Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors？

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R（＋）-rabeprazole] （10 mg） was found to be more effective than rabeprazole （20 mg） in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors （PPIs）. A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships （QSARs） are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.     

猪囊尾蚴特异循环免疫复合物致病作用的研究

本文对脑型和混合型猪囊尾蚴病患者脑脊液（ＣＳＦ）中特异循环免疫复合物（ＣＩＣ）进行了检测，其结果与患者ＣＴ表现及吡喹酮治疗第一个疗程过程中患者出现的高颅压情况存在一定联系。人工免疫复合物（ＩＣ）对ＢＡＬＢ／ｃ鼠作用后进行病理检查，发现脑实质和肾脏小血管均出现充血现象．部分小血管内皮细胞遭到破坏。因此认为特异循环免疫复合物可能是脑型、混合型猪囊尾蚴病患者在第一疗程中出现高颅压反应的主要因素之一。     

Development of extended multidrug resistance in HL60 promyelocytic leukaemia cells

Summary. In an attempt to mimic clinical conditions for the treatment of leukaemia, the HL60 promyelocytic cell line was treated for 18 h with low, clinically relevant, levels of the anthracycline epirubicin and the Vinca alkaloid vinblastine. The resulting drug-resistant sublines not only expressed P-glycoprotein and the MDR phenotype but were also cross-resistant to chlorambucil, methotrexate but were also cross-resistant to chlorambucil, methotrexate and cisplatinum, and had increased resistance to radiation. Development of resistance was associatted with an aberrant differentiation phenotype with decreased expression of myeloid antigens and expression of glycophorin A. an antigen normally associated with erythroid differentiation. The ability of HL60 cells to terminally differentiate in response to all- trans -retinoic acid (vitamin A acid) was lost in the sublines. These results suggest that either a single novel mechanism is responsible for multiple drug resistance or the initial response to drug treatment is the co-induction of multiple mechanisms. These cells and the method by which they were generated therefore provide a clinically relevant model for the study of the initial events in the development of not only multidrug resistance but also the extended multiple drug resistance usually encountered in the treatment of leukaemia.     

Automated reticulocyte counting using the Sysmex RAM-1

Reticulocyte counting using the Sysmex RAM-1 was evaluated. The results of 113 samples analysed on the Sysmex RAM-1 were compared with those from both flow cytometry (FCM) and a manual technique. Reticulocyte counting with the Sysmex RAM-1 showed excellent precision, with an overall coefficient of variance (CV) less than 5%, and almost no carry-over. Reticulocyte counts were stable after blood storage for 48 h at 4 degrees C and room temperature (RT). Linearity was demonstrated very well for Sysmex RAM-1 and FCM (rRAM=0.9998, rFCM=0.9974, P < 0.001) when reticulocyte counts were 5 x 109/l-480 x 109/l. Comparisons of methods showed a good relation for reticulocyte counts between Sysmex RAM-1 and manual counting (r=0.9760), FCM and manual counting (r=0.9623), and Sysmex RAM-1 and FCM (r=0.9527). Analysis of receiver operating characteristic curves showed that the true-positive rate (TPR) was 0.95 for Sysmex RAM-1, and 0.83 for FCM; the area under curve was 0.999 and 0.972 for Sysmex RAM-1, 0.990 and 0.900 for FCM. These findings confirm that Sysmex RAM-1 can make counting reticulocytes easier, more accurate and more reproducible.     

叶酸和维生素B类降低同型半胱氨酸能预防缺血性卒中吗?

流行病学证据表明,高同型半胱氨酸血症(HHcy)是缺血性卒中的重要危险因素,但这些证据并未得到随机对照试验证实,因此对HHcy是缺血性卒中的独立危险因素,还是缺血性卒中后的附带现象,目前仍有争议。进一步用叶酸和维生素B类降低同型半胱氨酸,是否能作为缺血性卒中的预防措施,意见也不一致。     

Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients

Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des-gamma carboxy-prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with alpha-fetoprotein (AFP). We conducted a cross-sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%-95%) and specificity (95%; 95% CI, 82%-96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively (P =.002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway.     

Pregnancy-related liver diseases

Opinion statement  

Molecular background of Rh D-positive,D-negative,D(el) and weak D phenotypes in Chinese

BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the genetic background of D-negative and D(el) in the Chinese population. MATERIALS AND METHODS: We investigated nine D-positive, 76 D-negative, 26 D(el) and three weak D Chinese individuals by amplification and sequencing of the complete coding region of the RHD gene from genomic DNA. A new RHD polymerase chain reaction with sequence-specific primers (PCR-SSP) method was developed with optimized specificity for typing Chinese individuals. RESULTS: In D-positive samples the RHD sequence was in complete concordance with RHD in other populations. In 12 of 76 (15.8%) D-negative individuals we detected regions of RHD. Three new alleles were found. All 26 D(el), as well as two weak D, individuals carried an RHD 1227A allele. In the remaining weak D sample we identified a weak D type 15. CONCLUSIONS: It should now be possible to correctly predict the RhD phenotype in Chinese subjects. D(el) can also be designated as a particular weak D type.     

Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation

Background Human minK protein is the β-subunit of I_Ks potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P < .0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)     

术前、术中肺通气功能与术后呼吸衰竭的关系

目的探讨机械通气时呼吸力学与术前肺功能的关系．确定术前通气功能参数能否预测术后呼吸衰竭。方法择期行肺切除术的原发性肺癌病人100例．ASAⅠ级或Ⅱ级，术前测定肺功能：一秒用力呼气容量（FEV1）、用力肺活量（FVC）、一秒用力呼气量与用力肺活量之比（FEV1／FVC％）、最大肺活量（VC）、最大通气量（MVV）、75％肺活量位用力呼气流速（FEh）、最大中期呼气流速（MMEFm）、功能残气量（FRC）、残气量与肺总量之比（RV/TLC％）；测定脉冲震荡肺功能：共振频率（Fres）、呼吸总阻抗（Zres）、中心阻力（Rc）、5Hz和20Hz时粘性阻力（R5、R30）。分别记录插管后机械通气初始和开胸单肺通气后双肺气道峰压（Tpeak）、双肺胸肺顺应性（TCT）和单肺气道峰压（Opeak）、单肺胸肺顺应性（OCT），取其平均值。Opeak和OCT与身高、体重及肺功能的关系采用多元逐步回归。一般情况和肺功能与术后呼吸衰竭的关系采用非条件Logistic回归分析。根据术后是否发生呼吸衰竭分为2组：呼吸衰竭组（RF）和非呼吸衰竭组（NRF）。结果Opeak与Zres、身高、体重和FEF。呈线性关系（R2=0．504），OCT与Zres、身高、VC和RVfrLC％呈线性关系（R^2=0.602）。与NRF组比较，RF组FEV1、FVC、FEV1／FVC％、MVV、MMEFw均降低（P〈0．01）。年龄≥60岁的老年患者FEV1≤60％、FEV1／FVC≤60％、MVV≤50％、MMEn％≤35％时，RF组术后呼吸衰竭发生率高于NRF组（P〈0．05）。Logistic回归表明．年龄和MVV是术后呼吸衰竭的两个主要影响因素。结论术中单肺通气时的气道峰压和胸肺顺应性分别与身高、体重和术前肺功能呈线性相关。中度肺功能减退的老年患者行胸科手术后发生呼吸衰竭的风险性大：年龄和MVV是术后呼吸衰竭的两个主要影响因素。