Thrombolytic-plus-anticoagulant therapy versus anticoagulant-alone therapy in submassive pulmonary thromboembolism [TVASPE study]: a randomized clinical trial

The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism [PTE] remains controversial We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE. We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin [1 mg/kg twice a day]] plus a thrombolytic [Alteplase [100 mg] or Streptokinase [1500000 u/2 hours]] or an anticoagulant [Enoxaparin [1 mg/kg twice a day]] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month. Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group [p value = 0.022]. At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group [p value = 0.018]; however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association [NYHA] functional class between the two groups at the end of the first month [p value = 0.213]. No fatal bleeding or cerebral bleeding occurred in the patients receiving an anticoagulant plus a thrombolytic. When given in conjunction with anticoagulants, thrombolytics may improve the clinical course of stable patients who have acute submassive pulmonary embolism and prevent clinical deterioration

5-fluorouracil induce the expression of TLR4 on HCT116 colorectal cancer cell line expressing different variants of TLR4

Two common single nucleotide polymorphisms [SNPs] of the human TLR4 gene, namely Asp299Gly [D299G] and Thr399Ile [T399I], have been shown to impair the ability of certain individuals to respond properly to TLR4 ligands. 5-Fluorouracil [5-FU] is widely used for the treatment of patients with advanced colon cancers. The present study examined the impact of two common polymorphisms of the TLR4 genes on the response of the HCT116 colorectal cancer cells to 5-FU. HCT116 was transfected with Flag-CMV1-TLR4 wild-type [WT] and D299G, T399I expression plasmids. The cytotoxic effect of 5-FU on transfected cells was assessed by MTT assay. FACS analysis was performed to show the effect of 5-FU and LPS on the expression of different variants of TLR4. The lowest IC[50]-value was measured in cells expressing the WT TLR4 and non-transfected cells were more resistance to the drug compared to the other cells. 5-FU significantly induced the expression of TLR4 protein in the presence and absence of LPS. 5-FU also induced HMGB1 secretion, Cas3 and PARP activity and these effects were stronger in cells expressing WT TLR4 than the other cells. In conclusion, 5-FU-induced TLR4 expression and LPS had synergistic effect with 5-FU to induced apoptosis in colorectal cancer cells

Seroprevalence of hepatitis A among students enrolled in Tehran University of Medical Sciences during 2011

Hepatitis A is often asymptomatic in children, however it can become a serious disease in adults. For countries that do not have a universal vaccination strategy targeted vaccination for high risk groups is recommended. Health workers could be at a higher risk of infection with hepatitis A virus [HAV] compared to the general population. The aim of this study is to investigate the seroprevalence of hepatitis A among enrolled students in Tehran University of Medical Sciences in 2011. This study included all students enrolled in Tehran University of Medical Sciences during 2011. We checked serum samples for anti-HAV antibody and participants completed a simple questionnaire. From 1864 health sciences students enrolled in Tehran University of Medical Sciences, 1813 samples were analyzed for anti-HAV IgG antibody. The results showed that 970 [53.5%] were seronegative, 722 [39.8%] were seropositive, and 121 [6.7%] were equivocal. There were significantly higher seropositive results for males [54%] compared to females [37%; RR = 1.46; 95% CI: 1.31-1.62]. The seroprevalence of HAV among enrolled medical science students is considerably lower than previous reports from Iran. Targeted vaccination for health sciences students prior to exposure should be seriously considered

Efficacy of HPV-16 E7 based vaccine in a TC-1 tumoric animal model of cervical cancer

The human papillomavirus as an etiological agent of cervical cancer does not grow adequately in tissue culture systems. The tumor cell line TC-1 continuously expresses the E6 and E7 oncogenic proteins of HPV, and is considered a suitable tool in laboratory investigations and vaccine researches against cervical cancer The TC-1 cell line was grown in RPMI 1650 supplemented with 10% FBS, glutamine and antibiotics, and was used for tumor development in mice. Six to seven week-old tumor bearing C57BL/6 mice were divided into 3 groups consisting of 7 mice per group. The first group received pcDNA-E7, the second group received pcDNAS, and the third group received phosphate buffered saline [PBS]. The treated animals were monitored for their tumor size progression and survival. At last, the tumoric tissues from autopsied animals were fixed and examined with Mayer's hematoxylin and eosin [H and E]. All experiments were done in accordance with guidelines of the Laboratory Animal Ethical Commission of Tarbiat Modares University. Data analysis was performed using the oneway ANOVA followed by Tukey's test in both experimental and control groups. A p-value <0.05 was considered significant. There were significant decreases in tumor growth; there were also improvements in survival among mice in the treated groups [p<0.041]. H and E stained sections from untreated mice were studied independently in a blinded fashion by two observers and showed malignant neoplasms composed of severely pleomorphic tumor cells with nuclear enlargement, high nuclear-cytoplasmic [N/C] ratios, and prominent nucleoli in solid and fascicular patterns of growth. High mitotic activity with extensive necrosis was also noted in both test and control groups. The TC-1 lung metastatic model can be used to test the efficacy of various E7-based therapeutic cancer vaccine strategies for cervical cancer and the prevention of HPV-related neoplasia

Immediate results and six-month clinical outcome after percutaneous coronary intervention in patients with prior coronary artery bypass surgery

Redo coronary artery bypass grafting surgery [CABG] is associated with a higher risk of mortality than the first operation. However, the impact of percutaneous coronary intervention [PCI] on the outcome in such patients is currently unclear. We evaluated the in-hospital and six-month clinical outcomes of post-CABG patients who underwent PCI in our center. Between April 2008 and July 2009, 71 post-CABG patients [16 women and 55 men] underwent 110 stent implantations [75% drug-eluting stents] for 89 lesions. Sixty percent of the PCI procedures were performed on the native coronary arteries, 32% on graft arteries, and 8% on both types of vessels. Major adverse cardiac events [MACE] were recorded in hospital and at six months' follow-up. The procedural success rate was 93%, and the in-hospital MACE rate was 5.6% [1 death, 3 myocardial infarctions]. At 6 months, the incidence of MACE WAS 5.6% [no death or myocardial infarction, but 4 target lesion revascularizations] and 4 [5.6%] in-stent restenoses. There was no statistically significant difference in the comparison of MACE between the patients treated in either native arteries or in the grafts [15% vs. 12%, p value =0.8]. According to the univariate analysis, hypertension and the use of the bare metal stent vs. the drug-eluting stent were the significant predictors of MACE, whereas the multivariate analysis showed that only hypertension [OR = 3.7, 95% CI 3.44-4, p value < 0.048] was the independent predictor of MACE. The mean of the left ventricular ejection fraction had no effect on the incidence of MACE [p value = 0.9]. The multivariate analysis showed hypertension [p value < 0.048] and the use of the bare metal stent [p value <0.018] were the independent predictors of MACE. The chronic total occlusion [CTO] [p value <0.01] was the independent predictor of the success rate. The prevalence of diabetes had no impact on the incidence of MACE according to the univariate analysis [p value= 0.9]. Our multivariate analysis showed that hypertension and use of the bare metal stent were the independent predictors of MACE and that chronic total occlusion was the independent predictor of the procedural failure rate. PCI is preferable to redo CABG for post-CABG patients. The independent predictors of MACE were hypertension and bare metal stents

Evaluation of the effect of elective percutaneous coronary intervention as a treatment method on the left ventricular diastolic dysfunction in patients with coronary artery disease

Although percutaneous coronary intervention [PCI] is an excellent therapy for coronary artery disease, there is a paucity of information on the efficacy of PCI in improving diastolic function, especially in Iran. Because of the high prevalence of left diastolic dysfunction in coronary artery disease patients and its probable progression to heart failure, an evaluation of the role of PCI in improving diastolic function is required. Thirty patients scheduled for elective PCI were enrolled in this study providing that their systolic ejection fraction was > 40%. Before PCI and 48 hours and 3 months after PCI, echocardiography was done to evaluate some diastolic values in these patients. The mean age of all the patients was 54 +/- 10 year, and 20 patients were male. All the patients had a low degree of left ventricular diastolic dysfunction. Isovolumic relaxation time [115 +/- 10 before treatment versus 120 +/- 1 and 119 +/- 3 respectively 48 hours and 3 months after treatment], mitral E wave velocity in septal [0.70 +/- 0.05 before treatment vs. 0.71 +/- 0.15 and 0.72 +/- 0.12 respectively 48 hours and 3 months after treatment], and the peak velocity of late filling due to atrial contraction [mitral A wave velocity] in septal [0.74 +/- 0.02 before treatment vs. 0.73 +/- 0.01 and 0.68 +/- 0.16 respectively 48 hours and 3 months after treatment] showed improvement after PCI. It is notable that early diastolic mitral annulus velocity [E'] wave velocity in the septal part of the mitral annulus improved significantly 48 hours and 3 months after PCI [p value < 0.05]. The early-to-late diastolic tissue velocity ratio of the mitral annulus [E/A] ratio of the mitral inflow improved 48 hours after PCI; it was statistically significant [p value = 0.05]. Also, mitral A wave velocity in septal and the E/A ratio of the mitral inflow improved significantly 3 months after PCI [p value < 0.05]. Improvement in some of values related to left ventricular diastolic function followed by PCI shows thai this method can be used to improve cardiac diastolic function in patients with symptomatic coronary artery disease