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1.
Lancet ; 403(10442): 2395-2404, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38761811

RESUMO

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.


Assuntos
Hemorragia Cerebral , Craniectomia Descompressiva , Humanos , Pessoa de Meia-Idade , Masculino , Craniectomia Descompressiva/métodos , Feminino , Hemorragia Cerebral/cirurgia , Idoso , Adulto , Resultado do Tratamento , Terapia Combinada
2.
Ecotoxicol Environ Saf ; 258: 114984, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37172406

RESUMO

Elevated concentrations of sulfate in waterways are observed due to various anthropogenic activities. Elevated levels of sulfate can have harmful effects on aquatic life in freshwaters: sulfate can cause osmotic stress or specific ion toxicity in aquatic organisms, especially in soft waters where Ca2+ and Mg2+ concentrations are low. Formerly, chronic toxicity test data in soft water have been scarce. The chronic and acute sulfate toxicity tests conducted with aquatic organisms from 10 families across various trophic levels in this study multiplied the number of tests conducted in soft freshwater conditions and enabled derivation of the species sensitivity distribution (SSD) and sulfate hazardous concentrations for soft freshwaters. The cladoceran Daphnia longispina and freshwater snail Lymnaea stagnalis were the most sensitive to sulfate among the studied species. Harmful effects on the reproduction of D. longispina were observed at 49 mg SO4 /L while growth of L. stagnalis was inhibited at 217 mg SO4 /L. Most studied organisms tolerated high sulfate concentrations: the median of chronic effective concentrations (EC10 or LC10) was 1008 mg/L for all the species tested in this study. Based on the species sensitivity distribution of the studied species the hazardous concentration for 5 % of aquatic organism (HC5) in soft waters was 117-194 mg SO4/L. Different data set combinations were used to demonstrate the data variability in SSD-based HC5 estimates. The lowest values were produced from combining biotest results from the present study and earlier literature, while the highest values were calculated from the present study only. The derived chronic no-effect concentrations (PNEC) varied between 39 and 65 mg SO4/L.


Assuntos
Organismos Aquáticos , Poluentes Químicos da Água , Animais , Sulfatos/toxicidade , Poluentes Químicos da Água/análise , Água Doce , Testes de Toxicidade Aguda
3.
Ecotoxicol Environ Saf ; 208: 111763, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396083

RESUMO

Sulfate occurs naturally in the aquatic environment but its elevated levels can be toxic to aquatic life in freshwater environments. We investigated the toxicity of sulfate in humic, soft freshwater to whitefish (Coregonus lavaretus) from fertilization of eggs to hatching i.e. during the critical phases of whitefish early development. Anadromous Kokemäenjoki whitefish eggs and sperm during fertilization, embryos and larvae were exposed in the long-term 175-day incubation to seven different sodium sulfate (Na2SO4) concentrations from 44 to 2 000 mg SO4 L-1. Endpoint variables were the fertilization success, offspring survival and larval growth. Egg fertilization and early embryonic development were the most sensitive developmental stages of whitefish to sulfate, although the fertilization success and survival of embryos decreased only in the highest concentration of 2 000 mg SO4 L-1. The survival during late embryonic period, hatching and the 5-day larval period was high and no difference between the control and sulfate treatments were observed. LC50-values of sulfate for early embryonic period and for the entire embryonic and larval period was 1 413 and 1 161 mg L-1, respectively. The NOEC (No-observed Effect Concentration) of sulfate for the both periods was 1 207 mg L-1. The tolerance of whitefish early stages to sulfate toxicity seems to be on the same level as the tolerance of other salmonids' early stages.


Assuntos
Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Salmonidae/embriologia , Sulfatos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Água Doce/química , Larva , Dose Letal Mediana , Masculino , Salmonidae/crescimento & desenvolvimento , Espermatozoides
4.
Water Sci Technol ; 84(1): 89-100, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34280157

RESUMO

Microplastics (MPs) from households, stormwater, and various industries are transported to wastewater treatment plants (WWTPs), where a high proportion of them are captured before discharging their residuals to watersheds. Although recent studies have indicated that the removed MPs are mainly retained in wastewater sludge, sludge treatment processes have gained less attention in MP research than water streams at primary, secondary, and tertiary treatments. In this study, we sampled 12 different process steps in a tertiary-level municipal WWTP in central Finland. Our results showed that, compared to the plant influent load, three times more MPs circulated via reject water from the sludge centrifugation back to the beginning of the treatment process. Fibrous MPs were especially abundant in the dewatered sludge, whereas fragment-like MPs were observed in an aqueous stream. We concluded that, compared to the tertiary effluent, sludge treatment is the major exit route for MPs into the environment, but sludge treatment is also a return loop to the beginning of the process. Our sampling campaign also demonstrated that WWTPs with varying hydraulic conditions (such as the one studied here) benefit from disc filter-based tertiary treatments in MP removal.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Finlândia , Microplásticos , Plásticos , Esgotos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água/análise
5.
Arch Environ Contam Toxicol ; 79(2): 270-281, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32696228

RESUMO

One of the world's largest, but low-grade, sulfide nickel deposits in northeastern Finland has been exploited by a bioheapleaching technology since 2008. Bioheapleaching is a relatively new, cost-effective technology, but humid climate, e.g., in boreal temperate environments, causes challenges to the management of the water balance in the ore heaps with wide catchment area, and the mining effluents have caused substantial metal and salting contamination of the receiving waterbodies. In our study, the impacts of metal-extracting bioheapleaching mine effluents on muscle and liver element concentrations, body condition, liver and testes mass, and sperm count and motility of male perch Perca fluviatilis were analysed. Liver, testes, and carcass mass of perch in relation to their length were lower in the mining-impacted lakes than in the reference lake, which may be due to the metal contamination, food availability, and energy demand under multistressor conditions. The sperm counts of the males in the mining-impacted lakes were lower, but the endurance of their sperm motility was longer than the endurance of sperm of the reference males. These findings suggested that the condition and sperm characteristics of perch were altered in lakes receiving metal mining effluents. Measured variables seem to be useful indicators for metal mining impacts on freshwater fish but only if high natural variation in these characteristics can be controlled by multiyear monitoring scheme.


Assuntos
Metais/toxicidade , Mineração , Percas/fisiologia , Espermatozoides/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Monitoramento Ambiental , Finlândia , Humanos , Lagos , Fígado/química , Masculino , Metais/análise , Níquel , Motilidade dos Espermatozoides , Poluentes Químicos da Água/análise
6.
J Clin Monit Comput ; 34(5): 971-994, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573056

RESUMO

Current accepted cerebrovascular reactivity indices suffer from the need of high frequency data capture and export for post-acquisition processing. The role for minute-by-minute data in cerebrovascular reactivity monitoring remains uncertain. The goal was to explore the statistical time-series relationships between intra-cranial pressure (ICP), mean arterial pressure (MAP) and pressure reactivity index (PRx) using both 10-s and minute data update frequency in TBI. Prospective data from 31 patients from 3 centers with moderate/severe TBI and high-frequency archived physiology were reviewed. Both 10-s by 10-s and minute-by-minute mean values were derived for ICP and MAP for each patient. Similarly, PRx was derived using 30 consecutive 10-s data points, updated every minute. While long-PRx (L-PRx) was derived via similar methodology using minute-by-minute data, with L-PRx derived using various window lengths (5, 10, 20, 30, 40, and 60 min; denoted L-PRx_5, etc.). Time-series autoregressive integrative moving average (ARIMA) and vector autoregressive integrative moving average (VARIMA) models were created to analyze the relationship of these parameters over time. ARIMA modelling, Granger causality testing and VARIMA impulse response function (IRF) plotting demonstrated that similar information is carried in minute mean ICP and MAP data, compared to 10-s mean slow-wave ICP and MAP data. Shorter window L-PRx variants, such as L-PRx_5, appear to have a similar ARIMA structure, have a linear association with PRx and display moderate-to-strong correlations (r ~ 0.700, p < 0.0001 for each patient). Thus, these particular L-PRx variants appear closest in nature to standard PRx. ICP and MAP derived via 10-s or minute based averaging display similar statistical time-series structure and co-variance patterns. PRx and L-PRx based on shorter windows also behave similarly over time. These results imply certain L-PRx variants may carry similar information to PRx in TBI.


Assuntos
Lesões Encefálicas Traumáticas , Circulação Cerebrovascular , Humanos , Pressão Intracraniana , Projetos Piloto , Estudos Prospectivos
7.
Arch Environ Contam Toxicol ; 76(1): 51-65, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30218120

RESUMO

The applicability of an in situ incubation method in monitoring the effects of metal mining on early life stages of fish was evaluated by investigating the impacts of a biomining technology utilizing mine on the mortality, growth, and yolk consumption of brown trout (Salmo trutta) and whitefish (Coregonus lavaretus) embryos. Newly fertilized eggs were incubated from autumn 2014 to spring 2015 in six streams under the influence of the mine located in North-Eastern Finland and in six reference streams. Although the impacted streams clearly had elevated concentrations of several metals and sulfate, the embryonic mortality of the two species did not differ between the impacted and the reference streams. Instead, particle accumulation to some cylinders had a significant impact on the embryonic mortality of both species. In clean cylinders, mortality was higher in streams with lower minimum pH. However, low pH levels were evident in both the reference and the mine-impacted groups. The embryonic growth of neither species was impacted by the mining activities, and the growth and yolk consumption of the embryos was mainly regulated by water temperature. Surprisingly, whitefish embryos incubated in streams with lower minimum pH had larger body size. In general, the applied in situ method is applicable in boreal streams for environmental assessment and monitoring, although in our study, we did not observe a specific mining impact differing from the effects of other environmental factors related to catchment characteristics.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Monitoramento Ambiental/métodos , Mineração , Rios/química , Poluentes Químicos da Água/toxicidade , Animais , Finlândia , Metais/análise , Metais/toxicidade , Salmonidae/embriologia , Estações do Ano , Sulfatos/análise , Sulfatos/toxicidade , Truta/embriologia , Poluentes Químicos da Água/análise
8.
Rheumatol Int ; 37(5): 825-830, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28289873

RESUMO

Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient's global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician's global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19-3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01-2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
9.
Ann Rheum Dis ; 73(11): 1954-61, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23908187

RESUMO

OBJECTIVE: To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed. RESULTS: Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13). CONCLUSIONS: In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Radiografia , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
Ann Rheum Dis ; 72(6): 851-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22753402

RESUMO

OBJECTIVE: Early treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome. METHODS: 99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26. RESULTS: At 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058). CONCLUSIONS: Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Anti-Inflamatórios/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Intervenção Médica Precoce , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Quimioterapia de Indução/métodos , Infliximab , Estudos Longitudinais , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Sulfassalazina/uso terapêutico , Resultado do Tratamento
12.
Polymers (Basel) ; 13(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799897

RESUMO

The abundance of microplastics (MPs) in the atmosphere, on land, and especially in water bodies is well acknowledged. In this study, we establish an optical method based on three different techniques, namely, specular reflection to probe the medium, transmission spectroscopy measurements for the detection and identification, and a speckle pattern for monitoring the sedimentation of MPs filtrated from wastewater sludge and suspended in ethanol. We used first Raman measurements to estimate the presence and types of different MPs in wastewater sludge samples. We also used microscopy to identify the shapes of the main MPs. This allowed us to create a teaching set of samples to be characterized with our optical method. With the developed method, we clearly show that MPs from common plastics, such as polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS), and polyethylene (PE), are present in wastewater sludge and can be identified. Additionally, the results also indicate that the density of the plastics, which influences the sedimentation, is an essential parameter to consider in optical detection of microplastics in complex natural environments. All of the methods are in good agreement, thus validating the optics-based solution.

13.
J Lipid Res ; 51(2): 431-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19734566

RESUMO

Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL(2) and HDL(3) (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries.


Assuntos
Biologia Computacional/métodos , Lipoproteínas/metabolismo , Fenótipo , Apolipoproteínas B/sangue , Apolipoproteínas B/isolamento & purificação , Apolipoproteínas B/metabolismo , Biologia Computacional/economia , Feminino , Humanos , Lipoproteínas/sangue , Lipoproteínas/isolamento & purificação , Masculino , Metabolômica , Reconhecimento Automatizado de Padrão , Ultracentrifugação
14.
Duodecim ; 126(12): 1496-507, 2010.
Artigo em Fi | MEDLINE | ID: mdl-20617753

RESUMO

The spectrum of small vessel vasculitides includes Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, Henoch-Schönlein purpura, cutaneous leukocytoclastic vasculitis and essential cryoglobulinemic vasculitis. The first three are characterized by the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA). The symptoms of vasculitis range from stable or slowly progressive to rapidly progressive glomerulonephritis or alveolar haemorrhage. The diagnosis of small vessel vasculitis should preferably rely on both clinical findings and histopathological examination of the organ involved. Cyclophosphamide combined with glucocorticoids is still standard therapy for remission induction in generalized ANCA-associated vasculitis. In severe cases the use of plasmapheresis treatment has been advocated. Medications suitable for remission maintenance include azathioprine, methotrexate, leflunomide and mycophenolate mofetil. Early experience with biologic drugs, particularly with rituximab, for refractory disease has been quite promising.


Assuntos
Imunossupressores/uso terapêutico , Vasculite/diagnóstico , Vasculite/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Progressão da Doença , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Isoxazóis/uso terapêutico , Leflunomida , Metotrexato/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Plasmaferese , Rituximab
15.
J Rheumatol ; 47(8): 1160-1164, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732558

RESUMO

OBJECTIVE: To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT00908089). RESULTS: There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%). CONCLUSION: Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Vértebras Cervicais/diagnóstico por imagem , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Resultado do Tratamento
16.
Nephrol Dial Transplant ; 24(7): 2131-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19196823

RESUMO

BACKGROUND: Chronic renal failure increases the risk of atherosclerosis. The clearance of low-density lipoprotein (LDL), a major risk factor for atherosclerosis, has been reported as being disturbed in dialysis patients. We studied LDL metabolism in non-dialyzed patients with chronic kidney disease (CKD). METHODS: LDL clearance was studied with a radiotracer method in 57 CKD patients and 10 healthy controls. RESULTS: In the CKD patients, the fractional catabolic rate of LDL apo B (LDL FCR), an indicator of LDL clearance from plasma, ranged from 0.13 to 0.56 pools/day with a mean value of 0.34 pools/day being comparable to that of the control subjects. In the renal patients, LDL FCR correlated significantly with estimated glomerular filtration rate (eGFR) (r = 0.340, P = 0.010) and this association remained significant after the adjustment with age, body mass index, gender, presence of diabetes and LDL cholesterol concentration (P = 0.004). In CKD patients with eGFR <15 mL/min/1.73 m(2) the mean LDL FCR was significantly reduced when compared to that of CKD patients with eGFR >30 mL/min/1.73 m(2) (P = 0.005). LDL apo B production rate was not associated with renal function or different between renal patients and control subjects. CONCLUSIONS: The clearance of LDL seems to be related to the severity of renal impairment, but a remarkable reduction in LDL catabolism can be observed only in patients with advanced renal failure.


Assuntos
Falência Renal Crônica/metabolismo , Lipoproteínas LDL/metabolismo , Adulto , Idoso , Feminino , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Duodecim ; 125(19): 2099-105, 2009.
Artigo em Fi | MEDLINE | ID: mdl-19938414

RESUMO

BACKGROUND: The most common symptoms and signs of systemic lupus erythematosus (SLE) are lesions of the skin and mucous membranes, joint pains, fever and fatigue. Organ lesions are found inter alia in the kidneys, lungs and central nervous system. PATIENTS AND METHODS: We investigated the lung and pleura findings of one hundred SLE patients treated during 1996-2004 at the Oulu University Hospital. RESULTS: Lung and pleural lesions were found in 25% of the patients; pulmonary infections in 13%, pleural lesions in 9%, interstitial pulmonary diseases in 4% and pulmonary hypertensions in 3%. CONCLUSIONS: Pulmonary infections and pleural lesions were the most common findings.


Assuntos
Pneumopatias/patologia , Lúpus Eritematoso Sistêmico/patologia , Feminino , Finlândia/epidemiologia , Humanos , Pneumopatias/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino
18.
Sci Total Environ ; 662: 88-98, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30690382

RESUMO

There are several methods for studying metal-contaminated freshwater sediments, but more information is needed on which methods to include in ecological risk assessment. In this study, we compliment the traditional Sediment Quality Triad (SQT) approach - including information on chemistry, toxicity and ecological status - with studies on metal bioavailability and metal body residues in local organisms. We studied four mining-affected boreal lakes in Finland by conducting chemical analyses of sediment and water, toxicity tests (L. variegatus, V. fischeri, C. riparius, L. stagnalis), and analysis of benthic organism community structure. In addition, we studied the relationships between metal loading, toxicity, metal bioavailability, and metal body residues in the field-collected biota. Chemistry and benthic organism community structures show adverse effects in those lakes, where the metal concentrations are the highest. However, toxicity was connected to low sediment pH during the experiment, rather than to high metal concentrations. Toxicity was observed in 4 out of 6 toxicity tests including growth test with L. variegatus, bulk sediment test with V. fischeri, and the L. stagnalis toxicity test. The C. riparius test did not show toxicity. Metal body residues in biota were not high enough to induce adverse effects (0.1-4.1 mg Cu/kg fw, 0.01-0.3 mg Ni/kg fw, 2.9-26.7 mg Zn/kg fw and 0.01-0.7 mg As/kg fw). Chemical analyses, metal bioavailability assessment and benthic community structures survey revealed adverse effects in the sediments, where metal concentrations are highest (Lake SJ and Lake KS). Standard toxicity tests were not suitable for studying acid, sulfide-rich sediments and, therefore, benthic structure study and chemical analyses are believed to give more reliable results of the ecological status of these sediments.


Assuntos
Peixes/metabolismo , Sedimentos Geológicos/análise , Invertebrados/efeitos dos fármacos , Lagos/análise , Metais/toxicidade , Vibrio/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Disponibilidade Biológica , Finlândia , Mineração , Medição de Risco , Testes de Toxicidade
19.
Sci Total Environ ; 645: 1253-1263, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30248850

RESUMO

We assessed potential ecotoxicity of lake sediments affected by biomining effluents in northeastern Finland. Growth, reproduction and behavior of the sediment-dwelling oligochaete Lumbriculus variegatus (Müller 1774) were used as ecotoxicity endpoints. Standardized chronic bioassays were used for growth and reproduction, and acute and chronic tests with Multispecies Freshwater Biomonitor (MFB) for behavior assessments. Sequential extractions were used to characterize metal bioavailability and exposure conditions in the sediments, which indicated mining-induced contamination gradients of S, Cu, Ni and U and also bioavailability gradients of S and Ni. Among the ecotoxicity endpoints, growth and reproduction responses of the standard bioassays appeared more sensitive than the behavioral responses at 21 d. In the two most mining-affected test sediments, mean number of worms and dry biomass decreased 35-42% and 46-51% in comparison to the reference sediment, respectively. The behavioral changes of worms, i.e. peristaltic and overall locomotory activity, decreased on average 20-70% and 2-61% at 21 d in the same sediments. However, these behavioral changes were observed at the onset of exposure indicating MFB technique is a suitable and rapid screening level ecotoxicity assessment tool.

20.
Chemosphere ; 210: 304-311, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30005352

RESUMO

Increasing metal consumption is driving the introduction of new techniques such as biomining to exploit low grade ores. The biomining impacts notably aquatic ecosystems, yet, the applicability of ecotoxicological tests to study the complex mixture effects of mining waters is insufficiently understood. The aim of the present work was to test if transcriptomic biomarkers are suitable and sensitive for the ecotoxicity assessment of biomining affected waters. The study site had been affected by a multimetal biomine, and the studied water samples formed a concentration gradient of contamination downstream from the biomining site. Cadmium and nickel were used as positive controls in the toxicity tests. Selected transcriptomic biomarkers, previously shown to be differentially regulated by metals, were used to evaluate the ecotoxicity of the water samples. Parallel samples were used to compare the transcriptomic biomarkers with the conventional acute D. magna toxicity test. In the acute test, one sample was acutely toxic to D. magna, when pH was adjusted according to the standard, whereas, in the native pH, three samples caused total immobility. Monooxygenase was up-regulated by the highest concentration of Cd in control samples and three of the water samples. Vtg-SOD was up-regulated by one of the water samples, and catalase by the second highest concentration of Cd. The results show that transcriptomic biomarkers in D. magna can be used as sensitive bioindicators for metal mixture toxicity assessment in complex environmental water samples.


Assuntos
Biomarcadores/análise , Cádmio/toxicidade , Daphnia/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Mineração , Níquel/toxicidade , Testes de Toxicidade Aguda/métodos , Transcriptoma/efeitos dos fármacos , Animais , Daphnia/efeitos dos fármacos
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