RESUMO
Idiopathic Spinal Cord Herniation (ISCH) is considered to be a rare cause of Thoracic Myelopathy. It is secondary to the gliding of the Spinal Cord through an anterior dural defect, without a completely defined cause. We present a case of ISCH which, even though was in its usual location, developed in a woman at a younger age than expected. The patient was 20 years old when diagnosed with Brown-Séquard Syndrome. MRI showed herniation at T4-T5 level, which was corrected using a posterior approach to expose the dural defect, reduce the herniation and place a heterologous graft. Postoperatively, neurological function improved, and adequate reduction was seen on imaging. Given the reports of recurrence and deterioration that have been seen after 18 months, follow-up was prolonged for a total of 2 years. We consider postoperative MRI performance important to establish the degree of reduction and alignment of the Spinal Cord.
Assuntos
Síndrome de Brown-Séquard/diagnóstico , Hérnia/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico , Medula Espinal/patologia , Feminino , Herniorrafia/métodos , Humanos , Laminectomia/métodos , Imageamento por Ressonância Magnética , Doenças Raras , Doenças da Medula Espinal/fisiopatologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carmustina/uso terapêutico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno AC133/genética , Antígeno AC133/metabolismo , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Carmustina/efeitos adversos , Proteína 1 Semelhante à Quitinase-3/genética , Colômbia , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Esquema de Medicação , Feminino , Genes erbB-1 , Genes p53 , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Masculino , Metilação , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , RNA Mensageiro/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Análise de Sobrevida , Proteínas Supressoras de Tumor/metabolismo , Adulto JovemRESUMO
Biomarkers are increasingly used for diagnosis and treatment of transplant-related complications including the first biomarker-driven interventional trials of acute graft-versus-host disease (GvHD). In contrast, the development of biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of manifestations, overlap with acute GvHD, a greater variation in time to onset and maximum severity, and lack of sufficient patient numbers within prospective trials. An international workshop organized by a North-American and European consortium was held in Marseille in March 2017 with the goal to discuss strategies for future biomarker development to guide cGvHD therapy. As a result of this meeting, two areas were prioritized: the development of prognostic biomarkers for subsequent onset of moderate/severe cGvHD, and in parallel, the development of qualified clinical-grade assays for biomarker quantification. The most promising prognostic serum biomarkers are CXCL9, ST2, matrix metalloproteinase-3, osteopontin, CXCL10, CXCL11, and CD163. Urine-proteomics and cellular subsets (CD4+ T-cell subsets, NK cell subsets, and CD19+CD21low B cells) represent additional potential prognostic biomarkers of cGvHD. A joint effort is required to verify the results of numerous exploratory trials before any of the potential candidates is ready for validation and subsequent clinical application.
Assuntos
Biomarcadores/metabolismo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , PrognósticoRESUMO
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved agents in GVHD underscore the importance of developing novel therapies. Better understanding of the biology of chronic GVHD has provided novel targets for treatment, and structured guidelines in diagnosis and in clinical trial design have provided a common language and pathways for research in this area. These, combined with the surge of drug development in Oncology and Immunology, are factors that have contributed to the accelerating field of drug development and clinical research in chronic GVHD. In these exciting times, it is possible to foresee long awaited advances in the treatment of this devastating complication of HCT. This review will summarize the ongoing clinical development for novel therapies in chronic GVHD.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Animais , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Biomarcadores , Doença Crônica , Descoberta de Drogas , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Janus Quinases/antagonistas & inibidores , Elastase de Leucócito/antagonistas & inibidores , Terapia de Alvo Molecular , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Transplante HomólogoRESUMO
The objective of the study was to determine the efficacy of vitamin C in reducing serum uric acid (UA). This study was a double-blind placebo-controlled randomized trial conducted in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh from July 2007 and August 2008. Study participants were included from out patient department (OPD) of Rheumatology of BSMMU suffering from various Rheumatological problems other than gouty arthritis. All of the participants were non-smokers, non-alcoholics, and randomized to take either placebo or vitamin C (500 mg/day) for 12 weeks. A total of 98 subjects were enrolled in the study; 71 completed the trial, with 34 in the placebo group and 37 receiving vitamin C. Serum uric acid levels were not significantly reduced in the experimental group and they increased in the placebo group. In the vitamin C group, the mean change was -0.32mg/dl [95% confidence interval -0.73, 0.77], whereas in the placebo group, the mean change was +0.12mg/dl [95% confidence interval was -0.22, 0.47]. Subgroups were defined by sex, body mass index, and quartiles of baseline serum uric acid levels. In a subgroup analysis, vitamin C lowered serum uric acid significantly in those who had comparatively higher baseline uric acid levels. Although vitamin C did not lower serum uric acid significantly, participants with higher baseline serum uric acid levels experienced a significant uric acid lowering effect, but as the sample size was very small, it is difficult to draw any definitive conclusion.
Assuntos
Ácido Ascórbico/farmacologia , Bangladesh , Método Duplo-Cego , Humanos , Ácido Úrico , VitaminasRESUMO
BACKGROUND: Uveitis refers to intraocular inflammation. The pattern of uveitis is largely influenced by a multitude of factors including genetic background. AIM: The purpose of our study was to identify the association between the polymorphism of the transmembrane region of MICA (MICA-TM) and uveitis in Tunisian patients with intraocular inflammation. PATIENTS AND METHODS: A total of 79 Tunisian patients and 123 healthy controls were enrolled in our study. HLA-class I phenotyping was performed by microlymphocytotoxicity complement dependent and MICA-TM was genotyped by a semiautomatic fluorescent-labelled PCR method, amplicons were analysed on ABI Prism 310 genotyper. Comparisons of allele frequencies between patients and controls, and between patients' subgroups were performed using SPSS 20.0. RESULTS: In our 79 patients, HLA-B27 showed a significant increased frequency when compared with healthy controls (P=0.003, 7.88 [95% IC=2.17-28.65]). The association was more significant when considering idiopathic anterior uveitis (P=0.00002, OR=11.65 [95% IC=3.06-45.17]). No MICA allele was significantly increased in uveitis groups compared to controls. In the idiopathic uveitis group, MICA-A4 was associated with late age of onset of disease (P=0.04). HLA-B51 and MICA-A6 were associated respectively with severe tyndall (P=0.008) and with the presence of synechiae (P=0.007). CONCLUSION: Some clinical features of uveitis may be influenced by specific MICA-TM alleles. In our South Tunisian population, MICA plays a disease modifying role, rather than being an important gene in the susceptibility for developing of uveitis.
Assuntos
Estudos de Associação Genética , Antígenos de Histocompatibilidade Classe I/genética , Uveíte/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/química , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estrutura Terciária de Proteína/genética , Tunísia/epidemiologia , Uveíte/epidemiologiaRESUMO
Activation and migration of regulatory T cells (Treg) into tissue is critical in control of inflammation, but has not been examined extensively in chronic graft versus host disease (cGVHD). In parallel studies of tissues and blood, we determined that FoxP3(+) T cells increased in proportion to T effectors (Teff) in tissue infiltrates in oral and cutaneous lichenoid cGVHD. These FoxP3(+) cells expressed distinguishing phenotypic and functional markers of Treg (CD3(+), CD4(+), CD27(+), ICOS(+) and CD39(+)), not found on FoxP3(-) Teff. Both Teff and FoxP3(+) Treg expressed T-bet and the chemokine receptor CXCR3, however, consistent with a common mechanism of chemokine-mediated migration into tissue. Furthermore, functional markers (ICOS and CD39) and chemokine receptors (CXCR3) were both present in a higher proportion of FoxP3(+) cells in tissues than in peripheral blood, consistent with recruitment and activation of Treg in cGVHD target tissues. Finally, the 'activated' CD45RA(-)FoxP3(hi) subset of Treg cells, which highly express functional markers, were found in comparable frequencies in cGVHD patients and normal controls, despite a significant deficit in naive 'resting' Treg. These findings are consistent with Treg capacity to upregulate functional markers and traffick into tissue in cGVHD.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Doença Enxerto-Hospedeiro/imunologia , Linfócitos T Reguladores/citologia , Adolescente , Adulto , Idoso , Antígenos CD/metabolismo , Apirase/metabolismo , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CXCR3/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto JovemRESUMO
BACKGROUND: Short sleep has been implicated in higher risk of obesity in humans, and is associated with insulin resistance. However, the effects of fragmented sleep (SF) rather than curtailed sleep on glucose homeostasis are unknown. METHODS: Wild-type and NADPH oxidase 2 (Nox2) null male mice were subjected to SF or sleep control conditions for 3 days to 3 weeks. Systemic and visceral adipose tissue (VAT) insulin sensitivity tests, glucose tolerance test, fluorescence-activated cell sorting and immunohistochemistry for macrophages and its sub-types (M1 and M2), and Nox expression and activity were examined. RESULTS: Here we show that SF in the absence of sleep curtailment induces time-dependent insulin resistance, in vivo and also in vitro in VAT. Oxidative stress pathways were upregulated by SF in VAT, and were accompanied by M1 macrophage polarization. SF-induced oxidative stress, inflammation and insulin resistance in VAT were completely abrogated in genetically altered mice lacking Nox2 activity. CONCLUSIONS: These studies imply that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of insulin resistance via activation of oxidative stress and inflammatory pathways, thereby opening the way for therapeutic strategies.
Assuntos
Tecido Adiposo/metabolismo , Inflamação/metabolismo , Resistência à Insulina , Macrófagos/metabolismo , NADPH Oxidases/metabolismo , Privação do Sono/metabolismo , Animais , Teste de Tolerância a Glucose , Humanos , Imuno-Histoquímica , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Transdução de Sinais , Privação do Sono/complicaçõesRESUMO
AIMS/HYPOTHESIS: Gestational exposures such as dietary changes can alter offspring phenotype through epigenetic modifications and promote increased risk for specific diseases, such as metabolic syndrome. We hypothesized that high-fat diet (HFD) during late gestation would lead increased risk for insulin resistance and hyperlipidemia via associated epigenetic alterations in tissue adipocytokine genes. METHODS: Offspring mice of mothers fed a HFD during late gestation (HFDO) were weighed and their food intake measured weekly till age 20 weeks at which time glucose and insulin tolerance tests, plasma lipid and adipocytokine levels were assessed, as well as mRNA expression in visceral fat. Adipocytokine gene methylation levels in visceral fat, liver and muscle were also assayed. RESULTS: HFDO mice had increased weight accrual and food intake, and exhibited insulin resistance, hyperlipidemia and hyperleptinemia, as well as hypoadiponectinemia. Furthermore, increased methylation of adiponectin and leptin receptor, and decreased methylation of leptin genes with unchanged glucagon-like peptide-1 methylation patterns emerged in HFDO mice. CONCLUSIONS: Taken together, late gestational HFD induces increased risk of metabolic syndrome in the progeny, which is coupled with hypoadiponectinemia as well as with leptin resistance, and concomitant presence of selective tissue-based epigenetic changes among adipocytokine genes.
Assuntos
Adiponectina/deficiência , Adiponectina/metabolismo , Dieta Hiperlipídica , Síndrome Metabólica/metabolismo , Erros Inatos do Metabolismo/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Acetilação , Animais , Animais Recém-Nascidos , Peso Corporal , Epigênese Genética , Feminino , Teste de Tolerância a Glucose , Insulina/metabolismo , Resistência à Insulina , Leptina/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Gravidez , Fatores de TempoRESUMO
Pemphigus foliaceus (PF) is an autoimmune blistering skin disease that partly results from genetic factors, especially from human leucocyte antigen (HLA) class II genes. Several data have reported the involvement of microsatellite (STR) markers across different regions of the HLA in many auto-immune diseases. To test the hypothesis of the existence of a major HLA haplotype predisposing to PF, we analyzed six polymorphisms of microsatellite loci at 6p21.3-21.4 spanning HLA: D6S291, D6S273, TNFa, MICA, D6S265 and D6S276 in 81 PF patients compared to 123 healthy individuals recruited from the south of Tunisia. In this study, after Bonferroni's correction, 3 STR alleles from the TNFa locus were associated with the disease: the allele TNFa(∗)2 (p(c) = 4.2×10(-6)) and, at a lower level, the TNFa(∗)5 (p(c) = 0.014) as susceptibility alleles and TNFa(∗)6 (p(c) = 0.014) as protective ones. Furthermore, the expression of the TNFa(∗)2/TNFa(∗)5 genotype seem to confer susceptibility to PF (p = 0.00001, OR = 11.25). Interestingly, no significant LD was found between TNFa2/TNFa5 alleles and DRB1(∗)03/DRB1(∗)04 alleles. However, the multivariant regression analysis indicates that both the HLA class II and the TNFa alleles remained significant (p < 0.001). Although, these findings rejected our hypothesis on the existence of HLA susceptibility haplotype, they assessed the role of TNFa loci. Accordingly, TNFa seem to contribute to the aethiopathogenesis of Tunisian endemic PF may be by the induction of a high TNFα production which is known to enhance the autoimmune cascade of the disease.
Assuntos
Cromossomos Humanos Par 6 , Cadeias HLA-DRB1/genética , Repetições de Microssatélites , Pênfigo/genética , Polimorfismo Genético/imunologia , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Loci Gênicos , Predisposição Genética para Doença , Cadeias HLA-DRB1/imunologia , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pênfigo/imunologia , Fator de Necrose Tumoral alfa/imunologia , TunísiaRESUMO
Chronic graft-vs.-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Oral cGVHD is manifested by mucosal, salivary, and/or sclerotic changes that have been linked to pain and poor quality of life. Our aim was to describe the demographic, clinical, and laboratory markers of oral cGVHD in alloHSCT patients (N = 187) enrolled in a cGVHD cross-sectional study at the NIH (#NCT00331968). We propose a meaningful and reproducible measure of disease defined by a cut-off point reflecting clinical minimally detectable change (0-2 = no oral cGVHD, 3-15 = oral cGVHD) on the 15-point NIH cGVHD clinician assessment scale. Forty-four patients had oral cGVHD. Oral cGVHD was associated with a quiescent or de novo type of cGVHD onset (p = 0.05), higher cGVHD severity (p = 0.033), lower albumin (p = 0.0008), higher total complement (p = 0.012), greater bother from foods or oral ulcers and greater mouth pain, and sensitivity (p < 0.0001). Multivariable logistic regression modeling with albumin, mouth pain, and total complement was 74.3% predictive of oral cGVHD and 80.2% predictive of non-oral cGVHD. We propose the use of >2 points on the NIH scale as a reproducible definition of clinically significant oral cGVHD, which may be useful in clinical settings or as eligibility criterion or as an endpoint in clinical trials.
Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Proteínas do Sistema Complemento/análise , Estudos Transversais , Progressão da Doença , Eritema/diagnóstico , Seguimentos , Alimentos , Previsões , Doença Enxerto-Hospedeiro/classificação , Humanos , Imunossupressores/uso terapêutico , Erupções Liquenoides/diagnóstico , Pessoa de Meia-Idade , Doenças da Boca/classificação , Mucocele/diagnóstico , Úlceras Orais/diagnóstico , Dor/diagnóstico , Albumina Sérica/análise , Estomatite/diagnóstico , Transplante Homólogo , Adulto JovemRESUMO
Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.
Assuntos
Proteína C-Reativa/análise , Doença Enxerto-Hospedeiro/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores , Doença Crônica , Complemento C3/análise , Estudos Transversais , Citocinas/sangue , Feminino , Doença Enxerto-Hospedeiro/sangue , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
There exists a need for effective salvage regimens for multiple myeloma patients being considered for reduced-intensity allogeneic hematopoietic SCT (RI-alloHSCT). We developed EPOCH-F, a regimen consisting of infusional etoposide, VCR and adriamycin with prednisone, CY and fludarabine to achieve both tumor control and host lymphocyte depletion to facilitate engraftment before RI-alloHSCT. In all, 22 multiple myeloma patients were treated with EPOCH-F before RI-alloHSCT. The median age was 53 years (range 36-65), and the median number of previous therapies was 2 (range 1-8). Patients received a median of three cycles (range 1-5) of EPOCH-F. Toxicities were primarily hematologic and manageable. Median lymphocyte counts decreased from 1423/µL (range 335-2788) to 519/µL (range 102-1420; P=0.0002). The overall response (≥PR) to EPOCH-F was 22 with 13% achieving a CR/near-complete response (nCR); only 1 patient progressed while on therapy. A total of 20 patients underwent RI-alloHSCT. Median day +100 donor chimerism was 100% (range 60-100). In all, 70% of patients achieved very good partial response or better response after transplant; 40% of patients achieved CR/nCR. TRM at 100 days and 5 years was 5 and 30%, respectively. Median OS after RI-alloHSCT was 46.1 months. EPOCH-F provides disease control and host lymphocyte depletion with consistent full donor engraftment in multiple myeloma patients undergoing RI-alloHSCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Terapia de Salvação/métodos , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/cirurgia , Prednisona/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vincristina/uso terapêuticoRESUMO
OBJECTIVE: To study HLA class I and class II association in Tunisian patients with reactive (ReA) and undifferentiated arthritis (UA). METHODS: The study included 17 patients with ReA defined according to the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), 11 patients classified as having undifferentiated arthritis and 100 unrelated healthy controls. HLA class I antigens were typed serologically and HLA class II alleles were genotyped molecularly by the polymerase chain reaction with sequence-specific primers technique. RESULTS: There was a major difference between HLA alleles in ReA and UA patients when compared separately with controls. Increased frequencies of HLA-B27 (p=7.76 10-12, OR=59.30), HLA-B51 (p=0.015, OR=4.91) and HLA-DRB1*04 (p=0.033, OR=2.90) alleles were found in patients with ReA but not in patients with UA. HLA-B27 was not expressed totally in our cohort of UA patients. A significant increase of HLA-B15 (p=0.002, OR=18.40) and a moderate increase of HLA-B7 (p=0.043, OR=5.15) was found in patients with UA, but not in patients with ReA. In the B27 negative patients, HLA-DRB1*04 association with ReA was found independently of B27. CONCLUSION: Our data confirmed a significant association of HLA-B27 with ReA in the Tunisian population. Our results also suggested that some of the additional HLA antigens were associated with ReA including HLA-B51 and HLA-DRB1*04 alleles. UA seemed to have a genetic background different from ReA in Tunisian patients.
Assuntos
Artrite Reativa/genética , Artrite/genética , Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Predisposição Genética para Doença , Adulto , Estudos de Casos e Controles , Feminino , Antígenos HLA-B/genética , Antígeno HLA-B15 , Antígeno HLA-B27/genética , Antígeno HLA-B51 , Antígeno HLA-B7/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-Idade , Proibitinas , Tunísia , Adulto JovemRESUMO
Adenovirus is a frequent cause of mild self-limiting upper respiratory tract infection, gastroenteritis, and conjunctivitis in infants and young children. Fatal infections (severe pneumonia progressing to respiratory failure, septic shock and/or encephalitis) are rare among immunocompetent adults. We report a case of severe adenovirus pneumonia in a young immunocompetent male who presented with sudden onset respiratory distress that progressed rapidly to respiratory failure and made a successful recovery on supportive measures. Systematic review of the literature identified 14 cases of severe adenovirus pneumonia (defined as respiratory failure requiring ventilatory support at any point during the course of illness) in otherwise healthy immunocompetent adults both in epidemic and community settings. We describe the clinical characteristics, radiological features, and outcome of identified cases.
Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/isolamento & purificação , Pneumonia Viral/virologia , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/terapia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Respiração Artificial , Insuficiência Respiratória , Ventiladores MecânicosRESUMO
Aging is associated clinically with increases in the frequency and severity of infectious diseases and an increased incidence of cancer, chronic inflammatory disorders and autoimmunity. These age-associated immune dysfunctions are the consequence of declines in both the generation of new naïve T and B lymphocytes and the functional competence of memory populations. These alterations collectively are termed immunosenescence.
Assuntos
Envelhecimento/imunologia , Imunidade Ativa/imunologia , Síndromes de Imunodeficiência/imunologia , Idoso , Animais , HumanosRESUMO
Trichosporon spp are well recognized as pathogens capable of causing invasive disease. Despite the increasing frequency and severity of trichosporonosis, data on the antifungal susceptibility of Trichosporon spp. are limited and recommendations for in vitro testing of this fungus are not included in the guidelines of the National Committee for Clinical Laboratory Standards. The purpose of this study was to determine the in vitro susceptibility of clinical Trichosporon isolates to systemic antifungals. We evaluated the in vitro activity of amphotericin B, fluconazole, itraconazole and voriconazole against 27 clinical isolates of Trichosporon spp. (14 T. mucoides and 13 T. asahii) using NCCLS M27-A2 reference microdilution, Etest and disk diffusion methods. In the microdilution and Etest methods Trichosporon spp. demonstrated relatively high minimum inhibitory concentrations (MICs) for fluconazole (MIC90 4 and 6 microg/ml, respectively) and relatively low MICs for voriconazole (MIC90 0.125 and 0.125 microg/ml, respectively). MICs for amphotericin B determined on antibiotic medium 3 were lower (MIC90 0.06 microg/ml) than those on RPMI (MIC90 1 microg/ml). Observed agreements were 81-100% according to these drugs. Disk diffusion zone diameters correlate inversely with MICs from dilution tests except for amphotericin B. Validation of the clinical significance of these observations demands determination of MIC breakpoints for Trichosporon and in vitro- in vivo correlation studies.
Assuntos
Antifúngicos/farmacologia , Técnicas Bacteriológicas/métodos , Trichosporon/efeitos dos fármacos , Meios de Cultura , Difusão , Farmacorresistência Fúngica , Estudos de Avaliação como Assunto , Humanos , Testes de Sensibilidade Microbiana , Técnicas de Tipagem Micológica , Micoses/diagnóstico , Micoses/tratamento farmacológico , Estudos de Amostragem , Sensibilidade e Especificidade , Trichosporon/classificaçãoRESUMO
Rheumatic fever remains a significant health problem in Jordan. We retrospectively reviewed medical charts of 28 boys and 22 girls (mean age at presentation 10.5 +/- 2.6 years) with confirmed diagnosis based on modified Jones criteria at Queen Alia Heart Institute from February 1999 to February 2002. Arthritis was the commonest major manifestation (88%; 68% migratory), carditis was second commonest (48%; 8% silent carditis) and chorea was seen in 6%. None had subcutaneous nodules or erythema marginatum. The mitral valve was most commonly affected (80%); both mitral and aortic valves were affected in 25%. Pericarditis was seen in 12.5% and acute congestive heart failure in 4%. Practitioners should be aware of diverse clinical presentations and emphasize strict adherence to prophylaxis guidelines.
Assuntos
Febre Reumática/diagnóstico , Febre Reumática/epidemiologia , Doença Aguda , Adolescente , Distribuição por Idade , Antibacterianos/uso terapêutico , Criança , Proteção da Criança , Coreia/etiologia , Países em Desenvolvimento , Ecocardiografia Doppler , Eritema/etiologia , Feminino , Fidelidade a Diretrizes , Insuficiência Cardíaca/etiologia , Humanos , Jordânia/epidemiologia , Masculino , Pericardite/etiologia , Guias de Prática Clínica como Assunto , Saúde Pública , Estudos Retrospectivos , Febre Reumática/complicações , Febre Reumática/tratamento farmacológico , Sensibilidade e Especificidade , Distribuição por SexoRESUMO
El tumor fibroso solitario se localiza principalmente en la pleura. Su localización extrapleural es rara, en cabeza y cuello se han encontrado pocos casos, principalmente en los senos paranasales y rinofaringe. De igual manera es de presentación infrecuente la localización en los tejidos blandos de la órbita, la cual ha sido descrita recientemente. El objetivo de este informe es la presentación clínica patológica y por imágenes de un caso tratado en la Fundación Santa Fe de Bogotá, en conjunto con la Clínica Barraquer