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1.
Biophys J ; 123(14): 2122-2135, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38549370

RESUMO

Acid-sensing ion channels (ASICs) are proton-gated cation channels that contribute to fast synaptic transmission and have roles in fear conditioning and nociception. Apart from activation at low pH, ASIC1a also undergoes several types of desensitization, including acute desensitization, which terminates activation; steady-state desensitization, which occurs at sub-activating proton concentrations and limits subsequent activation; and tachyphylaxis, which results in a progressive decrease in response during a series of activations. Structural insights from a desensitized state of ASIC1 have provided great spatial detail, but dynamic insights into conformational changes in different desensitizing conditions are largely missing. Here, we use electrophysiology and voltage-clamp fluorometry to follow the functional changes of the pore along with conformational changes at several positions in the extracellular and upper transmembrane domain via cysteine-labeled fluorophores. Acute desensitization terminates activation in wild type, but introducing an N414K mutation in the ß11-12 linker of mouse ASIC1a interfered with this process. The mutation also affected steady-state desensitization and led to pronounced tachyphylaxis. Although the extracellular domain of this mutant remained sensitive to pH and underwent pH-dependent conformational changes, these conformational changes did not necessarily lead to desensitization. N414K-containing channels also remained sensitive to a known peptide modulator that increases steady-state desensitization, indicating that the mutation only reduced, but not precluded, desensitization. Together, this study contributes to our understanding of the fundamental properties of ASIC1a desensitization, emphasizing the complex interplay between the conformational changes of the extracellular domain and the pore during channel activation and desensitization.


Assuntos
Canais Iônicos Sensíveis a Ácido , Canais Iônicos Sensíveis a Ácido/química , Canais Iônicos Sensíveis a Ácido/metabolismo , Canais Iônicos Sensíveis a Ácido/genética , Animais , Camundongos , Concentração de Íons de Hidrogênio , Ativação do Canal Iônico , Conformação Proteica , Mutação , Domínios Proteicos , Xenopus laevis
2.
JCI Insight ; 7(6)2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35167493

RESUMO

Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1ß pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the potential implication of ER stress in KD pathophysiology has not been investigated to our knowledge. We used human patient data and the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to characterize the impact of ER stress on the development of cardiovascular lesions. KD patient transcriptomics and single-cell RNA sequencing of the abdominal aorta from LCWE-injected mice revealed changes in the expression of ER stress genes. Alleviating ER stress genetically, by conditional deletion of inositol-requiring enzyme 1 (IRE1) in myeloid cells, or pharmacologically, by inhibition of IRE1 endoribonuclease (RNase) activity, led to significant reduction of LCWE-induced cardiovascular lesion formation as well as reduced caspase-1 activity and IL-1ß secretion. These results demonstrate the causal relationship of ER stress to KD pathogenesis and highlight IRE1 RNase activity as a potential new therapeutic target.


Assuntos
Lacticaseibacillus casei , Síndrome de Linfonodos Mucocutâneos , Vasculite , Animais , Modelos Animais de Doenças , Endorribonucleases/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas Serina-Treonina Quinases/genética , Ribonucleases
3.
JCI Insight ; 6(18)2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34403365

RESUMO

Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Murine and human data suggest that the NLRP3-IL-1ß pathway is the main driver of KD pathophysiology. NLRP3 can be activated during defective autophagy/mitophagy. We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to examine the role of autophagy/mitophagy on cardiovascular lesion development. LCWE-injected mice had impaired autophagy/mitophagy and increased levels of ROS in cardiovascular lesions, together with increased systemic 8-OHdG release. Enhanced autophagic flux significantly reduced cardiovascular lesions in LCWE-injected mice, whereas autophagy blockade increased inflammation. Vascular smooth muscle cell-specific deletion of Atg16l1 and global Parkin-/- significantly increased disease formation, supporting the importance of autophagy/mitophagy in this model. Ogg1-/- mice had significantly increased lesions with increased NLRP3 activity, whereas treatment with MitoQ reduced vascular tissue inflammation, ROS production, and systemic 8-OHdG release. Treatment with MN58b or Metformin (increasing AMPK and reducing ROS) resulted in decreased cardiovascular lesions. Our results demonstrate that impaired autophagy/mitophagy and ROS-dependent damage exacerbate the development of murine KD vasculitis. This pathway can be efficiently targeted to reduce disease severity. These findings enhance our understanding of KD pathogenesis and identify potentially novel therapeutic avenues for KD treatment.


Assuntos
Autofagia , Mitofagia , Síndrome de Linfonodos Mucocutâneos/patologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/sangue , Animais , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Butanos/farmacologia , Extratos Celulares , Parede Celular , Vasos Coronários/patologia , DNA Glicosilases/genética , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Lacticaseibacillus casei , Masculino , Metformina/farmacologia , Camundongos , Mitofagia/genética , Síndrome de Linfonodos Mucocutâneos/induzido quimicamente , Síndrome de Linfonodos Mucocutâneos/genética , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Compostos Organofosforados/farmacologia , Compostos de Piridínio/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquitina-Proteína Ligases/genética
5.
J Neurol ; 264(6): 1132-1135, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28484839

RESUMO

Monoclonal IgM anti-myelin-associated glycoprotein (MAG) antibody-related peripheral neuropathy (anti-MAG neuropathy) is predominantly a demyelinating sensory neuropathy with ataxia and distal paresthesia. The clinical course of anti-MAG neuropathy is usually slowly progressive making difficult the identification of clear criteria to start a specific treatment. Although no consensus treatment is yet available, a rituximab-based regimen targeting the B-cell clone producing the monoclonal IgM may be proposed, alone or in combination with alkylating agents or purine analogs. However, in some rare cases, an acute and severe neurological deterioration can occur in few days leading to a rapid loss of autonomy. In these cases, a treatment rapidly removing the monoclonal IgM from the circulation might be useful before initiating a specific therapy. We report successful treatment with plasma exchanges (PE) in four patients presenting with acute neurological deterioration. PE allowed a dramatic and rapid neurological improvement in all patients. PE are safe and may be useful at the initial management of these cases of anti-MAG neuropathy.


Assuntos
Autoanticorpos/sangue , Glicoproteína Associada a Mielina/imunologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Troca Plasmática/métodos , Polineuropatias/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/sangue , Polineuropatias/imunologia , Resultado do Tratamento
6.
QJM ; 110(11): 701-711, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28525589

RESUMO

BACKGROUND: Besides peripheral cytopenias, bone marrow abnormalities, such as fibrosis, pure red cell aplasia and aplastic anemia have been reported in patients with systemic lupus erythematosus (SLE), suggesting that bone marrow may be a 25 target organ in SLE. AIM: Our objective was to describe this bone marrow involvement. METHODS: This registry is a nationwide retrospective study. Centers provided data concerning medical history, SLE manifestations, type of hematologic disorder, treatments and outcome. Bone marrow aspirations and/or biopsies were transferred for centralized review. RESULTS: Thirty patients from 19 centers were included. Central hematologic manifestations comprised bone marrow fibrosis (n = 17; 57%), pure red cell aplasia (n = 8; 27%), myelodysplastic syndrome (n = 3; 10%), aplastic anemia and agranulocytosis (n = 1; 3% each). Bone marrow involvement was diagnosed concomitantly with SLE in 12 patients. Bone marrow biopsies showed fibrosis in 19 cases, including one case of pure red cell aplasia and one case of agranulocytosis and variable global marrow cellularity. Treatments included corticosteroids (90%), hydroxychloroquine (87%), rituximab (33%), intravenous immunoglobulins (30%), mycophenolate mofetil (20%) and ciclosporine (20%). After a median follow-up of 27 months (range: 1-142), 24 patients manifested complete improvement. No patient died. CONCLUSIONS: This registry comprises the largest series of SLE patients with bone marrow involvement. It demonstrates the strong link between SLE and bone marrow fibrosis. Patients with atypical or refractory cytopenia associated with SLE should undergo bone marrow examination to enable appropriate, and often effective, treatment. Long-term prognosis is good.


Assuntos
Medula Óssea/patologia , Lúpus Eritematoso Sistêmico/complicações , Pancitopenia/complicações , Adolescente , Adulto , Idoso , Criança , Feminino , Fibrose , França , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Pancitopenia/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Leukemia ; 31(1): 123-129, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27435002

RESUMO

We retrospectively reviewed 49 patients with light chain (LC) Fanconi syndrome (FS). Patients presented with chronic kidney disease (median estimated glomerular filtration rate (eGFR) of 33 ml/min/1.73 m2) and tubular proteinuria. All patients tested had elevated fractional excretion of phosphate, uric acid, generalized aminoaciduria and/or normoglycemic glycosuria. Thirty-eight patients had monoclonal gammopathy of renal significance and eleven patients had an overt hematological malignancy. The monoclonal LC isotype was kappa in 46/49 cases. Kidney biopsy in 39 patients showed various proximal tubular lesions and characteristic LC intracytoplasmic crystalline inclusions in 24 patients. Forty-two patients received chemotherapy. Patients with plasma cell proliferation (n=38) received bortezomib-based regimens (n=11), immunomodulatory agents (n=7) or alkylating agents (n=6). High-dose melphalan (HDM) followed by autologous stem cell transplantation was performed in 14 patients. Hematological response was obtained in 90% of evaluable patients, assessed on serum free light chains (FLC). GFR remained stable as long as hematological response was maintained and declined when serum FLC level rebounded. Improvement in proximal tubule function occurred in 13 patients. In patients with LC-associated FS, chemotherapy using HDM and/or new generation anti-myeloma agents can stabilize renal function and improve proximal tubule function. Serum FLC should be used to assess the hematological response, related to renal outcome.


Assuntos
Síndrome de Fanconi/terapia , Cadeias Leves de Imunoglobulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Neoplasias Hematológicas/terapia , Humanos , Nefropatias , Masculino , Pessoa de Meia-Idade , Paraproteinemias/patologia , Paraproteinemias/terapia , Estudos Retrospectivos , Resultado do Tratamento
10.
Allergy ; 72(2): 177-182, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27564982

RESUMO

BACKGROUND: Schnitzler syndrome is characterized by an urticarial rash, a monoclonal gammopathy, and clinical, histological, and biological signs of neutrophil-mediated inflammation. The aim of this study was to assess the applicability and validity of the existing diagnostic criteria in real-life patients. METHODS: This multicentric study was conducted between 2009 and 2014 in 14 hospitals in which patients with Schnitzler syndrome or controls with related disorders were followed up. We compared the sensitivities and specificities and calculated the positive and negative predictive values of the Lipsker and of the Strasbourg criteria for the patients with Schnitzler syndrome and for the controls. We included 42 patients with Schnitzler syndrome, 12 with adult-onset Still's disease, 7 with cryopyrin-associated periodic disease, 9 with Waldenström disease, and 10 with chronic spontaneous urticaria. RESULTS: All patients with Schnitzler syndrome met the Lipsker criteria. According to the Strasbourg criteria, 34 patients had definite Schnitzler syndrome, five had probable Schnitzler syndrome, and three did not meet the criteria. One control met the Lipsker criteria and had probable Schnitzler syndrome according to the Strasbourg criteria. Sensitivity and specificity of the Lipsker criteria were 100% and 97%, respectively. For the Strasbourg criteria, sensitivity for definite and probable diagnosis was 81% and 93%, respectively, with a corresponding specificity of 100% and 97%. CONCLUSION: Diagnostic criteria currently in use to diagnose Schnitzler syndrome are reliable. More investigations must be done to attest their efficiency in patients with recent-onset manifestations.


Assuntos
Síndrome de Schnitzler/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Avaliação de Sintomas , Adulto Jovem
11.
Lupus ; 25(7): 735-40, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26876692

RESUMO

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.


Assuntos
Antirreumáticos/sangue , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Qualidade de Vida , Adulto , Método Duplo-Cego , Feminino , França , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
12.
Arthritis Rheumatol ; 67(8): 2176-84, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25989906

RESUMO

OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.


Assuntos
Corticosteroides/uso terapêutico , Antirreumáticos/farmacocinética , Hidroxicloroquina/farmacocinética , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antirreumáticos/sangue , Antirreumáticos/uso terapêutico , Índice de Massa Corporal , Creatinina/sangue , Feminino , Humanos , Hidroxicloroquina/sangue , Hidroxicloroquina/uso terapêutico , Contagem de Leucócitos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos/citologia , Obesidade/complicações , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Trombocitopenia , Fatores de Tempo , Adulto Jovem
13.
Allergy ; 68(5): 562-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23480774

RESUMO

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended.


Assuntos
Síndrome de Schnitzler/diagnóstico , Síndrome de Schnitzler/tratamento farmacológico , Seguimentos , Humanos
14.
Bone Marrow Transplant ; 46(2): 250-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20400980

RESUMO

We retrospectively studied a series of 23 patients (median age 50 years, range 29-59 years) with multiple myeloma (MM), treated in first relapse by a sequential autologous-allogeneic tandem approach. Tandem transplantation (TT) consisted in high dose melphalan (HDT) and auto-SCT followed by an (allo-SCT) preceded by two gray TBI non-myeloablative conditioning. All patients received a first HDT as frontline treatment. At day 100 post allo-SCT, complete donor chimerism was detected in 22 patients (95%). Acute GVHD was observed in 19 patients (15 grade I-II (65%) and 4 grade III-IV (17%)). Ten patients (43%) developed an extensive chronic GVHD. The non-relapse mortality at 1 year was 17%. After TT, the overall response rate was 91% (17% partial response, 35% very good partial remission and 39% complete remission). At 2 years, OS was 61%. Median event-free survival and OS were 36.8 and 60 months, respectively. Based on the propensity score matching method, a significant survival advantage could be seen in patients treated with TT as compared with non-allografted patients. Thus, allo-SCT, in TT approach, provides a high response rate with low toxicity and may improve survival of patients with relapsing MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/cirurgia , Condicionamento Pré-Transplante , Adulto , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva , Estudos Retrospectivos , Quimeras de Transplante , Transplante Autólogo , Transplante Homólogo
15.
Br J Haematol ; 136(4): 609-14, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17223917

RESUMO

The t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases, indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which has potential transforming activity and may represent a therapeutic target. To detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive newly diagnosed (n = 116) or relapsing (n = 74) MM patients was studied by flow cytometry (FC) using anti-CD138 and anti-FGFR3 antibodies. FC data was compared to real time quantitative-polymerase chain reaction (RQ-PCR) of the IGH-MMSET and FGFR3 transcripts. An IGH-MMSET transcript was found in 24/200 patients (12%). In 20 of these, FC detected CD138(+)/FGFR3(+) cells. No expression of FGFR3 was detected in the 4 FGFR3(-) cases by RQ-PCR. FGFR3 was never expressed on PC without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally, coexisting FGFR3(+) and FGFR3(-) CPC were observed. Fluorescent in situ hybridisation (FISH) analysis of the FGFR3(-) subclones showed deletion of the der(14) in one patient. In conclusion, as a supplemental method to RQ-PCR or FISH, FC analysis of FGFR3 expression is a reliable and routinely available method for the detection and management of new therapeutic approaches of t(4;14) MM.


Assuntos
Biomarcadores Tumorais/metabolismo , Mieloma Múltiplo/metabolismo , Plasmócitos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Biomarcadores Tumorais/sangue , Células da Medula Óssea/metabolismo , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 4/genética , Feminino , Citometria de Fluxo/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase/métodos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/sangue , Translocação Genética , Células Tumorais Cultivadas
16.
Rev Med Interne ; 27(1): 54-8, 2006 Jan.
Artigo em Francês | MEDLINE | ID: mdl-16236399

RESUMO

INTRODUCTION: The cytomegalovirus (CMV) infection is most often asymptomatic. The grave forms concern the immunocompromised patients. We report a new case pf acute CMV hepatitis complicated with portal thrombosis in an immunocompetent patient. EXEGESIS: A 29 year old man has presented a CMV hepatitis proved by the presence of pp65 protein and the viral DNA in serum. This infection was complicated by a portal thrombosis and the evolution was rapidly favourable under anticoagulant treatment. Eleven cases of major thrombosis complicating acute CMV infection in immunocompetent patients were previously reported in the English and French literature. The absence of local and general cause, the remission without anticoagulation, the elevated risk of thrombosis in both HIV and CMV seropositive patients, and in CMV seropositive renal transplant patients suggest a causal relation. Various pathogenic hypotheses were raised: presence of antiphospholipid antibodies, absent in our case, procoagulant phenotype induction of infected endothelial cells, proliferation induction of smooth cells. CONCLUSION: The acute CMV infection can be considered such as a possible cause of major thrombosis.


Assuntos
Infecções por Citomegalovirus/complicações , Veia Porta , Trombose/complicações , Adulto , Anticoagulantes/uso terapêutico , Humanos , Imunocompetência , Masculino , Trombose/tratamento farmacológico , Trombose/epidemiologia
17.
Eur Arch Otorhinolaryngol ; 262(10): 847-51, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15959795

RESUMO

Intracranial abscesses are serious complications of chronic suppurative otitis media (COM). This study included 32 patients presenting with intracranial abscesses from 780 patients hospitalized for treatment of COM. The 32 patients had 59 intracranial complications. Perisinus abscess (13 of 32) was the most common intracranial abscess, followed by temporal lobe abscess (8 of 32), epidural abscess (7 of 32), cerebellar abscess (6 of 32) and subdural empyema (2 of 32). Headache (93%), fever (87%) and altered mental status (62%) were the most common presenting symptoms and signs, along with symptoms of COM. All patients were treated with intravenous antibiotics and canal wall down mastoidectomy. Cholesteatoma with granulation tissue and bony defects at the sinus plate and/or dural plate were seen in most of the patients. Gram negative bacilli and anaerobes were the most common organisms cultured from the abscesses. Three patients had neurological sequels. One patient died. The early diagnosis of these complications requires a high index of suspicion and imaging studies. A multidisciplinary and coordinated approach is important for the management of these patients.


Assuntos
Abscesso Encefálico/etiologia , Otite Média Supurativa/complicações , Adolescente , Adulto , Abscesso Encefálico/fisiopatologia , Abscesso Encefálico/terapia , Criança , Pré-Escolar , Colesteatoma/complicações , Doença Crônica , Doenças dos Nervos Cranianos , Empiema Subdural/etiologia , Empiema Subdural/fisiopatologia , Empiema Subdural/terapia , Abscesso Epidural/etiologia , Abscesso Epidural/fisiopatologia , Abscesso Epidural/terapia , Feminino , Febre , Cefaleia , Humanos , Masculino , Processo Mastoide/cirurgia , Pessoa de Meia-Idade , Otite Média Supurativa/fisiopatologia , Otite Média Supurativa/terapia , Estudos Retrospectivos
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