Pulmonary Emboli and Deep Venous Thrombosis during Adolescence

Pulmonary emboli (PE) and deep venous thrombus (DVT) are two conditions considered to affect primarily adults. These conditions, however, can and do affect neonates, toddlers, school-age children, and adolescents. Factors contributing to the development of PE and DVT are often associated with genetic mutations in Antithrombin III, Protein C, and Protein S. This article presents a primary care case study of an adolescent who was diagnosed with and underwent treatment for bilateral PE and a DVT, and reviews the underlying primary genetic mutations, diagnostic workup, and management of his clinical condition.     

Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application

Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complement activity. Consistently, subsequent genetic and pharmacological studies in rodents have implicated the central complement component C3 and downstream signaling pathways in periodontal host-microbe interactions that promote dysbiosis and inflammatory bone loss. This review discusses these mechanistic advances and moreover focuses on the compstatin family of C3 inhibitors as a novel approach to treat periodontitis. In this regard, local application of the current lead analog Cp40 was recently shown to block both inducible and naturally occurring periodontitis in non-human primates. These promising results from non-human primate studies and the parallel development of Cp40 for clinical use highlight the feasibility for developing an adjunctive, C3-targeted therapy for human periodontitis.     

Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

Thalidomide (TM) has been reported to have anti‐cancer and anti‐inflammatory properties, and dexamethasone (DX) is known to reduce inflammation and inhibit production of inflammatory cytokines. Many studies have reported that combinatorial therapy with TM and DX is clinically used to treat multiple myeloma and lupus nephritis, but the mechanism responsible for its effects has not been elucidated. In this study, we determined that TM and DX co‐treatment had an enhanced immune‐modulatory effect on T cells through regulating the expression of co‐stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort‐purified and cultured for CD4⁺ T cell proliferation and regulatory T (Treg) cell conversion in the presence of TM and/or DX. Following incubation with the drugs, cells were collected and OX40, 4‐1BB, and glucocorticoid‐induced tumour necrosis factor receptor‐related protein (GITR) expression was quantified by flow cytometry. TM (1 or 10 μm ) decreased CD4⁺ T cell proliferation in a dose‐dependent manner, whereas TM/DX (0·1 or 1 nm ) co‐treatment further decreased proliferation. Treg cell populations were preserved following drug treatment. Furthermore, expression of co‐stimulatory molecules decreased upon TM/DX co‐treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic CD4⁺ T cells isolated from TM‐ and DX‐treated mice exhibited the same patterns of Teff and Treg cell populations as observed in vitro. Considering the selective effect of TM on different T cell subsets, we suggest that TM may play an immunomodulatory role and that TM/DX combinatorial treatment could further enhance these immunomodulatory effects by regulating GITR, OX40, and 4‐1BB expression in CD4⁺ T cells.     

Myasthenia gravis after allogeneic bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells

A patient who developed myasthenia gravis (MG) 25 months after allogeneic bone marrow transplant was immunologically analyzed. OX40+CD4+ T cells in the peripheral blood prominently increased one month before the onset of MG. CD4/CD8 ratios, usually abnormally inverted in patients with chronic graft-vs.-host disease (cGVHD), showed pseudonormalization during the course of MG. We succeeded in uneventful rapid tapering of prednisolone (PSL) using mycophenolate mofetil (MMF). Monitoring of OX40+CD4+ T cells supported the tapering of PSL and MMF as a marker of cGVHD activity. This case suggested the utility of MMF and monitoring of OX40+CD4+ T cells in the management of cGVHD-associated autoimmune diseases.     

Efficacy of plasma exchange therapy for Kawasaki disease intractable to intravenous gamma-globulin

Kawasaki disease (KD) causes coronary artery lesions (CALs) in 500 Japanese children each year. Intravenous gamma-globulin (IVGG) decreases the incidence of these lesions from 25% to 8% of the total KD cases. We examined whether plasma exchange is a safe and effective prophylaxis against CALs in children with KD intractable to IVGG therapy. Eighty-nine children with KD at high risk of CALs were selected on the basis of increases in fractional changes in inflammatory markers such as white blood cell count, neutrophil count, and C-reactive protein between the baseline and 1–2 days after IVGG treatment. Of 105 children who received a second course of IVGG therapy because the initial course was ineffective, plasma exchange (PE) was performed in 46 children who had not responded to the second IVGG treatment. The outcome was compared with the results when a third course of IVGG therapy was given to the other 59 children. No complications occurred with the plasma exchange therapy. CALs developed in only 8 of the 46 children (17.3%) who underwent plasma exchange, but they occurred in 24 of the 59 (40.7%) who had received a third course of IVGG therapy (P 0.0012). We concluded that PE was a safe, effective prophylactic measure against CALs in children with KD intractable to IVGG therapy. PE should be performed at an early stage, as soon as fractional increases in inflammatory markers are found after IVGG therapy.     

Clinical profile,management and outcome of pulmonary embolism in Shahid Gangalal National Heart Centre,Kathmandu, Nepal

Background and aims

Pulmonary embolism (PE) is associated with a significant mortality and morbidity. We aim to study clinical profile, management and outcome of PE at Shahid Gangalal National heart Centre, Kathmandu, Nepal.

CD40反义RNA对系统性红斑狼疮患者B淋巴细胞功能的影响

目的　探讨瞬间表达的CD4 0反义RNA对EB病毒转染的系统性红斑狼疮 (SLE)患者B淋巴细胞CD4 0分子表达、细胞增生以及免疫球蛋白 (Ig)分泌功能的影响。 方法　构建人CD4 0反义RNA的真核表达载体CD4 0 /pcDNA3,并将其转染入EB病毒转染的SLE患者B淋巴细胞中。应用流式细胞仪 (FACS)检测观察B淋巴细胞膜上CD4 0分子表达的变化 ;应用四甲基偶氮唑盐微量酶反应比色法 (MTT)观察反义CD4RNA对B淋巴细胞增生能力的影响 ;应用酶联免疫吸附试验(ELISA)测定转染后的B淋巴细胞的Ig分泌功能。结果　与转染pcDNA3空载体组相比 ,转染CD4 0 / pcDNA3组的CD4 0分子的表达明显降低 (P <0 0 1) ;细胞的增生能力明显降低 (P <0 0 5 ) ;细胞的Ig分泌功能明显受抑制 (P <0 0 1)。结论　CD4 0反义RNA对SLE患者的B淋巴细胞有明显的免疫调控作用。     

Echocardiographic criteria for aortic root dissection.

Echocardiographic findings from 10 patients without clinical indications of aortic root dissection or aortic valve disease from 1 patient with angiographic confirmation of aortic root dissection are reported and compared. Previously reported echocardiographic findings were confirmed in the patient with aortic root dissection. These include (1) a widened posterior or anterior aortic wall, or both; (2) parallel motion of the separated margins of the aortic walls; and (3) aortic root dilatation (42 mm or more at end-systole). However, all three findings were also noted in 5 of the 10 patients without clinical indications of aortic root dissection or aortic valve disease, and at least two of the three findings were noted in the remaining 5 patients. Echocardiographic detection of aortic root dissection appears to be most reliable when clinical indications of the anomaly are present.