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1.
Niger J Clin Pract ; 26(11): 1652-1658, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38044770

RESUMO

AIMS: The aim of this study was to estimate cutoff values of mid-upper arm circumference (MUAC) and calf circumference (CC) for reduced muscle mass and analyze their accuracy in identifying malnutrition among individuals of 65 years of age or older in Bosnia and Herzegovina. MATERIALS AND METHODS: The study is a secondary analysis dataset assessing nutritional risk and malnutrition among 446 community-dwellers and nursing home residents in Bosnia and Herzegovina. Malnutrition assessment included phenotypic criterions (weight loss, low body mass index, and reduced muscle mass) and etiologic criterions (inadequate food intake, disease-related inflammation, or albumin levels) according to recommendations of the Global Leadership Initiative on Malnutrition (GLIM). Receiver operating curves were used to calculate MUAC and CC's cutoff values as compared to the Mini Nutritional Assessment (MNA). RESULTS: The optimal cutoff value for MUAC in men was 24 cm (AUC = 0.910, sensitivity 100%, specificity 77%), and in women 23 cm (AUC = 0.792, sensitivity 64%, specificity 83%). Optimal cutoff value of CC in men was 31 cm (AUC = 0.818, sensitivity 100%, specificity 67%) and in women 29 cm (AUC = 0.882, sensitivity 86%, specificity 74%). Two hundred fifty nine elderly individuals were categorized as malnourished/at risk for malnutrition per MNA. The prevalence of malnutrition based on GLIM criteria ranged from 19% to 30%. CONCLUSIONS: The study suggested that MUAC and CC may be used as the alternative indicators of muscle mass when other assessment methods are unavailable. Future validation and reliability studies for GLIM using anthropometric parameters as a proxy of reduced muscle mass are needed.


Assuntos
Desnutrição , Estado Nutricional , Masculino , Humanos , Feminino , Idoso , Reprodutibilidade dos Testes , Liderança , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Avaliação Nutricional , Redução de Peso , Músculos
2.
Transp Res D Transp Environ ; 107: 103287, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35784496

RESUMO

A new vehicle testing procedure (WLTP - Worldwide Light duty vehicle Test Procedure) was introduced in the European Union (EU) in 2017. In order to examine its actual impact on CO2 emissions for different vehicle technologies and categories, this study analysed data from vehicles certified and registered in the EU in 2019 and 2020. It was found that in average, for all vehicles sold in 2020, the increase in CO2 emissions due to the intoduction of the WLTP was 21% for passenger cars and 27% for vans. Also that diesel vehicles are impacted more than gasoline ones and that the impact on conventional hybrid vehicles is 27% and plug-in hybrid vehicles between 0% (in 2020) and 11% (in 2019). Models employed revealed that the increase in CO2 is mainly due to the higher test masses and more realistic road load coefficients of WLTP that result in higher cycle energy demands. Moreover, results confirmed that the impact of the WLTP's introduction is in line, both in terms of absolute increase and variability, with model-based predictions performed before fleet-wide data were made available.

3.
Rev. méd. Chile ; 148(8)ago. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1389307

RESUMO

In Chile, 7.1% of people aged over 60 years have some type of cognitive disorder. The frequency of the latter increases to 13% in people between 75-79 years and 36.2% in people over 85 years. The concept of mild cognitive impairment (MCI) and dementia have evolved over time. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term minor and major neurocognitive disorder, replacing the DCL and dementia respectively. Major cognitive disorder impairs functional performance while minor disorders does not. There is an arbitrary discrimination against the elderly. A form of discrimination is the request made by some notaries of a medical certification of the cognitive function for older people willing to carry out a legal procedure. This request has the sole effect of pre-establishing evidence in favor of the notary and not protecting the testator or the vulnerable person. Assessing the ability of older people to care for themselves and their possessions has important implications for them and their families, since there is a serious risk of prejudice when someone is declared as disabled. Thus, considering the epidemiology of cognitive disorders in our country we propose a series of legal and medical discussion points aimed to protect autonomy and to protect individuals and their possessions when they have difficulties to control their decisions.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Autonomia Pessoal , Disfunção Cognitiva , Chile/epidemiologia , Cognição , Tomada de Decisões , Manual Diagnóstico e Estatístico de Transtornos Mentais , Disfunção Cognitiva/diagnóstico
4.
Rev Med Chil ; 148(8): 1183-1188, 2020 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-33399784

RESUMO

In Chile, 7.1% of people aged over 60 years have some type of cognitive disorder. The frequency of the latter increases to 13% in people between 75-79 years and 36.2% in people over 85 years. The concept of mild cognitive impairment (MCI) and dementia have evolved over time. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term minor and major neurocognitive disorder, replacing the DCL and dementia respectively. Major cognitive disorder impairs functional performance while minor disorders does not. There is an arbitrary discrimination against the elderly. A form of discrimination is the request made by some notaries of a medical certification of the cognitive function for older people willing to carry out a legal procedure. This request has the sole effect of pre-establishing evidence in favor of the notary and not protecting the testator or the vulnerable person. Assessing the ability of older people to care for themselves and their possessions has important implications for them and their families, since there is a serious risk of prejudice when someone is declared as disabled. Thus, considering the epidemiology of cognitive disorders in our country we propose a series of legal and medical discussion points aimed to protect autonomy and to protect individuals and their possessions when they have difficulties to control their decisions.


Assuntos
Disfunção Cognitiva , Autonomia Pessoal , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Tomada de Decisões , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pessoa de Meia-Idade
5.
Transpl Infect Dis ; 20(5): e12934, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29809312

RESUMO

INTRODUCTION: Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an individual's viral-specific immune response. METHODS: Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV <0.1 IU/mL was considered non-reactive. RESULTS: 50/59 (84.7%) had a reactive QFN-CMV by M6. 38/59 (64.4%) had antiviral prophylaxis or treatment before M6, with 31/38 (81.6%) developing a reactive QFN-CMV by 6 months. Over 90% already had a reactive result as early as 3 months post transplant, 3 patients (5.08%) developed late CMV between 6-12 months (median 251 days)-all had a non-reactive M6 QFN-CMV. And 2/3 experienced CMV disease. Non-reactive M6 QFN-CMV was significantly associated with late CMV (OR = 54.4, PPV = 0.33, NPV = 1.00, P = .003). CONCLUSION: Although only 5% of recipients developed late CMV, 2/3 suffered CMV disease. M6 QFN-CMV has an excellent NPV for late CMV, suggesting patients who exhibit a robust ex vivo immune response at M6 can safely cease CMV monitoring. Furthermore, >90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients.


Assuntos
Infecções por Citomegalovirus/sangue , Citomegalovirus/fisiologia , Transplante de Fígado/efeitos adversos , Linfócitos T/imunologia , Ativação Viral , Antibioticoprofilaxia/métodos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Testes Sorológicos/instrumentação , Testes Sorológicos/métodos , Resultado do Tratamento , Carga Viral/imunologia
6.
Rev. méd. Chile ; 145(9): 1213-1217, set. 2017. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-902610

RESUMO

Heparin-induced thrombocytopenia (HIT) is immune-mediated. It occurs more frequently with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). It is associated with thromboembolic rather than hemorrhagic events, as opposed to thrombocytopenia of other etiologies. The key in therapy is the cessation of heparin and the start of another anticoagulant. We report a 58 years old female with HIT secondary to the use of Enoxaparin who was successfully managed with Rivaroxaban. Our goal is to report a novel therapy and provide the evidence that supports its use.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Heparina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Anticoagulantes/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
7.
Rev Med Chil ; 145(9): 1213-1217, 2017 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-29424412

RESUMO

Heparin-induced thrombocytopenia (HIT) is immune-mediated. It occurs more frequently with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). It is associated with thromboembolic rather than hemorrhagic events, as opposed to thrombocytopenia of other etiologies. The key in therapy is the cessation of heparin and the start of another anticoagulant. We report a 58 years old female with HIT secondary to the use of Enoxaparin who was successfully managed with Rivaroxaban. Our goal is to report a novel therapy and provide the evidence that supports its use.


Assuntos
Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Heparina/efeitos adversos , Rivaroxabana/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
8.
Antimicrob Agents Chemother ; 57(8): 4058-60, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23733466

RESUMO

In a prospective study of solid-organ transplant recipients (n = 22; 15 hepatic and 7 renal) receiving valganciclovir for cytomegalovirus (CMV) prophylaxis, electronic estimation of glomerular filtration rate (eGFR) underestimated the true GFR (24-h urine creatinine clearance) by >20% in 14/22 (63.6%). Its use was associated with inappropriate underdosing of valganciclovir, while the Cockroft-Gault equation was accurate in 21/22 patients (95.4%). Subtherapeutic ganciclovir levels (≤ 0.6 mg/liter) were common, occurring in 10/22 patients (45.4%); 7 had severely deficient levels (<0.3 mg/liter).


Assuntos
Ganciclovir/análogos & derivados , Taxa de Filtração Glomerular , Transplante de Rim , Transplante de Fígado , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Creatina/urina , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Processamento Eletrônico de Dados , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Valganciclovir
9.
Rev. chil. urol ; 77(2): 141-145, 2012. tab
Artigo em Espanhol | LILACS | ID: lil-783401

RESUMO

El score de Gleason (SG) es el sistema más utilizado en la etapificación del cáncer prostático (CP). La correlación entre el SG de la biopsia prostática por punción (BP) y el obtenido en la prostatectomía radical (PR) no es exacta. El objetivo de este estudio fue comparar el SG de la BP con el obtenido en la pieza quirúrgica de la PR en nuestro hospital. Creemos que existe un nivel moderado de concordancia entre ambas muestras. Se incluyeron los pacientes sometidos a PR entre 1993 y 2010 en el Hospital Militar de Santiago (HOSMIL). Se estableció como SG sobreestimado cuando el SG de la biopsia por punción era mayor al de la PR, y SG subestimado cuando el SG obtenido en la biopsia era menor al obtenido en la PR. Se utilizó la medida estadística Kappa (K) para determinar su nivel de concordancia. El estudio incluyó 534 pacientes. Se encontró una concordancia de 62 por ciento. La sobreestimación fue de 6,7 por ciento y la subestimación fue 31,2 por ciento. El valor del índice de concordancia Kappa (K) fue de 0,3186. Se encontró un índice de concordancia débil. Esto se podría explicar por la escasa muestra disponible en la biopsia, comparada con la pieza completa de la PR, entre otros factores. Se asemeja a resultados internacionales, que afirman que la subestimación es la situación más frecuente...


Gleason Score (SG) is the most frequently used system for prostate cancer (CP) staging. The correspondence between the SG of the prostate biopsy and the radical prostatectomy is not exact. The purpose of this study was to compare the SG of the biopsy with that obtained at radical surgery in our hospital. We relieve that there is a moderate level of correspondence between both specimens. We included all patients who underwent Radical Prostatectomy between 1993 and 2010 in the Hospital Militar de Santiago (HOSMIL). We defined overestimation when the SG in the biopsy was higher than in the Radical Prostatectomy; and underestimated when lower. The statistical measurement Kappa (K) was used for the analysis. 534 patients where studied. The correspondence was 62 percent. Overestimation was 6,7 percent and underestimation was 31.2 percent. Kappa (K) was 0.3186 and this is considered weak. This could be explained in part due to the small size of the tissue sample, when compared to the complete prostate after surgery. Our experience is similar to International reports, where underestimation is also frequent...


Assuntos
Humanos , Masculino , Adulto , Biópsia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Prostatectomia , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Valor Preditivo dos Testes
10.
J Clin Virol ; 51(4): 229-33, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21641274

RESUMO

BACKGROUND: Cytomegalovirus (CMV) remains the leading viral cause of disease following orthotopic liver transplantation (OLT) despite the availability of antiviral agents for prophylaxis and therapy. OBJECTIVE: Examine the viral factors that influence the outcome of CMV infection following valganciclovir prophylaxis or laboratory-guided preemptive therapy in OLT recipients. STUDY DESIGN: The value of valganciclovir prophylaxis and laboratory-guided preemptive therapy for the prevention of CMV infection and disease was observed in 64 OLT recipients. Prophylaxis was given to all CMV seronegative recipients receiving a liver from a seropositive donor (D+R-; n=15), and all other recipients were randomised to receive either prophylaxis (n=24) or laboratory-guided preemptive therapy (n=25). Recipients were monitored for CMV DNAemia, viral load, emergence of antiviral resistant strains and co-infections. RESULTS: CMV end-organ disease and antiviral resistant strains only occurred in D+R- recipients despite the use of prophylaxis in these patients. The D+R- recipients commencing prophylaxis immediately following transplantation had better outcomes compared to those for whom prophylaxis was delayed due to renal impairment. Prophylaxis reduced the incidence of CMV DNAemia, persistent infection, and high viral loads for CMV seropositive (D-R+and D+R+) recipients, but laboratory-guided preemptive therapy effectively controlled CMV infection and prevented disease in these OLT recipients. CONCLUSION: Delaying the commencement of valganciclovir prophylaxis may be associated with worse outcomes for high-risk OLT recipients. Laboratory-guided pre-emptive therapy remains an alternative approach for seropositive recipients at lower risk of CMV disease.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Ganciclovir/análogos & derivados , Transplante de Fígado/efeitos adversos , Transplante , Adulto , Quimioprevenção/métodos , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/administração & dosagem , Humanos , Resultado do Tratamento , Valganciclovir
11.
Vnitr Lek ; 56(2): 154-6, 2010 Feb.
Artigo em Tcheco | MEDLINE | ID: mdl-20329587

RESUMO

Myxoma is the most frequent primary cardiac tumor. In the typical clinical picture mostly dominate signs of intracardial obstruction, embolisation or general signs of neoplastic process. The myxoma can mimic the course of acute endocarditis. Genuine proof of infection is rare. We report on a patient with familiar form of infected myxoma, who was treated succesfully with antiobiotic therapy and surgical extirpation of the tumor.


Assuntos
Endocardite/diagnóstico , Infecções por Enterobacteriaceae/diagnóstico , Neoplasias Cardíacas/diagnóstico , Mixoma/diagnóstico , Doença Aguda , Ecocardiografia , Infecções por Enterobacteriaceae/complicações , Feminino , Neoplasias Cardíacas/complicações , Humanos , Pessoa de Meia-Idade , Mixoma/complicações
12.
Protein Eng Des Sel ; 23(4): 279-88, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20164216

RESUMO

To demonstrate the utility of phage display in generating highly specific antibodies, affinity selections were conducted on 20 related Src Homology 2 (SH2) domains (ABL1, ABL2, BTK, BCAR3, CRK, FYN, GRB2, GRAP2, LYN, LCK, NCK1, PTPN11 C, PIK3R1 C, PLCgamma1 C, RASA1 C, SHC1, SH2D1A, SYK N, VAV1 and the tandem domains of ZAP70). The domains were expressed in Escherichia coli, purified and used in affinity selection experiments. In total, 1292/3800 of the resultant antibodies were shown to bind the target antigen. Of the 695 further evaluated in specificity ELISAs against all 20 SH2 domains, 379 antibodies were identified with unique specificity (i.e. monospecific). Sequence analysis revealed that there were at least 150 different clones with 1-19 different antibodies/antigen. This includes antibodies that distinguish between ABL1 and ABL2, despite their 89% sequence identity. Specificity was confirmed for many on protein arrays fabricated with 432 different proteins. Thus, even though the SH2 domains share a common three-dimensional structure and 20-89% identity at the primary structure level, we were able to isolate antibodies with exquisite specificity within this family of structurally related domains.


Assuntos
Especificidade de Anticorpos , Biblioteca de Peptídeos , Domínios de Homologia de src/imunologia , Bacteriófagos/química , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Engenharia de Proteínas/métodos
13.
Neuropediatrics ; 37(1): 13-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16541363

RESUMO

AIM: The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. METHODS: Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. RESULTS: 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. CONCLUSION: After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.


Assuntos
Inteligência/fisiologia , Processos Mentais/fisiologia , Testes Neuropsicológicos/estatística & dados numéricos , Acidente Vascular Cerebral/fisiopatologia , Adolescente , Fatores Etários , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Criança , Pré-Escolar , Escolaridade , Feminino , Seguimentos , Humanos , Testes de Inteligência , Masculino , Avaliação de Resultados em Cuidados de Saúde , Caracteres Sexuais , Suíça/epidemiologia
14.
Dis Markers ; 22(5-6): 277-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17264398

RESUMO

BPD_28D (O2 dependency at 28 days of life) and BPD_36W (O2 dependency at 36 wks post-menstrual age) are diseases of prematurely born infants exposed to mechanical ventilation and/or oxygen supplementation. In order to determine whether genetic variants of surfactant proteins (SPs-A, B, C, and D) and SP-B-linked microsatellite markers are risk factors in BPD, we performed a family based association study using a Greek study group of 71 neonates (<30 wks gestational age) from 60 families with, 52 BPD_28D and 19 BPD_36W, affected infants. Genotyping was performed using newly designed pyrosequencing assays and previously published methods. Associations between genetic variants of SPs and BPD subgroups were determined using Transmission Disequilibrium Test (TDT) and Family Based Association Test (FBAT). Significant associations (p

Assuntos
Displasia Broncopulmonar/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Associadas a Surfactantes Pulmonares/genética , Alelos , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Recém-Nascido , Masculino , Repetições de Microssatélites , Proteína A Associada a Surfactante Pulmonar/genética , Proteína B Associada a Surfactante Pulmonar/genética , Proteína C Associada a Surfactante Pulmonar/genética , Proteína D Associada a Surfactante Pulmonar/genética , Análise de Sequência de DNA
15.
Neuropediatrics ; 36(2): 90-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15822021

RESUMO

We report the results of three years of the population-based, prospective Swiss NeuroPaediatric Stroke Registry (SNPSR) of children (up to 16 years) with childhood arterial ischaemic stroke (AIS1), neonatal stroke (AIS2), or symptomatic sinus venous thrombosis (SVT). Data on risk factors (RF), presentation, diagnostic work-up, localisation, and short-term neurological outcome were collected. 80 children (54 males) have been included, 40 AIS1, 23 AIS2, and 17 SVT. The data presented will be concentrated on AIS. The presentation for AIS1 was hemiparesis in 77% and cerebellar symptoms and seizures in 20%, respectively. AIS2 presented in 83% with seizures and in 38% with abnormality of muscle tone. Two or more RF were detected in 54%, one RF in 35%. The most prominent RF for AIS1 were infections (40%), followed by cardiopathies and coagulopathies (25% each). AIS2 were frequently related to birth problems. Neurological outcomes in AIS1 and AIS2 were moderate/severe in 45 % and 32 %, respectively. The outcome correlated significantly with the size of infarction (p = 0.013) and age at stroke (p = 0.027). The overall mortality was 6%. Paediatric stroke is a multiple risk problem, which leads to important long-term sequelae.


Assuntos
Estudos de Coortes , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Adolescente , Fatores Etários , Análise de Variância , Infarto Encefálico/diagnóstico , Criança , Pré-Escolar , Feminino , Lateralidade Funcional , História Antiga , Humanos , Incidência , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Exame Neurológico/métodos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/classificação , Inquéritos e Questionários , Suíça/epidemiologia , Fatores de Tempo
16.
J Mol Med (Berl) ; 79(2-3): 133-42, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11357937

RESUMO

Vaccination against tumors relies on tumor-associated antigens, and has been quite successful with synthetic peptides used as immunogens. Gp100 is a human melanoma-associated antigen (hgp100) with a highly homologous mouse counterpart, pmel17/gp100 (mgp100), that is expressed in melanocytes and highly tumorigenic B16 melanoma cells. Since mgp100 is poorly immunogenic in mice, we used a xenoimmunization approach and vaccinated with the hgp100 immunogene. To that end, plasmid DNA encoding hgp100 was applied as a vaccine in combination with three synthetic peptides corresponding to putative cytotoxic T cell epitopes of hgp100. Immunization with DNA and peptide-pulsed spleen cells had a synergistic effect and provided significant protection against a challenge with poorly immunogenic B16-F0 malignant melanoma cells in the syngeneic C57BL/6 mouse model. Vaccination with either plasmid DNA or peptides alone delayed the onset of tumor formation, and reduced tumor growth 2-fold and 30-fold, respectively. However, while all animals vaccinated with DNA encoding hgp100 or with peptides eventually developed tumors, 30% of the animals treated with both vaccines remained tumor free and survived for the entire observation period of 150 days. Depletion of T cell subsets revealed that the protective effect observed after vaccination with plasmid DNA was mediated by CD4+ and CD8+ T cells, while protection following vaccination with DNA encoding hgp100 in combination with peptides appears to depend on CD4+ T cells only. Furthermore, we could also demonstrate a therapeutic effect of the combined DNA/peptide regime. A single treatment cycle consisting of injections of plasmid DNA and peptide-pulsed spleen cells led to a fourfold reduction in the growth rate of preexisting tumors. The data presented demonstrate that immunization with xenoantigens induces cross-species priming leading to an immunological response against the tumor-specific antigens.


Assuntos
Vacinas Anticâncer/imunologia , Melanoma Experimental/imunologia , Glicoproteínas de Membrana/imunologia , Proteínas de Neoplasias/imunologia , Sequência de Aminoácidos , Animais , Vacinas Anticâncer/administração & dosagem , DNA de Neoplasias/imunologia , Glicoproteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Vacinação , Vacinas de DNA , Antígeno gp100 de Melanoma
17.
J Virol ; 75(7): 3343-51, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11238860

RESUMO

Knowledge of the mechanisms of virus dissemination in acute measles is cursory, but cells of the monocyte/macrophage (MM) lineage appear to be early targets. We characterized the dissemination of the Edmonston B vaccine strain of measles virus (MV-Ed) in peripheral blood mononuclear cells (PBMC) of two mouse strains expressing the human MV-Ed receptor CD46 with human-like tissue specificity and efficiency. In one strain the alpha/beta interferon receptor is defective, allowing for efficient MV-Ed systemic spread. In both mouse strains the PBMC most efficiently infected were F4/80-positive MMs, regardless of the inoculation route used. Circulating B lymphocytes and CD4-positive T lymphocytes were infected at lower levels, but no infected CD8-positive T lymphocytes were detected. To elucidate the roles of MMs in infection, we depleted these cells by clodronate liposome treatment in vivo. MV-Ed infection of splenic MM-depleted mice caused strong activation and infection of splenic dendritic cells (DC), followed by enhanced virus replication in the spleen. Similarly, depletion of lung macrophages resulted in strong activation and infection of lung DC. Thus, in MV infections of genetically modified mice, blood monocytes and tissue macrophages provide functions beneficial for both the virus and the host: they support virus replication early after infection, but they also contribute to protecting other immune cells from infection. Human MM may have similar roles in acute measles.


Assuntos
Antígenos CD/fisiologia , Macrófagos/fisiologia , Sarampo/imunologia , Glicoproteínas de Membrana/fisiologia , Receptores de Interferon/fisiologia , Animais , Células Dendríticas/virologia , Humanos , Macrófagos/virologia , Vírus do Sarampo/fisiologia , Proteína Cofatora de Membrana , Camundongos , Monócitos/fisiologia , Monócitos/virologia , Receptor de Interferon alfa e beta , Replicação Viral
18.
Blood ; 97(2): 523-7, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11154232

RESUMO

Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-gamma is a natural inhibitor of T-helper 2 cells and IFN-alpha is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vbeta antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4(+) cells, but not the nonclonal CD4(+) cells, appeared resistant to IFN-gamma and IFN-alpha stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNgammaR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-alpha priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.


Assuntos
Resistência a Medicamentos , Interferons/fisiologia , Linfoma Cutâneo de Células T/patologia , Células Clonais/patologia , Células Clonais/fisiologia , Células Clonais/virologia , Regulação para Baixo/efeitos dos fármacos , Humanos , Interferon-alfa/farmacologia , Interferon-alfa/fisiologia , Interferon gama/farmacologia , Interferon gama/fisiologia , Interferons/farmacologia , Linfoma Cutâneo de Células T/fisiopatologia , Linfoma Cutâneo de Células T/virologia , Receptores de Interferon/efeitos dos fármacos , Receptores de Interferon/fisiologia , Síndrome de Sézary/patologia , Síndrome de Sézary/fisiopatologia , Síndrome de Sézary/virologia , Transdução de Sinais/efeitos dos fármacos , Células Th2/patologia , Células Th2/fisiologia , Células Th2/virologia , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/fisiologia , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacos , Vírus da Estomatite Vesicular Indiana/crescimento & desenvolvimento
19.
J Virol ; 75(3): 1371-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11152510

RESUMO

Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR(-/-) mice lacking the alpha/beta interferon (IFN-alpha/beta) receptor but remained attenuated in IFN-gamma receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-alpha/beta production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-alpha/beta and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-alpha/beta production, we infected susceptible IFNAR(-/-) mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-alpha/beta production. These results demonstrate that the ability of RVFV to inhibit IFN-alpha/beta production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist.


Assuntos
Interferon-alfa/antagonistas & inibidores , Interferon beta/antagonistas & inibidores , Vírus da Febre do Vale do Rift/patogenicidade , Proteínas não Estruturais Virais/fisiologia , Animais , Interferon-alfa/fisiologia , Interferon beta/fisiologia , Camundongos , Camundongos Endogâmicos , Receptores de Interferon/fisiologia , Vírus da Febre do Vale do Rift/crescimento & desenvolvimento , Virulência
20.
Lijec Vjesn ; 122(3-4): 56-60, 2000 Mar.
Artigo em Servo-Croata (Latino) | MEDLINE | ID: mdl-10932529

RESUMO

Primary health care of preschool children is organized in the Republic of Croatia by pediatricians, general practitioners and family/general practice specialist. The aim of this study is to evaluate the care for preschool children in the well baby clinics led by general/family specialist. Vaccination and visits data were collected from the medical records of 148 children born from January 1st 1992 till December 31st 1997, registered in two family practice offices in the well baby clinics at the Dugave-Travno Health Station of the "Novi Zagreb" Health Center. Comparison was made between data on compulsory immunization minimum in the Republic of Croatia and data from the Croatian National Institute of Public Health on vaccination of infants and preschool children in the Republic of Croatia in 1997. Diphtheria, tetanus and poliomyelitis vaccination was 100%, pertussis vaccination was 97.2%, measles and parotitis vaccination was 92.2% and rubella vaccination was 91.5%. Diphtheria and tetanus revaccination of children in the second year of life was 97.6%, pertussis revaccination was 94.4% and poliomyelitis revaccination was 96.8%. Comparison of those results proves the efficacy of compulsory immunization program of preschool children in family/general specialists' offices. The accessibility of general/family practice, appropriate education of general/family specialists during the specialization in family medicine for primary care of preschool children as well as for other family members, the ability of family physician to offer integrated continuous care and good cooperation of the family physician and the public nurse are the factors that enable appropriate primary care for preschool children in general practice/family medicine.


Assuntos
Medicina de Família e Comunidade/estatística & dados numéricos , Imunização/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Serviços de Saúde da Criança/estatística & dados numéricos , Pré-Escolar , Croácia , Humanos , Lactente
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