三环氟喹诺酮类化合物的合成及抗菌活性

芦氟沙星(Rufloxacin)是氟喹诺酮类抗菌药物,由于它在体内有高效、广谱、长效和口服吸收良好等特点,我们在保留芦氟沙星母核基本骨架的基础上进行结构修饰,合成了12个新化合物。体外抑菌试验发现随着10位边链的极性增大,对革兰氏阴性(G^-)菌的抗菌活性增强,而对革兰氏阳性(G⁺)菌活性则变化不大。     

Individual differences in the use of the response scale determine valuations of hypothetical health states: an empirical study

Background  

The effects of socio-demographic characteristics of the respondent, including age, on valuation scores of hypothetical health states remain inconclusive. Therefore, we analyzed data from a study designed to discriminate between the effects of respondents' age and time preference on valuations of health states to gain insight in the contribution of individual response patterns to the variance in valuation scores.     

Premature chromosome condensation studies in human leukemia: 5. Prediction of early relapse

Previous reports have suggested that the technique of premature chromosome condensation (PCC) is useful for predicting relapse in patients with acute leukemia. However, these studies involved patients had been in complete remission (CR) for various periods of time and had heterogeneous expectations for relapse. The purpose of this study was to further determine the value of PCC in predicting relapse by examining the PCC characteristics of bone marrow specimens from patients with acute leukemia on a common therapeutic regimen after similar periods in CR. The remission durations after the PCC determinations were compared between patients with high or low proliferative potential indices (PPI, or the fraction of G1 cells in late G1 phase). Of 60 patients studied between two and eight weeks after achieving CR, 14 of the 16 patients exhibiting high PPI values (greater than or equal to 35) have relapsed. The mean time from PCC measurement to relapse was 23 weeks. In contrast, only 19 of the 44 patients exhibiting low PPI values have relapsed, with an estimated mean time to relapse of 68+ weeks. Likewise, of 38 patients studied between nine and 15 weeks of CR, nine of the ten patients exhibiting high PPI values have relapsed (mean time to relapse, 23 weeks), while only 16 of 28 patients with low PPI values have relapsed (estimated mean time to relapse, 54+ weeks). The predictive value of the PCC technique was found to be independent of other prognostic factors for the duration of CR, and it identified those patients within the poor prognostic category with a high likelihood of imminent relapse. While similar trends were observed at later time intervals in CR, the differences in relapse rate between patients with high or low PPI values is not significant. These results confirm the usefulness of the PCC technique in predicting relapse in acute leukemia and could aid in the identification of patients who might benefit by an alteration of therapeutic strategy.     

Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis

Median survival of patients with AL amyloidosis with clinically significant cardiac involvement is 5 months when treated with cyclic melphalan and prednisone. We investigated a regimen of continuous oral melphalan as a single agent for patients with cardiac amyloidosis who were unable to tolerate prednisone or more aggressive chemotherapy. Thirty patients with amyloid cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients, evaluable after 3-4 months of treatment, achieved a partial haematological response and three achieved a complete haematological response; six patients have survived for > 1 year. This regimen appeared to be effective in inducing haematological responses in patients who received total doses of melphalan > 300 mg.     

Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell- associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti- CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti- CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.     

High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial

Summary:A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.     

MRI isolation of infected renal cyst in autosomal dominant polycystic kidney disease

The use of gadolinium-enhanced magnetic resonance (MR) to isolate an infected renal cyst in the setting of autosomal dominant polycystic kidney disease (ADPKD) has not been previously described. A case in which T1- and T2-weighted and gadolinium-enhanced MR images were used to identify a single purulent cyst in a patient with ADPKD is herein presented. We suggest that gadolinium-enhanced MR be considered useful in the evaluation of ADPKD patients with suspected infected cyst.