Search

To evaluate the dynamic changes of inflammation-related indices in blood during the development of venous thromboembolism (VTE) and the association between these indices and VTE.A total of 95 VTE hospitalized patients(41 males,54 females) were recruited from Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital from January 2010 to December 2010. Comparisons of inflammation-related indices including white blood cell (WBC), neutrophil (NE), fibrinogen (FBG), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were conducted between VTE patients and normal ranges. And the dynamic changes of these indices during the development of VTE were evaluated. Then they were divided into subgroups according to disease stage, gender, age, VTE type, body mass index, smoking status and clinical manifestations. And statistical analyses were performed to elucidate the associations between these indices and VTE.The levels of NE and CRP in VTE patients (0.72, 15.0 mg/L) and ESR in male VTE patients (20.0 mm/1 h) were elevated compared with normal ranges; while WBC (male 7.27×10(9)/L, female 8.67×10(9)/L), FBG (male 3621 mg/L, female 3201 mg/L) and female ESR (19.5 mm/1 h) in VTE patients were within the normal ranges. The level of CRP was higher in acute (mean rank order value: 49.72) and sub-acute (mean rank order value: 44.80) VTE patients than chronic VTE patients (mean rank order value: 30.25). The level of FBG, CRP and ESR in patients ≥ 50 years old increased versus those50 years old (mean rank order values 48.83 vs 34.53, 44.32 vs 28.90 and 45.95 vs 27.84 respectively), the patients whose body mass index (BMI)25 kg/m(2) had higher WBC level than those whose BMI ≥ 25 kg/m(2) (mean rank order values 52.96 vs 36.46); smoking VTE patients had elevated FBG and CRP levels than non-smoking VTE patients (mean rank order values 57.75 vs 42.69 and 53.92 vs 37.75 respectively); compared with those without clinical manifestations of periphery pulmonary artery involved, the patients with clinical manifestations had higher levels of FBG, CRP and ESR (mean rank order values 59.24 vs 37.39, 52.68 vs 33.19 and 50.08 vs 36.55 respectively). The above differences had statistical significance (all P0.05).Some inflammation-related indices frequently used in clinical settings become elevated in VTE patients. Part of these indices show higher levels in VTE acute and sub-acute stages, and in older, non-obese, smoking and periphery pulmonary artery involved VTE patients.

To evaluate the acute effects of inhaled iloprost on hemodynamics and oxygenation in chronic thromboembolic pulmonary hypertension (CTEPH).A prospective study was made. Eighteen patients with CTEPH were enrolled. At right heart catheterisation, iloprost was inhaled at 20 microg for 10 - 15 min. Compare the value of heart rate (HR), mean blood pressure (mBP), mean pulmonary arterial hypertension (mPAP), right atrium pressure (RAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), mixed venous saturation (SvO2), pulmonary shunt fraction (Qs/Qt), alveolar-arterial partial pressure of oxygen [P ( A-a) O2] before to after inhaled iloprost in these patients.Significant changes (before to after inhalation): mPAP, (53 +/- 11) to (47 +/- 14) mm Hg (P0.01); PVR, (821 +/- 194) to (681 +/- 199) dyn x s x cm(-5) (P0.01); RAP, (10 +/- 6) to (7 +/- 6) mm Hg (P0.01). However, HR, PAWP, mBP, CO and SVR had no significant changes. At the same time, inhaled iloprost significantly decreased PaO2 from (58 +/- 11) to (52 +/- 6) mm Hg (P0.01) and increased Qs/Qt from (27 +/- 11)% to (33 +/- 9)% (P0.01)and P(A-a) O2 from (86 +/-39) to (93 +/- 38) mm Hg (P0.01).Inhaled iloprost might instantly improve hemodynamics in CTEPH, but at the same time it increased arteriovenous shunts which resulted in lower PaO2.

To study the changes of blood coagulative and fibrinolytic system and the function of pulmonary vascular endothelium in the course of acute pulmonary thromboembolism (PTE) and after anticoagulant or thrombolytic treatment.Twenty patients with acute non-massive PTE, 10 males and 10 females, aged (57 +/- 11) underwent anticoagulant treatment and 17 sex-, and age-matched acute massive PTE patients underwent thrombolytic treatment. The plasma level of D-dimer (D-D), thrombomodulin (TM), protein C (PC), protein S (PS), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and antithrombin-III (AT-III) activity were measured by ELISA before and after normal subjects severed as control group were included in the study. The plasma level of D-D, PS, PC, TM, t-PA and PAI-1 were measured by a method of ELISA before the treatment and six days after the anticoagulant treatment or 24 hours after the thrombolytic treatment. AT-III activity was measured by chromo-substrate method at the same time points. Forty sex- and age-matched healthy persons were used as controls.The plasma levels of D-D, t-PA, PS, and TM level of the anticoagulant group were all significantly higher and the AT-III activity of the 2 treatment groups was significantly lower than those of the controls before treatment (all P0.05); the plasma levels of D-D, t-PA, PAI-1, PS, and TM of the thrombolytic group were ala significantly higher and the AT-III activity was significantly lower than those of the control group before the treatment (all P0.05). After anticoagulant therapy, the plasma levels of D-D, t-PA, PS, and PC were significantly lower than those before treatment (all P0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. The plasma levels of D-D, t-PA, PS, PC, and TM after treatment of the thrombolytic group were all significantly lower than those before treatment (all P0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment.Apparent imbalance in the blood coagulative and fibrinolytic system and pulmonary vascular endothelium damage occur in the patients with acute PTE. Combination tests of plasma D-D, AT-III, PS, PC, TM, t-PA and PAI-1 can give a more comprehensive explanation of the imbalance in the blood coagulative and fibrolytic system. Anticoagulant treatment and thrombolytic treatment play important roles in the regulation of the imbalance of coagulative and fibrinolytic system and protection of the function of pulmonary vascular endothelium of PTE patients.

To evaluate the short-term efficacy and safety of sildenafil in treatment of pulmonary artery hypertension (PAH).Literatures in regard to sildenafil treatment of PAH were searched in PubMed (from 01/01/1968 to 01/05/2006), Embase (from 1980 to 2006) and China National Knowledge Infrastructure (CNKI) (from 1994 to 2006). Randomized-controlled trials (RCTs) of sildenafil versus placebo in the treatment of PAH were conducted. The quality of the included trials was evaluated by two reviewers independently. Meta-analysis was done by using the Cochrane Collaboration's RevMan 4.2.8.Ten literatures were retrieved. Four RCTs, including 328 patients, were included and were graded in terms of the quality of randomization, allocation, concealment and blinding. One study was graded as level A and the other three were graded as level B. The meta-analysis showed that compared with placebo treatment, sildenafil therapy can (1) improve the exercise capacity of the PAH patients measured as distance covered in a 6 minute walk test with an increase of 55.76 meters on average in 6 minutes' walk (95% confidence interval, 41.26 to 70.25; P0.01), (2) increase the exercise time of the PAH patients by 221.13s on average (95% confidence interval, 146.13 to 296.14; P0.01), (3) decrease the pulmonary artery systolic pressure by 11.51 mmHg on average (95% confidence interval, 1.41 to 21.60, P = 0.03), and (4) alleviate the exacerbation of clinical conditions with a total odds ratio (OR) of 0.36 (95% confidence interval, 0.16 to 0.78, P = 0.01); however, it failed to alleviate the headache and hypotension in comparison with the placebo group. No sexual disturbance was seen in the patients treated with sildenafil.Sildenafil therapy improves the clinical symptoms and exercise capacity, and decreases the pulmonary artery systolic pressure of the PAH patients; and causes no serious side effects.

To determine the prevalence of polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphisms in Chinese Han population and to investigate whether they are associated with pulmonary thromboembolism (PTE).Samples of peripheral venous blood were collected from 101 patients with PTE diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography (CTPA) as well as medical history and clinical manifestations, 67 males and 34 females, aged 48 +/- 15, and 101 age and sex-matched healthy controls from the same geographic area as controls. The genome DNA was extracted from the whole blood using potassium iodide-phenol-chloroform method. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC), and sequence analysis were used to screen the single nucleotide polymorphisms and the genotype distribution of -675 4G/5G located in the promoter region of the PAI-1 gene.The frequencies of the allele 4G of PAI-1 gene in the controls were 0.495, significantly lower than in the PTE patients (0.733, chi(2) = 24.060, P0.01). The frequencies of the allele 5G of PAI-1 gene in the controls were 0.505, significantly higher than that in the PET patients. The genotype frequency of 4G4G of the PET patients was 57.4%, significantly higher than that of the controls (30.7%, P = 0.000). The genotype frequencies of 4G5G and 5G5G of the PET patients were 31.7% and 10.9% respectively, not significantly different from those of the controls (37.6 and 31.7% respectively). The presence of 4G allele of PAI-1 gene was found to be a greater risk factor for PTE. In comparison with the controls, the OR of 4G4G + 4G5G, 4G4G, and 4G5G in the PET patients were 3.794 (1.786 - 8.060), 5.443 (2.416 - 12.260), and 2.450 (1.067 - 5.623) respectively with the P values of 0.001, 0.000, and 0.035 respectively.The 4G/5G and 4G/4G genotypes are associated with the pathogenesis of PET.T.

To investigate the inhibitory effect of vascular endothelial growth factor (VEGF) antisense oligonucleotides or/and dalteparin sodium (fragmin) on tumor growth and metastasis of mice Lewis lung cancer.40 mice with Lewis lung cancer were randomizedly divided into five groups: control group, VEGF antisense oligonucleotides (ASODN) group, VEGF mismatch sense oligonucleotides (MSODN) group, low molecular weight heparin (LMWH) group, and combined group. Sodium chloride, VEGF-ASODN, VEGF -MSODN, fragmin, and VEGF-ASODN plus fragmin were given respectively (once every two days, 15 times altogether). The volume and weight of subcutaneous tumors were measured, and the rates of lung metastasis were detected by HE staining. The microvessel density (MVD) in tumor mass were measured by immunohistochemistry staining. VEGF protein level in tumor tissue were detected by Western blot assay.After treatment, the tumor growth inhibitory rates were 47.34%, 27.31% and 59.03%, and the rates of lung metastasis were 37.5%, 37.5% and 25% in ASODN, LMWH, and the combined group, respectively. Tumor MVD and VEGF protein expression of the above three groups were lower than those of the control group. There was a significant difference in regard to the tumor growth inhibitory rates and MVD between the above three treated groups and the control group as well as the MSODN group (P0.05).VEGF-ASODN and fragmin may down-regulate VEGF gene expression and inhibit angiogenesis, Combined use of fragmin can enhance anti- tumor effect of VEGF-ASODN.