Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin's disease

CONTEXT and OBJECTIVE: Tumor cells in Hodgkin's disease (HD) express cell proliferation markers that are evaluated according to the oncogenes involved or the expression of their proteins. Correlations between the protein expression grade and clinical data are now important for disease prognosis.DESIGN and SETTING: This was a retrospective analysis on proliferating cell nuclear antigen (PCNA), p53 and MDM2 (murine double minute-2) expression using immunohistochemistry, on formalin-fixed, paraffin-embedded tissues from diagnostic biopsies on 51 patients with HID. the study was conducted at the Division of Hematology and Transfusion Medicine, Hospital São Paulo, Universidade Federal de São Paulo.METHODS: Antigen expression was evaluated as the proportions of positive Hodgkin and Reed-Sternberg (HRS) cells and reactive lymphocytes (L), which were compared using Spearman correlation coefficients. the Friedman test was used for comparisons between the markers. the Pearson test was used to investigate associations between marker expression and clinical and laboratory parameters, marrow involvement, complete remission (CR) and overall survival (OS) rates.RESULTS: There was overexpression of antigen proteins in HRS, in relation to L (p < 0.001). in HRS, MDM2 was higher than p53 and PCNA (p < 0.003), while the latter two were equivalent. in L, p53 was lower than MDM2 and PCNA (p < 0.001), while the latter two were equivalent. There was no relationship between protein expression and clinical and laboratory variables or outcome.CONCLUSIONS: PCNA, p53 and MDM2 are tumor markers for HID, but showed no clinical or prognostic significance in our analysis.Universidade Federal de São Paulo, Hosp São Paulo, Escola Paulista Med, Div Hematol & Transfus Med, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, Escola Paulista Med, Div Hematol & Transfus Med, BR-04023900 São Paulo, BrazilWeb of Scienc

Late recurrence of Burkitt’s lymphoma in the jaw: numb chin syndrome as the only symptom

The Numb Chin Syndrome (NCS) is defined as facial and oral numbness restricted to the mental nerve’s distribution involving the lower lip, skin of the chin, or gingiva of the lower anterior teeth. Hypoesthesia can occur unilaterally or bilaterally. Although this syndrome is rare, its importance is related to the fact that it represents the clinical manifestations of malignant diseases. Breast cancer and non-Hodgkin lymphoma are the most common cause of NCS. The patient, a 58-year-old woman, treated for a Burkitt Lymphoma (BL) nine years ago, described a two-week history of change in sensitivity and pain in the chin region, without relief with the use of analgesics. She had no headache, speech disturbance, dysphagia, visual disturbance, or other neurological symptoms. No surgical intervention has been performed recently. The intraoral examination revealed a healthy oral mucosa and a small area adjacent to the right mental nerve region that was uncomfortable to palpation. No changes were found in the bone trabeculae at cone-beam computed tomography. The contrasted magnetic resonance features made it possible to identify a change in the mandibular body extending to the entire right side, coinciding with the patient’s complaint, indicating a probable mandibular medullary invasion. The patient was submitted to a biopsy to rule out a possible recurrence of BL. The microscopic findings were consistent with the diagnosis of BL. The present report described a very unusual presentation of late recurrent BL nine years after the first treatment, which manifested as an NCS

Trombose venosa cerebral e hepatite: relato de caso

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.Dentre as várias causas infecciosas de trombose venosa cerebral (TVC), a hepatite viral tem sido reconhecida como causa rara de TVC. Relatamos sobre um homem de 56 anos com TVC associada a coinfecção pelos vírus B e C da hepatite, ressaltando possíveis mecanismos patogênicos. Sugerimos que sorologia para vírus da hepatite B e C deveria ser solicitado em todos os casos de TVC de origem indeterminada.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departments of NeurologyUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPM, Departments of NeurologyUNIFESP, EPMSciEL

Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P &lt; 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P &lt; 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT

Effect of B-vitamin supplementation in markers of thrombin generation, fibrinolysis and endothelial function in patients with venous thromboembolism: a randomized, double-blind, placebo-controlled trials

Background: Mild hyperhomocysteinemia is associated with an increased risk of venous thromboembolism (VTE) and other cardiovascular diseases. Previous studies suggest impaired endothelial function and increased thrombin generation in hyperhomocysteinemic patients. Whether decreasing homocysteine with B-vitamin supplementation interferes with its procoagulant effects is to be determined. Objectives: To evaluate the correlation between homocysteine and markers of thrombin generation and endothelial function and to evaluate the effect of lowering homocysteine by Bvitamin supplementation on these markers in patients with VTE. Patients/Methods: This study was a multicentre, randomized, double-blind, placebo-controlled trial. We randomized 105 patients with a first event of objectively confirmed VTE, aged between 18 and 70 years, to receive either vitamin supplementation (folic acid 5 mg, vitamin B6 50 mg and vitamin B12 0.4 mg) or placebo. Blood was collected at randomization and 8 weeks after the intervention period. Results: Ninety-nine (94.3%) completed the 8-week period of treatment. In patients treated with vitamins, there was a 29% decrease in the homocysteine levels and a significant increase in the tissue plasminogen activator (t-PA) levels (p=0.0008). Both t-PA and plasminogen activator inhibitor type 1 (PAI-1) levels significantly increased in the group of patients above the highest tertile of basal homocysteine (12.6 μmol/L) who received vitamin supplementation (p=0.0004 and p=0.014, respectively). There was no change in the levels of these two markers in patients with homocysteine levels below the lowest tertile or in patients who received placebo independently of the homocysteine level. All other markers (prothrombin fragment 1+2, thrombin-antithrombin complex, D-dimer, Factor VIII:C and von Willebrand factor antigen) were unaffected by both vitamins and placebo, even in patients above the highest tertile of homocysteine. There was no difference between patients with homocysteine above the highest tertile and those below the lowest tertile (9.9 μmol/L) in the levels of these markers. Conclusions: In patients with VTE, homocysteine reduction by B-vitamin supplementation significantly increased both t-PA and PAI-1 in patients with higher levels of homocysteine. However, there was no effect of homocysteine reduction by B-vitamin supplementation on other markers of endothelial function, fibrinolysis and thrombin generation.Introdução: Hiperhomocisteinemia leve está associada com aumento do risco de tromboembolismo venoso (TEV) e doenças cardiovasculares. Estudos anteriores sugerem associação entre níveis elevados de homocisteína e marcadores de disfunção endotelial, fibrinólise e geração de trombina. Não está ainda definido, entretanto, se a redução da homocisteína pela suplementação vitamínica é capaz de modificar o nível desses marcadores. Objetivos: Avaliar o efeito da suplementação vitamínica nos níveis de homocisteína e em parâmetros de ativação da coagulação, fibrinólise e função endotelial e avaliar a associação entre os níveis de homocisteína e os níveis de marcadores. Métodos: Nesse estudo randomizado, duplo-cego, controlado com placebo, 105 pacientes foram randomizados para receber suplementação vitamínica com folato 5 mg, vitamina B12 0,4 mg e piridoxina 50 mg por 8 semanas. Foram incluídos pacientes com TEV objetivamente confirmado, com idade entre 18 e 70 anos. Resultados: Foram avaliadas amostras basais de 104 pacientes e 99 (94,3%) completaram as 8 semanas de intervenção. Houve redução de 29% no nível de homocisteína dos pacientes tratados com suplementação vitamínica e elevação significativa de t-PA (ativador de plasminogênio tecidual) nesse mesmo grupo (p=0,0008). Não houve modificação nos demais parâmetros analisados (complexo trombina-antitrombina, fragmento 1+2 da protrombina, dímeros D, antígeno do fator de von Willebrand, fator VIII, fibrinogênio e inibidor do ativador de plasminogênio tipo-1 PAI-1). Quando analisamos apenas pacientes com níveis de homocisteína acima do tercil superior (12,6 μmol/L), observou-se que houve elevação tanto de t-PA como de PAI-1 no grupo que recebeu suplementação vitamínica (p=0,014 e p=0,0004, respectivamente). Foi ainda observada correlação positiva entre os níveis basais de homocisteína e os níveis basais de t-PA (r=0,2154). Não houve correlação entre a homocisteína e os demais parâmetros e não houve diferença entre pacientes com homocisteína acima do tercil superior e aqueles com homocisteína abaixo do tercil inferior (9,9 μmol/L) em relação ao nível dos demais marcadores. Conclusões: Em pacientes com TEV, a suplementação vitamínica causou elevação de t-PA e de PAI-1, ambos marcadores de lesão endotelial, em pacientes com níveis mais elevados de homocisteína. Não foi observado efeito da suplementação vitamínica sobre os demais marcadores de lesão endotelial, fibrinólise e geração de trombina.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 03/12387 - 5TEDEBV UNIFESP: Teses e dissertaçõe