The consequences of H2 receptor antagonist — piroxicam coadministration in patients with joint disorders

Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L^–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC_0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC_0-24(5-OHP)], the ratio of these i.e. AUC_0-24(5-OHP):AUC_0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC_0-23(5-OHP):AUC_0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.     

Circular dichroism detection in high-performance liquid chromatography: Evaluation of the anisotropy factor

The application of a circular dichroism (c.d.) detection system in HPLC using a chiral stationary phase is presented. The simultaneous measurement of the absorbance and c.d. signal allows the evaluation of the anisotropy factor (g = Δ/) and thus the determination of the enantiomeric excess (e.e.) of the eluates. When this detection system is used in preparative chiral chromatography the collection of the enantiomeric fractions can be readily optimized.     

异环磷酰胺为主的联合方案治疗晚期复发鼻咽癌

[目的]观察比较异环磷酰胺(IFO)、顺铂(DDP)、5-氟尿嘧啶(5-Fu)联合方案(IPF方案)与DDP,5-Fu(PF方案)治疗晚期复发鼻咽癌(Ⅲ-Ⅳ期)的近期疗效及毒副反应。[方法]136例均经病理证实为晚期复发鼻咽癌患者,随机分为IPF组69例,PF组67例(对照组)[结果]IPF组和PF组有效率分别为69.56％(48/69)和43.3％(29/67),两组间差异有显著性(X2=8.519,P<0.01)。中位生存期:IPF组16个月(8-34个月),PF组为6.5个月(4-21个月),两组间差异有显著性(X2=22.36,P<0.05)。毒副作用主要为骨髓抑制,Ⅲ-Ⅳ度白细胞下降率IPF组为49.4％,PF组为5.97％,两组差异有显著性(X2=29.54,P<0.01)。Ⅲ-Ⅳ度血小板下降率IPF组为29.18％,PF组为0％(X2=30.29,P<0.01);Ⅲ-Ⅳ度消化道反应两组的发生率分别为15.94％和11.94％(x2=0.234,P>0.01).且以Ⅲ度为主。[结论]以IFO为主的方案联合治疗晚期复发鼻咽癌疗效好,毒副反应能耐受,可作为一线方案。     

奥兰扎平治疗精神分裂症58例临床观察

目的观察奥兰扎平治疗精神分裂症的临床疗效与安全性.方法选择58例精神分裂症病人,开始给予奥兰扎平5mg*d-1,3d后根据临床疗效、副反应情况酌情增加剂量,最大剂量不超过20mg*d-1,治疗8周.治疗前及治疗后每2周用PANSS、CGI、TESS量表评定1次.结果治疗后PANSS总分、各因子分较治疗前显著下降(P<0.01),副反应主要有抗胆碱症状、过度镇静、体重增加、一过性丙氨酸氨基转移酶升高.结论奥兰扎平是一种安全、有效、副作用较轻的抗精神病药.     

甲状腺机能亢进危象：附14例临床分析

本文报道14例甲亢危象,其发病率为4.5％,其发病与感染、劳累、情绪激动及同位素治疗有关。指出同位素治疗甲亢初期应服用抗甲状腺药物,讨论了淡漠型危象的有关问题。     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.