864 research outputs found
Embedding theorems with an exponential weight on the real semiaxis
We state embedding theorems between spaces of functions defined on the real semi-axis, which can grow exponentially both at 0 and at +â
Clinical and in vitro efficacy of colistin plus vancomycin and rifampin against colistin-resistant Acinetobacter baumannii causing ventilator-associated pneumonia
We present the case of a patient with ventilator-associated pneumonia (VAP) caused by a pan-resistant Acinetobacter baumannii successfully treated with the combination colistin plus vancomycin plus rifampin, whose in vitro activity was investigated by checkerboard method and killing testing. Furthermore, the serum bactericidal activity (SBA) was assessed. Our case shows that an innovative regimen consisting of colistin plus antimicrobials active only against Gram-positive microorganisms might represent a valid therapeutic option for severe infections caused by colistin-resistant A. baumannii
Thrombotic microangiopathies: thrombotic thrombocytopenic purpura / hemolytic uremic syndrome
Thrombotic microangiopathies (TMAs) are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic- uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Other disorders occasionally present with similar manifestations. Depending on whether renal or brain lesions prevail, two pathologically indistinguishable but somehow clinically different disorders have been described: HUS and TTP. Injury to the endothelial cell is the central and likely inciting factor in the sequence of events leading to TMA. Loss of physiological thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal von Willebrand factor release and fragmentation, and increased vascular shear stress may then sustain and amplify the microangiopathic process. Intrinsic abnormalities of the complement system and of the von Willebrand factor pathway may account for a genetic predisposition to the disease that may play a paramount role in particular in familial and recurrent forms. In the case of diarrhea-associated HUS (D+HUS), renal endothelial damage is mediated (at least in large part) by the bacterial agent Shigatoxin (Stx), which is actually a family of toxins elaborated by certain strains of Escherichia coli and Shigella dysenteriae. Outcome is usually good in childhood, Shiga toxin-associated HUS, whereas renal and neurological sequelae are more frequently reported in adult, atypical, and familial forms of HUS and in TTP. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease ADAMTS13, due to deficiency of ADAMTS13 can be genetic or more common, acquired, resulting from autoimmune production of inhibitory anti-ADAMTS13 antibodies, that causes TTP. During the last decade, atypical HUS (aHUS) has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13. Platelet transfusions are contraindicated. Plasma infusion or exchange (PE) is the only treatment of proven efficacy.As microangiopatias trombĂłticas (MATs) sĂŁo condiçÔes caracterizadas por oclusĂŁo microvascular generalizada por trombos de plaquetas, trombocitopenia, e anemia hemolĂtica microangiopĂĄtica. Duas manifestaçÔes fenotĂpicas tĂpicas das MATs sĂŁo a sĂndrome hemolĂtica urĂȘmica (SHU) e a pĂșrpura trombocitopĂȘnica trombĂłtica (PTT). Outras doenças ocasionalmente apresentam manifestaçÔes similares. Na dependĂȘncia de prevalecer a lesĂŁo renal ou a cerebral, duas entidades patologicamente indistinguĂveis, mas de alguma forma clinicamente diferentes, tĂȘm sido descritas: a SHU e a PTT. InjĂșria das cĂ©lulas endoteliais Ă© o fator desencadeante central na sequĂȘncia de eventos que levam a MAT. Perda da trombo resistĂȘncia fisiolĂłgica, adesĂŁo de leucĂłcitos no endotĂ©lio lesado, consumo de complemento, liberação e fragmentação anormais do fator de von Willebrand (FvW), e aumento do estresse de cisalhamento vascular podem sustentar e ampliar o processo microangiopĂĄtico. Anormalidades intrĂnsecas do sistema do complemento e do FvW podem acompanhar a predisposição genĂ©tica Ă doença, que pode ter um papel chave, em particular nas formas recorrentes e familiares. Nos casos de SHU associada Ă diarreia (SHU+D), o dano endotelial renal Ă© mediado (pelo menos em parte) pela Shigatoxina (Stx) bacteriana, uma famĂlia de toxinas elaboradas por certas cepas da Escherichia coli e Shigella dysenteriae. A evolução Ă© geralmente boa na criança, na SHU associada a Stx, enquanto sequelas renais e neurolĂłgicas sĂŁo mais frequentemente encontradas em adultos, formas familiares e atĂpicas da SHU e na PTT. Estudos recentes tĂȘm demonstrado que a deficiĂȘncia na clivagem do FvW pela proteinase ADAMTS13 pode ser genĂ©tica ou mais comumente adquirida, resultante da produção de anticorpos inibidores da ADAMTS13, causando a PTT. Durante a Ășltima dĂ©cada, demonstrou-se que a SHU atĂpica (SHU-D) Ă© uma doença de desregulação da via alternativa do complemento. Uma sĂ©rie de mutaçÔes e polimorfismo em genes que codificam proteĂnas reguladoras do complemento sozinhas ou em combinação podem levar a SHU atĂpica. Aproximadamente 60% dos casos de SHU atĂpica tĂȘm mutaçÔes do tipo perda da função em genes que codificam as proteĂnas reguladoras do complemento, as quais protegem as cĂ©lulas hospedeiras da ativação do complemento: fator H do complemento (FHC), fator I (FIC) e proteĂna cofator de membrana (PCM ou CD46), ou mutaçÔes do tipo ganho da função em genes que codificam o FHC ou C3. AlĂ©m disso, aproximadamente 10% dos pacientes com SHU atĂpica tĂȘm deficiĂȘncia na função do FHC devido a anticorpos anti-FHC. Mesmo que as MATs sejam condiçÔes altamente heterogĂȘneas, um terço dos pacientes tem deficiĂȘncia severa da ADA-MTS13. TransfusĂ”es de plaquetas sĂŁo contraindicadas nesses pacientes. InfusĂŁo de plasma ou plasma exchange (PE) Ă© o Ășnico tratamento eficiente.Conselho Nacional de Desenvolvimento CientĂfico e TecnolĂłgico (CNPq)Universidade Federal de SĂŁo Paulo (UNIFESP) Setor de GlomerulopatiasUNIFESP, Setor de GlomerulopatiasSciEL
Changes in T cell effector functions over an 8-year period with TNF antagonists in patients with chronic inflammatory rheumatic diseases
The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNÎł by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFNÎł responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25/CD134 in CD4+compared to CD8+T cells both in patients and controls. The in vitro addition of anti-TNF agents induced a significant decrease of both the IFNÎł response and of CD25/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID
Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: A case report
Rationale: Tuberculous meningitis is a highly morbid, often fatal disease.
Patient concern: We describe a case of an Italian child.
Diagnoses: we diagnosed early a Tuberculous meningitis complicated by the occurrence of hydrocephalus, stroke, and
paradoxical reaction with brain pseudo-abscesses.
Interventions: The child started readily a specific therapy associated with steroids and thalidomide was introduced few month later.
Outcomes: the patient had a favorable outcome without neurologic sequelae.
Lessons: Despite the prompt specific anti-tubercular and adjuvant corticosteroid therapies, only the addition of thalidomide to the
treatment allow to a favorable clinical outcome
Higher levels of osteoprotegerin and immune activation/immunosenescence markers are correlated with concomitant bone and endovascular damage in HIV-suppressed patients
HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4+/CD8+ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4+ and CD8+ activated, CD8+ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases
Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: A case report
Background:
Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treat
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ment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates.
Case presentation:
This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history
of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with
predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify
Myco
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bacterium tuberculosis
were negative, while a non classical method based on intracellular cytokine flow cytometry
response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by
a nested polymerase chain reaction amplifying a 123 base pair fragment of the
M. tuberculosis
DNA.
Conclusions:
We diagnosed tuberculous meningitis at an early stage through an innovative immunological
approach, supported by a nested polymerase chain reaction for detection of
M. tuberculosis
DNA. An early diagnosis is
required in order to promptly initiate a therapy and to increase the patientâs surviva
Dynamic changes of mmp-9 plasma levels correlate with jvc reactivation and immune activation in natalizumab-treated multiple sclerosis patients
The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples. T-lymphocyte phenotype was assessed with flow cytometry. MMP-9 plasma levels resulted increased from 12 to 24 natalizumab infusions. Stratifying plasma samples according to JCV-DNA detection, MMP-9 plasma levels were significantly increased in JCV-DNA positive than JCV-DNA negative samples. MMP-9 plasma levels resulted positively correlated with JCV viral load. CD4 immune senescence, CD8 immune activation and CD8 effector percentages were positively correlated to MMP-9 plasma levels, whereas a negative correlation between CD8 naĂŻve percentages and MMP-9 plasma levels was found. Our data indicate an increase of MMP-9 plasma levels between 12 and 24 natalizumab infusions and a correlation with JCV-DNA detection in plasma, T-lymphocyte immune activation and senescence. These findings could contribute to understand PML pathogenesis under natalizumab treatment, suggesting a potential role of MMP-9 as a predictive marker of PML in RRMS patients
Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosis
Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment
Heart, COVID-19, and echocardiography.
AbstractAlthough clinical manifestations of coronavirus disease of 2019 (COVIDâ19) mainly consist of respiratory symptoms, a severe cardiovascular damage may occur. Moreover, previous studies reported a correlation of cardiovascular metabolic diseases with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and actually, many COVIDâ19 patients show comorbidities (systemic hypertension, cardioâcerebrovascular disease, and diabetes) and have a raised risk of death. The purpose of this review is to focus the cardiovascular effects of 2019ânCoV on the base of the most recent specific literature and previous learnings from SARS and MERS and analyze the potential role of echocardiography during the current critical period and shortâ and longâterm followâup
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