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1.
Chemosphere ; 288(Pt 1): 132479, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34626662

RESUMO

The main hydrometeorological, microbiological and physico-chemical characteristics of the Nervión river were monitored during a year, including 10 antibiotics and the presence of bacteria resistant to these antibiotics among faecal coliforms (FC) and total aerobic bacteria at 22 °C (TAB22). The characteristics of the river water were variable without a clear seasonal component, strongly influenced by rainfall, with a good quality for drinking water production throughout the year according to the physico-chemical parameters. The antibiotic resistant bacteria isolated from the water of the Nervión river were especially resistant to ß-lactams and macrolide antibiotics, highlighting the absence of resistance to derivatives of tetracyclines among strains of TAB22. A third of the isolated strains were multi-resistant to antibiotics with a seasonal component in its presence, with multi-resistant FC more abundant during summer and multi-resistant TAB22 more abundant during winter. The presence of antibiotics in the waters of the Nervión river was not very significant, with total absence of ß-lactams, minocycline and ciprofloxacin. Erythromycin and clarithromycin can be considered ubiquitous with mean concentrations of 2.5 ± 2.3 ngL-1 and 5.7 ± 4.6 ngL-1 respectively, and the presence of sulfamethoxazole and trimethoprim was also noticeable with maximum concentrations of 78.3 ngL-1 for sulfamethoxazole. Dilution due to the increase of rainfall was observed for several analysed antibiotics, but without significant seasonal differences.


Assuntos
Antibacterianos , Rios , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias
2.
Philos Trans A Math Phys Eng Sci ; 378(2179): 20190523, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32762429

RESUMO

The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue 'Stokes at 200 (part 2)'.


Assuntos
Luz , Microbiota/fisiologia , Microbiota/efeitos da radiação , Modelos Biológicos , Fototaxia/fisiologia , Fenômenos Biofísicos , Chlamydomonas/fisiologia , Chlamydomonas/efeitos da radiação , Hidrodinâmica , Conceitos Matemáticos
3.
Philos Trans A Math Phys Eng Sci ; 378(2179): 20190529, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32762433

RESUMO

Diatoms are one of the most abundant, diverse and ecologically relevant phytoplanktonic group, contributing enormously to global biogeochemical processes like the carbon and silica cycles. This large success has been partly attributed to the mechanical and optical properties of the silica shell (the frustule) that envelops their body. But since they lack motility it is difficult to conceive how they cope with the fast-fluctuating environment they live in and where distributions of resources are very heterogeneous and dynamical. This pinpoints an important but yet poorly understood feature of diatoms physiology: buoyancy regulation that helps them controlling their sinking speed and position in the water column. While buoyancy regulation by light and nutrients availability has been well studied, the effect of hydromechanical stress via fluid shear has been rather overlooked when considering diatoms dynamics. Here, we aim to start filling this gap by first presenting direct experimental evidences for buoyancy control in response to hydro-mechanical stress and then review recent theoretical models where simple couplings between local shear and buoyancy control always result in heterogeneous cell distributions, specific accumulation regions within complex flows and increased sedimentation times to the depths, features of direct ecological relevance. We conclude by suggesting future experiments aiming to unveil such coupling and therefore gain better understanding on the fate of these fascinating microorganisms in their natural habitat. This article is part of the theme issue 'Stokes at 200 (part 2)'.


Assuntos
Diatomáceas/fisiologia , Modelos Biológicos , Fitoplâncton/fisiologia , Fenômenos Biomecânicos , Ecossistema , Hidrodinâmica , Oceanos e Mares , Dióxido de Silício/metabolismo , Estresse Mecânico , Viscosidade
4.
Ginecol Obstet Mex ; 84(3): 136-42, 2016 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-27424439

RESUMO

BACKGROUND: Screening programs for breast cancer include self and clinical examination and Imaging studies to obtain the BIRADS (Breast Imaging Reporting and Data System) grade has been described as an important tool. In México, breast cancer is the leading death cause from malignancy in women and thus an early detection and prompt treatment is an important public health concern OBJECTIVE: To compare the BIRADS classification with histopathological findings and cases of malignancy. METHODS: This is a retrospective, observational and descriptive study about of the correlation between histopathological reports and BIRADS classification. RESULTS: Records of 1551 patients were reviewed, of which only 176 met the inclusion criteria. There was a predominance of fibrocystic condition. 44 patients had cancer, with varying degrees of detection according to each category of the classification where BIRADS 5 corresponded to 100% of the malignant cases. CONCLUSION: Consistent with the results reported by other authors, highlighting some situations like BIRADS 4C (where there was a slight difference compared to literature) and the BIRADS 5 in which a detection of 100% of cases of cancer was achieved.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia , Ultrassonografia Mamária , Adulto , Idoso , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Transl Psychiatry ; 4: e358, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24495969

RESUMO

To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 × 10(-)(9)).


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fatores de Transcrição/genética , Seguimentos , Loci Gênicos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Espanha
6.
Mol Psychiatry ; 19(6): 682-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23857120

RESUMO

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.


Assuntos
Doença de Alzheimer/genética , Translocases Mitocondriais de ADP e ATP/genética , Idoso de 80 Anos ou mais , Estudos de Coortes , Simulação por Computador , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
7.
Rev. biol. trop ; Rev. biol. trop;60(supl.3): 257-273, nov. 2012. ilus, mapas, tab
Artigo em Inglês | LILACS, SaludCR | ID: lil-672094

RESUMO

Isla del Coco is an oceanic island 500km off the Pacific coast of Costa Rica. It is a National Park and its marine fauna has been relatively well protected. The island is famous for its elasmobranch (sharks, rays and skates) sightings in shallow waters. Here we present a catalogue of the deepwater elasmobranchs observed with the DeepSee submersible. Five species of sharks, six species of skates and one ray have been observed between 45 and 330m depth. Triaenodon obesus, the white tip reef shark, was commonly observed between 80 and 301m, but only in the afternoons. Sphyrna lewini, the scalloped hammerhead shark, was observed as deep a 303m, but commonly between 45 and 90m, and close to the island. Odontaspis ferox, the smalltooth sand tiger shark, was observed between 82 and 316m. Echinorhinus cookei, the prickly shark, was observed between 91 and 320m. Rhincodon typus, the whale shark, was observed only close to the island, between 77 and 80m. Taeniura meyeni, the marbled ray, was observed only close to the island, between 45 and 90m. A Dasyatis sp., similar to the the diamond stingray, was observed only once close to the island at 60m; this is the first report of this genus at Isla del Coco National Park. Manta birostris, the giant manta, was only observed close to the island at 90m. Mobula tarapacana, the sicklefin devil ray, was observed between 60 and 326m, extending its maximum depth almost 10 times what has been reported. Aetobatus narinari, the spotted eagle ray, was observed only close to the island between 60 and 82m. Torpedo peruana, the Peruvian torpedo ray, was observed only once at 313m, and is the first record of this species from Isla del Coco National Park.


La Isla del Coco es una isla oceánica a 500km de la costa Pacífica de Costa Rica. Es un Parque Nacional donde la fauna marina ha estado relativamente bien protegida. La isla es famosa por los elasmobranquios (tiburones y rayas) en aguas poco profundas. Aquí presentamos un catálogo de elasmobranquios observados con el sumergible DeepSee. Cinco especies de tiburones y siete especies de rayas han sido observadas entre 45 y 330m de profundidad. Triaenodon obesus, tiburón punta blanca de arrecifes o tiburón cazón coralero, observado comúnmente entre 80 y 301m pero solo en las tardes. Sphyrna lewini, el tiburón martillo o cornuda común, registrado hasta 303m, pero comúnmente entre 45 y 90m, y cerca de la Isla del Coco. Odontaspis ferox, tiburón solrayo, visto entre 82 y 316m. Echinorhinus cookei, tiburón negro espinoso, avistado entre 91 y 320m. Rhincodon typus, tiburón ballena, observado solamente cerca de la isla, entre 77 y 80m. Taeniura meyeni, raya moteada, vista solamente cerca de la isla, entre 45 y 90m. Dasyatis sp., parecida a la raya látigo, registrada solamente una vez, cerca de la isla a 60m; este es el primer informe de esta especie en el Parque Nacional Isla del Coco. Manta birostris, manta gigante, observada únicamente cerca de la isla a 90m. Mobula tarapacana, manta cornuda o manta moruma, vista entre 60 y 326m, extendiendo su profundidad máxima casi 10 veces a lo informado en la literatura. Aetobatus narinari, chucho pintado o raya águila, observada solamente cerca de la isla entre 60 y 82m. Por último, Torpedo peruana, raya torpedo eléctrico o raya peruana, solamente vista una vez a 313m y es el primer informe de esta especie en el Parque Nacional Isla del Coco.


Assuntos
Tubarões/anatomia & histologia , Rajidae/classificação , Elasmobrânquios/classificação , Biodiversidade , Costa Rica
9.
Nutr Hosp ; 25(3): 375-7, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20593117

RESUMO

Given the high prevalence of the hyponutrition state among haemodialysis patients and knowing that this implies an increase in the rates of infection, hospitalisation and hospital stay, which translates into an increase in global morbid-mortality, the Spanish Society of Nephrology (SEN) and the Spanish Society of Parenteral and Enteral Nutrition (SENPE) have reached a consensus on the indications, contraindications, and limitations of Intra-Dialysis Parenteral Nutrition (IDPN.) This consensus considers IDPN as a valid alternative to other types of nutritional support when these show their lack of efficacy. The bases are set regarding the timing of nutritional intervention with IDPN, its ideal composition, the time of administration, its controls, follow-up schedules, and the time at which the nutritional support has to be discontinued.


Assuntos
Falência Renal Crônica/terapia , Desnutrição/terapia , Nutrição Parenteral , Diálise Renal , Humanos , Falência Renal Crônica/complicações , Desnutrição/etiologia , Diálise Renal/efeitos adversos
12.
Nephron Clin Pract ; 114(1): c67-73, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19816045

RESUMO

BACKGROUND: Haemodialysis (HD) exacerbates oxidative stress (OS). The polymethyl-methacrylate (PMMA)-BK-F membrane ameliorates OS and inflammation markers compared to polyacrylonitrile (PAN/AN69) and cellulose membranes. This may be due to the size of pore radius, high flux or other specific properties of PMMA membranes. AIM: To compare OS and inflammatory status in HD-treated end stage renal disease patients with membranes of different pore size radius and flux. METHODS: 47 patients of both sexes were studied. The HD membranes with which the patients were normally treated were changed to BK-P or B-3 membranes for 6 months. Intracellular and extracellular components of the oxidant-antioxidant balance (OAB), C-reactive protein (CRP), beta2-micro-globulin (beta2mu-globulin), albumin and transferrin were measured. RESULTS: A significant decrease in red cell membrane thiobarbituric acid reacting substances and an increase in cytosolic superoxide dismutase (SOD) and plasma total antioxidant substances were observed in all patients after 6 months of treatment with BK-P and B-3 membranes except SOD and CRP in patients previously dialysed with triacetate cellulose membranes. Albumin and transferrin remained unmodified. beta2mu-globulin significantly decreased after treatment with PMMA membranes. CONCLUSION: BK-P and B-3 HD membranes improved the OAB, beta2mu-globulin and CRP compared to PAN/AN69 and cellulose diacetate membranes.


Assuntos
Falência Renal Crônica/metabolismo , Membranas Artificiais , Estresse Oxidativo , Diálise Renal , Adulto , Idoso , Proteína C-Reativa/análise , Comorbidade , Desenho de Equipamento , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Albumina Sérica/análise , Superóxido Dismutase/metabolismo , Transferrina/análise , Microglobulina beta-2/sangue
13.
J Nutr Health Aging ; 13(3): 214-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19262956

RESUMO

OBJECTIVES: The genetic basis of Alzheimer's disease (AD) is being analyzed in multiple whole genome association studies (WGAS). The GAB2 gene has been proposed as a modifying factor of APOE epsilon 4 allele in a recent case-control WGAS conducted in the US. Given the potential application of these novel results in AD diagnostics, we decided to make an independent replication to examine the GAB2 gene effect in our series. DESIGN: We are conducting a multicenter population-based study of AD in Spain. PARTICIPANTS: We analyzed a total of 1116 Spanish individuals. Specifically, 521 AD patients, 475 controls from the general population and 120 neurologically-normal elderly controls (NNE controls). METHODS: We have genotyped GAB2 (rs2373115 G/T) and APOE rs429358 (SNP112)/rs7412 (SNP158) polymorphisms using real time-PCR technologies. RESULTS: As previously reported in Spain, APOE epsilon 4 allele was strongly associated with AD in our series (OR=2.88 [95% C.I. 2.16- 3.84], p=7.38E-11). Moreover, a large effect for epsilone 4/epsilone 4 genotype was also observed (OR=14.45 [95% C.I., 3.34-125.2], p=1.8E-6). No difference between the general population and the NNE controls series were observed for APOE genotypes (P > 0.61). Next, we explored GAB2 rs2373115 SNP singlelocus association using different genetic models and comparing AD versus controls or NNE controls. No evidence of association with AD was observed for this GAB2 marker (p > 0.17). To evaluate GAB2-APOE genegene interactions, we stratified our series according to APOE genotype and case-control status, in accordance with the original studies. Again, no evidence of genetic association with AD was observed in any strata of GAB2-APOE loci pair (p > 0.34). CONCLUSION: GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Heterozigoto , Idoso , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Polimorfismo Genético/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de Risco , Espanha/epidemiologia
14.
J Nutr Health Aging ; 12(10): 714-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19043646

RESUMO

The European Dementia Consensus Network (EDCON) is a special project of the Madariaga Foundation located in Brussels. The Madariaga Foundation seeks to facilitate collaboration between European countries and between the public and private sector. This paper will review the differences in the definitions of Severe Dementia and summarise the EDCON consensus on their implications for management. EDCON recommends that:--The attributes of the person suffering from dementia should be given as much attention (and are as important for care) as the severity of cognitive decline in dementia;--The dementia syndrome (particularly in it's severe form) is inadequately defined by criteria which only includes the domain of cognition;--Physical, legal, social and cultural factors defining the environment of patients and their families should be carefully examined and that the results of this examination should be used in conjunction with the results of the somatic and psychiatric assessment in planning care and placement of the patient;--patients with severe dementia should have access to palliative care; - family members should be included in the care plans for those with severe dementia who are in institutional care.


Assuntos
Demência/diagnóstico , Demência/terapia , Demência/psicologia , Progressão da Doença , Meio Ambiente , Humanos , Cuidados Paliativos , Índice de Gravidade de Doença
16.
Nutr Hosp ; 23(3): 253-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18560702

RESUMO

OBJECTIVES: To design and validate a scale to evaluate preferences of type 2 diabetic patients towards nutritional supplements (Madrid scale) and to discover those taste attributes that are more discriminating. CONTEXT: ambulatory patients with type 2 diabetes mellitus. MATERIALS AND METHODS: 18 controls and 106 type 2 diabetic patients received 2 of the 7 stimuli studied (6 nutritional supplements and a differential salty stimulus) and then completed both scales and a criterion question. Two weeks later, 30 diabetic patients received a retest. The psychometric properties of the Madrid scale were studied and the relative importance of each stimuli attribute was assessed. RESULTS: Feasibility: The Madrid scale consists of 8 questions and is completed in less than five minutes; Dimensionality: A single dimension which explains 45.1% of the variance. Reliability: Cronbach's , 0.806; intraclass correlation coefficient, 0.835 (95% confidence interval: 0.653-0.922). Concurrent validity: Correlation indexes of the corrected total score with the criterion question and the Modified Wine-Tasting Scale, 0.731 (p < 0.0005) and 0.774 (p < 0.0005), respectively. The scale discriminated between subjects younger and older than 75 years and between supplements and the differential stimulus. Preferences: Glucerna SR chocolate, Glucerna SR strawberry, Glucerna SR vanilla, Diasip vanilla, Clinutren vanilla and Resource diabet vanilla. CONCLUSION: The Madrid scale has adequate psychometric properties for its use in research and daily clinical practice.


Assuntos
Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Preferências Alimentares , Inquéritos e Questionários , Idoso , Feminino , Humanos , Masculino
17.
An Pediatr (Barc) ; 68(5): 490-5, 2008 May.
Artigo em Espanhol | MEDLINE | ID: mdl-18447995

RESUMO

A world increase in multidrug-resistant tuberculosis (MDR-TB) has been reported over the last few years. A larger number of diagnoses are being seen in Spain, due to the increase of immigration from high endemic TB countries. Articles published on this are anecdotal in children, and there is no clear directives for treatment of MDR-TB, or latent tuberculosis infection (ITBL) or on prophylaxis after exposure to active pulmonary MDR-TB. We present the initial management and progression of nine children after close contact exposure to an Ecuadorian woman diagnosed with active pulmonary TB, resistant to Isoniazid, Rifampicin and Pyrazinamide.


Assuntos
Exposição Ambiental/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Isoniazida , Masculino , Pirazinamida , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
18.
An Pediatr (Barc) ; 68(5): 425-31, 2008 May.
Artigo em Espanhol | MEDLINE | ID: mdl-18447985

RESUMO

Paediatric Human Immunodeficiency Virus infection (HIV) nowadays is a chronic disease with an excellent long term prognosis, but lifelong combined antiretroviral treatment is required. However, an improved quality of life in this population is limited by adverse drug effects. The highest risk of treatment toxicity is developing a complete metabolic syndrome including: Hyperlipemia, lipodystrophy, insulin resistance, lactic acidosis, osteopenia, hypertension, and specific system and organ toxicity, such as the kidney, liver, CNS or bone marrow. The risk of cardiovascular disease adult life and also definitive bone mass damage are the most significant metabolic costs that have to paid for increased survival. Most of these toxicities were able to be adequately treated but, pharmacological interferences, patient intolerance and the high number of drugs are the problems that limit the adherence to treatment, which is essential for a good therapeutical efficacy. In this article, we present four HIV paediatric patients who presented with almost the whole range of metabolic toxicities, and a practical overview of therapeutical management.


Assuntos
Antirretrovirais/efeitos adversos , Infecções por HIV/tratamento farmacológico , Zidovudina/efeitos adversos , Acidose Láctica/induzido quimicamente , Adolescente , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Hiperlipidemias/induzido quimicamente , Hipertensão/induzido quimicamente , Resistência à Insulina , Lipodistrofia/induzido quimicamente , Síndrome Metabólica/induzido quimicamente , Radiografia
20.
Cochrane Database Syst Rev ; (3): CD000202, 2007 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-17636619

RESUMO

BACKGROUND: Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease, often accompanied by abnormal behaviour and physical decline. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. The efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0.61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0.43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2.8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. AUTHORS' CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Nootrópicos/uso terapêutico , Tacrina/uso terapêutico , Humanos
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