesão Intercelular/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Estatística como Assunto , Estresse Mecânico , Transfecção , Veias Umbilicais/química , Veias Umbilicais/citologiaRESUMO
BACKGROUND: Costs for treating patients with end-stage renal disease (ESRD) have grown noticeably. However, most of the cost estimates to date have taken the perspective of the payers. Hence, direct costs of treating ESRD are not accurately known. METHODS: Files of all adult patients with ESRD who entered dialysis therapy between January 1, 1991, and December 31, 1996, were studied retrospectively, and all use of health care resources and services was recorded. Follow-up continued until December 31, 1996. RESULTS: Two hundred fourteen patients fulfilled the study criteria, 138 patients started with in-center hemodialysis (HD) therapy, and 76 patients started with continuous ambulatory peritoneal dialysis (CAPD) therapy. Patients were followed up until death (72 patients) or treatment modality changed for more than 1 month. Fifty-five patients received a cadaveric transplant, and after transplantation (TX), they were examined as a separate group of TX patients. Direct health care costs for the first 6 months in the HD, CAPD, and TX groups were 32,566 US dollars, 25,504 dollars, and 38,265 dollars, and for the next 6 months, 26,272 dollars, 24,218 dollars, and 7,420 dollars, respectively. During subsequent years, annual costs were 54,140 US dollars and 54,490 dollars in the HD group, 45,262 dollars and 49,299 dollars in the CAPD group, and 11,446 dollars and 9,989 dollars in the TX group. Regression analyses showed 4 variables significantly associated with greater daily costs in dialysis patients: age, ischemic heart disease, nonprimary renal disease, and HD treatment. CONCLUSION: Compared with HD, CAPD may be associated with lower costs, yet the absolute difference is not striking. After the TX procedure is performed once, annual costs decline remarkably, and cadaveric TX is less costly than both dialysis modalities.
Assuntos
Terapia de Substituição Renal/economia , Adulto , Idoso , Cadáver , Comorbidade , Custos e Análise de Custo , Custos de Medicamentos , Feminino , Finlândia , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Custos Hospitalares , Humanos , Falência Renal Crônica/economia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Transplante de Rim/economia , Transplante de Rim/estatística & dados numéricos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/economia , Diálise Peritoneal Ambulatorial Contínua/estatística & dados numéricos , Diálise Renal/economia , Diálise Renal/estatística & dados numéricos , Terapia de Substituição Renal/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Transporte de Pacientes/economiaRESUMO
BACKGROUND: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis with mesangial hypercellularity and diffuse IgM deposits. METHODS: We studied clinical presentation, morphological findings, and prognostic factors in 110 patients with IgM nephropathy without systemic diseases. The series included both pediatric and adult patients with nephrotic syndrome (NS) or minor urinary abnormalities. RESULTS: Mean postbiopsy follow-up was 8 years. During 15 years of follow-up, 36% of patients developed renal insufficiency and 23% reached end-stage renal failure. In multivariate analysis, hypertension at the time of renal biopsy was the only significant risk factor for renal insufficiency. Of histological parameters, interstitial fibrosis had the strongest prognostic value. Hypertension was diagnosed in 50% of patients with a postbiopsy follow-up of 15 years. Twenty-nine percent of nephrotic patients had disease resistant to corticosteroids, whereas 80% of patients with steroid-sensitive disease were steroid dependent. Eleven patients, 8 patients with NS and 3 patients with asymptomatic proteinuria, underwent repeated renal biopsy. In five samples, typical morphological characteristics of focal and segmental glomerulosclerosis were seen. CONCLUSION: We propose that IgM nephropathy can be divided into two subgroups with similar renal biopsy findings, but differences in sex distribution and initial presentation.