Clinical trials with a new amoebicidal agent, AI 307.
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BACKGROUND: The aim of this study was to better delineate the characteristics, treatments and outcomes of patients with acute coronary syndromes in Emilia Romagna, a region of Italy, with 4 million inhabitants. METHODS: From January 10 to March 12, 2000, we performed a prospective survey (24/27 hospitals of the region) on 1074 consecutive patients with a discharge diagnosis of acute coronary syndrome. RESULTS: Based on the initial electrocardiogram, patients were classified as having an ST-elevation acute coronary syndrome in 41% of cases, a non-ST-elevation acute coronary syndrome in 54%, and an acute coronary syndrome with an undetermined electrocardiographic pattern in 5%. The discharge diagnosis was Q wave myocardial infarction in 43%, non-Q wave myocardial infarction in 26%, and unstable angina in 31% of patients. The use of antiplatelet, beta-blockers, ACE-inhibitors, and antithrombin agents for patients with ST-elevation acute coronary syndromes were 96, 62, 56, and 93%, respectively, with corresponding rates of 93, 63, 53, and 87% for non-ST-elevation acute coronary syndromes. During the initial admission, coronary angiography, percutaneous coronary intervention, and coronary bypass surgery were performed in 31, 15, and 1% of ST-elevation acute coronary syndrome patients, respectively, with corresponding rates of 43, 15, and 5% for non-ST-elevation acute coronary syndromes. Among patients with ST-elevation acute coronary syndromes, 61% received a reperfusion treatment; 58% coronary thrombolysis, and 3% primary percutaneous coronary intervention. The in-hospital mortality of patients with ST-elevation acute coronary syndromes was 10%, of patients with non-ST-elevation acute coronary syndromes 3%, and of patients with underdetermined electrocardiographic acute coronary syndromes 8%. At 6 months, the mortality rate increased to 16, 8, and 18%, respectively. CONCLUSIONS: Our data show the use of evidence-based pharmacological treatments in this population. This is associated with clinical outcomes which favorably compare with those observed in clinical trials. However, there is still room for improvement in the implementation of the invasive treatment.
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Efflux of [14C]cholesterol from various cells was monitored in the presence of discoidal complexes of egg phosphatidylcholine and purified apolipoproteins, containing either apoAI, AII, or Cs. Particles containing apoAI were more efficient acceptors than those containing apoAII or Cs when the donor cells were J774 macrophages. No differences were observed when the same acceptor preparations were exposed to Fu5AH rat hepatoma or rabbit aortic smooth muscle cells. The differential efficiency of apolipoproteins in stimulating cholesterol removal from J774 cells was maintained in a plasma membrane-enriched fraction isolated from the same cells. Nonlinear regression analysis of kinetic data obtained from J774 cells exposed to apoAI complexes indicated that cholesterol efflux was best fitted to a curve describing the release from two kinetic compartments. Approximately 10% of cholesterol was transferred from a rapidly exchangeable pool with a t1/2 ranging between 1.5 and 3 h, and the remaining fraction was released from a slower pool with a t1/2 of about 20 h. Modulation of cholesterol efflux from J774 cells by either varying the concentration or the apolipoprotein composition of the acceptors influenced the size of the pools and the t1/2 of the slow pool. Kinetics of cholesterol efflux from membranes isolated from J774 cells also best fit a two-compartment model and modification of the apolipoprotein composition of the acceptor induced a pattern of changes in pool size and half-time similar to that described for whole cells. In the three cell lines studied, we consistently resolved a slow pool with a half-time ranging between 15 and 20 h. In smooth muscle cells only the slow pool was evident, whereas in Fu5AH a very large fast pool was also resolved. In contrast to J774 cells, apolipoprotein composition of the acceptor did not influence the pools in these two cell lines. These results led us to propose a new model regarding the influence of multiple kinetic pools of cholesterol on the regulation of cholesterol desorption from the cell membrane.
The aim of this study was to determine the long-term changes in spine and trunk alignment in patients who have undergone scoliosis surgery. Twenty-three (16F; 7M; at age of surgery 15.7 +/- 4.9 years) patients with adolescent idiopathic scoliosis agreed to participate and had posterior-anterior radiographs and surface topography prior to derotation surgery, within 6 months of surgery, at 2 years post-operatively and 5-10 years (mean follow-up period 6.11 +/- 1.6 years) after surgery. Cobb angles, surface trunk rotations, and cosmetic scores were measured at each visit. A questionnaire assessed back appearance and pain at the 5-10 year follow-up. The results of the questionnaire were compared to 25 patients with idiopathic scoliosis who had recently undergone surgery. A paired two-tailed Student's t-test with p=0.05 was used to compare the deformity between visits. The Cobb angle and cosmetic score improved after surgery while the change in trunk rotation was insignificant (p=0.37). Between the two-year and 5-10 year review, the Cobb angle, cosmetic score, and surface trunk rotation significantly increased. Self-perception of appearance and pain were similar to the control group. Surgical correction of scoliosis is not completely maintained during adulthood although the radiographic and surface deterioration does not appear to be clinically significant.
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We have demonstrated previously that HDL-mediated efflux of plasma membrane cholesterol is independent of specific binding of apolipoproteins to the high density lipoprotein (HDL) receptor in either control or cholesterol-enriched cells (Karlin, J. B., Johnson, W. J., Benedict, C. R., Chacko, G. K., Phillips, M. C., and Rothblat, G. H. (1987) J. Biol. Chem. 262, 12557-12564 and Johnson, W. J., Mahlberg, F. H., Chacko, G. K., Phillips, M. C., and Rothblat, G. H. (1988) J. Biol. Chem. 263, 14099-14106). The present studies were conducted to determine if the process for removal of intracellular (lysosomal) cholesterol is similar to that of membrane cholesterol or if, in contrast, it is selectively regulated by specific apolipoproteins of HDL. For these reasons, we examined the influence of each of the major apolipoproteins of human HDL, apoAI, apoAII, and apoCs on the metabolism of membrane and lysosomal cholesterol in a macrophage foam cell model. We developed an experimental system which allows, for the first time, the simultaneous determination of lysosomal hydrolysis of cholesteryl ester and efflux and esterification of both lysosomal and membrane cholesterol. J774 and elicited mouse peritoneal macrophages were loaded with cholesteryl ester within lysosomes through phagocytosis of sonicated lipid droplets. Membrane and lysosomal pools of cholesterol were differentially radiolabeled. Discoidal complexes of egg phosphatidylcholine and purified apolipoproteins having a similar size and composition were used as cholesterol acceptors. Our results demonstrate that lysosomal hydrolysis of cholesteryl ester is independent of the presence of extracellular acceptors. Lysosomal production of cholesterol stimulates the esterification by acyl-CoA:cholesterol acyltransferase of membrane and lysosomal cholesterol. All the particles tested induce the efflux of both pools of cholesterol at a similar ratio. As efflux is stimulated, esterification by acyl-CoA:cholesterol acyltransferase is reduced. We conclude that none of these apolipoproteins selectively influences the efflux or the esterification of membrane of lysosomal cholesterol. In addition, we observe that particles containing apoAI are the most efficient acceptors, but this effect is not linked to specific binding to the HDL receptor.
H5N1 subtype influenza virus A/Duck/Shandong/093/2004 (A/SD/04) strain was chosen as the master strain for rescue research. 11 sets of primers for 8 plasmids construction were designed base on the sequencing of the full-length of A/SD/04. Eleven fragments of A/SD/04 were amplified by the designed primers and were ligated with PHW2000 for rescue plasmid construction. Eight transcription/expression plasmids were obtained, which encoded the eight segments of A/SD/04, and designated as 241, 242, 243, 244, 245, 246, 247 and 248, respectively. The COS-1 cell was cotransfected with eight plasmids with different combination of A/SD/04 and PR8. The eight reassortants shared the same HA (from A/SD/04) but contained different internal genes and NA. All of the eight reassorted viruses had some similar bio-characteristics, such as the viral title in fertilized eggs was range from 256 to 1024, the EID50 were between 10(-8.5) to approximately 10(-9), and MDT were between 34 to approximately 46h. But the IVPI of the eight reassortants was differently and all were lower than the wild-type A/SD/04. These results confirmed that different recombination of internal genes of H5N1 has influence on viral virulence to 6-week SPF chicken but not on viral replication ability in embryonated chicken eggs. The establishment of eight-plasmid rescue system for A/SD/04 is the base for farther research on genes function of H5N1. And A/SD/04 can be used as a backbone to replace PR8 entirely in generation of H5 AIV vaccine candidate.
In the present paper, the composition of complex Al-CAS-CTMAB was studied with the ratio of double peak values at dual-wavelengths by UV spectrophotometry. First, the composition of complex of Al-CAS was determined in this method, Al:CAS = 1:2. The absorption of ternary complex(Al-CAS-CTMAB) was determined with reference reagent of the complex Al-CAS. The epsilon values of Al-CAS and Al-CAS-CTMAB were determined with water reference. The composition of complex Al (CAS)n1 (CTMAB)n2 was calculated with the formula: [formula: see text] CAS:CTMAB = 1:1; Al:CAS:CTMAB = 1:2:2. The calculated value and that obtained by traditional method are agreeable. The method is reliable for determining composition of ternary complexes.
UNLABELLED: A new questionnaire (The Bad Sobernheim Stress Questionnaire BSSQ) has been developed to assess the psychological stress scoliosis patients develop as a consequence of their deformity. The aim of this study was to determine this stress level in a sample of adolescents with scoliosis. MATERIALS AND METHODS: 206 Patients were recruited to the study and completed a questionnaire (8 items). The average age was 15.7 years with an average Cobb angle of 35.8 degrees. All subjects returned a fully completed questionnaire. Plausibility of the results was assessed by examining for consistent responses to two plausibility questions. RESULTS: The average stress value was 19.97 / 24, which can be regarded as "low stress". The average stress value in the group meeting the plausibility threshold (n = 155) was 21 / 24 while the average stress value in the group not meeting the threshold (n = 51) was 15.9 / 24, regarded as "medium stress". This correlated negatively with the Cobb angle (r = -.54; p < 0,001). The Cobb angle / test value correlation was highest in thoracic curves (n = 87; r = -.49; p < 0,001) and lowest in double major curves (n = 46; r = -.27; p = 0,03). CONCLUSIONS: Adolescents with scoliosis have on average only "low stress" associated with their deformity. Not fulfilling a plausibility threshold seems to be a predictor for more stress associated with the scoliotic deformity.
This study is part of a larger project regarding the development of a Spine Surgery Simulator (S3), which has shown good results for posterior instrumentation surgeries. The aim was to develop a biomechanical model for the anterior instrumentation of the scoliotic spine. A biomechanical model using flexible mechanism was developed and surgical manoeuvres (instrumentation, rod installation and compression) were reproduced. Validation of the model was done by comparing the results for the instrumented part of the spine to the post-operative data (analytical Cobb angles in the frontal and sagittal planes, plane of maximum deformity, etc.). To date, surgeries of four patients operated by thoracotomy were reproduced. Preliminary results show that anterior instrumentation of the scoliotic spine can be adequately modelled using pre-operative geometric data and using mechanical properties from literature. Once validated with a larger sample of cases, the anterior instrumentation model could be implemented into S3 and used by orthopaedic surgeons to test various instrumentation strategies in virtual reality before performing the actual surgery.
The authors describe the production, via recombinant DNA technology, of bifunctional polypeptides for immunoenzymatic assays. These molecules contain an apolipoprotein moiety fused to an active beta-galactosidase enzyme, and are used as tracers in competition assays with specific monoclonal antibodies. The final colorimetric result is inversely correlated with the apolipoproteins plasma values. This technology, named RIECA (Recombinant Immunoenzymatic Competition Assay) is very accurate and flexible and may be applied to a wide range of diagnostic interest.
The levels of total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B in the serum were measured in a selected series of 100 CAD patients (77 men and 23 women) who underwent coronary angiography and 141 non-CAD controls. Mean values of those variables differed significantly between the CAD and non-CAD groups matched in age, body weight, hypertension and smoking. There are significant difference in apolipoproteins A1, B and the ratio of apolipoprotein B to A1 between angina and myocardial infarction groups. Using stratified and multivariate stepwise regression analysis, it was shown that the apo A1, apoB/apoA1 are more sensitive and specific than the ordinary indices (e.g. total cholesterol, triglycerides, LDL-C and HDL-C) in estimating the degree of coronary artery stenosis and the differentiation of CAD from other diseases.
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Effects of BAI therapy on 86 cases of lung cancer were evaluated in three groups: single-use of MMC group after intravenous PEP administration (PEP (iv).MMC group), PEP and MMC combination use group (PEP + MMC group) and single use of MMC group. Tumor regression rate determined by chest X-ray film 2 or 3 weeks after BAI was highest in the PEP (iv).MMC group followed by the PEP + MMC and MMC group. Cavity formation was more typical in the group treated with PEP + MMC. Histopathological effects were best for the PEP + MMC group followed by those of the PEP (iv).MMC and MMC group. As for side effects, pulmonary fibrosis and necrotizing bronchitis were noted in 8% of the PEP + MMC group, but side effects in the other two groups were mild. In conclusion single use of MMC after intravenous PEP administration was found to be the best way to give BAI in these three groups.