Objective: To investigate the mechanism of scorpion venom active peptides(SVAPs) on platelet aggregation. Methods: Platelet aggregation in vivo and vitro was determined by turbidimetry. Carotid thrombosis model was induced by electrostimulation. The determination of 6 keto PGF 1 and TXB 2 were performed by radioimmunoassay. Results: SVAPs 0.125,0.25,0.5mg?ml -1 significantly inhibited the rabbit platelet aggregation triggered by thrombase 0.03u.ml -1 , ADP 10u.ml -1 in vitro( P

BACKGROUNDAdvances in catheter ablation procedures for the treatment of supraventricular arrhythmias have created the need to understand better the morphological and electrophysiological characteristics of the inferior nodal extension (INE) and transitional cellular band (TCB) in the atrioventricular (AV) junctional area.

METHODSFirstly, we observed the histological features of 10 rabbit AV junctional areas by serial sections under light microscopy. Then we recorded the action potentials (APs) of transitional cells (TCs) in the INE, TCBs, AV node, and ordinary right atrial myocytes from the AV junctional area of 30 rabbits using standard intracellular microeletrode techniques.

RESULTSUnder light microscopy, the INE appeared to be mostly composed of transitional cells linking upward to the AV node. Four smaller TCBs originated in the orifice of the coronary sinus, the region between the septal leaflet of the tricuspid valve and the coronary sinus, the inferior wall of the left atrium, and the superior interatrial septum, respectively, all linking to the INE or the AV node. Compared with ordinary atrial myocytes, the AP of the TCs in both the INE and the TCBs had a spontaneous phase 4 depolarization (not present in ordinary atrial myocytes), with a less negative maximum diastolic potential, a smaller amplitude, a slower maximum velocity of AP upstroke, and a longer action potential duration at 50% repolarization (APD50) and at 30% repolarization (APD30). The AP characteristics of these TCs were similar to those of the AV node, except that the velocities of the phase 4 spontaneous depolarization were slower and their action potential durations at 90% repolarization (APD90) were shorter. Moreover, APD50 and APD30 of the TCs of the TCBs were shorter than in the case of TCs of the AV node.

CONCLUSIONSThe TCs of the INE and TCBs are similar to slow response automatic cells. They provide a substrate for slow pathway conduction. In addition, repolarization heterogeneity exists in the AV junctional area.

Action Potentials ; Animals ; Atrioventricular Node ; cytology ; physiology ; Female ; Male ; Rabbits

BACKGROUNDEndostatin is a potent inhibitor of tumor angiogenesis. In the preliminary studies, we developed a mutant endostatin containing Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) sequences. In this study, we compared the antitumor effects of mutant endostatin and Bcl-2 antisense oligonucleotides both in combination and individually.

METHODSThe artificially synthesized Bcl-2 ASODN (antisense oligonucleotides) included a translation-initiation site and was transfected into the bladder cancer cells by Lipofectamine. Cell growth was investigated by the tumor cell growth chart, MTT assay, caspase-3 activity detection assay, AO/EB fluorescein stain, and the annexin V-FITC apoptosis detection assay. In the in vivo study, UM-UC-3 bladder cancer cells were subcutaneously implanted into nude mice and the growth of tumor was examined. The ultrastructure of the tumor tissues in the treated and control groups were observed.

RESULTSThe cell growth chart showed that the cell population of the treated combination group decreased by 52.04% compared to the control group. The inhibition rate of the treated combination group was (79.66 ± 6.79)%, whereas those of the individual ASODN and ES groups were (53.39 ± 3.22)% and (50.22 ± 5.46)% respectively. In the caspase-3 activity detection using AO/EB fluorescein stain and annexin V-FITC apoptosis detection assay, the co-inhibitory effect was higher than the individual inhibitory effects (P < 0.05). There were significant differences in the inhibition of the solid tumor growth in the in vivo study.

CONCLUSIONSOur findings indicated that Bcl-2 antisense oligonucleotides enhance the antitumor effects of mutant endostatin both in vitro and in vivo. We noted the synergistic effects of Bcl-2 antisense oligonucleotides combined with mutant endostatin.

Angiogenesis Inhibitors ; administration & dosage ; Animals ; Cell Line, Tumor ; Drug Synergism ; Endostatins ; administration & dosage ; Mice ; Thionucleotides ; administration & dosage ; Urinary Bladder Neoplasms ; pathology

OBJECTIVETo analyze the experiences on surgical treatment of severe aortic valve stenosis.

METHODSFrom December 1990 to December 2006, 171 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR). There were 135 males and 36 females aged from 10 to 75 years old, with a mean of (45.8 +/- 15.6) years old. The intervals between the first episode of exertion dyspnea and administration to operation were 2 months to 52 years. The pathological lesions of the group were rheumatic aortic valve stenosis in 75 cases, calcified aortic stenosis in 66 cases, bicuspid aortic valve in 26 cases and other congenital aortic valve stenosis in 4 cases. One hundred and twenty-four patients underwent AVR, 7 AVR combined with replacement of the ascending aorta, 5 AVR with coronary artery bypass grafting, 19 AVR with mitral valve plasty (MVP), 8 AVR with plasty of the ascending aorta and 8 AVR with enlargement of the aortic root.

RESULTSThe averaged operation time was (4.4 +/- 0.6) h. Cardiopulmonary bypass (CPB) time was (124.7 +/- 38.5) min and the aorta clamp time was (78.3 +/- 21.7) min. The averaged blood loss during operation was (754.5 +/- 518.4) ml. All the procedures were successfully performed and all patients were weaned off CPB uneventfully. The indication of early complications was 12.3% (21/171), including low cardiac output syndrome in 7 cases, multi-organ failure in 3 cases, endocarditis in 1 case, renal dysfunction in 4 cases, ventricular fibrillation in 1 case, excessive bleeding in 2 cases, III atrial-ventricular block in 2 cases, and mediastinal infection in 1 case. The total mortality was 5.8% (10/171) with the main causes as cardiac failure for 4 cases, arrhythmia for 1 case, multi-organ failure for 4 cases, and infectious endocarditis for 1 case.

CONCLUSIONSSuccessful management of severe aortic valve stenosis requires sophisticated surgical techniques and experienced peri-operative care. Satisfactory results can be achieved if valve replace surgery is performed adequately.

Adolescent ; Adult ; Aged ; Aortic Valve ; surgery ; Aortic Valve Stenosis ; surgery ; Child ; Female ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo identify the side effect of all-trans retinoic acid (ATRA), and improve early therapeutic response in patients with acute promyelocytic leukemia (APL).

METHODThe first case of Sweet's syndrome (SS) developed in a APL patient treated with ATRA was reported in mainland of China, and reviewed correlative literature.

RESULTSOnly 14 cases of SS associated with ATRA therapy in APL have been reported in the literature, including the present case. The median age was 49.5 years (9 -84) and 10 were women and 4 men. Of them, SS was restricted to the skin in 10 case, the other 4 muscle, fascia, kidney, and lung were involved. SS appeared after a median of 18 days of ATRA therapy (6 - 34 days). The median WBC count was 7.05 (0.80 - 23.00) x 10(9)/L. Four patients continued with the ATRA therapy without interruption, 13 patients treated with steroids and 12 responded. One patient improved without any treatment. Two cases of SS developed retinoic acid syndromes after ATRA therapy.

CONCLUSIONSweet's syndrome is a rare adverse effect of ATRA, and has similar features with inflammatory or infective dermatosis. The corticosteroids treatment could improve the systemic and cutaneous symptoms. When ATRA therapy was restarted after SS subsided, no recurrence of rashes was observed.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Sweet Syndrome ; chemically induced ; Tretinoin ; adverse effects ; therapeutic use

OBJECTIVETo investigate the incidence, risk factors, prognosis and high risk patients of invasive fungal infections (IFI) in patients with hematological diseases.

METHODS: Over 2-week hospitalized patients from January 2007 to December 2008 were retrospectively reviewed. Logistic regression was used to analyze the risk factors of IFI, and recursive partitioning to reveal high risk patients. Incidence of IFI was estimated by cumulative incidence function, and the prognosis by Kaplan-Meier method.

RESULTSA total of 1048 assessable treatment cycles were recorded and 93 cases of IFI were diagnosed, with an incidence of 8.87 per 100 treatment cycles. Multivariate logistic regression revealed the following risk factors: age (OR 1.025, 95% CI 1.010-1.041, P = 0.002), duration of neutropenia (OR 1.028, 95% CI 1.014-1.042, P < 0.0001) and uncontrolled underlying diseases (OR 2.620, 95% CI 1.608-4.268, P = 0.0001). Recursive partitioning found two groups of high risk patients: (1) patients with uncontrolled underlying diseases and neutropenia duration > or = 58 days (7/12, 58.3%), (2) patients with uncontrolled underlying diseases and age > or = 33 years (40/208, 19.2%). At the end of follow-up, 111 cases of IFI were recorded in 451 patients, with a 1-year cumulative incidence of 27.1%. In patients with established IFI, overall survival rate and IFI related mortality rate at 12 weeks after diagnosis were 83.4% and 13.5% respectively.

CONCLUSIONAge, duration of neutropenia and uncontrolled underlying diseases are risk factors of IFI; patients with uncontrolled underlying diseases and age > or = 33 years were at high risk of IFI and need major concern. IFI has a better prognosis and a lower related mortality in this study.

Female ; Hematologic Diseases ; diagnosis ; microbiology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Logistic Models ; Male ; Multivariate Analysis ; Mycoses ; epidemiology ; Prognosis ; Retrospective Studies ; Risk Factors

Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survival rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome of patients; application of imatinib before transplant and achievement of complete hematologic remission could not improve the prognosis; severe aGVHD among post-transplant events was proven to be a negative prognostic factor. It is concluded that for advanced CML patients received allo-HSCT, clonal evolution and blast percentage are prognostic factors, and the pre-transplant use of imatinib did not influence the outcome.
Adolescent ; Adult ; Benzamides ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; surgery ; therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Young Adult

This study was purposed to evaluate the outcome of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in complete remission, and to study the prognostic factors. 75 cases of AML in complete remission receiving allo-HSCT from January 2000 to December 2007 were retrospectively analyzed. Major end points of study included overall survival (OS), disease free survival (DFS), relapse rate and transplantation related mortality (TRM). The results showed that 3-year OS and DFS of the study population reached to 58.4% and 53.9% respectively, and the relapse rate and TRM leaded to 16.9% and 29.9% respectively. Incidence of acute GVHD was 59.6%, with 18.7% II-IV aGVHD. Different prognosis was observed between HSCT recipients of alternative donor and HLA-matched related donor (MRD) (3-year DFS was 34.3% vs 60.0%, p = 0.019), between patients of refractory leukemia and the control (3-year DFS was 35.7% vs 58.2%, p = 0.048), between recipients with and without severe aGVHD (3-year DFS was 35.7% vs 54.4%, p = 0.059). Further analysis revealed significantly high TRM in recipients receiving allo-HSCT of alternative donor (p = 0.033) and high rate of severe aGVHD (p = 0.010). Multivariate analysis revealed three negative prognostic factors: donor availability (alternative vs MRD) (p = 0.049, RR = 2.09, 95%CI 1.01 - 4.36), refractory leukemia (p = 0.038, RR = 2.33, 95%CI 1.05 - 5.20) and severe aGVHD (p = 0.040, RR = 2.33, 95%CI 1.04 - 5.20). It is concluded that allo-HSCT is a choice for the AML case at complete remission and TRM is the major cause of the transplantation failure. Donor availability, refractory leukemia and severe aGVHD are confirmed as risk factors of poor prognosis for allo-HSCT patients with AML in CR.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myeloid, Acute ; mortality ; surgery ; Male ; Middle Aged ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT.

METHODSWe used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008.

RESULTSRecipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other.

CONCLUSIONIn HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.

Adolescent ; Adult ; Alleles ; Child ; Child, Preschool ; Female ; Genotype ; HLA Antigens ; immunology ; Hematologic Diseases ; genetics ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-gamma ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Siblings ; Tissue Donors ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of leukemia relapsed after first allo-HSCT.

METHODSNine patients with relapsed acute leukemia (5 AML, 4 ALL) and one with chronic myelogenous leukemia (CML) who showed cytogenetic relapse after first allo-HSCT received second allo-HSCT. The median relapse time from the first allo-HSCT was 141 days. Conditioning regimens for second allo-HSCT were combination chemotherapy based on moderate-dose Ara-C (n = 5), Bu (n = 3), conventional-dose Ara-C (n = 1) and Flud/Mel (n = 1). Prophylaxis for acute graft-versus-host disease (aGVHD) were CsA alone (n = 2), CsA/MTX (n = 1), FK506 (n = 1), and no prophylaxis in 6. The median number of peripheral blood mononuclear cells transfused was 6.1 x 10(8)/kg.

RESULTSEight cases were evaluable. All of them were engrafted and 7 developed aGVHD (grade I 4, grade II 3). The median time for absolute neutrophil count (ANC) > 0.5 x 10(9)/L and platelets > 20 x 10(9)/L were 11 and 12 days, respectively. Five cases developed localized chronic GVHD. Of all the 10 cases received second allo-HSCT, 8 died from interstitial pneumonia (n = 2), multiple-organ failure (n = 1), sepsis (n = 1), fungous pneumonia (n = 1), and leukemia relapse (n = 3), and 2 survived without leukemia for +986 and +1913 days, respectively. The leukemia free survival, transplantation related mortality and relapse rate at 2 year were 20%, 50% and 30%, respectively.

CONCLUSIONSecond allo-HSCT is a therapeutic alternative for selected patients with relapsed leukemia after first allo-HSCT.

Adult ; Disease-Free Survival ; Female ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; pathology ; surgery ; Male ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome